JP2023044747A - Method for producing 5-hydroxy-2-adamantanone - Google Patents

Abstract

To provide a method for producing 5-hydroxy-2-adamantanone by a more economical and simple process than a conventionally well-known production method.SOLUTION: A method for producing 5-hydroxy-2-adamantanone includes a process in which in the presence of aluminum halide and/or metal aluminum and aliphatic halide, 2-adamantanone is reacted with bromine, and then water is added for hydrolysis.SELECTED DRAWING: None

Description

The present invention relates to a novel method for producing 5-hydroxy-2-adamantanone.
Adamantane derivatives are expanding their applications in various industrial fields due to their properties such as high heat resistance and transparency. For example, they are known to be useful as electronic materials such as photoresists for manufacturing semiconductors, functional materials, and raw materials for pharmaceuticals and agricultural chemicals.

As a method for producing 5-hydroxy-2-adamantanone, for example, a method of oxidizing 2-adamantanone using an aqueous sodium perchlorate solution or nitric acid has been proposed (see, for example, Patent Document 1, etc.).
A method of oxidizing unsubstituted adamantane using sulfuric acid and nitric acid has also been proposed (see, for example, Patent Document 2).
However, in the methods described in Patent Document 1 or Patent Document 2, it is difficult to obtain high-purity 5-hydroxy-2-adamantanone due to by-production of dihydroxy compounds, residual raw materials, etc., and recrystallization or the like is difficult. It is necessary to repeat the purification operation.

As another production method, a method has been proposed in which 2-adamantanone is used as a raw material, bromination is performed with carbon tetrabromide to obtain 5-bromo-2-adamantanone, and then hydrolysis is performed using sodium hydroxide. (For example, see Non-Patent Document 1, etc.).
However, the method described in Non-Patent Document 1 has the problem that the bromination reaction requires a high temperature condition of 170° C. and that harmful carbon tetrabromide must be used. Furthermore, there is also the problem that 5-bromo-2-adamantanone must be isolated once after the bromination reaction. In addition, when the present inventor attempted to produce 5-hydroxy-2-adamantanone using the production method described in Non-Patent Document 1, the hydrolysis reaction did not proceed and the target compound could not be obtained. It was difficult.

China Patent No. 104725194. Russian Patent No. 2557249.

Russian Journal of Organic Chemistry, 2015, Vol. 51, pp. 184-187.

An object of the present invention is to provide an economical and convenient method for producing 5-hydroxy-2-adamantanone in view of these prior arts.

The present inventors have extensively studied an inexpensive and simple method for producing 5-hydroxy-2-adamantanone.
That is, bromination of 2-adamantanone with bromine in the presence of an aluminum halide and/or metallic aluminum and various aliphatic halides to produce 5-bromo-2-adamantanone as an intermediate. . After that, water is added as a post-treatment to deactivate the aluminum halide and/or metal aluminum, and the aluminum halide hydrate and the hydrobromic acid produced as a by-product of the bromination reaction are added to the reaction system. hold in the presence of By this retention, the 5-bromo-2-adamantanone can be hydrolyzed without isolating 5-bromo-2-adamantanone, and as a result, 5-hydroxy-2-adamantanone can be easily produced. This led to the completion of the present invention.

That is, the present invention relates to the following.
[1] Aluminum halide and / or metal aluminum, 2-adamantanone and bromine are reacted in the presence of an aliphatic halide, and then water is added to hydrolyze the 5-hydroxy - A method for producing 2-adamantanone.
[2] Item [1], wherein the aliphatic halide is at least one selected from the group consisting of linear, branched, or cyclic aliphatic halides having 2 to 8 carbon atoms. Method of manufacture as described.
[3] The production method according to item [1] or [2], wherein the aluminum halide is at least one selected from the group consisting of aluminum chloride, aluminum bromide, and aluminum iodide.
[4] A method for producing 5-hydroxy-2-adamantanone, which comprises hydrolyzing 5-bromo-2-adamantanone in the presence of hydrogen bromide, aluminum halide hydrate, and water. .

According to the production method of the present invention, 5-hydroxy-2-adamantanone can be produced economically and simply.

The present invention will be described in detail below.
The method of the present invention comprises reacting an aluminum halide and/or metal aluminum with 2-adamantanone and bromine in the presence of an aliphatic halide, and then adding water to eliminate the aluminum halide and/or metal aluminum. The present invention relates to a method for producing 5-hydroxy-2-adamantanone, characterized in that it is kept in an activated state and hydrolyzed without isolating 5-bromo-2-adamantanone.

Specific examples of aluminum halides used in the method of the present invention include aluminum chloride, aluminum bromide, aluminum iodide and the like, and these can be used alone or as a mixture. Of these, aluminum chloride and/or aluminum bromide are usually selected in consideration of reactivity, economy and availability.

In the method of the present invention, when metallic aluminum is used, commonly used known forms of aluminum can be used as they are. Specific examples include forms such as powder, granules, flakes, chips, and lumps.

The amount of aluminum halide or metal aluminum used in the method of the present invention, or when both are used in combination, is not particularly limited, but usually 0.5 times per 1 mol of 2-adamantanone It is used in the range of 1.2 to 10 mol, and considering the reactivity and the complexity of the post-treatment process, it is preferably in the range of 1.2 to 5 mol.

Specific examples of aliphatic halides used in the process of the invention include ethyl chloride, ethyl bromide, ethyl iodide, n-propyl chloride, n-propyl bromide, n-propyl iodide, iso-propyl chloride, iso-propyl bromide, iso-propyl iodide, n-butyl chloride, n-butyl bromide, n-butyl iodide, sec-butyl chloride, sec-butyl bromide, sec-butyl iodide, iso-butyl chloride, iso-butyl bromide, iso-butyl iodide, tert-butyl chloride, tert-butyl bromide, tert-butyl iodide, n-pentyl chloride, n-pentyl bromide, n-pentyl iodide, n-hexyl chloride, n-hexyl bromide, n-hexyl iodide, n-heptyl chloride , n-heptyl bromide, n-heptyl iodide, n-octyl chloride, n-octyl bromide, n-octyl iodide, cyclopentyl chloride, cyclopentyl bromide, cyclopentyl iodide, cyclohexyl chloride, cyclohexyl bromide, cyclohexyl iodide, 1, linear, branched or cyclic aliphatic halides having 2 to 8 carbon atoms such as 2-dichloroethane, 1,2-dibromoethane, 1,2-diiodoethane, 1-bromo-3-chloropropane, etc.; These can be used alone or as mixtures in any combination.

In the method of the present invention, the amount of the aliphatic halide to be used is not particularly limited, but it is used in the range of 0.1 to 10 moles per 1 mole of 2-adamantanone, and the reactivity In consideration of cost and economy, it is preferably in the range of 0.5 to 3.0 mol.

The amount of bromine used in the method of the present invention is not particularly limited, but it is used in the range of 1.0 to 50 moles per 1 mole of 2-adamantanone. Considering the complexity of , it is preferably in the range of 3.0-fold to 30-fold mol.

In the method of the present invention, bromine used as a brominating agent may be used as a solvent, but halogenated hydrocarbon solvents such as dichloromethane, dibromomethane, dichloroethane, and dibromoethane may also be used as necessary. When a halogenated hydrocarbon solvent is used, it is used in an amount of 1 to 20 parts by weight per 1 part by weight of 2-adamantanone.

The reaction temperature for bromination in the method of the present invention is in the range of 20°C to 65°C, preferably in the range of 40°C to 60°C. Although the reaction time varies depending on the aliphatic halide used, the bromination reaction is usually completed by carrying out the reaction for 5 to 48 hours.

After completion of the bromination reaction in the method of the present invention, water is added to deactivate the aluminum halide and/or metallic aluminum. The amount of water to be added is not particularly limited, but it is used in the range of 2 to 120 parts by weight per 1 part by weight of 2-adamantanone. After adding water, hydrolysis may be performed while maintaining the temperature as it is, or hydrolysis may be performed after heating once to distill off excess bromine and then maintaining the temperature at the predetermined temperature.

In the method of the present invention, 5-hydroxy-2-adamantanone, which is an intermediate in the production of 5-hydroxy-2-adamantanone from 2-adamantanone, is not isolated and purified. Adamantanone can be manufactured.
In the method of the present invention, once the intermediate 5-bromo-2-adamantanone is isolated, or when commercially available 5-bromo-2-adamantanone is used, hydrogen bromide , an aluminum halide hydrate and water are added and heated to cause hydrolysis to produce the desired product, 5-hydroxy-2-adamantanone.

The amount of hydrogen bromide to be used in the method of the present invention is not particularly limited, but is in the range of 0.1 to 10 moles, more preferably 1 mole of 5-bromo-2-adamantanone. It is preferably used in the range of 0.5-fold molar to 5-fold molar.

Specific examples of the aluminum halide hydrate used in the method of the present invention include aluminum (III) chloride hexahydrate, aluminum (III) bromide hexahydrate and the like, and these are used alone or as a mixture. be able to.

The amount of aluminum halide hydrate to be used in the method of the present invention is not particularly limited, but it is in the range of 0.5 to 10 moles per 1 mole of 5-bromo-2-adamantanone. More preferably, it is used in an amount of 1.0- to 5-fold mol, and considering the reactivity and the complexity of post-treatment steps, the range is preferably 1.2- to 5-fold mol.

The hydrolysis reaction temperature in the method of the present invention is in the range of 50°C to 110°C, preferably in the range of 80°C to 110°C. The reaction time is generally 12 to 72 hours to complete the hydrolysis reaction.

After the hydrolysis reaction is completed, the remaining bromine is deactivated by a conventional method, and the product is extracted. Subsequently, the organic layer is washed with water, the solvent is distilled off, and the target 5-hydroxy-2-adamantanone is obtained by a normal purification operation such as recrystallization.

Examples of the present invention are shown below, but the present invention should not be construed as being limited to these examples.

In addition, about a yield, it is the value calculated|required by the following conditions by gas chromatography (GC).
<Measurement by gas chromatography (GC)>
・ Apparatus: GC7820A (manufactured by Agilent Technologies, Inc.)
・ Column: Capillary column TC-1 (manufactured by GL Sciences Co., Ltd.)
・Internal standard: cyclododecane

Moreover, the conditions of mass spectrometry are as follows.
<Measurement by mass spectrometry (GCMS)>
・ Apparatus: GCMS-QP2010Plus (manufactured by Shimadzu Corporation)
・ Column: Capillary column TC-1 (manufactured by GL Sciences Co., Ltd.)

Example 1 Preparation of 5-Hydroxy-2-adamantanone Into a 100 mL eggplant flask equipped with a stir bar was added 2-adamantanone (1.0 g, 6.66 mmol), aluminum chloride (1.78 g, 13.3 mmol), bromine. (21.3 g, 133 mmol) was added, cooled to 0° C. with stirring, and tert-butyl bromide (0.59 g, 4.33 mmol) was added dropwise at the same temperature. After the dropwise addition, the temperature was raised to 50° C. and aged for 24 hours.
The reaction solution obtained by the above operation was cooled to 0° C. and water (60 g) was added to deactivate aluminum chloride. Thereafter, a simple distillation apparatus was attached to the eggplant flask containing the reaction solution, and the reaction solution was heated from 60° C. to 100° C. to distill off bromine. After distilling off the bromine, the residue consisting of the oil and water layers in the eggplant flask was kept at 100° C. for 24 hours with further stirring.
After completion of the reaction, a sodium sulfite saturated aqueous solution (1 mL) was added to the reaction solution to reduce a trace amount of residual bromine. After that, dichloromethane (20 mL) was added for extraction, and the organic layer was separated. The obtained organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate (10 mL), and the solvent was distilled off under reduced pressure.
The compound obtained as described above was analyzed by mass spectrometry, and as a result, the compound was confirmed to be 5-hydroxy-2-adamantanone. Moreover, the yield and purity determined by gas chromatography were 95.5% and 99.5%, respectively. The results are shown in Table 1.

Examples 2-14 Preparation of 5-Hydroxy-2-adamantanone Using the same reactor as in Example 1, varying the aliphatic halide and aluminum species under the conditions shown in Table 1, similar reactions were carried out. did Table 1 shows the results obtained.

Example 15 Preparation of 5-Hydroxy-2-adamantanone Into a 100 mL eggplant flask equipped with a stir bar was added 5-bromo-2-adamantanone (1.0 g, 4.36 mmol), aluminum (III) chloride hexahydrate. (1.58 g, 6.54 mmol), 48%-hydrobromic acid (2.0 g) and water (9 g) were added, and after attaching a Dimroth condenser, the mixture was reacted at 100° C. for 20 hours while stirring.
After completion of the reaction, the post-treatment was carried out in the same manner as in Example 1 to obtain the desired product, 5-hydroxy-2-adamantanone, with a yield of 82.0% (purity of 99.2%).

Comparative Example 1 Preparation of 5-hydroxy-2-adamantanone by hydrolysis reaction of 5-bromo-2-adamantanone 5-bromo-2-adamantanone (1.0 g, 4.36 mmol), 20% H ₂ SO ₄ aqueous solution (10 mL), and ethanol (10 mL) were added, and after attaching a Dimroth condenser, the mixture was aged at 78° C. for 18 hours while stirring.
Analysis of the reaction solution by gas chromatography revealed that almost no reaction occurred and the yield was less than 0.1%. The results are shown in Table 2 together with other examples.

Comparative Examples 2-4 Preparation of 5-hydroxy-2-adamantanone by hydrolysis reaction of 5-bromo-2-adamantanone Alternatively, the same hydrolysis reaction was performed by changing various bases. Table 2 shows the results obtained.

The results of Examples 1 to 14 are shown in Table 1, and the results of Comparative Examples 1 to 4 are shown in Table 2.

Abbreviations shown in Tables 1 and 2 are as follows.
¹⁾ All molar and weight ratios refer to 2-adamantanone.
²⁾ represents the abbreviation for tert-butyl bromide;
³⁾ represents the abbreviation for tert-butyl chloride.
⁴⁾ represents the abbreviation for tert-butyl iodide.
⁵⁾ Indicates the abbreviation for sec-butyl bromide.
⁶⁾ Indicates the abbreviation for iso-propyl bromide.
⁷⁾ represents the abbreviation for cyclohexyl bromide;

According to Table 1, 2-adamantanone and bromine were reacted in the presence of an aluminum halide such as AlCl ₃ or metallic aluminum (Al powder) and an aliphatic halide such as tert-butyl halide, followed by water 2-adamantanone can be brominated in a high yield of 50% or more.
Further, by adding water to this reaction solution and aging it, the desired product, 5-hydroxy-2-adamantanone, was hydrolyzed, yielding a high yield of 48% or more and a high purity (99.0% in Example 1). 5%), 5-hydroxy-2-adamantanone can be obtained.

According to Table 2, even if an aqueous solution of acid or base is added to 5-hydroxy-2-adamantanone alone, hydrolysis of 5-hydroxy-2-adamantanone does not occur, or even if it occurs, it takes 48 hours. It was found that the yield was as low as about 40% in the reaction, and when compared with the results in Table 1, a large difference was recognized.

INDUSTRIAL AND LOW COST PRODUCTION OF 5-HYDROXY-2-ADAMANTANONE The method of the present invention is industrially very useful as a raw material for electronic materials, functional materials, and pharmaceutical and agrochemical intermediates.

Claims (4)

Aluminum halide and / or metal aluminum, 2-adamantanone and bromine are reacted in the presence of an aliphatic halide, and then hydrolyzed by adding water, 5-hydroxy-2- A method for producing adamantanone. The production method according to claim 1, wherein the aliphatic halide is at least one selected from the group consisting of linear, branched, or cyclic aliphatic halides having 2 to 8 carbon atoms. . 3. The production method according to claim 1, wherein the aluminum halide is at least one selected from the group consisting of aluminum chloride, aluminum bromide and aluminum iodide. A method for producing 5-hydroxy-2-adamantanone, which comprises hydrolyzing 5-bromo-2-adamantanone in the presence of hydrogen bromide, aluminum halide hydrate, and water.