JP7668180B2 - Method for producing 5-bromo-2-adamantanone - Google Patents

Description

The present invention relates to a novel process for producing 5-bromo-2-adamantanone.
Adamantane derivatives are being used in a wide range of industrial applications due to their high heat resistance, transparency, and other properties. For example, they are known to be useful as electronic materials such as photoresists for semiconductor manufacturing, as functional materials, and as raw materials for pharmaceuticals and agrochemicals.

As a method for producing 5-bromo-2-adamantanone, for example, a method has been proposed in which 2-adamantanone is brominated using bromine in the presence of aluminum bromide and tert-butyl bromide (see, for example, Non-Patent Document 1). However, this production method requires expensive aluminum bromide and tert-butyl bromide, and the reaction takes two days, so it is difficult to say that it is an industrially advantageous method.

In addition, a method of brominating with carbon tetrabromide using a quaternary ammonium salt as a phase transfer catalyst (see, for example, Non-Patent Document 2) and a method of brominating with carbon tetrabromide using an iron catalyst (see, for example, Non-Patent Document 3) have been proposed.
However, both Non-Patent Document 2 and Non-Patent Document 3 use harmful carbon tetrabromide as a brominating agent. In addition, the production method described in Non-Patent Document 2 has a low yield of 5-bromo-2-adamantanone of 31%, and the production method described in Non-Patent Document 3 has a problem in that a reaction at a high temperature of 170° C. is required.

Synthetic Communications, 1979, Vol. 9, pp. 825-830. Chemistry-A European Journal, 2001, Vol. 7, pp. 4996-5003. Runssian Journal of Organic Chemistry, 2015, Volume 51, Pages 184-187.

In view of these conventional techniques, the object of the present invention is to provide a method for economically and simply producing 5-bromo-2-adamantanone.

As a result of extensive research into an inexpensive and simple method for producing 5-bromo-2-adamantanone, the inventors discovered that 5-bromo-2-adamantanone can be produced by easily brominating 2-adamantanone using bromine in the presence of aluminum chloride and/or metallic aluminum and various aliphatic halides, thus completing the present invention.

That is, the present invention relates to the following.
[1] A method for producing 5-bromo-2-adamantanone, comprising reacting 2-adamantanone with bromine in the presence of aluminum chloride and/or metallic aluminum and an aliphatic halide.
[2] The method according to 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.

The production method of the present invention allows 5-bromo-2-adamantanone to be produced economically and simply using inexpensive aluminum chloride and/or metallic aluminum and various aliphatic halides. It is also useful in that it allows the reaction time to be shortened.

The present invention is described in detail below.

As described above, the method of the present invention relates to a method for producing 5-bromo-2-adamantanone, which is characterized by reacting 2-adamantanone with bromine in the presence of aluminum chloride and/or metallic aluminum and an aliphatic halide.

There is no particular limitation on the amount of aluminum chloride or metallic aluminum used in the method of the present invention, or when both are used in combination, but they are usually used in an amount within a range of 0.5 to 10 times by mole per mole of 2-adamantanone, and in consideration of reactivity and the complexity of post-treatment steps, a range of 1.0 to 5 times by mole is preferable.
When metallic aluminum is used in the method of the present invention, aluminum in a commonly used and known form can be used as it is, specifically, in the form of powder, granules, flakes, chips, lumps, etc.

Specific examples of aliphatic halides used in the method of the present invention include ethyl chloride, ethyl bromide, ethyl iodide, n-propyl chloride, n-propyl bromide, n-propyl iodide, isopropyl chloride, isopropyl bromide, isopropyl iodide, n-butyl chloride, n-butyl bromide, n-butyl iodide, sec-butyl chloride, sec-butyl bromide, sec-butyl iodide, isobutyl chloride, isobutyl bromide, isobutyl iodide, tert-butyl chloride, tert-butyl bromide, tert-butyl iodide, n-pentyl chloride, n-pentyl bromide, n-pentyl iodide. Examples of the halides include linear, branched, or cyclic aliphatic halides having 2 to 8 carbon atoms, such as 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, 1,2-dichloroethane, 1,2-dibromoethane, 1,2-diiodoethane, and 1-bromo-3-chloropropane, which can be used alone or in any combination of any mixtures.

Among these aliphatic halides, linear or branched aliphatic halides having 2 to 8 carbon atoms, further sec- or tert-branched aliphatic halides, particularly tert-branched aliphatic halides, are preferably used. Furthermore, aliphatic halides having 3 to 5 carbon atoms are preferably used. Furthermore, as the chloride, bromide, and iodide halides, from the viewpoint of economic efficiency, chloride and bromide are more preferably used, and chloride is more preferably used.
In the method of the present invention, the amount of the aliphatic halide used is not particularly limited, but is used in a range of 0.1 to 10 times by mole relative to 1 mole of 2-adamantanone, and in consideration of reactivity and economic efficiency, it is preferably used in a range of 0.5 to 3.0 times by mole.

The amount of bromine used in the method of the present invention is not particularly limited, but is in the range of 1.0 to 50 times by mole relative to 1 mole of 2-adamantanone, and in consideration of reactivity and the complexity of post-treatment steps, it is preferably in the range of 3.0 to 20 times by mole.
In the method of the present invention, bromine used as a brominating agent may be used as a solvent, but if necessary, a halogenated hydrocarbon solvent such as dichloromethane, dibromomethane, dichloroethane, dibromoethane, etc. When a halogenated hydrocarbon solvent is used, 1 to 20 parts by weight are used per 1 part by weight of 2-adamantanone.

The reaction temperature 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. The reaction time varies depending on the aliphatic halide used, but the reaction is usually completed after 5 to 48 hours.

After the reaction is complete, the active substance is deactivated in the usual way and the product is extracted. The organic layer is then washed with water, the solvent is removed by distillation, and the desired 5-bromo-2-adamantanone is obtained by the usual purification procedures, such as recrystallization.

The following examples of the present invention are provided, but the present invention should not be construed as being limited to these examples.

The yield was determined by gas chromatography (GC) under the following conditions.
<Measurement by Gas Chromatography (GC)>
Apparatus: GC7820A (Agilent Technologies, Inc.)
Column: Capillary column TC-1 (GL Sciences, Inc.)
Internal standard: cyclododecane Measurement and quantification were carried out according to the operating method of the GC apparatus, by the internal standard method using cyclododecane.

The conditions for nuclear magnetic resonance and mass spectrometry are as follows.
<Measurement by Nuclear Magnetic Resonance>
・Apparatus: Avance 400 (manufactured by Bruker Corporation)
Solvent: deuterated chloroform <Measured by mass spectrometry (GCMS)>
・Apparatus: GCMS-QP2010Plus (manufactured by Shimadzu Corporation)
Column: Capillary column TC-1 (GL Sciences, Inc.)

Example 1 Preparation of 5-bromo-2-adamantanone 2-adamantanone (1.0 g, 6.66 mmol), aluminum chloride (1.78 g, 13.3 mmol), and bromine (21.3 g, 133 mmol) were added to a 100 mL recovery flask equipped with a stirrer, and the mixture was 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 mixture was heated to 50° C. and aged for 24 hours.
After the reaction was completed, water (5 mL) was added to the reaction solution to inactivate aluminum chloride, and then saturated aqueous sodium sulfite solution (50 mL) was added to reduce bromine. Then, dichloromethane (20 mL) was added for extraction, and the organic layer was separated. The obtained organic layer was washed with saturated aqueous sodium hydrogen carbonate solution (10 mL), and the solvent was distilled off under reduced pressure.
The compound obtained as described above was analyzed by nuclear magnetic resonance and mass spectrometry, and as a result, the compound was confirmed to be 5-bromo-2-adamantanone. The yield determined by gas chromatography was 96.7%.

Examples 2 to 16 Preparation of 5-bromo-2-adamantanone Using the same reaction apparatus as in Example 1, the same reaction was carried out by changing the aliphatic halides and their molar ratios under the conditions shown in Table 1. The results obtained are shown in Table 1.

Comparative Example 1: No Aliphatic Halide Used The same reaction apparatus as in Example 1 was used, and the same procedure as in Example 1 was repeated except that tert-butyl bromide was not used.
The compound obtained as described above was analyzed by gas chromatography, and it was found to be almost unreacted, with a yield of less than 0.1%. The results are shown in Table 1 together with other examples.

Comparative Example 2 (Without Aliphatic Halide) The same reaction apparatus as in Example 1 was used, except that tert-butyl bromide was not used and aluminum bromide was used instead of aluminum chloride, and the same procedure as in Example 1 was repeated. The results are shown in Table 1.

Reference Example 1
The reaction shown in the following reaction formula described in Non-Patent Document 1 was carried out using the same reaction apparatus as in Example 1. Specifically, tert-butyl bromide (t-BuBr) was added dropwise to a reaction apparatus containing 2-adamantanone and aluminum bromide, and the reaction was carried out. It took 48 hours for the reaction to be completed. The obtained results are shown in Table 1.
Synthetic Communications, 1979, Vol. 9, pp. 825-830 (Non-patent Document 1).
Incidentally, the aluminum bromide used in Reference Example 1 is currently expensive and can be difficult to handle due to its high hygroscopicity, and can be distinguished from the present invention, which is an economical or simple method for producing 5-bromo-2-adamantanone.

The results of Examples 1 to 16, Comparative Examples 1 and 2, and Reference Example 1 are shown in Table 1.

The abbreviations shown in Table 1 above are as follows.
¹⁾ The abbreviation for tert-butyl bromide.
²⁾ The abbreviation for tert-butyl chloride.
³⁾ The abbreviation for tert-butyl iodide.
⁴⁾ The abbreviation for sec-butyl bromide.
⁵⁾ The abbreviation for sec-butyl chloride.
⁶⁾ The abbreviation for isopropyl bromide.
⁷⁾ The abbreviation for cyclohexyl bromide.

The method of the present invention makes it possible to produce 5-bromo-2-adamantanone industrially and inexpensively, which is extremely useful industrially as a raw material for electronic materials, functional materials, and pharmaceutical and agricultural intermediates.

Claims (4)

A method for producing 5-bromo-2-adamantanone, comprising reacting 2-adamantanone with bromine in the presence of aluminum chloride and an aliphatic chloride or an aliphatic iodide . The method according to claim 1 , wherein the aliphatic chloride or aliphatic iodide is at least one selected from the group consisting of linear, branched, or cyclic aliphatic chlorides or aliphatic iodides having 2 to 8 carbon atoms. A method for producing 5-bromo-2-adamantanone, comprising reacting 2-adamantanone with bromine in the presence of metallic aluminum and an aliphatic halide. 4. The method according to claim 3, 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.