JP7699028B2 - 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 halide and/or aluminum metal and various unsaturated aliphatic compounds, thus completing the present invention.

That is, the present invention relates to the following.
[1] A method for producing 5-bromo-2-adamantanone, which comprises reacting 2-adamantanone with bromine in the presence of an aluminum halide and/or metallic aluminum and an unsaturated aliphatic compound.
[2] The method according to item [1], wherein the unsaturated aliphatic compound is at least one selected from the group consisting of linear, branched, or cyclic unsaturated aliphatic compounds having 2 to 8 carbon atoms.

The manufacturing method of the present invention allows for economical and simple production of 5-bromo-2-adamantanone using inexpensive aluminum halide and/or aluminum metal and various unsaturated aliphatic compounds.

The present invention is described in detail below.

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 an aluminum halide and/or metallic aluminum and an unsaturated aliphatic compound.

Aluminum halides that can be used in the method of the present invention include aluminum chloride, aluminum bromide, and aluminum iodide.
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.

The unsaturated aliphatic compound used in the method of the present invention is preferably at least one selected from the group consisting of linear, branched, or cyclic unsaturated aliphatic compounds having 2 to 8 carbon atoms. That is, it is a linear, branched, or cyclic aliphatic compound having 2 to 8 carbon atoms that contains an unsaturated bond between carbon atoms in the molecule.
Specific examples thereof include ethylene, propylene, 1-butene, 2-butene, isobutene, 1-pentene, 2-pentene, 3-pentene, 2-methyl-1-butene, 2-methyl-2-butene, 3-methyl-1-butene, 1-hexene, 2-hexene, 3-hexene, 2-methyl-1-pentene, 2-methyl-2-pentene, 1-heptene, 2-heptene, 3-heptene, 4-heptene, 2-methyl-1-hexene, 2-methyl-2-hexene, 1-octene, 2-octene, 3-octene, 4-octene, 2-methyl-1-heptene, and 2-methyl-2-heptene. compounds containing a double bond between carbon-carbon atoms in the molecule, such as cyclobutene, cyclopentene, cyclohexene, cycloheptene, and cyclooctene; compounds containing a cyclic structure in the molecule, such as acetylene, propyne, 1-butyne, 2-butyne, 1-pentyne, 2-pentyne, 1-hexyne, 2-hexyne, 3-hexyne, 1-heptyne, 2-heptyne, 3-heptyne, 1-octyne, 2-octyne, 3-octyne, and 4-octyne; and the like. These can be used alone or in any combination as a mixture.

In the method of the present invention, there is no particular limitation on the amount of unsaturated aliphatic compound used, but it is used in the range of 0.1 to 10 moles per mole of 2-adamantanone, and in consideration of reactivity and economic efficiency, it is preferable that the amount is in the range of 0.5 to 3.0 moles.

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 10 to 72 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 1-pentene (0.47 g, 6.66 mmol) was added dropwise at the same temperature. After the dropwise addition, the temperature was raised to 50° C. and the mixture was 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 93.8%.

Examples 2 to 10 Preparation of 5-bromo-2-adamantanone Using the same reaction apparatus as in Example 1, the same reaction was carried out by changing the unsaturated aliphatic compounds and their molar ratios under the conditions shown in Table 1. The results obtained are shown in Table 1.

Comparative Example 1 In the Case Where No Unsaturated Aliphatic Compound Was Used The same reaction apparatus as in Example 1 was used, and the procedure was the same as in Example 1, except that 1-pentene 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 (In the Case Where No Unsaturated Aliphatic Compound Was Used) The same reaction apparatus as in Example 1 was used, and the procedure was repeated except that 1-pentene was not used and aluminum bromide was used instead of aluminum chloride. The results are shown in Table 1.

なお、参考例１で用いた臭化アルミニウムは、現時点では高価で、吸湿性が高いため取り扱いづらくなることがあり、経済的あるいは簡便な５－ブロモ－２－アダマンタノンの製造方法という本発明とは区別できる。
以上の実施例１～１０、比較例１～２、及び参考例１の結果を表１に示した。

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 10, Comparative Examples 1 and 2, and Reference Example 1 are shown in Table 1.

Table 1 reveals the following:
Looking at the results of Examples 1 to 4, it appears that the reaction rate varies depending on the amount of unsaturated aliphatic compounds relative to the amounts of bromine and Al species in the reaction. That is, the amount of 1-pentene is large in Example 2, which has a short reaction time, followed by Example 3, Example 1, and Example 4. This seems to indicate that the reaction rate is determined by the unsaturated aliphatic compounds in the bromination reaction, and shows that the presence of the unsaturated aliphatic compounds in the present invention acts favorably on an efficient reaction.

For the various unsaturated aliphatic compounds used in Examples 1 to 10, good results were obtained in terms of reaction rate and yield, and no significant differences were observed among the types of unsaturated aliphatic compounds that were tried as to which was the most suitable compound.

Comparing Example 2 and Example 7, Example 2 is an example in which _AlCl3 was used as the Al species, and Example 7 is an example in which Al powder was used as the Al species. No significant difference was observed in the reaction yields, but the reaction time was 8 hours in Example 2 and 36 hours in Example 7, and it is believed that _AlCl3 was more likely to act as a form related to the reaction.

Comparing Example 2 and Comparative Example 1, the reaction conditions are generally similar except that both use _AlCl3 as the Al species and Comparative Example 1 does not use an unsaturated aliphatic compound. Also, comparing Example 3 and Comparative Example 2, the reaction conditions are generally similar except that both use _AlBr3 as the Al species and Comparative Example 2 does not use an unsaturated aliphatic compound. As a result, the reaction yields in Comparative Examples 1 and 2 are less than 0.1%, and the target product is not substantially produced. This shows that the presence of an unsaturated aliphatic compound is essential for the production of the target product.
Here, in Reference Example 1, _AlBr3 was used as the Al species, as in Example 3 and Comparative Example 2, with the difference being that t-BuBr was used instead of the unsaturated aliphatic compound. In Reference Example 1, as shown in Table 1, the reaction yield was relatively high at 97.9%, but the reaction time was required to be extremely long at 48 hours. Furthermore, although not stated in Table 1, the table on page 827 of Non-Patent Document 1 indicates that the reaction required a long period of time, from 3 days (72 hours) to 10 days (240 hours), which is not practical.
Therefore, even from the results of Example 2 alone, it can be seen that the present invention is a practical method for producing 5-bromo-2-adamantanone.

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, etc.

Claims (2)

A method for producing 5-bromo-2-adamantanone, characterized by reacting 2-adamantanone with bromine in the presence of an aluminum halide and/or metallic aluminum and an unsaturated aliphatic compound. The method according to claim 1, characterized in that the unsaturated aliphatic compound is at least one selected from the group consisting of linear, branched, or cyclic unsaturated aliphatic compounds having 2 to 8 carbon atoms.