JP2001354605A - Method for manufacturing tertiary alcohol - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for manufacturing a tertiary alcohol capable of lowering the yield of byproducts and greatly improving the yield of an alkylated compound. SOLUTION: In the method for manufacturing a tertiary alcohol from a ketone by using an alkylmagnesium compound, a lithium halide is used together with the alkylmagnesium compound.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a method for producing a tertiary alcohol, and more particularly, to a method for producing a tertiary alcohol capable of reducing the yield of by-products and obtaining an alkylated product in a high yield. It is about the method.

[0002]

2. Description of the Related Art Conventionally, when an organic magnesium compound such as a Grignard reagent is generally used for alkylating a ketone, a reduced alcohol is mainly produced in addition to the alkylated product which is a target product. For example, when 2-adamantanone is reacted with a Grignard reagent having an ethyl group in order to ethylate 2-adamantanone, adamantanone is reduced in addition to the target product, 2-ethyladamantanol. -Adamantanol is known to be produced in large amounts (2-ethyladamantanol yield 40%, 2-adamantanol yield 60%; JACh
em. Soc, Vol. 9, No. 13, p4248-4634 (1972)). It is also known to use organolithium to prevent the reductant, and the reaction proceeds almost quantitatively. However,
Organolithium reagents are expensive and require careful handling, and thus have the problem of increasing product costs. On the other hand, in recent years, applications of the adamanthanone derivative have been developed in various fields, and development of 2-ethyladamantanol as a resist raw material has been advanced. However, as described above, the by-product 2
-There is a problem that the yield of adamantanol is high and the production cost is high due to the use of the organolithium reagent, and a method capable of producing an adamantanone derivative such as 2-ethyladamantanol at low cost has been desired.

[0003]

SUMMARY OF THE INVENTION The present invention is intended to reduce the yield of by-products and significantly improve the yield of alkylated products in the production of tertiary alcohols under such circumstances. It is an object of the present invention to provide a method for producing a tertiary alcohol.

[0004]

Means for Solving the Problems The present inventors have made intensive studies to solve the above-mentioned problems, and as a result, in a method for producing a tertiary alcohol from a ketone using an alkyl magnesium compound, It has been found that coexistence of a lithium halide reduces the yield of by-products and significantly improves the yield of alkylated products. The present invention has been completed based on such findings. That is, the present invention provides a method for producing a tertiary alcohol from a ketone using an alkylmagnesium compound, wherein a lithium halide is allowed to coexist with the alkylmagnesium compound. Is provided.

[0005]

BEST MODE FOR CARRYING OUT THE INVENTION Ketones to be alkylated by the production method of the present invention include, in addition to general ketones such as acetone and methyl ethyl ketone, 2-adamantanones and substituted adamantanones having a substituent on an adamantane skeleton.
Examples include bulky ketones such as 2, diisopropyl ketone, di-t-butyl ketone, and benzophenone. Here, as the substituted adamantanone-2, 1-methyl-2
-Adamantanone, 1-ethyl-2-adamantanone and the like. The alkylmagnesium compound used in the method of the present invention includes a compound represented by the formula RMgX [R
Is an alkyl group or substituted alkyl group having β hydrogen, X represents a halogen atom], and a dialkylmagnesium represented by the formula R ₂ Mg. In the above formula, as the alkyl group, an ethyl group, n
-Propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, n-
Examples thereof include an alkyl group having 2 to 10 carbon atoms such as an amyl group, an isoamyl group, an n-hexyl group, an n-heptyl group, an n-octyl group, and an isooctyl group. Examples of the substituent of the substituted alkyl group include a methoxy group and an ethoxy group. Examples of the halogen atom include chlorine, iodine, bromine, and fluorine. In the present invention, as the Grignard reagent, ethylmagnesium chloride and ethylmagnesium bromide are preferable. Examples of the alkyl group and the substituted alkyl group in the dialkylmagnesium include the same as those described above. In the present invention, it is preferable to use dialkylmagnesium as the alkylmagnesium compound from the viewpoint of obtaining an alkylated product as a target product in a high yield. The amount of the alkylmagnesium compound to be used is preferably 1 to 10 equivalents, more preferably 1 to 5 equivalents, per 1 equivalent of the ketone.

[0006] Examples of lithium halide coexisting with the alkyl magnesium compound include lithium fluoride, lithium chloride, lithium bromide and lithium iodide. The amount of the lithium halide to be used is preferably from 0.1 to 100 equivalents, more preferably from 0.5 to 10 equivalents, per equivalent of the alkylmagnesium compound.

The production method of the present invention comprises a reaction formula R'R "C = O + RMgX → R'R" .CROH 2R'R "C = O + R ₂ Mg → 2R'R" .CROH (where R and X are As above, R′R ″ represents a divalent residue of a ketone.) In the production of a tertiary alcohol, the ketone may be added to the alkyl magnesium compound, and vice versa. The reaction temperature can be usually −30 to 100 ° C., preferably around room temperature, and the pressure during the reaction may be normal pressure, but may be slightly reduced or increased. It is preferably completed in 1.5 to 10 hours, preferably 1 to 5. The reduced form of the by-product may be separated by direct separation and purification, or may be separated by reaction in the next step. As the solvent, a solvent generally used for an alkylation solvent may be used. And diethyl ether, THF (tetrahydrofuran), hexane, anisole, 1,4-dioxane, HMPA (hexamethylphosphoric triamide) and the like can be used.

[0008]

Next, the present invention will be described in more detail with reference to examples, but the present invention is not limited to these examples. Example 1 After drying a 50 ml three-volume flask under reduced pressure,
7.5 ml of ethyl magnesium chloride solution (7.5 mmol (1 equivalent to 1 equivalent of 2-adamantanone)
5 mol); 1 mol / l in a tetrahydrofuran solution) and 0.3 g of lithium chloride (7.5 mmol (1.5 equivalent per 1 equivalent of 2-adamantanone)) were dissolved in a tetrahydrofuran solvent at room temperature. The 2-adamantanone was added dropwise over 10 minutes (the amount of adamantanone contained was 5 mmol) over 10 minutes. 3 after dropping
After an hour, an aqueous ammonium chloride solution was added to terminate the ethylation reaction. The reaction mixture was extracted with ether, and the extract was analyzed by gas chromatography. As a result, it was confirmed that 2-ethyladamantanol was formed. 2
The yield of -ethyladamantanol was 46%. The yield of by-product 2-adamantanol was 54%.
%Met.

Example 2 In Example 1, ethyl magnesium chloride was replaced with ethyl magnesium bromide, and the amount of lithium chloride was doubled to 0.6 g (15 mmol (3 equivalents per equivalent of 2-adamantanone)). An ethylation reaction was carried out in the same manner as in Example 1 except for the above. Perform ether extraction of the reaction solution,
The extract was analyzed by gas chromatography.
-Ethyl adamantanol was formed. The yield of 2-ethyladamantanol was 53%. The yield of by-product 2-adamantanol was 47%.

Example 3 A 50 ml three-necked flask was dried under reduced pressure.
7.5 ml of a previously prepared diethylmagnesium solution (3.75 mmol (1.5 equivalents per equivalent of 2-adamantanone); 0.5 mol / l in tetrahydrofuran solution) and 0.6 g (15 mmol) of lithium chloride (3 equivalents per 1 equivalent of 2-adamantanone)) and 10 ml of 2-adamantanone dissolved in tetrahydrofuran solvent (the amount of adamantanone contained was 5 mmol) was added dropwise at room temperature over 10 minutes. 3 after dropping
After an hour, an aqueous ammonium chloride solution was added to terminate the ethylation reaction. The reaction mixture was extracted with ether, and the extract was analyzed by gas chromatography. As a result, it was confirmed that 2-ethyladamantanol was formed. 2
The yield of -ethyladamantanol was 64%. The yield of by-product 2-adamantanol was 36.
%Met. Comparative Example 1 An ethylation reaction was carried out in the same manner as in Example 1 except that lithium chloride was not made to coexist with ethylmagnesium chloride, and the same analysis was carried out. As a result, the yield of 2-ethyladamantanol was 31%. . The yield of 2-adamantanol as a by-product was 69%. Comparative Example 2 An ethylation reaction was carried out in the same manner as in Example 2 except that lithium chloride was not allowed to coexist with ethylmagnesium bromide, and the same analysis was performed. As a result, the yield of 2-ethyladamantanol was 29%. . The yield of by-product 2-adamantanol was 71%. Comparative Example 3 An ethylation reaction was carried out in the same manner as in Example 3 except that lithium chloride was not made to coexist in diethylmagnesium, and analysis was conducted in the same manner. As a result, the yield of 2-ethyladamantanol was 41%. In addition, 2 which is a by-product
-The yield of adamantanol was 59%.

[0011]

According to the present invention, in a method for producing a tertiary alcohol from a ketone using an alkylmagnesium compound, the yield of by-products is reduced and the yield of alkylated products is significantly improved. Thus, tertiary alcohols can be produced at low cost.

Continued on the front page F term (reference) 4H006 AA02 AC41 AD16 BA03 BA06 BA37 BA44 BB15 BB25 BC10 BC19 BC34 FC36 FE12

Claims (3)

[Claims] 1. A method for producing a tertiary alcohol from a ketone using an alkylmagnesium compound, wherein a lithium halide is allowed to coexist in the alkylmagnesium compound. 2. The method according to claim 1, wherein the alkyl magnesium compound is a Grignard reagent or dialkyl magnesium.
A method for producing the tertiary alcohol according to the above. 3. The method for producing a tertiary alcohol according to claim 1, wherein the ketone is 2-adamantanone or substituted adamantanone.