JP2003238463A - Method for producing allyl alcohol - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method by which highly pure allyl alcohol compound can profitably be produced. <P>SOLUTION: This method for producing allyl alcohol represented by general formula (2) [X and Y represent each H, or X and Y together represent a carbon - carbon bond; (n) is an integer of ≥1] comprises (i) making a vinyl Grignard reagent to act on a ketone represented by general formula (1), (ii) making at least one compound selected from the group consisting of isocyanates, acid halides and acid anhydrides to act on a reaction mixture, and then (iii) isolating allyl alcohol represented by general formula (2). <P>COPYRIGHT: (C)2003,JPO

Description

Description: TECHNICAL FIELD [0001] The present invention relates to a compound represented by the following general formula (2): Wherein X and Y each represent a hydrogen atom or together represent a carbon-carbon bond;
Represents an integer of 1 or more. ) [Hereinafter referred to as allyl alcohol (2)] with high purity. Allyl alcohols (2) obtained according to the invention, such as geranyl linalool (X and Y together being a carbon-carbon bond, n
= 3 is compound) is useful as a synthetic raw material for vitamin K _2, a isophytol (X and Y are each a hydrogen atom, n = a 3 compounds) are useful as synthetic raw material for vitamin E . [0004] Conventionally, as a method for producing allyl alcohol (2), general formula (1) is used. Wherein X and Y each represent a hydrogen atom or together represent a carbon-carbon bond;
Represents an integer of 1 or more. (Hereinafter referred to as ketone compound (1)) is reacted with vinyl Grignard reagent [Perfection Chemistry Directory [II], Hirokawa Shoten, p. 614 (1980)]
reference]. [0007] In the above-mentioned method, a by-product having a small difference in physical properties such as a boiling point close to that of the target allyl alcohol (2) is produced. ) Was difficult to obtain efficiently. Accordingly, an object of the present invention is to provide a method capable of industrially and advantageously producing a high-purity allyl alcohol (2) required particularly in applications such as the field of pharmaceutical raw materials in a high yield. According to the present invention, the above object is achieved by (i) reacting a ketone compound (1) with a vinyl Grignard reagent to obtain a reaction mixture; After at least one compound selected from the group consisting of an isocyanate compound, an acid halide and an acid anhydride is allowed to act on the mixture, (iii) allyl alcohol (2)
And a method for producing allyl alcohol (2), characterized in that In the above formula, n is an integer of 1 or more, preferably 1 or more and 10 or less. First, the step of reacting a ketone compound (1) with a vinyl Grignard reagent to obtain a reaction mixture containing allyl alcohol (2) [hereinafter sometimes abbreviated as step (i)] will be described. . As the vinyl Grignard reagent, vinyl magnesium chloride, vinyl magnesium bromide,
Vinyl magnesium halide such as vinyl magnesium iodide, tetrahydrofuran, diethyl ether,
And a solution dissolved in ether such as isopropyl ether [hereinafter, this may be abbreviated as a vinyl Grignard reagent solution]. The amount of the vinyl Grignard reagent used is not strictly limited, but is usually preferably in the range of 0.5 to 10 mol, and more preferably in the range of 1 to 3 mol, per 1 mol of the ketone compound (1). More preferably, there is. The reaction of step (i) can be carried out in the presence or absence of a solvent. Solvents that can be used include, for example, aromatic hydrocarbons such as benzene, toluene and xylene; aliphatic hydrocarbons such as hexane and heptane;
Examples thereof include ethers such as tetrahydrofuran, diethyl ether, and isopropyl ether. When a solvent is used, its use amount is not particularly limited, but is usually preferably 20 times by mass or less based on the ketone compound (1). The reaction temperature in step (i) is from -30 to 100
C., and more preferably -10 to 50C. As a reaction method of the step (i), for example, a solution obtained by dissolving a ketone compound (1) in a solvent as required is set to a predetermined temperature, and a solution of a vinyl Grignard reagent is intermittently or continuously added to this solution. A method of adding the ketone compound (1) or a solution of the ketone compound (1) in a solvent intermittently or continuously while maintaining a predetermined temperature, to the solution of the vinyl Grignard reagent; ) Is dissolved in a solvent as necessary, and a solution of a vinyl Grignard reagent is simultaneously added to a reactor while maintaining a predetermined temperature, and there is no particular limitation. The reaction mixture obtained in step (i) is
Although it is possible to directly subject it to the next step, water, hydrochloric acid aqueous solution, sulfuric acid aqueous solution, acetic acid aqueous solution, ammonium chloride aqueous solution and the like are added to the reaction mixture, and then extraction is performed with toluene, ethyl acetate, dichloromethane and the like. After that, the obtained organic layer can be subjected to the next step. Next, a step of allowing at least one compound selected from the group consisting of an isocyanate compound, an acid halide and an acid anhydride to act on the reaction mixture obtained in step (i) [hereinafter referred to as step (ii) ) May be abbreviated). Examples of the isocyanate compound include trimethylene diisocyanate, tetramethylene diisocyanate, pentamethylene diisocyanate, hexamethylene diisocyanate, octamethylene diisocyanate, 1,5-diisocyanato-2-methylpentane,
1,3-bis (isocyanatomethyl) cyclohexane,
Isophorone diisocyanate, 1,3-bis (isocyanatomethyl) benzene, 3-isopropenyl-α, α-
Dimethylbenzyl isocyanate, toluene-2,4-
Examples thereof include diisocyanate, 4,4′-diphenylmethane diisocyanate, phenyl isocyanate, 1-naphthyl isocyanate, and 2-naphthyl isocyanate. These compounds may be used alone or as a mixture of two or more. Among these, from the viewpoint of operability and the like, it is preferable to use an isocyanate compound having 6 or more carbon atoms. It is particularly preferable to use a polyisocyanate or the like. Examples of the acid halide include phthalic acid chloride, terephthalic acid dichloride, benzoic acid chloride, 2,4-dichlorobenzoyl chloride, paranitrobenzoyl chloride, adipic acid chloride, acetic acid chloride, propionic acid chloride, caprylic acid chloride, Palmitic acid chloride, stearic acid chloride and the like can be mentioned. These compounds may be used alone or as a mixture of two or more. Among these, from the viewpoint of operability and the like, it is preferable to use an acid halide having 4 or more carbon atoms, and it is particularly preferable to use adipic acid chloride, phthalic acid chloride, palmitic acid chloride and the like. Examples of the acid anhydride include acetic anhydride, propionic anhydride, phthalic anhydride, succinic anhydride, maleic anhydride, pyromellitic anhydride, citraconic anhydride, trimellitic anhydride, benzoic anhydride, and adipic anhydride. And the like. These compounds may be used alone or as a mixture of two or more. Among them, it is preferable to use an acid anhydride having 4 or more carbon atoms from the viewpoint of selectivity and operability of the reaction, and it is particularly preferable to use phthalic anhydride, succinic anhydride, pyromellitic anhydride and the like. The amount of the isocyanate compound, acid halide and / or acid anhydride is not particularly limited.
Usually, 0.001 to 1 mol of the ketone compound (1)
It is preferably in the range of 1 mol, and more preferably in the range of 0.01 to 0.1 mol from the viewpoints of economy, operability and the like. In the step (ii), amines such as pyridine, triethylamine and N-methylpiperazine; sodium methoxide, potassium methoxide,
Metal alkoxides such as sodium t-butoxide and potassium t-butoxide may be further added. When these compounds are used, the amount used is not particularly limited, but is usually 0.1 to 1 mol of the ketone compound (1).
It is preferably in the range of 001 to 10 mol, and 0.05
More preferably, it is in the range of 0.5 mol. Step (ii) can be performed in the presence or absence of a solvent. Examples of usable solvents include aromatic hydrocarbons such as benzene, toluene and xylene; aliphatic hydrocarbons such as pentane, hexane and heptane; diethyl ether, diisopropyl ether and di-
ethers such as n-butyl ether, tetrahydrofuran, dimethoxyethane, diglyme and dioxane; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, 1,2-dichloroethane and trifluoromethylbenzene. These solvents may be used alone or as a mixture of two or more. When a solvent is used, its use amount is not particularly limited, but is preferably in the range of 0.1 to 100 times the mass of the ketone compound (1). The temperature in step (ii) is -20 to 200 ° C.
Is preferable, and from the viewpoints of stability and reactivity of the allyl alcohol (2), the temperature is more preferably in the range of 0 to 130 ° C. In the step (ii), for example, after adding a solvent as necessary to the reaction mixture obtained in the step (i), an isocyanate compound, an acid halide and / or an acid anhydride are added, and Then, after further adding amines and metal alkoxides, the mixture is stirred at a predetermined temperature or, if necessary, a solvent is added to the reaction mixture obtained in the step (i). , Acetic acid aqueous solution, ammonium chloride aqueous solution and the like, and then toluene,
After performing an extraction operation with ethyl acetate, dichloromethane or the like, an isocyanate compound, an acid halide and / or an acid anhydride are added to the obtained organic layer, and further amines and metal alkoxides are added as necessary. It can be performed by stirring at a predetermined temperature. After the completion of the step (ii), the resulting mixture may be directly subjected to the following allyl alcohol (2) isolation step, but water: an alcohol such as methanol, ethanol or isopropanol may be used. After the addition, the resulting mixture can be subjected to the following allyl alcohol (2) isolation step. Further, after water is added to the mixture to perform liquid separation extraction, the obtained organic layer can be subjected to a purification step. When the reaction mixture obtained in the step (i) is directly subjected to the step (ii), the step (i)
After completion of the reaction in i), water, an aqueous solution of hydrochloric acid, an aqueous solution of sulfuric acid, an aqueous solution of acetic acid, an aqueous solution of ammonium chloride, and the like are added to the obtained mixture, followed by extraction with toluene, ethyl acetate, dichloromethane, and the like. The obtained organic layer is subjected to the next step. Finally, the step of isolating the allyl alcohol (2) will be described. Allyl alcohol (2) from the mixture containing allyl alcohol (2) obtained in step (ii)
Is isolated and purified in the same manner as that generally used in the isolation and purification of organic compounds. For example, the reaction mixture obtained in the step (ii) is concentrated if necessary, and the residue is further purified by means such as distillation and column chromatography. EXAMPLES The present invention will be described below in more detail with reference to examples, but the present invention is not limited by these examples. Example 1 (a) Equipped with a stirrer, the internal volume of which was replaced with nitrogen and was 5000 m.
l, 2948 g of vinylmagnesium chloride prepared from vinyl chloride and metallic magnesium (1
6.0 mass% tetrahydrofuran solution, 5.43 mo
l) and then 1092 g of farnesyl acetone
(4.16 mol) was added dropwise at 22 ° C., and the mixture was further reacted at the same temperature for 2 hours. The obtained reaction mixture was gradually added to 1000 g of water, and then a 11.7% by mass aqueous hydrochloric acid solution 33 was added.
After gradually adding 74 g, 2,500 g of toluene was added to separate an organic layer and an aqueous layer. The obtained organic layer was washed with 2000 g of a 3% aqueous sodium carbonate solution, and then the solvent was distilled off.
1410 g of crude geranyl linalool was obtained as a residue.
The residue was subjected to gas chromatography (column: J & W capillary column DB-WAX 30 mx 0.25 m
m, film thickness: 0.25 μm, carrier gas: helium,
Injection temperature: 220 ° C, detection temperature: 230 ° C, column temperature: 200 ° C to 230 ° C, 1 ° C
/ Min, and analyzed by detector: FID).
Geranyl linalool is contained at 81.4% by mass (1148 g), and 6,10,14-trimethylpentadeca-5,9,13-trien-2-ol is contained at 0.82% by mass (11.6 g). I was (B) 140 g of the crude geranyl linalool obtained in the above (a) (114 g of geranyl linalool,
6,10,14-trimethylpentadeca-5,9,13
-Trien-2-ol (containing 1.15 g), 7.47 g of hexamethylene diisocyanate (98.0% by mass,
43.5 mmol) and 3.44 g of pyridine (43.
5 mmol) and stirred at 90 ° C. for 10 hours. After adding 50 g of methanol to the obtained solution and refluxing for 5 hours, low-boiling components were distilled off from the mixture. After degassing the residue under reduced pressure, the residue is distilled with a thin-film distillation apparatus (temperature: 140 ° C, 113.
3 Pa), 5 g (99.0% by mass of geranyl linalool, 6,10,14-trimethylpentadeca-5,9,13-trien-2-ol 0.0 g as initial fraction)
95.2 g (geranyl linalool 99.5 mass%, 6,10,14-trimethylpentadeca-5,9,13-trien-2-ol 0.1%).
(Analysis under the same gas chromatography analysis conditions as in Example 1). Example 3 145 g of crude geranyl linalool (118 g of geranyl linalool, obtained by the method described in Example 1 (a),
6,10,14-trimethylpentadeca-5,9,13
-Trien-2-ol (containing 1.19 g), 8.24 g (45.0 mmol) of adipic acid chloride and 24.1 g (0.304 mol) of pyridine were added, and the mixture was added at 23 ° C.
For 30 hours. 50 g of a saturated aqueous solution of sodium carbonate and 100 g of hexane were added to the obtained solution to separate an organic layer and an aqueous layer. The low-boiling components were distilled off from the obtained organic layer, and the obtained residue was subjected to deaeration under reduced pressure, followed by distillation with a thin-film distillation apparatus (temperature: 140 ° C., 13.3 Pa) to obtain 7 g as an initial fraction ( Geranyl linalool containing 99.2% by mass, 6,10,14-trimethylpentadeca-
5,9,13-trien-2-ol is not detected),
99.2 g (geranyl linalool 99.8) as the main fraction
6,10,14-trimethylpentadeca-%
5,9,13-Trien-2-ol was not detected) (analyzed under the same gas chromatography analysis conditions as in Example 1). Example 4 140 g of crude geranyl linalool (114 g of geranyl linalool, obtained by the method described in Example 1 (a)
6,10,14-trimethylpentadeca-5,9,13
-Trien-2-ol (containing 1.15 g), 2.6 g (17.4 mmol) of phthalic anhydride and 8.8 g (87.0 mmol) of triethylamine were added, and the mixture was stirred at 85 ° C for 10 hours. To the obtained solution, 100 g of a 10% aqueous solution of sodium carbonate and 100 g of toluene were added to separate an organic layer and an aqueous layer. The low-boiling components were distilled off from the obtained organic layer, and the obtained residue was subjected to deaeration under reduced pressure, followed by distillation with a thin film distillation apparatus (temperature: 140 ° C., 13.3 Pa) to obtain 5 g as an initial fraction ( Geranyl linalool containing 99.5% by mass, 6,10,14-trimethylpentadeca-
5,9,13-trien-2-ol is not detected),
101.3 g (geranyl linalool 99.g) as a main fraction
6% by mass, 6,10,14-trimethylpentadeca-5,9,13-trien-2-ol not detected)
(Analyzed under the same gas chromatography analysis conditions as in Example 1). REFERENCE EXAMPLE 1 Crude geranyl linalool was distilled as it was 141 g of geranyl linalool crude obtained in Example 1 (114.8 g of geranyl linalool, 6,10,14-trimethylpentadeca-5,9,13-triene-) After degassing the 2-ol (containing 1.16 g) under reduced pressure, the mixture was distilled (temperature: 140 ° C., 13.3 Pa) using a thin-film distillation apparatus. As a first fraction, 30 g (geranyl linalool 98.3) was obtained.
Mass%, 6,10,14-trimethylpentadeca-5
9,13-trien-2-ol 0.8% by mass), 70.2 g (geranyl linalool 98.5% by mass, 6,10,14-trimethylpentadeca-5,9,9
Thus, 13-trien-2-ol (0.8% by mass) was obtained (analyzed under the same gas chromatography analysis conditions as in Example 1). According to the present invention, high-purity allyl alcohol (2) can be produced industrially and advantageously in high yield.

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Claims (1)

[Claim 1] (i) General formula (1) (Wherein, X and Y each represent a hydrogen atom or together represent a carbon-carbon bond, and n represents an integer of 1 or more) by reacting a vinyl Grignard reagent with a ketone compound represented by the following formula: A reaction mixture is obtained, and (ii) at least one compound selected from the group consisting of an isocyanate compound, an acid halide and an acid anhydride is allowed to act on the reaction mixture, and (iii) a compound represented by the general formula (2): Formula 2 (Wherein, X, Y and n are as defined above)
A method for producing an allyl alcohol represented by the general formula (2), wherein the allyl alcohol represented by the following formula (2) is isolated.