JP2003040884A - Method for producing mevalolactone - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for producing mevalolactone in high efficiency on an industrial scale from a raw material available at a low cost. SOLUTION: The method for the production of mevalolactone comprises the reaction of 3-methylpentane-1,3,5-triol with hydrogen peroxide in an aqueous solvent in the presence of a tungstic acid compound.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for producing mevalolactone. The mevalolactone obtained in the present invention is known as a precursor of natural isoprenoid, and is useful as a raw material for the synthesis of medicines and agricultural chemicals, and as a raw material for the synthesis of resist materials in the field of electronics (see Japanese Patent Laid-Open No. 10-78658). .

[0002]

2. Description of the Prior Art Mevalolactone is treated with 3-methylpentane-
As a method for producing 1,3,5-triol as a raw material, (1) a method of oxidizing using silver carbonate (tetrahedron letter (Tetrahedron Let)
t. ), Vol. 31, p. 171 (1975)),
(2) A method of oxidizing with peracetic acid in the presence of sodium bromide (Bullin of Chemical Society Japan (Bull. Chem. Soc. Jp.
n. ), 65, 703 (1992)),
(3) Method of oxidizing with sodium bromate (Synthetic Communications (Synth. Co
mmun. ), 28, 123-130 (1998).
(4), (4) A method of oxidizing with sodium hypochlorite in a mixed solvent of water and acetonitrile in the presence of a bromide such as sodium bromide (JP-A-2000-3
No. 8383) is known.

[0003]

The above method (1) is
The cost is high because a large amount of expensive silver carbonate is used. The above method (2) has a problem that it is difficult to handle because the peracetic acid used is unstable and there is a risk of explosion or the like. The above-mentioned method (3) is not industrially manufactured for sodium bromate to be used, and it is difficult to apply it to large-scale manufacturing. Also, the above method (4)
Has mild reaction conditions, but has a problem that the reaction time is relatively long and the productivity is low because a large amount of solvent is used.

An object of the present invention, therefore, is to provide a method capable of efficiently and industrially producing mevalolactone using inexpensively available raw materials.

[0005]

DISCLOSURE OF THE INVENTION The inventors of the present invention have noticed that the above-mentioned conventional methods are all production methods under oxidation reaction conditions, and 3-methylpentane-1,3,5-triol The inventors have made extensive studies on a method capable of producing mevalolactone as a raw material efficiently and industrially advantageously.

[0006] Alcohols are oxidized with hydrogen peroxide in the presence of tungstic acids and quaternary ammonium hydrogensulfates to obtain ketones from secondary alcohols and aldehydes or carboxylic acids from primary alcohols. Are known. For example, JP-A-11-158107
The publication discloses that when a secondary alcohol and a primary alcohol coexist in the molecule, hydroxyketones in which the secondary alcohol is selectively oxidized are obtained. Specific examples of such alcohols are disclosed. 2-methyl-as an example
1,3-hexanediol, 2-methyl-1,4-hexanediol, 2-methyl-1,5-hexanediol, 2-ethyl-1,3-hexanediol, 2-ethyl-1,4-hexanediol , 2-ethyl-1,5-
Hexanediol is shown, Example 8 of which is
An example in which 2-ethyl-1-hydroxy-3-hexanone was obtained from 2-ethyl-1,3-hexanediol is described. Also, Bulletin of Chemical Society Japan (Bull. Chem. Soc. J.
pn. ), 72, 2287-2306 (1999).
1) from 9,11-nonadecanediol in Table 5
An example is given in which 1-hydroxynonadecan-9-one is obtained. However, no mention is made of products from polyhydric alcohol compounds having a plurality of primary alcohols such as diols and triols other than the above alcohols in the molecule.

In the above reaction, when a polyhydric alcohol compound having a plurality of primary alcohols such as diol and triol in the molecule is used as a raw material, a polyhydric aldehyde compound such as a dialdehyde compound or a dicarboxylic acid compound or It is expected that a polycarboxylic acid compound will be obtained. However, when the present inventors reacted 3-methylpentane-1,3,5-triol with hydrogen peroxide in the presence of tungstic acids and a quaternary ammonium salt in a water solvent, it was surprising. In particular, it was found that mevalolactone can be obtained in a good yield, and a patent application was previously filed (see Japanese Patent Application No. 2000-303081).

Further, the inventors of the present invention have conducted extensive studies by paying attention to the fact that the above reaction can be carried out in an aqueous solvent, and as a result, 3-methylpentane-1,3 has been added without adding a quaternary ammonium salt. , 5-triol is reacted with hydrogen peroxide in the presence of tungstic acids in a water solvent, mevalolactone is obtained in a good yield, and the heat of reaction in the reaction is water. It was found that the heat can be efficiently removed and the reaction time can be shortened by removing it by the latent heat of vaporization.

That is, the present invention is a method for producing mevalolactone, which comprises reacting 3-methylpentane-1,3,5-triol with hydrogen peroxide in the presence of tungstic acids in a water solvent. is there.

In a preferred embodiment, the amount of hydrogen peroxide used is in the range of 1.5 to 2.5 mol per mol of 3-methylpentane-1,3,5-triol.

In a preferred embodiment, the heat of reaction is removed by the latent heat of vaporization of water which is a solvent.

[0012]

BEST MODE FOR CARRYING OUT THE INVENTION Examples of the tungstic acid used in the present invention include tungstic acid, sodium tungstate, potassium tungstate, lithium tungstate, ammonium tungstate, phosphotungstic acid, silicotungstic acid and the like. Among these, sodium tungstate and potassium tungstate are preferably used. These tungstic acids may be in the form of anhydride or hydrate. The amount of tungstic acid used is 0.001 to 100 relative to 3-methylpentane-1,3,5-triol in consideration of the yield and productivity of the reaction.
It is preferably in the range of mol%, more preferably in the range of 0.01 to 10 mol%, and in the range of 0.01 to 5 mol%.
Is particularly preferable.

Hydrogen peroxide is commercially available 10
An aqueous hydrogen peroxide solution with a concentration in the range of -60% can be used as is. Considering the yield and productivity of the reaction, the amount of hydrogen peroxide used is 1.5 in terms of hydrogen peroxide contained relative to 1 mol of 3-methylpentane-1,3,5-triol. The range is preferably from 2.5 to 2.5 mols, more preferably from 1.7 to 2.3 mols, still more preferably from 1.8 to 2.2 mols. The amount of hydrogen peroxide used is 3-methylpentane-1,
When less than 1.5 mol per mol of 3,5-triol, the yield of mevalolactone decreases as the amount used decreases, and when more than 2.5 mol, the production of mevalolactone decreases. The side reaction such as oxidative decomposition of the lactone ring of the mevalolactone proceeds, and the mevalolactone yield tends to decrease.

The reaction is carried out using water as a solvent. The amount of water used is not particularly limited, but usually 3-methylpentane-1,
It is preferably in the range of 0.1 to 50 times the weight of 3,5-triol, and more preferably in the range of 0.5 to 10 times the weight from the viewpoint of economy and volume efficiency.

The reaction temperature is preferably in the range of -10 ° C to 110 ° C. Considering the reactivity and stability of hydrogen peroxide in the reaction system, the range of 30 ° C to 100 ° C is more preferable. preferable. The reaction is carried out under the pressure that can achieve the above temperature range, that is, 200 to 76 in consideration of the stability of the product.
It is preferably carried out in the range of 0 Torr.

The present invention can be carried out in the atmosphere, but from the viewpoint of safety, it is preferably carried out in an atmosphere of a gas inert to the reaction such as nitrogen and argon.

The reaction is preferably carried out while removing the heat of reaction by the latent heat of evaporation of water as a solvent, from the viewpoint of shortening the reaction time. For example, a method of carrying out the reaction while distilling water out of the reaction system, A method of carrying out the reaction while refluxing water can be applied.

There are no particular restrictions on the method of charging the raw materials, and for example, a predetermined amount of 3-methylpentane-1,3,5-triol and tungstic acid can be added in an atmosphere of a gas inert to the reaction such as nitrogen or argon. The solution is dissolved in water to a predetermined temperature and a predetermined pressure, an aqueous hydrogen peroxide solution is added little by little to the obtained mixed solution, and the reaction is carried out while distilling the water out of the reaction system or while refluxing the water.

The mevalolactone obtained by the above method can be isolated / purified by the usual isolation / purification operation carried out in the organic synthesis reaction. For example, after adding sodium sulfite, sodium hydrogen sulfite, etc. to the reaction mixture to decompose the peroxide, the mixture is extracted with an organic solvent such as ethyl acetate, the extracts are combined and concentrated, and the resulting crude product is distilled. Alternatively, it is purified by column chromatography or the like.

The 3-methylpentane-1,3,5-triol used in the present invention is commercially available at a low cost and can be easily obtained.

[0021]

EXAMPLES The present invention will be described in detail below with reference to examples, but the present invention is not limited to these examples.

Example 1 In a three-necked flask having a capacity of 200 ml equipped with a mechanical stirrer, a thermometer and a dropping funnel, 0.825 g (2.5 mmol) of sodium tungstate dihydrate,
3-Methylpentane-1,3,5-triol 33.5
After adding g (0.25 mol) and 25 g of water, the system was replaced with nitrogen to prepare a mixed solution. Then, the temperature of this mixed solution was raised to 90 ° C. with stirring, 59.54 g (0.613 mol) of 35% hydrogen peroxide aqueous solution was added dropwise over 2 hours, and then the mixture was stirred at the same temperature for 10 hours. The obtained reaction mixture was cooled, 1.0 g of sodium sulfite was added, and then the mixture was extracted 6 times with 100 ml of ethyl acetate. The extracts were combined and concentrated, and 37.6 g of the obtained crude mevalolactone was purified by silica gel column chromatography (developing solvent: hexane / ethyl acetate = 7/3 (volume ratio)) to give mevalolactone 2
9.0 g (0.22 mol, 89% yield) was obtained.

Example 2 The same operation as in Example 1 was carried out except that 0.815 g (2.5 mmol) of potassium tungstate was used instead of 0.825 g (2.5 mmol) of sodium tungstate dihydrate. Done, 27.0 g of mevalolactone
(0.21 mol, yield 83%) was obtained.

Example 3 3.30 g (0.01 mol) of sodium tungstate dihydrate and 3-methylpentane-1,3 were placed in a 5-necked flask having a capacity of 1 L equipped with a mechanical stirrer, a thermometer and a dropping funnel. , 5-triol 134.2g
After adding (1.0 mol) and 100 g of water, the system was replaced with nitrogen to prepare a mixed solution. Subsequently, the temperature of this mixed liquid was raised to 90 ° C. with stirring, and 238.1 g (2.5 mol) of 35% hydrogen peroxide aqueous solution was added dropwise over 4 hours, followed by stirring at the same temperature for 8 hours. After cooling the obtained reaction mixture, 37.2 g of sodium sulfite was added, and then the mixture was extracted 6 times with 400 ml of ethyl acetate. The extracts were combined and concentrated to obtain the crude mevalolactone 14
By refining 2.2 g using silica gel column chromatography (developing solvent: hexane / ethyl acetate = 7/3 (volume ratio)), 110.6 g of mevalolactone was obtained.
(0.85 mol, yield 85%) was obtained.

Example 4 In a 5-necked flask having a capacity of 1 L equipped with a mechanical stirrer, a thermometer, a dropping funnel and a reflux device, 3.30 g (10 mmol) of sodium tungstate dihydrate,
3-Methylpentane-1,3,5-triol 134.
After adding 2 g (1.0 mol) and 100 g of water, the system was replaced with nitrogen to prepare a mixed solution. Subsequently, the temperature of this mixed solution was raised to 90 ° C. with stirring, and then 238.1 g (2.45 mol) of a 35% hydrogen peroxide aqueous solution was added dropwise over 2 hours, and after completion of the addition, the mixture was further heated at 100 ° C. for 2 hours. It was stirred. Water 15 is added during the dropping of the hydrogen peroxide solution and during the reaction.
While diluting 0 ml, the distilled water was returned to the reactor. After cooling the resulting reaction mixture, 19.15 g of sodium sulfite was added, followed by 10% ethyl acetate.
Extracted 6 times with 0 ml. The extracts were combined and concentrated, and 150.4 g of the crude mevalolactone obtained was purified by silica gel column chromatography (developing solvent: hexane / ethyl acetate = 7/3 (volume ratio)) to give 117.2 g of mevalolactone. (0.90 mol, yield 90
%) Was obtained.

[0026]

INDUSTRIAL APPLICABILITY According to the present invention, mevalolactone can be produced efficiently and industrially advantageously using raw materials that can be obtained at low cost.

Claims (3)

[Claims] 1. A process for producing mevalolactone, which comprises reacting 3-methylpentane-1,3,5-triol with hydrogen peroxide in the presence of tungstic acids in a water solvent. 2. The amount of hydrogen peroxide used is 1.5 to 1 mol of 3-methylpentane-1,3,5-triol.
The production method according to claim 1, wherein the amount is 2.5 mol. 3. The production method according to claim 1, wherein the heat of reaction is removed by latent heat of vaporization of water which is a solvent.