JP2002080473A - Method of producing mevalolactone - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method of efficiently producing mevalolactone from inexpensively available raw materials with industrial advantage. SOLUTION: In the method for producing mevalolactone according to this invention, 3-methylpentane-1,3,5-triol is characteristically allowed to react with hydrogen peroxide in the presence of a tungstic acid, an acid, and a quaternary ammonium salt in an aqueous medium.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a method for producing mevalolactone. The mevalolactone obtained in the present invention is known as a precursor of a natural isoprenoid, and is useful as a raw material for synthesizing pharmaceuticals and agricultural chemicals and as a resist material in electronics.
No. 78658).

[0002]

2. Description of the Related Art Mevalolactone is converted to 3-methylpentane-
As a method for producing 1,3,5-triol as a raw material, (1) a method of oxidizing using silver carbonate (Tetrahedron Lets)
t. ), Vol. 31, p. 171 (1975)),
(2) Oxidation using peracetic acid in the presence of sodium bromide (Britin of Chemical Society)
Japan (Bull. Chem. Soc. Jpn.),
Vol. 65, p. 703 (1992)), (3) Oxidation using sodium bromite (Synthetic Communications (Synth. Commu)
n. ), Vol. 28, pp. 123-130 (1998)), (4) Oxidation using sodium hypochlorite in a mixed solvent of water and acetonitrile in the presence of a bromide such as sodium bromide ( JP-A-2000-38383
Is known.

[0003]

The method of the above (1) is as follows.
A large amount of expensive silver carbonate must be used. The method (2) has a problem that the peracetic acid used is unstable and has a risk of explosion and the like, and is difficult to handle. In the method (3), the sodium bromite used is not industrially manufactured, and is difficult to apply to large-scale manufacturing. In addition, the method (4) has a problem that, although the reaction conditions are mild, 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 for producing mevalolactone efficiently and industrially advantageously using raw materials which can be obtained at low cost.

[0005]

The present inventors have focused on the fact that all of the above-mentioned conventional methods are production methods under oxidation reaction conditions, and have converted 3-methylpentane-1,3,5-triol. The present inventors have conducted intensive studies on a method for producing mevalolactone efficiently and industrially advantageously as a raw material.

It is already known to oxidize alcohols with hydrogen peroxide in the presence of tungstic acids and quaternary ammonium hydrogensulfate to obtain ketones from secondary alcohols and aldehydes or carboxylic acids from primary alcohols. Have been. For example, JP-A-11-158107
The publication discloses that when a secondary alcohol and a primary alcohol coexist in a molecule, hydroxyketones in which the secondary alcohol is selectively oxidized are obtained. For example, 2-methyl-
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, and Example 8 includes:
An example is described in which 2-ethyl-1-hydroxy-3-hexanone was obtained from 2-ethyl-1,3-hexanediol. In addition, Bulletin of Chemical Society Japan (Bull. Chem. Soc. J.
pn. ), Vol. 72, pp. 2287-2306 (1999)
Year 5) shows that from 9,11-nonadecanediol
An example in which 1-hydroxynonadecan-9-one was obtained is shown. However, there is no description of a product derived from a polyhydric alcohol compound having a plurality of primary alcohols such as diols and triols in the molecule other than the above alcohols.

In the above reaction, when a polyhydric alcohol compound having a plurality of primary alcohols such as diols and triols in a molecule is used as a raw material, a polyhydric aldehyde compound such as a dialdehyde compound, a dicarboxylic acid compound or the like is used. It is expected that a polycarboxylic acid compound will be obtained. However, the present inventors have proposed that 3-methylpentane-1,3,5-triol can be prepared by adding tungstic acids and quaternary ammonium hydrogen sulfate or quaternary ammonium salt in an aqueous solvent.
When reacted with hydrogen peroxide in the presence of a quaternary ammonium organic sulfonate, it was surprisingly found that mevalolactone was obtained in good yield.

The present inventors have further studied the above reaction and found that 3-methylpentane-1,
It has been found that reacting 3,5-triol with hydrogen peroxide in an aqueous solvent in the presence of tungstic acids, acids and quaternary ammonium salts gives mevalolactone in good yield.

That is, the present invention relates to the reaction of 3-methylpentane-1,3,5-triol with hydrogen peroxide in an aqueous solvent in the presence of tungstic acids, acids and quaternary ammonium salts. A method for producing mevalolactone, characterized in that 3-methylpentane-1,3,5-triol is formed from tungstic acids and a quaternary ammonium hydrogen sulfate and a quaternary ammonium organic sulfonate in an aqueous solvent. A method for producing mevalolactone, comprising reacting with hydrogen peroxide in the presence of a quaternary ammonium salt selected from the group.

[0010]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The tungstic acids used in the present invention include, for example, 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 preferred. These tungstic acids may be in the form of an anhydride or a hydrate. The amount of tungstic acids used is determined in consideration of the yield and productivity of the reaction.
The range of 0.001 to 100 mol% relative to triol is preferable, the range of 0.01 to 10 mol% is more preferable, and the range of 0.01 to 5 mol% is particularly preferable.

As the quaternary ammonium salt, a quaternary ammonium salt soluble in water is preferable, for example, tetramethylammonium chloride, tetraethylammonium chloride, tetrapropylammonium chloride, tetrabutylammonium chloride, trimethylethylammonium chloride,
Trimethylbenzylammonium chloride, dimethyldiethylammonium chloride, triethylmethylammonium chloride, triethylbenzylammonium chloride, tripropylmethylammonium chloride, methylpyrrolidinium chloride, ethylpyrrolidinium chloride, methylpiperidinium chloride, ethylpiperidinium chloride, Methyl morpholinium chloride, ethyl morpholinium chloride, methyl pyridinium chloride, cetyl pyridinium chloride,

Tetramethylammonium bromide, tetraethylammonium bromide, tetrapropylammonium bromide, tetrabutylammonium bromide, trimethylethylammonium bromide, trimethylbenzylammonium bromide, dimethyldiethylammonium bromide, triethylmethylammonium bromide, Triethylbenzylammonium bromide, tripropylmethylammonium bromide, methylpyrrolidinium bromide, ethylpyrrolidinium bromide, methylpiperidinium bromide, ethylpiperidinium bromide, methylmorpholinium bromide, bromide Ethyl morpholinium,
Methylpyridinium bromide, cetylpyridinium bromide,

Tetramethylammonium iodide, tetraethylammonium iodide, tetrapropylammonium iodide, tetrabutylammonium iodide, trimethylethylammonium iodide, trimethylbenzylammonium iodide, dimethyldiethylammonium iodide, triethylmethylammonium iodide, Triethylbenzylammonium iodide, tripropylmethylammonium iodide, methylpyrrolidinium iodide, ethylpyrrolidinium iodide, methylpiperidinium iodide,
Ethylpiperidinium iodide, methylmorpholinium iodide, ethylmorpholinium iodide, methylpyridinium iodide, cetylpyridinium iodide,

Tetramethyl ammonium hydrogen sulfate, tetraethyl ammonium hydrogen sulfate, tetrapropyl ammonium hydrogen sulfate, tetrabutyl ammonium hydrogen sulfate,
Trimethylethyl ammonium hydrogen sulfate, trimethylbenzyl ammonium hydrogen sulfate, dimethyl diethyl ammonium hydrogen sulfate, triethylmethyl ammonium hydrogen sulfate, triethylbenzyl ammonium hydrogen sulfate, tripropylmethyl ammonium hydrogen sulfate, methylpyrrolidinium hydrogen sulfate, ethylpyrrolidinium hydrogen sulfate , Methylpiperidinium hydrogen sulfate, ethylpiperidinium hydrogen sulfate, methylmorpholinium hydrogen sulfate, ethylmorpholinium hydrogen sulfate, methylpyridinium hydrogen sulfate, cetylpyridinium hydrogen sulfate,

[0015] Tetramethylammonium methanesulfonate, tetraethylammonium methanesulfonate, tetrapropylammonium methanesulfonate, tetrabutylammonium methanesulfonate, trimethylethylammonium methanesulfonate, trimethylbenzylammonium methanesulfonate, dimethyldiethylammonium methanesulfonate , Triethylmethylammonium methanesulfonate, triethylbenzylammonium methanesulfonate, tripropylmethylammonium methanesulfonate, methylpyrrolidinium methanesulfonate, ethylpyrrolidinium methanesulfonate, methylpiperidinium methanesulfonate, methanesulfonic acid Ethyl piperidinium, methyl morpholinium methanesulfonate, methanesulfo Ethyl morpholinium, methyl methanesulfonate pyridinium, methanesulfonic acid cetylpyridinium,

Tetramethylammonium benzenesulfonate, tetraethylammonium benzenesulfonate,
Tetrapropylammonium benzenesulfonate, tetrabutylammonium benzenesulfonate, trimethylethylammonium benzenesulfonate, trimethylbenzylammonium benzenesulfonate, dimethyldiethylammonium benzenesulfonate, triethylmethylammonium benzenesulfonate, triethylbenzylammonium benzenesulfonate, benzene Tripropylmethylammonium sulfonate, methylpyrrolidinium benzenesulfonate, ethylpyrrolidinium benzenesulfonate, methylpiperidinium benzenesulfonate, ethylpiperidinium benzenesulfonate, methylmorpholinium benzenesulfonate, benzenesulfonic acid Ethyl morpholinium, methyl pyridinium benzenesulfonate, ben Nsuruhon acid cetylpyridinium,

Tetramethylammonium toluenesulfonate, tetraethylammonium toluenesulfonate,
Tetrapropylammonium toluenesulfonate, tetrabutylammonium toluenesulfonate, trimethylethylammonium toluenesulfonate, trimethylbenzylammonium toluenesulfonate, dimethyldiethylammonium toluenesulfonate, triethylmethylammonium toluenesulfonate, triethylbenzylammonium toluenesulfonate, toluene Tripropylmethylammonium sulfonate, methylpyrrolidinium toluenesulfonate, ethylpyrrolidinium toluenesulfonate, methylpiperidinium toluenesulfonate, ethylpiperidinium toluenesulfonate, methylmorpholinium toluenesulfonate, toluenesulfonic acid Ethyl morpholinium, methyl pyridinium toluenesulfonate, toluene Such Nsuruhon acid cetylpyridinium.

The amount of the quaternary ammonium salt used depends on the yield and productivity of the reaction.
The range is preferably from 0.001 to 100 mol%, more preferably from 0.01 to 10 mol%, particularly preferably from 0.01 to 5 mol%, based on 1,3,5-triol.

Hydrogen peroxide is generally commercially available 10
An aqueous solution of hydrogen peroxide having a concentration in the range of ６０60% can be used as it is. In consideration of the reaction yield and productivity, the amount of hydrogen peroxide used is 1.5 parts per mole of 3-methylpentane-1,3,5-triol in terms of hydrogen peroxide contained. The range is preferably from 2.5 to 2.5 times, more preferably from 1.7 to 2.3 times.
A range of 8 to 2.2 mole times is particularly preferred. When the amount of hydrogen peroxide used is less than 1.5 mol times, the yield of mevalolactone decreases as the amount used decreases, and when it is more than 2.5 mol times, the produced mevalolactone Side reactions such as oxidative decomposition of the lactone ring of
The yield of mevalolactone tends to decrease.

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

An organic solvent that does not adversely affect the reaction may further coexist. Examples of the organic solvent include aliphatic hydrocarbons such as hexane, heptane, octane, cyclohexane, and methylcyclohexane; benzene, toluene, Aromatic hydrocarbons such as xylene, mesitylene and cumene; ethers such as diethyl ether, dipropyl ether and diisopropyl ether; esters such as methyl acetate, ethyl acetate, isopropyl acetate, methyl butyrate and ethyl butyrate; carbon tetrachloride, chloroform;
Halogenated hydrocarbons such as methylene chloride, chlorobenzene, and dichlorobenzene are exemplified. When these organic solvents are allowed to coexist, the use amount thereof is not particularly limited, but it is usually preferably 0.1 to 50 times by weight based on 3-methylpentane-1,3,5-triol. More preferably, it is in the range of 0.5 to 10 times by weight. From the viewpoint of economic efficiency and volumetric efficiency, it is preferable to carry out the reaction using only water as a solvent without particularly coexisting an organic solvent.

Examples of the acid used in the method of the present invention include mineral acids such as hydrochloric acid, sulfuric acid, nitric acid and phosphoric acid; methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, toluenesulfonic acid, trifluoromethanesulfonic acid and the like. And organic sulfonic acids. In carrying out the method of the present invention, the pH of the reaction system is preferably in the range of 1 to 6. When the pH value of the reaction system is less than 1, dehydration reaction of mevalolactone as a product tends to occur simultaneously, and when the pH value is more than 6, 3-hydroxy-3-methylglutaric acid , 3-hydroxy-3
-By-products such as -methylglutaraldehyde tend to increase, and in either case, the yield of the target mevalolactone decreases, which is not preferable. From such a viewpoint, the amount of the acid used is usually 0.1 to the quaternary ammonium salt used.
Preferably it is in the range of 5 to 2 molar equivalents.

When a quaternary ammonium hydrogen sulfate or a quaternary ammonium organic sulfonate is used as the quaternary ammonium salt, a good yield can be obtained even if the reaction is carried out without adding such an acid. To obtain mevalolactone.

The reaction temperature is preferably in the range of -10 ° C to 120 ° C, and more preferably in the range of 30 ° C to 100 ° C in consideration of the reactivity and stability of hydrogen peroxide in the reaction system. preferable.

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

The reaction is carried out, for example, by dissolving a predetermined amount of 3-methylpentane-1,3,5-triol, tungstic acid, acid and quaternary ammonium salt in water, and adding an organic solvent to the resulting aqueous solution if necessary. , And the temperature is adjusted to a predetermined temperature, and an aqueous solution of hydrogen peroxide is added little by little to the mixed solution. In addition, quaternary ammonium salts
When a quaternary ammonium hydrogen sulfate or a quaternary ammonium organic sulfonate is used, a predetermined amount of 3-methylpentane-1,3,5-triol, tungstic acids and a quaternary ammonium salt are dissolved in water, It is preferable that the obtained aqueous solution is mixed with an organic solvent, if necessary, to a predetermined temperature, and the mixed solution is added with an aqueous solution of hydrogen peroxide little by little.

The mevalolactone thus obtained can be isolated and purified by the usual isolation and purification operations performed in an organic synthesis reaction. For example, sodium peroxide or sodium hydrogen sulfite is added to the reaction mixture to decompose the peroxide, then the organic layer is separated, and the aqueous layer is extracted with an organic solvent such as ethyl acetate. The separated organic layers are combined and concentrated, and the obtained crude product is purified by distillation or column chromatography.

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

[0029]

EXAMPLES The present invention will be described in more detail with reference to the following Examples, which should not be construed as limiting the invention thereto.

Example 1 A 200-ml three-necked flask equipped with a mechanical stirrer, a thermometer and a dropping funnel was charged with 0.2 g (0.6 mmol) of sodium tungstate, 0.06 g (0.6 mmol) of tetramethylammonium chloride, 3
-Methylpentane-1,3,5-triol 13.4 g
(0.1 mol) and 10 g of water were added to replace the inside of the system with nitrogen, and 1.2 ml of a 10% aqueous sulfuric acid solution was further added.
A mixture was prepared. At this point, the pH of the mixture was 1.4.
Met. Subsequently, the temperature was raised to 90 ° C. with vigorous stirring, and 27.8 g of a 30% aqueous hydrogen peroxide solution was added to the mixture.
(0.22 mol) was added dropwise over 30 minutes, and after completion of the addition, the mixture was further stirred at the same temperature for 6 hours. After cooling the reaction mixture, 1.0 g of sodium sulfite was added to separate the organic layer and the aqueous layer, and the aqueous layer was extracted four times with 100 g of ethyl acetate.
The extract and the previously separated organic layer were combined and concentrated, and 14.9 g of the obtained residue was subjected to silica gel column chromatography (developing solvent: hexane / ethyl acetate = 7/3 (volume ratio)). By refining, 11.5 g of mevalolactone was obtained (89% yield).

Example 2 A mixed solution was prepared in the same manner as in Example 1, except that 0.5 ml was added instead of 1.2 ml of a 10% aqueous sulfuric acid solution. At this point, the pH of the mixture was 2.7.
Met. Subsequently, the reaction and isolation procedures were performed in the same manner as in Example 1 to obtain 10.7 g of mevalolactone (83% yield).

Example 3 A mixed solution was prepared in the same manner as in Example 1 except that 0.2 ml of a 30% phosphoric acid aqueous solution was added instead of 1.2 ml of a 10% sulfuric acid aqueous solution. The pH of the mixture at this point was 2.6. Subsequently, the reaction and isolation procedures were performed in the same manner as in Example 1 to obtain 10.4 g of mevalolactone (81% yield).

Example 4 A mixed solution was prepared in the same manner as in Example 1 except that 0.08 g of methanesulfonic acid was added instead of 1.2 ml of a 10% aqueous sulfuric acid solution. The pH of the mixture at this point was 1.9. Subsequently, the reaction and isolation procedures were performed in the same manner as in Example 1 to obtain 10.3 g of mevalolactone (80% yield).

Example 5 A 200 ml three-necked flask equipped with a mechanical stirrer, a thermometer and a dropping funnel was charged with 0.2 g (0.6 mmol) of sodium tungstate and 0.2 g (0.6 mmol) of tetrabutylammonium hydrogen sulfate. And 3-methylpentane-1,3,5-triol 13.4
g (0.1 mol), and 10 g of water.
The system was replaced with nitrogen. At this point, the pH of the mixture was 3.
It was one. Subsequently, the temperature was raised to 90 ° C. with vigorous stirring, and 27.8 g of a 30% aqueous hydrogen peroxide solution was added to the mixture.
(0.22 mol) was added dropwise over 30 minutes, and after completion of the addition, the mixture was further stirred at the same temperature for 6 hours. After cooling the reaction mixture, 1.0 g of sodium sulfite was added to separate the organic layer and the aqueous layer, and the aqueous layer was extracted four times with 100 g of ethyl acetate.
The extract and the previously separated organic layer were combined and concentrated, and the obtained residue (14.7 g) was subjected to silica gel column chromatography (developing solvent: hexane / ethyl acetate = 7/3 (volume ratio)). Purification gave 11.4 g of mevalolactone (88% yield).

Example 6 In Example 5, 0.2 g of sodium tungstate was used.
A mixture was prepared in the same manner as in Example 5, except that 0.22 g (0.6 mmol) of potassium tungstate was used instead of (0.6 mmol). At this time, the pH of the mixture was 3.8. Next, the reaction and isolation procedures were performed in the same manner as in Example 5 to obtain 10.7 g of mevalolactone (83% yield).

Example 7 In Example 5, 0.12 g (0.6 mmol) of dimethyldiethylammonium hydrogen sulfate was used instead of 0.2 g (0.6 mmol) of tetrabutylammonium hydrogen sulfate.
A mixed solution was prepared in the same manner as in Example 5 except that was used. At this time, the pH of the mixture was 3.2. Next, the reaction and isolation procedures were performed in the same manner as in Example 5 to obtain 10 g of mevalolactone (yield: 77%).

Example 8 In Example 5, 0.17 g (0.5 mmol) of tetrabutylammonium methanesulfonate was used instead of 0.2 g (0.5 mmol) of tetrabutylammonium hydrogen sulfate.
A mixed solution was prepared in the same manner as in Example 5 except that l) was used. The pH of the mixture at this point was 3.6.
Next, a reaction and isolation operation were performed in the same manner as in Example 5,
9.8 g of mevalolactone was obtained (76% yield).

[0038]

According to the present invention, mevalolactone can be produced efficiently and industrially advantageously using inexpensive raw materials.

Claims (3)

[Claims] 1. A mevalolactone comprising reacting 3-methylpentane-1,3,5-triol with hydrogen peroxide in an aqueous solvent in the presence of tungstic acids, an acid and a quaternary ammonium salt. Manufacturing method. 2. A method according to claim 1, wherein 3-methylpentane-1,3,5-triol is reacted with tungstic acids and quaternary acid in an aqueous solvent.
A method for producing mevalolactone, comprising reacting with hydrogen peroxide in the presence of a quaternary ammonium salt selected from the group consisting of quaternary ammonium hydrogen sulfate and quaternary ammonium organic sulfonate. 3. The amount of hydrogen peroxide used is 1.5 to 1 mol of 3-methylpentane-1,3,5-triol.
3. The production method according to claim 1, wherein the molar ratio is in the range of 2.5 times.