JP2000038383A - Production of mevalolactone - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject lactone under a mild condition using inexpensively available reagents by performing an oxidative cyclization of methylpentane triol in the presence of each specific amount of sodium hypochlorite and a bromide. SOLUTION: This method for producing a new mevalolactone is provided by performing an oxidative cyclization of 3-methylpentane-1,3,5-triol of formula I in the presence of an excessive molar amount, preferably 1.2-3 fold molar sodium hypochlorite and >=0.15 fold molar, preferably 0.2-1.5 fold molar bromide (suitably sodium bromide) based on sodium hypochlorite to obtain an objective compound of formula II. This reaction is preferably performed kn an inert solvent such as water, acetone, etc., at (-)10-60 deg.C. In general, after dissolving the compound of formula I in the reaction solvent, an aqueous solution containing sodium hypochlorite and the bromide is gradually added into the above solution. The reaction time of usually 1-24 hr is sufficient.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a process for producing mevalolactone which is useful as an intermediate of fine chemicals such as pharmaceuticals and agricultural chemicals, and also related to electronics, for example, a resist material as described in JP-A-10-78658. It is. This mevalolactone has the following structure:

[0002]

[0003]

2. Description of the Related Art Mevalolactone is well known as a precursor of natural isoprenoids, and is a fermentation method described in JP-A-60-251888, Tetrahedron, Vol.
p.171 (1975) using silver carbonate
-Method of oxidizing methylpentane-1,3,5-triol, Bull. Chem. Soc. Jpn. Vol. 65, p. 703 (1992)
It is also known that it can be produced by a method of oxidizing 3-methylpentane-1,3,5-triol in the presence of sodium bromide using peracetic acid as described in (1). However, these methods have not been industrially satisfactory, such as a long reaction time, an expensive reagent, and a reagent that is difficult to handle in disaster prevention.

On the other hand, a method for producing a lactone by oxidative cyclization of a primary diol using bromous acid or a salt thereof, for example, sodium bromite, is described in JP-A-60-123482, which is well known. is there. This publication only discloses an embodiment using a diol as a raw material. Further, since sodium bromite used in this method is not industrially produced at present and is difficult to obtain, this method also has many industrial problems.

[0005]

SUMMARY OF THE INVENTION An object of the present invention is to provide a useful method for producing mevalolactone under mild conditions using an inexpensively available drug.

[0006]

Means for Solving the Problems The inventors of the present invention have conducted intensive studies to achieve the above object, and as a result, a predetermined amount of sodium hypochlorite and at least a catalyst for the sodium hypochlorite have been added. The present inventors have found that mevalolactone can be produced in good yield by performing an oxidation reaction of 3-methylpentane-1,3,5-triol in the presence of an amount of bromide, and have completed the present invention.

That is, the present invention relates to 3-methylpentane-
1,3,5-triol is converted to its 3-methylpentane-
Oxidative cyclization by reaction in the presence of an excess molar amount of sodium hypochlorite with respect to 1,3,5-triol and 0.15 mole times or more of bromide with respect to the sodium hypochlorite And a method for producing mevalolactone. This reaction can be represented by the following reaction formula.

[0008]

Here, X is an atom or an atomic group constituting bromide.

[0010]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail.
3-Methylpentane-1,3,5-triol used as a raw material is commercially available, and mevalolactone can be obtained by oxidative cyclization of this compound. In the present invention, this oxidative cyclization reaction is performed in the presence of sodium hypochlorite and bromide. As is clear from the comparative examples described later, the yield of mevalolactone is low with sodium hypochlorite alone,
Coexistence of bromide is required.

In this reaction, sodium hypochlorite is required in an excess molar amount, that is, in an amount exceeding the equimolar amount, with respect to 3-methylpentane-1,3,5-triol. If sodium hypochlorite is equimolar or less than 3-methylpentane-1,3,5-triol, the oxidation reaction will not proceed sufficiently and the mevalolactone yield will be poor. Preferably, 3-methylpentane-1,
Sodium hypochlorite is used in a range of 1.2 to 3 times the molar amount of 3,5-triol. Sodium hypochlorite is usually used in the form of an aqueous solution.

The bromide can be in a catalytic amount to an excess amount with respect to sodium hypochlorite, but at least 0.15 mole times is necessary. Preferably, the bromide is used in a range of 0.2 to 1.5 mole times with respect to sodium hypochlorite. The bromide is usually an inorganic bromide, particularly a salt of hydrogen bromide, and specific examples include sodium bromide, potassium bromide, and ammonium bromide. Of these, alkali metal bromides such as sodium bromide and potassium bromide are preferred, and sodium bromide is particularly preferred.

The reaction is carried out in an inert solvent such as water, acetone, methyl ethyl ketone or acetonitrile, or in a mixed solvent consisting of two or more thereof.
It is carried out at a temperature of 50 to + 100 ° C, preferably -10 to + 60 ° C. The order of charging the reaction raw materials is arbitrary. For example, 3-methylpentane-1,3,5-triol, sodium hypochlorite and bromide may be charged at once, but generally, 3-methylpentane-1 is used. , 3,5-
It is advantageous to dissolve the triol in the reaction solvent and gradually add an aqueous solution containing sodium hypochlorite and bromide thereto. The reaction time varies depending on the amount and temperature of the oxidizing agent, but is generally about 1 to 24 hours. After completion of the reaction, mevalololactone can be obtained by decomposing the remaining oxidizing agent if necessary, and then performing ordinary post-treatment operations such as extraction, concentration, separation, and recrystallization.

[0014]

EXAMPLES Next, examples of the present invention will be described, but the present invention is not limited by these examples. In the examples,% representing the content is based on weight unless otherwise specified.

EXAMPLE 1 200 g of a 12% aqueous solution of sodium hypochlorite (0.32)
6.6 g (0.064 mol) of sodium bromide was added to the mixture and stirred at room temperature for 30 minutes to prepare an oxidizing agent aqueous solution. Separately, 30 g (0.22 mol) of 3-methylpentane-1,3,5-triol was dissolved in 300 g of acetonitrile, and the container was immersed in ice water and cooled. Dropped over minutes. After stirring overnight at room temperature, the excess oxidant was decomposed with sodium sulfite, checking with potassium iodide starch paper. After acidification (pH 2) with concentrated sulfuric acid and extraction with ethyl acetate, the organic layer was washed with water, dried and concentrated to give mevalolactone 2
6.0 g were obtained. Yield 89.4%. The synthesized mevalolactone was analyzed by nuclear magnetic resonance and gas chromatography and compared with a standard to identify.

Example 2 200 g of a 12% aqueous solution of sodium hypochlorite (0.32)
37.0 g (0.36 mol) of sodium bromide was added to the mixture and stirred at room temperature for 30 minutes to prepare an oxidizing agent aqueous solution. Separately, 30 g (0.22 mol) of 3-methylpentane-1,3,5-triol was dissolved in 300 g of acetonitrile, and the container was immersed in ice water and cooled, and the above aqueous solution of the oxidizing agent was cooled at 37 ° C. or lower for 15 minutes. It dripped over. After stirring overnight at room temperature, the reaction and post-treatment were carried out in the same manner as in Example 1 to obtain 25.0 g of mevalolactone. Yield 85.
9%.

Example 3 416 g of a 12% aqueous solution of sodium hypochlorite (0.67)
Mol), and 69.0 g (0.67 mol) of sodium bromide was added thereto, followed by stirring at room temperature for 30 minutes to prepare an oxidizing agent aqueous solution. Separately, 30 g (0.22 mol) of 3-methylpentane-1,3,5-triol was dissolved in 300 g of acetonitrile, and the container was immersed in ice water and cooled, and the above aqueous solution of the oxidizing agent was cooled at 37 ° C. or lower for 1 hour. It dripped over. After stirring overnight at room temperature, the reaction and post-treatment were carried out in the same manner as in Example 1 to obtain 18.7 g of mevalolactone. Yield 64.
3%.

Comparative Example 1 (Example using only sodium hypochlorite) 30 g of 3-methylpentane-1,3,5-triol
(0.22 mol) in 300 g of acetonitrile,
While the container was immersed in ice water and cooled, 200 g (0.32 mol) of a 12% aqueous sodium hypochlorite solution was added at 20 ° C.
In the following, the solution was dropped over 15 minutes. After stirring at room temperature overnight, the reaction and post-treatment were carried out in the same manner as in Example 1 to obtain 7.0 g of mevalolactone. Yield 24.1%.

Comparative Example 2 (Example in which the molar ratio of sodium bromide / sodium hypochlorite is 0.1) 200 g of a 12% aqueous solution of sodium hypochlorite (0.32)
Mol) was added and 3.3 g (0.032 mol) of sodium bromide was added thereto, followed by stirring at room temperature for 30 minutes to prepare an oxidizing agent aqueous solution. Thereafter, the reaction and post-treatment were carried out in the same manner as in Example 1 to obtain 11.7 g of mevalolactone. Yield 40.2%.

Comparative Example 3 (Example in which the molar ratio of sodium hypochlorite / triol is 1.0) 139 g of a 12% aqueous solution of sodium hypochlorite (0.22
Mol) was added and 23.0 g (0.22 mol) of sodium bromide was added thereto, followed by stirring at room temperature for 30 minutes to prepare an oxidizing agent aqueous solution. Separately, 30 g (0.22 mol) of 3-methylpentane-1,3,5-triol was dissolved in 300 g of acetonitrile, and the container was immersed in ice water and cooled, and the above aqueous solution of the oxidizing agent was cooled at 40 ° C. or lower for 30 minutes. It dripped over. After stirring overnight at room temperature, the reaction and post-treatment were carried out in the same manner as in Example 1 to obtain 10.4 g of mevalolactone. Yield 35.
7%.

[0021]

According to the present invention, mevalolactone, which is useful as an intermediate of fine chemicals such as medicines and agricultural chemicals, and also useful as electronics, especially as a resist material,
It can be manufactured industrially advantageously.

Claims (4)

[Claims] 1. A method according to claim 1, wherein 3-methylpentane-1,3,5-triol is dissolved in an excess molar amount of sodium hypochlorite and said hypochlorous acid with respect to said 3-methylpentane-1,3,5-triol. A process for producing mevalolactone, comprising reacting in the presence of bromide in an amount of 0.15 mole times or more of sodium to effect oxidative cyclization. 2. The process according to claim 1, wherein the reaction is carried out in the presence of 1.2 mol times or more of sodium hypochlorite based on 3-methylpentane-1,3,5-triol. 3. The process according to claim 1, wherein the reaction is carried out in the presence of 0.2 to 1.5 mole times bromide of sodium hypochlorite. 4. The method according to claim 1, wherein the bromide is sodium bromide or potassium bromide.