JP2008308419A - Method for producing tetrahydropyran-4-one - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an industrially suitable method for producing tetrahydropyran-4-one, producing the tetrahydropyran-4-one in a high yield from tetrahydropyran-4-ol by a simple method. <P>SOLUTION: This method for producing the tetrahydropyran-4-one is provided by reacting the tetrahydropyran-4-ol with a peroxide in the presence of a tungstate. Especially, it is preferable that the peroxide is hydrogen peroxide, and the tungstate is at least one selected from the group consisting of sodium tungstate and potassium tungstate. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a process for producing tetrahydropyran-4-one. Tetrahydropyran-4-one is, for example, a compound useful as a raw material for pharmaceuticals and agricultural chemicals and a synthetic intermediate (for example, see Patent Document 1).

International Publication No. 2005 / 110409A2 Pamphlet

  Conventionally, as a method for producing tetrahydropyran-4-one from tetrahydropyran-4-ol, for example, a method of reacting tetrahydropyran-4-ol and pyridinium chlorochromate in methylene chloride (for example, non-patent literature) 1) or tetrahydropyran-4-ol and fluorine are known (for example, see Non-Patent Document 2). However, in these production methods, it is necessary to use a highly toxic oxidizing agent or fluorine which is difficult to handle, and this is not satisfactory as an industrial production method of tetrahydropyran-4-one.

J. Org. Chem., 50, 2607 to 2613 (1985) Tetrahedron, 53, 15833-15842 (1997)

  The problem to be solved by the present invention is to solve the above-mentioned problems and industrially produce tetrahydropyran-4-one from tetrahydropyran-4-ol by an environmentally friendly and simple method under industrial conditions. The object is to provide a process for producing a suitable tetrahydropyran-4-one.

  The object of the present invention is solved by a process for producing tetrahydropyran-4-one, characterized by reacting tetrahydropyran-4-ol, tungstate, and peroxide.

  According to the present invention, tetrahydropyran-4-one can be produced in high yield from tetrahydropyran-4-ol by a simple method under mild conditions. In this case, since hydrogen peroxide used as a peroxide can be converted into water by reaction, an industrial and environmentally friendly method for producing tetrahydropyran-4-one is provided. be able to.

  The peroxide of the present invention preferably uses hydrogen peroxide. In this case, hydrogen peroxide may be used as an aqueous solution or mixed with a solvent that does not participate in the reaction. Further, the solvent may be used alone or in combination of two or more.

  The amount of the peroxide used is preferably 0.7 to 5 mol, more preferably 1 to 3 mol, and particularly preferably 1 to 2 mol with respect to 1 mol of tetrahydropyran-4-ol.

  Examples of the tungstate used in the reaction of the present invention include sodium tungstate, potassium tungstate, and calcium tungstate, preferably sodium tungstate and potassium tungstate are used, and more preferably tungstic acid. Sodium is used. In addition, these tungstates may be hydrates, and may be used alone or in admixture of two or more.

  The amount of the tungstate used is preferably 0.0005 to 0.05 mol, more preferably 0.001 to 0.01 mol, per 1 mol of tetrahydropyran-4-ol.

In the reaction of the present invention, an inorganic acid may be added. Examples of the inorganic acid include phosphoric acid, sulfuric acid, hydrochloric acid and the like, and phosphoric acid is preferably used. These inorganic acids may be aqueous solutions, or may be used alone or in combination of two or more.

The amount of the inorganic acid used is preferably 0 to 0.1 mol, more preferably 0 to 0.05 mol, per 1 mol of tetrahydropyran-4-ol.

The reaction of the present invention is carried out in the presence or absence of a solvent. The solvent to be used is not particularly limited as long as it does not inhibit the reaction. For example, water; amides such as N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone; N, N′— Examples include ureas such as dimethylimidazolidinone; ketones such as methyl ethyl ketone and methyl isobutyl ketone; and aromatic hydrocarbons such as toluene and xylene, preferably water, ketones, and more preferably water. In addition, you may use these solvents individually or in mixture of 2 or more types.

  The amount of the solvent used is appropriately adjusted depending on the uniformity and stirrability of the reaction solution, but is preferably 0 to 50 ml, more preferably 0 to 10 ml, and particularly preferably with respect to 1.0 g of tetrahydropyran-4-ol. 0-2 ml.

  The reaction of the present invention is performed by, for example, a method of mixing tetrahydropyran-4-ol, tungstate, and peroxide and reacting them while stirring. The reaction temperature in that case becomes like this. Preferably it is 50-150 degreeC, More preferably, it is 80-120 degreeC. At that time, the reaction pressure is not particularly limited.

  The reaction product, tetrahydropyran-4-one, is isolated and purified by a general method such as extraction, concentration, distillation, column chromatography, etc. after completion of the reaction.

  As a preferred embodiment of the present invention, it is carried out by a method such as adding hydrogen peroxide to a mixed solution of tetrahydropyran-4-ol and tungstate at 50 to 150 ° C. with stirring to react. At that time, the reaction pressure is not particularly limited.

  Next, the present invention will be specifically described with reference to examples, but the scope of the present invention is not limited thereto.

Example 1 (Synthesis of tetrahydropyran-4-one)
In a 200-ml glass pressure vessel equipped with a stirrer, dropping funnel and thermometer, 60.1 g (0.588 mol) tetrahydropyran-4-ol and 0.973 g (0.00295 mol) sodium tungstate dihydrate were added. ) Was heated to 90 ° C., then 116 g (1.18 mol) of 34.5 mass% hydrogen peroxide aqueous solution was added, and the mixture was reacted at a liquid temperature of 84 to 93 ° C. with stirring for 6 hours. After completion of the reaction, 38.4 g of a 20% by mass aqueous sodium thiosulfate solution and 19.7 g of sodium thiosulfate pentahydrate were added to the reaction solution. When this solution was analyzed by gas chromatography (internal standard calibration method), 43.9 g of tetrahydropyran-4-one was produced in the reaction solution (reaction yield; 74%).
Subsequently, a part (79.5 g) of this reaction solution was extracted with methylene chloride, and then concentrated. The obtained concentrate was distilled under reduced pressure (88-92 ° C./7.3 kPa) to obtain 11.7 g of tetrahydropyran-4-one (isolated yield based on tetrahydropyran-4-ol; 56% ).

Example 2 (Synthesis of tetrahydropyran-4-one)
In a 30-ml glass pressure vessel equipped with a stirrer, a dropping funnel and a thermometer, 3.1 g (30 mmol) of tetrahydropyran-4-ol, 0.049 g (0.15 mmol) of sodium tungstate dihydrate, A liquid mixture with 85 mass% phosphoric acid 0.060 g (0.52 mmol) was heated to 80 ° C, then 4.1 g (42 mmol) of 34.5 mass% hydrogen peroxide aqueous solution was added, and the liquid temperature was 75-89 ° C. The reaction was allowed to proceed for 6 hours with stirring. When the obtained reaction solution was analyzed after completion of the reaction, tetrahydropyran-4-one was produced at a reaction yield of about 55%.

  The present invention relates to a process for producing tetrahydropyran-4-one from tetrahydropyran-4-ol. Tetrahydropyran-4-one is a useful compound, for example, as a raw material for pharmaceuticals, agricultural chemicals, and synthetic intermediates.

Claims (3)

  A process for producing tetrahydropyran-4-one, characterized by reacting tetrahydropyran-4-ol with a peroxide in the presence of tungstate.   The method for producing tetrahydropyran-4-one according to claim 1, wherein the peroxide is hydrogen peroxide.   The method for producing a tetrahydropyran-4-one compound according to claim 1, wherein the tungstate is at least one tungstate selected from the group consisting of sodium tungstate and potassium tungstate.