JP2013032362A - Method for producing tetrahydropyran-4-one compound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for producing a tetrahydropyran-4-one compound, capable of producing the tetrahydropyran-4-one compound from a tetrahydropyran-4-ol compound in high yield.SOLUTION: The method for producing a tetrahydropyran-4-one compound represented by formula (2) (wherein R represents hydrogen atom or the like) includes reacting a tetrahydropyran-4-ol compound represented by formula (1) (wherein R represents hydrogen atom or the like) with a metallic hypochlorite compound in formic acid or the like.

Description

  The present invention relates to a method for producing a tetrahydropyran-4-one compound. Tetrahydropyran-4-one compounds are useful compounds as raw materials for pharmaceuticals and agricultural chemicals and synthetic intermediates.

  Conventionally, as a method for producing a tetrahydropyran-4-one compound from a tetrahydropyran-4-ol compound, for example, a method of reacting tetrahydropyran-4-ol and pyridinium chlorochromate in methylene chloride, tetrahydropyran- A method of reacting 4-ol with a fluorine molecule is known (for example, see Non-Patent Documents 1 and 2). However, in these production methods, an oxidizing agent that is difficult to handle and highly toxic must be used, which is not satisfactory as an industrial production method for tetrahydropyran-4-one compounds.

J. Org. Chem., 50, 2607 (1985) Tetrahedron, 53,15833 (1997)

  An object of the present invention is to solve the above-mentioned problems and to produce a tetrahydropyran-4-one compound in a high yield from a tetrahydropyran-4-ol compound by a simple method under mild conditions. It is an object of the present invention to provide a process for producing a particularly suitable tetrahydropyran-4-one compound.

  The subject of this invention is general formula (1).

(In the formula, R represents a hydrogen atom or an alkyl group.)
A tetrahydropyran-4-ol compound represented by general formula (2) is reacted with a metal hypochlorite compound in an organic carboxylic acid.

(In the formula, R is as defined above.)
The tetrahydropyran-4-one compound represented by

  INDUSTRIAL APPLICABILITY According to the present invention, an industrially suitable tetrahydropyran-4-one compound capable of producing a tetrahydropyran-4-one compound from a tetrahydropyran-4-ol compound in a high yield by a simple method under mild conditions The manufacturing method can be provided.

  The tetrahydropyran-4-ol compound used in the reaction of the present invention is represented by the general formula (1). In the general formula (1), R is a hydrogen atom or an alkyl group. Examples of the alkyl group include a methyl group, an ethyl group, a propyl group, a butyl group, a pentyl group, a hexyl group, a heptyl group, an octyl group, C1-C10 alkyl groups, such as a nonyl group and a decyl group, are mentioned. These groups include various isomers.

  Examples of the metal hypochlorite used in the reaction of the present invention include sodium hypochlorite, potassium hypochlorite, calcium hypochlorite, etc., preferably sodium hypochlorite is used. Is done. In addition, you may use these hypochlorous acid metal compounds individually or in mixture of 2 or more types.

  The amount of the hypochlorous acid metal compound used is preferably 0.9 to 2.5 mol, more preferably 1.0 to 2.0 mol, per 1 mol of the tetrahydropyran-4-ol compound.

  Examples of the organic carboxylic acid used in the reaction of the present invention include formic acid, acetic acid, propionic acid, trifluoroacetic acid, chloroacetic acid, dichloroacetic acid, and trichloroacetic acid, and acetic acid is preferably used. In addition, you may use these organic carboxylic acid individually or in mixture of 2 or more types.

  The amount of the organic carboxylic acid to be used is preferably 1.0 to 25 mol, more preferably 2.0 to 15 mol, relative to 1 mol of the tetrahydropyran-4-ol compound.

  The reaction of the present invention is carried out in the presence or absence of a solvent other than the organic carboxylic acid. 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′— Ureas such as dimethylimidazolidinone; alcohols such as methanol, ethanol, n-propyl alcohol, isopropyl alcohol, n-butyl alcohol, isobutyl alcohol; tetrahydrofuran, diisopropyl ether, dioxane, cyclopropyl methyl ether, t-butyl methyl ether Ethers such as toluene, xylene, etc .; acetates such as methyl acetate, ethyl acetate, butyl acetate, and the like, preferably ethers, acetates, more preferably tetrahydrofuran, ethyl acetate Is used. 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 stirring properties of the reaction solution, but is preferably 0 to 100 ml, more preferably 0 to 50 ml, and particularly preferably 0 to 1 g of the tetrahydropyran-4-ol compound. ~ 30ml.

  The reaction of the present invention is carried out, for example, by a method of mixing a tetrahydropyran-4-ol compound, a hypochlorous acid metal compound and an organic carboxylic acid and reacting them with stirring. The reaction temperature at that time is preferably 0 to 40 ° C., more preferably 0 to 30 ° C., and the reaction pressure is not particularly limited.

  The tetrahydropyran-4-one compound as the final product is isolated and purified by a general method such as neutralization, extraction, filtration, concentration, distillation, recrystallization, column chromatography, etc. after the reaction is completed. Is done.

  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)
After adding 10.24 g (100.3 mmol) of tetrahydropyran-4-ol and 69.1 g of acetic acid to a glass container having an internal volume of 300 ml equipped with a stirrer, a dropping funnel and a thermometer, the liquid temperature was kept at 21 ° C. or lower. After slowly adding 68.4 g (120.4 mmol) of a 13.1% by mass aqueous sodium hypochlorite solution, the mixture was reacted at the same temperature for 4.5 hours with stirring. After completion of the reaction, 1 ml of a saturated aqueous sodium hydrogen sulfite solution and 50 ml of saturated brine were added to the reaction solution, and then extracted 6 times with 100 ml of t-butyl methyl ether. After adding 50 ml of water, 48 mass% sodium hydroxide aqueous solution and 20% sodium carbonate aqueous solution in this order to the obtained extract, the organic layer was separated and dried over magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the resulting concentrate was distilled under reduced pressure (82 to 84 ° C., 7.3 kPa) to obtain 3.65 g of tetrahydropyran-4-one (isolation yield; 36.3%).

Example 2 (Synthesis of tetrahydropyran-4-one)
After adding 110.3 g (1.08 mol) of tetrahydropyran-4-ol and 743.8 g of acetic acid to a 2 L glass container equipped with a stirrer, dropping funnel and thermometer, keeping the liquid temperature at 30 ° C. or lower Then, 734.5 g (1.29 mol) of a 13.1 mass% sodium hypochlorite aqueous solution was slowly added, and the mixture was reacted at the same temperature for 2 hours while stirring. After completion of the reaction, 12 g of a 16.7% by mass aqueous sodium hydrogen sulfite solution was added, and the reaction solution was analyzed by gas chromatography. As a result, 93.5 g of tetrahydropyran-4-one was produced (reaction yield; 86.5%).

Example 3 (Synthesis of 2-methyltetrahydropyran-4-one)
To a glass container having an internal volume of 100 ml equipped with a stirrer, a dropping funnel and a thermometer, 5.0 g (43.0 mmol) of 2-methyltetrahydropyran-4-ol and 34.8 ml of acetic acid were added. After slowly adding 40 ml (56.4 mmol) of an aqueous sodium hypochlorite solution at room temperature, the mixture was reacted at the same temperature for 1 hour with stirring, and then left overnight. Further, 20 ml (28.2 mmol) of an aqueous sodium hypochlorite solution having an effective chlorine content of 5% was added and reacted for 3 hours. After completion of the reaction, 300 ml of a 10% by weight aqueous sodium carbonate solution and 3 ml of a saturated aqueous sodium hydrogen sulfite solution were added to the reaction solution, followed by extraction three times with 30 ml of methylene chloride. The obtained extract was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The obtained concentrate was distilled under reduced pressure (65 ° C., 2.7 kPa) to obtain 2.94 g of 2-methyltetrahydropyran-4-one (isolation yield: 60.0%).

  The present invention relates to a method for producing a tetrahydropyran-4-one compound from a tetrahydropyran-4-ol compound. Tetrahydropyran-4-one compounds are useful compounds as raw materials for pharmaceuticals and agricultural chemicals and synthetic intermediates.

Claims (2)

General formula (1)

(In the formula, R represents a hydrogen atom or an alkyl group.)
A tetrahydropyran-4-ol compound represented by general formula (2) is reacted with a metal hypochlorite compound in an organic carboxylic acid.

(In the formula, R is as defined above.)
A process for producing a tetrahydropyran-4-one compound represented by the formula:   The tetrahydropyran according to claim 1, wherein the metal hypochlorite compound is at least one metal hypochlorite compound selected from the group consisting of sodium hypochlorite, potassium hypochlorite and calcium hypochlorite. Preparation of 4-one compounds.