JP6247959B2 - Process for producing 4-methyl-3,4-dihydro-2H-pyran - Google Patents

Description

  The present invention relates to a process for producing 4-methyl-3,4-dihydro-2H-pyran. Specifically, the present invention relates to a method for producing high-purity 4-methyl-3,4-dihydro-2H-pyran, which can be used as a raw material for synthesizing pharmaceutical and agrochemical compounds and electronic materials that require high quality. .

3,4-Dihydro-2H-pyrans including 4-methyl-3,4-dihydro-2H-pyran are known to be useful as protecting groups (for example, protecting groups for hydroxyl groups) in organic synthesis reactions. In addition, it is useful as a raw material for the synthesis of various medical and agrochemical compounds. In recent years, applications as electronic components such as lithium ion batteries, electrolytic solutions for capacitors, and resist materials are expected.
As a method for producing 4-methyl-3,4-dihydro-2H-pyran, 4-methyl-5,6-dihydro-2H-pyran is isomerized in the presence of a ruthenium catalyst and hydrogen gas (see Patent Document 1). ); A method of reacting 3-methyl-3-buten-1-ol with carbon monoxide and hydrogen in the presence of a group VIII or VIB metal catalyst (see Patent Document 2); 3-methylpropane-1,5 -The method of dehydrating and dehydrogenating diol (refer patent document 3) etc. are mentioned.

Japanese Patent Laid-Open No. 51-13777 U.S. Pat. No. 4,246,177 JP 49-69657 A

In the method of Patent Document 1, when xylene is used as a solvent, the yield is as high as 92%, but the purity of 4-methyl-3,4-dihydro-2H-pyran in the product is unknown, and it relates to purification. There is no description at all. In addition, it is difficult to obtain 4-methyl-5,6-dihydro-2H-pyran as a raw material industrially at low cost.
In the method of Patent Document 2, when the conversion rate of 3-methyl-3-buten-1-ol is 73.5%, the selectivity of 4-methyl-3,4-dihydro-2H-pyran is 54%, which is not good. This is sufficient, and there is room for improvement in reaction selectivity. In the method of Patent Document 3, there is still room for improvement in reaction selectivity.
Therefore, an object of the present invention is to provide a method capable of producing 4-methyl-3,4-dihydro-2H-pyran industrially advantageously, inexpensively and with high purity.

According to the present invention, the above object is
[1] 4-methyl-3,4-dihydro-2H-pyran comprising the step (1) of dehydrating 2-hydroxy-4-methyltetrahydropyran in the presence of an acid and / or acid salt Manufacturing method of
[2] 4 of [1], wherein the acid and / or acid salt is at least one inorganic acid selected from the group consisting of phosphoric acid, sulfuric acid, hydrochloric acid, nitric acid, and perchloric acid, or a salt of the inorganic acid. -Method for producing methyl-3,4-dihydro-2H-pyran;
[3] An amine compound is added to the reaction product containing 4-methyl-3,4-dihydro-2H-pyran obtained in step (1), and then distilled to 4-methyl-3,4-dihydro-2H. -The method for producing 4-methyl-3,4-dihydro-2H-pyran according to [1], further comprising a step (2) of obtaining pyran;
[4] The addition amount of the amine compound is in the range of 0.5 to 50% by mass with respect to the mass of the reaction product containing 4-methyl-3,4-dihydro-2H-pyran obtained in step (1). [3] A process for producing 4-methyl-3,4-dihydro-2H-pyran according to [3]; and [5] the amine compound is a primary or secondary amine having a boiling point of 130 ° C. or higher under atmospheric pressure. , [3] or [4] of 4-methyl-3,4-dihydro-2H-pyran;
Is achieved by providing

  According to the present invention, high-purity 4-methyl-3,4, which can be used for electronic materials such as synthetic raw materials for medical and agricultural chemical compounds, electrolytes for lithium ion batteries and capacitors, and electronic parts such as resist materials. -Dihydro-2H-pyran can be produced industrially advantageously, inexpensively and with high purity.

The method for producing 4-methyl-3,4-dihydro-2H-pyran (hereinafter abbreviated as αMDHP) of the present invention comprises converting 2-hydroxy-4-methyltetrahydropyran (hereinafter abbreviated as MHP) to an acid and / or Or it has the process (1) dehydrated in presence of an acid salt.
Suitably, the manufacturing method of (alpha) MDHP of this invention further has the process (2) which, after adding an amine compound to the reaction product containing (alpha) MDHP obtained at the said process (1), distills and acquires (alpha) MDHP. Hereinafter, each step will be described.

  MHP used as a starting material in the method of the present invention is a method in which 3-methyl-3-buten-1-ol is reacted with carbon monoxide and hydrogen in the presence of a rhodium compound, as described in, for example, Japanese Patent No. 4890107. Can be obtained industrially.

There are no particular limitations on the type of acid and / or acid salt used in step (1) of the method of the present invention, and examples include organic acids, inorganic acids, organic acid salts, inorganic acid salts, solid acids, acidic ion exchange resins, and the like. Either can be used.
Examples of the organic acid include sulfonic acids such as p-toluenesulfonic acid, benzenesulfonic acid, methanesulfonic acid, trifluoromethanesulfonic acid, camphorsulfonic acid, and fluorosulfonic acid; methylphosphonic acid, ethylphosphonic acid, propylphosphonic acid, isopropylphosphonic acid Phosphonic acids such as acids, n-butylphosphonic acid, tert-butylphosphonic acid, n-hexylphosphonic acid, n-octylphosphonic acid, n-decylphosphonic acid, phenylphosphonic acid; formic acid, acetic acid, propionic acid, butanoic acid, Examples thereof include carboxylic acids such as pentanoic acid, hexanoic acid, heptanoic acid, and octanoic acid.
Examples of the organic acid salt include alkali metal salts such as sulfonic acid, phosphonic acid, and carboxylic acid, alkaline earth metal salts, and transition metal salts.
Examples of inorganic acids include phosphoric acid, sulfuric acid, hydrochloric acid, nitric acid, perchloric acid, and polyphosphoric acid.
Examples of the inorganic acid salt include alkali metal salts, alkaline earth metal salts, transition metal salts of the inorganic acids described above, and examples thereof include potassium hydrogen phosphate, sodium hydrogen phosphate, potassium hydrogen sulfate, and sodium hydrogen sulfate. Can be mentioned.
Examples of solid acids include γ-alumina, zeolite, and solid acids doped with other elements such as metals.
Examples of the acidic ion exchange resin include Amberlist 15, Amberlist 16 [both trade names, manufactured by Rohm & Haas Co., Ltd.], Dowex Marathon C [trade names, manufactured by Dow Chemical Co.], Diaion SK-1B. Acid type [trade name, manufactured by Mitsubishi Chemical Corporation] and the like.
In view of ease of acquisition, ease of handling, selectivity of the reaction, and viewpoint of smoothly proceeding the reaction, inorganic acids or salts of inorganic acids are preferred among the above, and phosphoric acid, sulfuric acid, hydrochloric acid, nitric acid, excess More preferably, it is at least one inorganic acid selected from the group consisting of chloric acid or a salt of said inorganic acid, more preferably phosphoric acid, potassium hydrogen sulfate, sodium hydrogen sulfate, and particularly phosphoric acid or potassium hydrogen sulfate. preferable.

There is no strict limitation on the amount of acid and / or acid salt used. However, when using an organic acid, a salt of an organic acid, an inorganic acid, or a salt of an inorganic acid, such as decomposition of MHP or polymerization of αMDHP. From the viewpoint of suppressing side reactions, usually, the charge amount ratio with respect to MHP initially charged in the reactor is preferably in the range of 0.005 mol% to 15 mol%, more preferably in the range of 0.05 mol% to 10 mol%.
On the other hand, when a solid acid or acidic ion exchange resin is used, the range of 0.5 to 20% by mass is usually preferable with respect to the volume of the reaction solution present in the reaction system at the start of the reaction.
In addition, as described later, step (1) of the production method of the present invention is produced as MHP is continuously or intermittently added to a reaction system in which an acid and / or an acid salt are present, and the reaction proceeds. It is preferable to carry out the reaction while removing αMDHP out of the reaction system. In such a case, the amount of acid and / or acid salt present in the reaction system is usually preferably in the range of 0.05 mol% to 10 mol% as the mass ratio with respect to MHP initially charged into the reactor.

  Step (1) of the production method of the present invention can be performed in the presence or absence of a solvent. When carried out in the presence of a solvent, the type of solvent should not affect the reaction of dehydrating MHP in the presence of an acid and / or acid salt and is inert to αMDHP, the target product of the reaction. There is no particular limitation, for example, saturated aliphatic hydrocarbons such as hexane, heptane, octane, nonane, decane, dodecane, pentadecane, and liquid paraffin; aromatics such as benzene, toluene, ethylbenzene, xylene, cumene, mesitylene, diisopropylbenzene, and naphthalene Hydrocarbons: linear or cyclic such as diisopropyl ether, dibutyl ether, diisoamyl ether, dioctyl ether, tetrahydrofuran, tetrahydropyran, dioxane, 2-methyltetrahydrofuran, 4-methyltetrahydropyran, cyclopentylmethyl ether Japanese ether; aprotic such as 1,3-dimethyl-2-oxazolidinone, dimethyl sulfoxide, sulfolane, hexamethylphosphoric triamide, acetonitrile, N, N-dimethylformamide, N-methylpyrrolidone, α-methyl-γ-butyrolactone Polar solvent; and the like. When using a solvent, there is no restriction | limiting in particular in the usage-amount. When using a solvent in the method of the present invention, from the viewpoint of ease of separation from the product αMDHP, it is extremely preferable to have a boiling point higher than that of αMDHP at atmospheric pressure. In atmospheric pressure, the boiling point is preferably 15 ° C. or higher than that of αMDHP, more preferably 30 ° C. or higher, and even more preferably 50 ° C. or higher.

  In step (1) of the production method of the present invention, the reaction temperature, reaction time, reaction pressure, reaction atmosphere and the like are not particularly limited as long as the reaction proceeds. The reaction temperature is usually preferably in the range of 50 ° C to 250 ° C, more preferably in the range of 80 ° C to 200 ° C, and still more preferably in the range of 100 ° C to 200 ° C from the viewpoint of allowing the reaction to proceed smoothly. Although the reaction time may vary depending on the embodiment of the reaction and the degree of progress, it is usually preferably 1 minute to 48 hours. The reaction can be carried out under atmospheric pressure, reduced pressure, or increased pressure. The reaction is preferably performed in an inert gas atmosphere such as nitrogen, helium, or argon, but may be in an air atmosphere as long as the progress of the reaction is not hindered.

  There is no restriction | limiting in particular in the reaction form of the process (1) of the manufacturing method of this invention, Any of a batch type reaction, a continuous type reaction, or another reaction form may be sufficient. In step (1) of the production method of the present invention, MHP is intermittently or continuously added to a reaction system in which a mixture of an acid and / or an acid salt and, if necessary, a solvent is present, and a reaction containing αMDHP. It is preferable to carry out the reaction while continuously distilling the product out of the reaction system. In addition, when adding MHP intermittently or continuously as needed, an acid and / or an acid salt may be added to the reaction system.

In the reaction product containing αMDHP obtained in the step (1), for example, aldehyde compounds represented by the following formula are included as main by-products. Since these aldehyde compounds have a small difference in boiling point from αMDHP [boiling point (atmospheric pressure): MHP 188 ° C., αMDHP 117 ° C., aldehyde compound (1-a) 116 ° C., aldehyde compound (1-b) 126 ° C., aldehyde Compound (1-c) 123 ° C.] By simply distilling the reaction product containing αMDHP obtained in step (1), it is difficult to obtain αMDHP with high purity in a high yield.
In the method of the present invention, after adding an amine compound to the reaction product containing αMDHP obtained in the step (1), the method further includes a step (2) of obtaining αMDHP by distillation to obtain a highly pure αMDHP. Can get well.

  The amine compound used in step (2) of the method of the present invention is preferably a primary or secondary amine compound having a boiling point of 130 ° C. or higher under atmospheric pressure. Examples of such primary amine compounds include hexylamine, heptylamine, octylamine, 2-ethylhexylamine, nonylamine, decylamine, undecylamine, dodecylamine, benzylamine, 4-phenylbutylamine, 2-phenylbutylamine and the like. Examples of the secondary amine compound include di (2-ethylhexyl) amine, diisobutylamine, dioctylamine, dibenzylamine, diphenylamine and the like. These amine compounds may be used individually by 1 type, and may use 2 or more types together. From the viewpoint of ease of separation from αMDHP in the distillation operation in the step (2), the amine compound has a boiling point that is higher than the boiling point of αMDHP at atmospheric pressure. It is preferable that it has a boiling point 15 ° C. or higher than that of αMDHP, more preferably 30 ° C. or higher, and even more preferably 50 ° C. or higher.

In step (2), the addition amount of the amine compound is not strictly limited, but from the viewpoint of the operability of step (2) and the like, the reaction containing αMDHP usually obtained in step (1) is preferable. It is the range of 0.01-50 mass% with respect to the mass of a product, More preferably, it is the range of 0.1-20 mass%. Moreover, Preferably it is the range of 0.01-50 mass% with respect to the mass of (alpha) MDHP in the reaction product containing (alpha) MDHP obtained at a process (1), More preferably, it is the range of 0.1-20 mass%. is there. In addition, it is preferable that the addition amount of this amine compound is satisfy | filling that it is equimolar or more with respect to the aldehyde compounds mentioned above contained in the reaction product containing (alpha) MDHP obtained at a process (1), etc. The range of mol-10 mol times is preferable and the range of 2-5 mol times is more preferable.
The amount of αMDHP in the reaction product containing αMDHP obtained in step (1) and the amount of aldehyde compounds are determined by ¹ H-NMR analysis of the reaction product or gas chromatography analysis using an internal standard method. Can be calculated.

In the step (2), there is no particular limitation on the form of addition of the amine compound. The amine compound may be added as it is, or in the form of a solution in which the amine compound is dissolved in a solvent, preferably a solvent that does not azeotrope with αMDHP and has a sufficient boiling point difference. As such a solvent, for example, the same type of solvent as that which can be used as necessary in the step (1) can be mentioned.
There is no particular limitation on the method of adding the amine compound, and the amine compound or a solution of the amine compound may be added all at once or continuously to the reaction product containing αMDHP obtained in step (1). The reaction product containing αMDHP obtained in step (1) may be added to the compound solution all at once or continuously. Industrially, for example, a method in which the reaction product containing αMDHP obtained in step (1) and an amine compound are fed to a line mixer for mixing or separately mixed in a tank and then distilled as a preferred embodiment. Can be mentioned.

  In the step (2), there are no particular restrictions on the distillation conditions and form after adding the amine compound, as long as the MHP and the amine compound can be separated from the target product αMDHP. At atmospheric pressure, reduced pressure, batch system or continuous system It may be. Preferably, from the viewpoint of thermal stability of αMDHP during the distillation operation, the distillation is preferably performed under a reduced pressure of 15 kPa to 80 kPa, and more preferably 40 kPa to 70 kPa. If distillation is performed under a reduced pressure condition set in such a pressure range, αMDHP can be obtained by distillation by setting the temperature of the liquid in the distillation kettle to 50 ° C to 110 ° C, preferably in the range of 70 ° C to 100 ° C. This is also advantageous from the viewpoint of thermal stability.

  In the distillation operation of step (2), triphenylphosphine, diethylphenylphosphine, phenyl are used from the viewpoint of suppressing the generation and concentration of peroxide from αMDHP, which is an ether compound, and improving the distillation yield and ensuring safety. Phosphine compounds such as dibutylphosphine, phenyldiisopropylphosphine, 1,1-bis (diphenylphosphino) methane, 1,1-bis (diphenylphosphino) ethane; sulfide compounds such as phenylmethyl sulfide; amine compounds such as aliphatic amines It is preferable that a processing agent (see Japanese Patent Application Laid-Open No. 6-248250) on which alumina is supported on alumina, silica gel or the like coexist in a range of 1 to 20% by mass with respect to the reaction product liquid containing αMDHP.

  The reason why the aldehyde compounds are contained in the reaction product containing αMDHP obtained in step (1) of the method of the present invention is, for example, that at least a part of the raw material MHP is the reaction condition in step (1). It is thought to be formed by ring opening and subsequent dehydration (see formula below).

  In the step (2), it is preferable to confirm that aldehyde compounds have disappeared by means such as gas chromatography analysis or NMR analysis before distillation.

EXAMPLES Hereinafter, although an Example demonstrates this invention concretely, this invention is not limited at all by these Examples. The measurement by gas chromatography was performed under the following conditions.
Analytical instrument: GC-14A (manufactured by Shimadzu Corporation)
Detection equipment: FID (hydrogen flame ionization detector) (manufactured by Shimadzu Corporation)
Column used: CBP-1 (length 50 m, inner diameter 0.22 mm, film thickness 0.25 μm)
(Manufactured by Chemical Substance Evaluation Research Organization)
Analysis conditions: Injection Temp. 250 ° C,
Detection Temp. 250 ° C
Temperature rising temperature condition: 50 ° C. (5 minutes) → Temperature rising at 10 ° C./min → 250 °

Example 1
[Step (1)]
In a three-necked flask with an internal volume of 100 ml equipped with a thermometer, dropping funnel, mechanical stirrer, condenser and receiver, in a nitrogen atmosphere, under a nitrogen atmosphere, MHP 60 g and phosphoric acid 0.12 g (0.2 mol% with respect to MHP) Put. Next, the temperature was raised until the liquid temperature reached 180 ° C., and 1200 g of MHP was slowly dropped from the dropping funnel, and the reaction product containing αMDHP was continuously extracted into the receiver by distillation and reacted for 13 hours. After completion of the reaction, the organic layer was separated from the reaction product in the receiver and analyzed by gas chromatography. The conversion rate of MHP was 95% and the selectivity for αMDHP was 97%. The recovered amount of the organic layer was 1040 g, and the content (GC area%) of each component was αMDHP 96.0%, MHP 1.5%, aldehyde compounds 2.1%, and other 0.4%.
[Step (2)]
Reaction product containing αMDHP, MHP, aldehyde compounds and other components obtained in the above step (1) in a three-necked flask having an internal volume of 1000 ml equipped with a thermometer, an electromagnetic stirring device, a gas blowing port and a sampling port ( 730 g of organic layer) and 36 g of n-octylamine (equivalent to about 5% by mass with respect to the content of αMDHP in the reaction product) were added, and the bath temperature was set to 80 ° C. and stirred for 3 hours (inside When the contents were analyzed by gas chromatography at a temperature of 77.9-81.0 ° C., the content of each component (GC area%) was αMDHP 96.0%, MHP 1.5%, other components The aldehyde compounds were disappeared at 2.5%. Add 36 g of triphenylphosphine (5% by mass with respect to the reaction product) and perform distillation purification using a distillation column with 10 theoretical plates under conditions of a heating medium temperature of 110 ° C., a reflux ratio of 3 and a degree of vacuum of 46 kPa. Thus, αMDHP having a purity of 99.9% or more was obtained with a distillation yield of 90%.

Example 2
In step (1) of Example 1, in a 100 ml three-necked flask equipped with a thermometer, a dropping funnel, a mechanical stirrer, a condenser tube and a receiver, 140 g of MHP and 1.6 g of potassium hydrogen sulfate (into MHP) were added in a nitrogen atmosphere. 40 mol of liquid paraffin was added as a solvent. Next, the temperature was raised until the liquid temperature reached 200 ° C., while slowly adding MHPg from the dropping funnel, the reaction product containing αMDHP to be produced was continuously extracted into the receiver by distillation and reacted for 13 hours. As a result, the conversion rate of MHP was 98%, and the selectivity to αMDHP was 96%. Subsequently, by performing distillation under the same distillation purification conditions as in step (2) of Example 1, αMDHP having a purity of 99.9% or more was obtained with a distillation yield of 90%.

Example 3
Except for using 70 g of di (2-ethylhexyl) amine (equivalent to approximately 10% by mass with respect to the content of αMDHP in the reaction mixture) instead of 36 g of octylamine in the step (2) of Example 1, The same operation as in Example 1 was performed. As a result, αMDHP having a purity of 99.9% or more was obtained with a distillation yield of 88%.

Example 4
In step (1) of Example 1, in a three-necked flask having an internal volume of 1000 ml equipped with a thermometer, a dropping funnel, a mechanical stirrer, a condenser tube and a receiver, 60 g of MHP and 0.12 g of phosphoric acid were added under a nitrogen atmosphere under a nitrogen atmosphere. (0.2 mol% with respect to MHP) was added. Next, the temperature was raised until the liquid temperature reached 180 ° C., and the reaction was performed for 9 hours while slowly dropping MHP745g from the dropping funnel. After completion of the reaction, the organic layer containing αMDHP was separated from the reaction mixture, and the contents were analyzed by gas chromatography. As a result, the conversion rate of MHP was 90% and the selectivity to αMDHP was 96%. Next, after removing unreacted MHP by a simple distillation apparatus, distillation is performed under the same distillation purification conditions as in step (2) of Example 1, thereby obtaining αMDHP having a purity of 99.9% or more in a distillation yield of 84%. Obtained.

Comparative Example 1
When the same reaction operation was carried out without adding phosphoric acid in the step (1) of Example 1, no distillation of the reaction product into the receiver was observed, and the contents in the reaction kettle were analyzed by gas chromatography. The product was analyzed, but αMDHP was not produced at all.

Comparative Example 2
When the same distillation operation was performed on the reaction mixture obtained in step (1) without adding n-octylamine in step (2) of Example 1, the purity of αMDHP obtained was 98%. Yes, it contained 1.9% of aldehyde compounds and 0.1% of other impurities.

  According to the production method of the present invention, high-purity 4-methyl-3,4-dihydro-2H-pyran can be provided industrially at a low cost and in a high yield, and a pharmaceutical and agrochemical compound for which high quality is required. It can be used for synthetic raw materials and electronic materials.

Claims (5)

2-hydroxy-4-methyltetrahydropyran have a step (1) to be dehydrated in the presence of an acid and / or salt and acid and / or salts, phosphoric acid, sulfuric acid, hydrochloric acid, nitric acid, perchloric acid at least one and said salt der Rukoto inorganic acid or the inorganic acid, process for preparing 4-methyl-3,4-dihydro -2H- pyran selected from the group consisting of. The reaction product containing 4-methyl-3,4-dihydro-2H-pyran obtained in the step (1) of dehydrating 2-hydroxy-4-methyltetrahydropyran in the presence of an acid and / or acid salt with an amine compound The method of producing 4 -methyl-3,4-dihydro-2H-pyran , further comprising the step (2) of obtaining 4-methyl-3,4-dihydro-2H-pyran by distillation after the addition of. The 4-acid according to claim 2, wherein the acid and / or acid salt is at least one inorganic acid selected from the group consisting of phosphoric acid, sulfuric acid, hydrochloric acid, nitric acid, and perchloric acid, or a salt of the inorganic acid. A method for producing methyl-3,4-dihydro-2H-pyran. The addition amount of the amine compound is in the range of 0.1 to 50% by mass with respect to the mass of the reaction product containing 4-methyl-3,4-dihydro-2H-pyran obtained in step (1). Item 4. The method for producing 4-methyl-3,4-dihydro-2H-pyran according to Item 2 or 3. The production of 4-methyl-3,4-dihydro-2H-pyran according to any one of claims 2 to 4, wherein the amine compound is a primary or secondary amine having a boiling point of 130 ° C or higher under atmospheric pressure. Method.