JPH08127577A - Production of 4-methylenetetrahydropyran - Google Patents

Abstract

PURPOSE: To obtain the subject compound useful as a raw material for medicines and agrochemicals by intermittently or continuously feeding hydroxy- methyltetrahydropyran into a reactor containing a sulfate suspended in a sulfate- insoluble solvent and carrying out the dehydrating reaction. CONSTITUTION: (A) 4-Hydroxy-4-methyltetrahydropyran of formula I is intermittently or continuously fed into a reactor containing (B) a sulfate (e.g. copper sulfate or sodium sulfate) suspended in a sulfate-insoluble solvent (e.g. toluene or hexane) and the dehydrating reaction is carried out while distilling away the resultant product in the reactor. Thereby, 4-methylenetetrahydropyran of formula II is obtained. The compound of formula I is obtained by hydrating 4-methyl-5,6-dihydro-2H-pyran which is an isomer of formula III in the presence of a mineral acid such as sulfuric acid. Furthermore, the amount of the sulfate is preferably 0.001-100 pts.wt., especially preferably 0.01-10 pts.wt. based on 100 pts.wt. component (A).

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an advantageous method for producing 4-methylenetetrahydropyran useful as a raw material for pharmaceuticals and agricultural chemicals on an industrial scale and economically.

[0002]

BACKGROUND OF THE INVENTION 4-Methylenetetrahydropyran is a compound which is effectively used as a raw material for pharmaceuticals and agricultural chemicals, and it is produced as a by-product from isobutene and formaldehyde in the synthesis of isoprene (Chem. Abstr. .77, 134876, 197
1) or alternatively it was mixed with the isomeric 4-methyl-5,6-dihydro-2Hpyran of formula (3) during the thermal decomposition of 4,4-dimethyl-1,3-dioxa-cyclohexane. Generate in state (Pet.Chem.USSR
(Engl., Transl,) 7 (1967) 92).
Is already known.

[0003]

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The following methods have been studied as a general method for producing pyrans. (1) A method utilizing a ring-closing reaction of diols represented by the formula (4), for example, a method of converting it into a sulfonate and then ring-closing with a base. (JP-A-3-7
(Japanese Patent No. 7879)

[0005]

[Chemical 4]

(2) The alcohol represented by the formula (1) is
A method of dehydrating with a solid catalyst such as neutral alumina, alumina impregnated with a base, or silica. (3) A method of dehydrating the alcohol represented by the formula (1) with a sulfate catalyst. (Japanese Patent Application No. 5-291324)

[0007]

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However, the above method (1) requires an equivalent amount or more of sulfonyl halide, and the sulfonate is precipitated after the ring-closing reaction, so that it is not practical as an industrial scale production method. Further, the method (2) has a drawback that isoprene and formaldehyde are produced by decomposition of the produced pyrans. Further, the method (3) has a high selectivity to pyrans, but has a low selectivity to the target 4-methylenetetrahydropyran, which is only about 35%.

[0009]

SUMMARY OF THE INVENTION The object of the present invention is to solve the above-mentioned various problems, and to improve efficiency on an industrial scale.
-To produce methylenetetrahydropyran.

[0010]

According to the present invention, the above object is achieved by the formula (1).

[0011]

[Chemical 6]

By dehydrating 4-hydroxy-4-methyltetrahydropyran represented by the formula (2) in the presence of a sulfate,

[0013]

[Chemical 7]

A method for producing 4-methylenetetrahydropyran represented by the following formula, wherein 4-hydroxy-4-methyltetrahydropyran is intermittently or continuously added to a reactor in which sulfate is suspended in a sulfate-insoluble solvent. It can be achieved by a method for producing 4-methylenetetrahydropyran, characterized in that the dehydration reaction is carried out while the product in the reactor is being distilled off while being fed to the reactor.

In the method for producing 4-methylenetetrahydropyran of the present invention, the raw material of formula (1)

[0016]

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4-hydroxy-4-methyltetrahydropyran of formula has the formula (3)

[0018]

[Chemical 9]

The isomer of 4-methyl-5,6-
It is easily obtained by hydrating dihydro-2Hpyran in the presence of a mineral acid such as sulfuric acid or phosphoric acid, or a solid acid such as an acidic ion exchange resin, zeolite or activated clay.

4-Hydroxy-4-methyltetrahydropyran is obtained by hydrating the isomeric 4-methyl-5,6-dihydro-2Hpyran under acidic conditions, neutralizing the system, and then using an organic solvent. It can be easily purified to sufficient purity for the next step reaction by extraction, removal of the extraction solvent, followed by simple evaporation.

The sulfate used in the present invention is, for example, copper sulfate, sodium sulfate, nickel sulfate, magnesium sulfate, potassium sulfate, zirconium sulfate, and hydrogen sulfate such as sodium hydrogen sulfate and potassium hydrogen sulfate.

These sulfates may be hydrates or anhydrides, commercially available products may be used as powders or crystals, and further commercially available products may be melted, You may use what was solidified and grind | pulverized to suitable size.

In the present invention, 4-hydroxy-4-methyltetrahydropyran is intermittently or continuously fed into a reactor suspended in a sulfate-insoluble solvent. Any sulfate-insoluble solvent used at that time may be used as long as it is stable under acidic conditions.
That is, aromatic hydrocarbons such as toluene, xylene,
Mesitylene, its halide dichlorobenzene, saturated hydrocarbons such as hexane, decane, dodecane,
Paraffin and ethers such as diphenyl ether and dioctyl ether are used. However, in the production method of the present invention, since the reaction temperature is high and the reaction system is a reaction distillation type, it is preferable that it can be used under normal pressure as an operation during the reaction, and still during distillation. It is needless to say that the one having a boiling point difference from the target substance which is not contained is preferable for distillation recovery after the reaction.

The reaction temperature for the dehydration reaction of 4-hydroxy-4-methyltetrahydropyran depends on the catalyst used, and is preferably about 170 ° C. when using copper sulfate and about 150 ° C. for sodium hydrogensulfate. Is good.

The reaction can be carried out under pressure or under reduced pressure. The reaction under reduced pressure is suitable for distilling the product out of the reaction system faster, but it may be under atmospheric pressure for easier reaction, which also provides sufficient reaction results. .

The amount of the sulfate as the reaction catalyst is the amount of 4-hydroxy-4-methyltetrahydropyran 1 initially charged.
It is about 0.001 to 100 parts by weight with respect to 00 parts by weight, and 0.01 to 10 parts by weight is suitable for obtaining higher selectivity.

The dehydration reaction of 4-hydroxy-4-methyltetrahydropyran is carried out by the liquid layer reactive distillation system as described above.

Specifically, 4-hydroxy-4-methyltetrahydropyran, a solvent and a catalyst are initially charged in a reactor and the temperature is raised to a predetermined temperature. The dehydration reaction proceeds with this temperature increase, and 4-methylenetetrahydropyran as a product and 4-methyl-5,6-dihydro-2 as an isomer.
H-piran and water begin to distill.

At this time, 4-hydroxy-4-methyltetrahydropyran is fed into the reaction system so that the catalyst concentration in the system does not change, whereby stable selectivity can be obtained.

At the start of the reaction, the mixing ratio of the initially charged solvent and 4-hydroxy-4-methyltetrahydropyran is preferably 2000 parts by weight or less of 4-hydroxy-4-methyltetrahydropyran with respect to 100 parts by weight of the solvent. Yes,
10 to 1000 parts by weight is preferable.

The reaction products obtained by the liquid layer reactive distillation are an organic layer and a water layer which are composed of a mixture of 4-methylenetetrahydropyran and 4-methyl-5,6-dihydro-2Hpyran which is an isomer of the compound. is there.

4-Methylenetetrahydropyran and the isomeric 4-methyl-5,6-dihydro-2H in the organic layer
Separation from pyran can be easily achieved by distillation under normal pressure. That is, the desired 4-methylenetetrahydropyran is obtained by distilling the organic layer obtained as a reaction product and then distilling it.

The isomer 4-methyl-5,6-dihydro-2Hpyran, which is a by-product of the reaction, is returned to the hydration step to give 4-hydroxy-4-methyltetrahydropyran, which is the 4-methylenetetrahydro of the present invention. It can be used as a raw material in the production method of pyran.

[0034]

EXAMPLES A specific method for producing 4-methylenetetrahydropyran of the present invention will be described below based on examples.

Reference Example (Production of 4-hydroxy-4-methyltetrahydropyran) 100 g of 4-methyl-5,6-dihydro-2Hpyran and 150 g of 35% sulfuric acid water were heated to 50 ° C. in a reactor,
Stir for 70 hours.

Next, the reaction system was neutralized, extracted with ethyl acetate, ethyl acetate was cut off, and then evaporated to obtain 106 g of 4-hydroxy-4-methyltetrahydropyran (yield 90%). .

Example 1 40 g of paraffin and 40 g in a 100 ml three-necked flask.
g of 4-hydroxy-4-methyltetrahydropyran and 0.2 g of sodium sulfate were added and the temperature was raised to 160 ° C. 4-Hydroxy-4-methyltetrahydropyran was fed along with the distillation of the product after the start of the reaction. Two
By carrying out the reaction for an hour, 97.1 g of distillate was obtained. The organic layer in the distillate was 81.1 g.
The concentration of the mixture of 4-methylenetetrahydropyran and the isomeric 4-methyl-5,6-dihydro-2Hpyran in this organic layer was 99.7% by weight, and 4-methylenetetrahydropyran and 4-methyl -5,6-dihydro-
The weight ratio with 2H pyran is 41:59. By distilling the above organic layer (81.1 g), 30.7 g
4-methylenetetrahydropyran (purity 99% or more)
I got

Example 2 40 g of paraffin and 20 g in a 100 ml three-necked flask.
g of 4-hydroxy-4-methyltetrahydropyran and 0.1 g of sodium hydrogensulfate were added and the temperature was raised to 160 ° C. 4-Hydroxy-4-methyltetrahydropyran was fed along with the distillation of the product after the start of the reaction. By carrying out the reaction for 2 hours, 111.1 g of distillate was obtained. The organic layer in the distillate was 92.8 g. 4-Methylenetetrahydropyran and the isomeric 4-methyl-5,6-dihydro-2H in this organic layer
The concentration of the mixture with pyran is 99.7% by weight,
The weight ratio of methylenetetrahydropyran to 4-methyl-5,6-dihydro-2Hpyran is 46:54. By distilling the above organic layer (92.8 g), 4
0.6 g of 4-methylenetetrahydropyran (purity 99
% Or more).

Example 3 40 g mesitylene and 40 g in a 100 ml three-necked flask.
g of 4-hydroxy-4-methyltetrahydropyran and 0.1 g of sodium sulfate were added and the temperature was raised to 165 ° C. 4-Hydroxy-4-methyltetrahydropyran was fed along with the distillation of the product after the start of the reaction. Two
122.8 g of distillate was obtained by carrying out the reaction for a period of time. The organic layer in the distillate was 102.1 g. The concentration of the mixture of 4-methylenetetrahydropyran and the isomeric 4-methyl-5,6-dihydro-2Hpyran in this organic layer was 99.8% by weight, and 4-methylenetetrahydropyran and 4-methyl The weight ratio with -5,6-dihydro-2Hpyran is 55:45. By distilling the above organic layer (102.1 g), 5
4.3 g of 4-methylenetetrahydropyran (purity 99
% Or more).

[0040]

INDUSTRIAL APPLICABILITY According to the present invention, 4-methylenetetrahydropyran useful as a raw material for pharmaceuticals and agricultural chemicals can be industrially obtained efficiently.

Claims (1)

[Claims] 1. Formula (1): 4-hydroxy-4-methyltetrahydropyran represented by the formula is dehydrated in the presence of a sulfate to give a compound of formula (2): A method for producing 4-methylenetetrahydropyran represented by the following formula, wherein 4-hydroxy-4-methyltetrahydropyran is intermittently or continuously fed into a reactor in which a sulfate is suspended in a sulfate-insoluble solvent. At the same time, a dehydration reaction is performed while distilling the product in the reactor, and a method for producing 4-methylenetetrahydropyran.