JPH11199577A - Production of hydroxyl-bearing cyclic ether compound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To easily obtain in high yield under mild conditions from readily available raw materials the subject compound useful as a raw material for e.g. physiologically active substances, tetrahydrofuran, by reaction between a specific unsaturated alcohol and a peroxide in a solvent. SOLUTION: This compound is obtained by reaction, in the presence of (A) a tianosilicate catalyst, between (B) a compound of the formula: R<1> R<2> C=CH (CH2 )n CHR<3> OH (R<1> to R<3> are each H, a 1-10C alkyl or alryl; (n) is 1-7) and (C) a peroxide (e.g. hydrogen peroxide) in (D) a solvent (e.g. water, an aliphatic alcohol, ketone); wherein the reaction is pref. carried out at 10-80 deg.C and atmospheric pressure to 50 kg/cm<2> with a batch system or continuous system such as of fixed bed or suspended bed type.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a novel method for producing a hydroxyl group-containing cyclic ether compound. The hydroxyl group-containing cyclic ether compound obtained in the present invention is an extremely useful compound as an important precursor of a physiologically active substance and as a raw material for tetrahydrofuran and tetrahydropyran derivatives.

[0002]

2. Description of the Related Art German Patent No. 3,308,931 discloses a process for producing a hydroxyl group-containing cyclic ether compound such as 3-hydroxy-tetrahydrofuran by using 1,2,4-.
A method is disclosed in which a polyhydric alcohol compound having three or more hydroxyl groups in a molecule, such as butanetriol, is heated to 165 ° C. in a liquid phase to be dehydrated.

[0003]

However, the method described in German Patent No. 3,308,931 requires a polyhydric alcohol compound having three or more hydroxyl groups as a starting material. Is not easy. Further, even if it is available, there is a problem that a multi-stage process of two or more stages is required from a readily available basic material in order to produce the desired hydroxyl group-containing cyclic ether compound. There is also a problem that a strict reaction condition of 165 ° C. in a liquid phase is required.

[0004] Japanese Patent Application Laid-Open No. 5-112550 and "The 68th Meeting of the Catalysis Society of Japan (A)", published by The Chemical Society of Japan, page 284, disclose the number of carbon atoms in the presence of a crystalline titanosilicate catalyst. It is disclosed that four or less unsaturated alcohols are reacted with hydrogen peroxide to epoxidize olefinic moieties to give the corresponding hydroxyepoxy compounds. However, Japanese Patent Application Laid-Open No. 5-112550 and “The 68th Meeting of the Catalysis Society of Japan (A) Preliminary Proceedings” published by The Chemical Society of Japan, page 284, disclose nothing about the production of ether compounds. There is no description to suggest.

The present invention has been made in view of the above problems, and has as its object to provide a method for producing a desired hydroxyl group-containing ether compound in one step from a readily available basic material as a starting material under mild conditions. It is to provide.

[0006]

The present inventors have conducted intensive studies to solve the above-mentioned problems, and as a result, in the presence of a titanosilicate catalyst, a specific unsaturated alcohol which is easily available and a peroxide. The present inventors have found that a hydroxyl group-containing cyclic ether compound can be produced under mild conditions and in a high yield by reacting the product in a solvent, and the present invention has been completed.

That is, according to the present invention, the following general formula (1) R ¹ R ² C ＝ CH (CH ₂ ) _n CHR ³ OH (1) (where R ¹ and R ^{2 are used} ) in the presence of a titanosilicate catalyst And R ³ each independently represent hydrogen, an alkyl group having 1 to 10 carbon atoms or an aryl group;
It is an integer of 7. A) reacting an unsaturated alcohol having 4 or more carbon atoms and a peroxide in a solvent in a solvent.

Next, the present invention will be described in more detail.

The unsaturated alcohol having 4 or more carbon atoms used in the present invention is a compound represented by the above general formula (1), and is not particularly limited.
Buten-1-ol, 4-penten-1-ol, 3-
Penten-1-ol, 4-methyl-3-pentene-1
-Ol, (±) 4-penten-2-ol, cis-4
-Hexen-1-ol, 3-hexen-1-ol,
(±) 5-hexen-3-ol, 4-heptene-1-
All, 3-hepten-1-ol, 6-heptene-4
-Ol, (±) 6-methyl-5-hepten-2-ol, 4-phenyl-3-buten-1-ol, 5-hexen-1-ol, 5-hepten-1-ol, 6-heptene- 1-ol, 7-octen-1-ol, 8-
Nonen-1-ol, 9-decene-1-ol and the like can be mentioned.

In the present invention, the desired hydroxyl group-containing cyclic ether compound can be produced by reacting an unsaturated alcohol having 4 or more carbon atoms represented by the general formula (1) with a peroxide in a solvent. Examples of the hydroxyl group-containing cyclic ether compound obtained by the method of the present invention include 3
-Hydroxy-tetrahydrofuran, tetrahydro-2
-Furanmethanol, 2-methyl-3-hydroxytetrahydrofuran, 2,2-dimethyl-3-hydroxytetrahydrofuran, 2-methyl-4-hydroxytetrahydrofuran, 2- (1-hydroxyethyl) tetrahydrofuran, 2-ethyl-3-hydroxy Tetrahydrofuran, 2-ethyl-4-hydroxytetrahydrofuran, 2- (1-hydroxy-n-propyl) tetrahydrofuran, 2- (n-propyl) -3-hydroxytetrahydrofuran, 2- (n-propyl) -4-hydroxytetrahydrofuran, 5-membered cyclic hydroxyl group-containing cyclic ether compounds such as 2- (1-hydroxy-1-methylethyl) -5-methyltetrahydrofuran and 2-phenyl-3-hydroxytetrahydrofuran; tetrahydro-2
6-membered cyclic hydroxyl group-containing cyclic ether compounds such as -pyranmethanol, 2- (1-hydroxyethyl) tetrahydropyran, 2-hydroxymethyloxepane, 2-hydroxymethyloxocan, 2-hydroxymethyloxonan, And 7- to 10-membered cyclic hydroxyl group-containing cyclic ether compounds such as hydroxymethyloxecan. The method of the present invention is preferably applied to the production of a 5- or 6-membered hydroxyl-containing cyclic ether compound among these,
In particular, 3-hydroxy-tetrahydrofuran can be obtained in high yield from the reaction between 3-buten-1-ol and hydrogen peroxide.

The peroxide used in the present invention is not particularly limited. Examples include peracids and hydrogen peroxide. Of these, hydrogen peroxide is preferably used in terms of availability and reactivity. These peroxides can be used alone, or two or more of them can be used as a mixture. In addition, these peroxides may be positively added to the reaction or may be generated in the reaction field.

The amount of the peroxide to be used is usually in the range of 0.1 to 10 equivalents, preferably 0.1 to 1 mol per mol of the unsaturated alcohol having 4 or more carbon atoms represented by the above general formula (1). It is in the range of 3-5 equivalents, more preferably 0.5-2 equivalents.

According to the present invention, a titanosilicate catalyst is used in the reaction between the unsaturated alcohol having 4 or more carbon atoms represented by the general formula (1) and the peroxide.

In the present invention, the titanosilicate is crystalline nTiO _2. (1) in which a part of silicon forming a crystal lattice of crystalline SiO ₂ having a zeolite structure (referred to as silicalite) is replaced by titanium. -n) SiO ₂
Means Here, n is in the range of 0.01 to 0.2.

The titanosilicate used in the present invention
The crystal structure of the crystal is not particularly limited, and for example, a crystal having a crystal structure of MFI type, beta type, mordenite type, faujasite type, MCM-41 type, or the like can be used. Of these, M
Titanosilicate having a FI-type or beta-type crystal structure is preferably used, and more preferably TS-1 type titanosilicate having an MFI-type crystal structure or Ti-beta-type titanosilicate having a beta-type crystal structure is used. Can be These titanosilicates can be used not only alone, but also in a mixture of two or more.

The titanosilicate used in the present invention
There is no particular limitation on the method for synthesizing the compound.
tud. Surf. Sci. Catal. 37,413
(1987) and Chem. Lett. 1997,677
And the like. For example, TS-
Type 1 titanosilicate is synthesized by hydrolyzing tetraalkylorthosilicate and tetraalkylorthotitanate with an aqueous solution of tetraalkylammonium hydroxide, and then hydrothermally. The titanosilicate used in the present invention may contain, if necessary, boron, aluminum, phosphorus, calcium, vanadium, chromium, manganese, iron,
Cobalt, nickel, copper, zinc, gallium, zirconium and the like may be contained, and a titanosilicate containing a different element can be synthesized by adding an oxide source of these metals.

The titanosilicate synthesized in the present invention may be used as it is, or may be used after molding. When molded and used, a binder is generally used, but the type of the binder is not particularly limited, and for example, silica, alumina and the like are used.

According to the present invention, the amount of titanosilicate catalyst used depends on the type of reaction. That is, in the case of the fixed bed continuous flow system, since it is determined by the reaction rate and the heat balance, it is difficult to unambiguously define it. When the reaction is carried out in a batch system, a semi-batch system or a continuous flow system in a suspension bed, the reaction is usually carried out in an amount of 0.1 to 1 g of the unsaturated alcohol having 4 or more carbon atoms represented by the general formula (1). -40% by weight, preferably 1-30% by weight, more preferably 5-25% by weight. If the amount is more than this range, stirring of the catalyst suspension may be hindered.

The reaction of the present invention is carried out in a liquid phase, but is specifically carried out using a solvent. Examples of the solvent include, but are not particularly limited to, water and aliphatic alcohols such as methanol, ethanol, butanol, pentanole, hexanole, heptanol, and octanol. Glycols such as ethylene glycol and propylene glycol; ethers such as dimethyl ether, diethyl ether, tetrahydrofuran and dimethoxyethane; ethylene glycol monomethyl ether; ethylene glycol monoethyl ether. Glycos such as ter, ethylene glycol monopropyl ether, ethylene glycol monobutyl ether, propylene glycol monomethyl ether, propylene glycol monoethyl ether, propylene glycol monopropyl ether, propylene glycol monobutyl ether, etc. -Ethers, acetone, Methyl ethyl ketone and methyl isobutyl ketone, and carboxylic acids such as acetic acid. Further, a hydroxyl group-containing cyclic ether compound which is a reaction product can also be used. Of these, water, aliphatic alcohols or ketones are preferably used from the viewpoint of easy handling. The above-mentioned solvents can be used alone or in combination of two or more. In the present invention,
The unsaturated alcohol having 4 or more carbon atoms represented by the general formula (1), which is a starting material, is not included in the solvent.

The amount of the solvent used is usually 2 to the unsaturated alcohol having 4 or more carbon atoms represented by the general formula (1).
-100 g equivalent, preferably 4-80 g equivalent, more preferably 6-50 g equivalent. If the amount of the solvent used is less than 2 g equivalent, a hydroxyepoxy compound is generated, and the yield of the intended hydroxyl group-containing cyclic ether compound may decrease. In addition, the amount of solvent used is 1
If the amount is more than 00 g equivalent, since the amount of the hydroxyl group-containing cyclic ether compound produced per reaction solution is small, there may be a problem in economical aspects such as deterioration in the efficiency of separation of the product and the solvent.

In the present invention, the reaction temperature is not particularly limited, but is usually in the range of 0 to 100 ° C, preferably in the range of 10 to 80 ° C. When the reaction temperature is lower than 0 ° C., the reaction rate is reduced, while the reaction temperature is 100 ° C.
When the ratio exceeds the above, side reactions tend to increase, and the selectivity of the hydroxyl group-containing cyclic ether compound may decrease. The reaction pressure is usually from normal pressure to 200 kg / cm ² ,
Preferably it is normal pressure to 50 kg / cm ² .

In the present invention, there is no particular limitation on the reaction method, and the batch method in which the unsaturated alcohol, peroxide, titanosilicate catalyst and solvent represented by the above general formula (1), which are the raw materials, are charged into the reactor at once is used. The continuous method of a fixed bed or a suspension bed for continuously supplying the unsaturated alcohol and the peroxide represented by the general formula (1) and continuously extracting the unreacted raw materials and the reaction solution is also used. Can be implemented.

The hydroxyl group-containing cyclic ether compound produced in this reaction can be easily separated by a known method such as successive distillation or extraction of the reaction mixture.

[0024]

According to the present invention, in the presence of a titanosilicate catalyst, an easily obtainable unsaturated alcohol and peroxide represented by the general formula (1) are represented by the general formula (1). Reaction in a solvent other than the unsaturated alcohol
A hydroxyl group-containing cyclic ether compound can be produced under mild conditions and in high yield.

[0025]

EXAMPLES The present invention will be described in more detail with reference to the following Examples, which are only for illustrating the outline of the present invention and the present invention is not limited to these Examples. . Example 1 Stud. Surf. Sci. Catal. 37, 41
3 (1987), TS-1 type titanosilicate (Si / Ti = 27) was prepared.

After sufficiently replacing a 50-ml two-necked flask equipped with a thermometer, a Dimroth condenser and a stirrer with nitrogen, 10 g of 2-butanol as a solvent and 3-buten-1-ol as a starting material were added. 44g
(0.02 mol), 2.3 g (0.02 mol) of a 30% by weight aqueous hydrogen peroxide solution, and then 0.29 g of the above-mentioned TS-1 titanosilicate as a catalyst (2% of the starting material).
0% by weight).

The reaction vessel was kept at 25 ° C. and stirred vigorously to start the reaction. While maintaining these reaction conditions, 1
The reaction was performed for 8 hours. After 18 hours, the reaction vessel was cooled to room temperature, and the product contained in the reaction solution was analyzed by gas chromatography. As a result, 3-hydroxy-
Tetrahydrofuran was obtained in a high yield of 82%.

Example 2 Example 1 was repeated except that water was used instead of 2-butanol as the reaction solvent, and the reaction time was 6 hours.
The reaction was carried out in the same manner as described above. 3-Hydroxy-tetrahydrofuran was obtained with a yield of 71%.

Example 3 A reaction was carried out in the same manner as in Example 1 except that (±) 4-penten-2-ol was used as a starting material and acetone was used as a reaction solvent. 2-methyl-
4-Hydroxytetrahydrofuran was obtained in a yield of 80% (trans: cis = 70: 30).

Example 4 Same as Example 1 except that (±) 4-penten-2-ol was used as a starting material, water was used as a reaction solvent, and the reaction time was 12 hours. The reaction was carried out. 2-Methyl-4-hydroxytetrahydrofuran was obtained in a yield of 70% (trans: cis = 67: 33).

Example 5 A reaction was carried out in the same manner as in Example 1 except that (±) 4-penten-2-ol was used as a starting material, and that the reaction temperature was 60 ° C. 2-Methyl-4-hydroxytetrahydrofuran was obtained in a yield of 84% (trans: cis = 75: 25).

Example 6 A reaction was carried out in the same manner as in Example 1 except that 4-penten-1-ol was used as a starting material. Tetrahydro-2-furanmethanol was obtained with a yield of 98%.

Example 7 A reaction was carried out in the same manner as in Example 1 except that 4-penten-1-ol was used as a starting material and acetone was used as a reaction solvent. Tetrahydro-2-furanmethanol was obtained with a yield of 99%.

Example 8 A reaction was carried out in the same manner as in Example 1 except that 4-penten-1-ol was used as a starting material and water was used as a reaction solvent. Tetrahydro-2-furanmethanol was obtained with a yield of 99%.

Example 9 The procedure of Example 1 was repeated except that cis-4-hexen-1-ol was used as a starting material, acetone was used as a reaction solvent, and the reaction temperature was 60 ° C. The reaction was performed. Tetrahydro-2-furan-1-ethanol was obtained with a yield of 92%.

Example 10 A reaction was conducted in the same manner as in Example 1 except that 5-hexen-1-ol was used as a starting material, acetone was used as a reaction solvent, and the reaction temperature was 60 ° C. Was done. Tetrahydro-2-pyranmethanol was obtained with a yield of 90%.

Example 11 Chem. Lett. According to the method of 1997, 677,
Ti-beta type titanosilicate (Si / Ti = 30)
Was prepared.

After a 50 ml two-necked flask equipped with a thermometer, a Dimroth condenser and a stirrer was sufficiently purged with nitrogen, 10 g of acetone was used as a solvent, and (±) 6-methyl-5-heptene-2 was used as a starting material. 2.88 g (0.02 mol) of all, 2.3 g (0.02 mol) of a 30% by weight aqueous hydrogen peroxide solution, and then 0.58 g of the above-mentioned Ti-beta titanosilicate as a catalyst.
(20% by weight of the starting material).

The reaction vessel was kept at 60 ° C. and stirred vigorously to start the reaction. While maintaining these reaction conditions, 4
A time reaction was performed. After 4 hours, the reaction vessel was cooled to room temperature, and the products contained in the reaction solution were analyzed by gas chromatography. As a result, 2- (1-hydroxy-1-methylethyl) -5-methyltetrahydrofuran was obtained in a yield of 60% (trans: cis = 72: 28).

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁶ Identification symbol FI // C07B 61/00 300 C07B 61/00 300

Claims (3)

[Claims] (1) In the presence of a titanosilicate catalyst, the following general formula (1): R ¹ R ² C ＝ CH (CH ₂ ) _n CHR ³ OH (1) (wherein R ¹ , R ² and R ³⁾ Each independently represents hydrogen, an alkyl group or an aryl group having 1 to 10 carbon atoms, and n represents 1 to
It is an integer of 7. A) reacting an unsaturated alcohol having 4 or more carbon atoms with a peroxide in a solvent in a solvent. 2. The solvent is one or two selected from the group consisting of water, aliphatic alcohols, glycols, ethers, glycol ethers, ketones and carboxylic acids.
The method for producing a hydroxyl group-containing cyclic ether compound according to claim 1, wherein the compound is at least one kind. 3. The method for producing a hydroxyl group-containing cyclic ether compound according to claim 1, wherein the peroxide is hydrogen peroxide.