JP2000033201A - Recovery of tetrahydrofuran - Google Patents

Abstract

PROBLEM TO BE SOLVED: To recover safely and easily tetrahydrofuran of a low water content by a method wherein a water-containing organic solvent containing tetrahydrofuran is added to a reacted solution obtained by a reaction using a Grignard reagent, and the organic solvent containing the tetrahydrofuran is distilled out from this mixed solution. SOLUTION: As a reacted solution obtained by a reaction using a Grignard reagent, a reacted solution obtained by a coupling reaction of a nonsubstituted or substituted phenylmagnesium chloride compound and an O-chlorobenzonitrile in a solution obtained by adding manganese dioxide and trimethylchlorosilane to tetrahydrofuran(THF), can be used. As a water-containing organic solvent containing THF, the water-containing organic solvent, or the like, containing the THF obtained by a method wherein, after reaction executed by a reaction using, for example, a Grignard reagent, a suitable amount of water and a pH regulator are added as an after treatment, and an aimed compound is extracted, and than distilled for condensation, is cited.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for recovering tetrahydrofuran (hereinafter referred to as THF). More specifically, the present invention relates to a method for recovering THF used in a chemical reaction at a low water content. The present invention is a method that can be suitably applied to, for example, recovering THF used at the time of producing a 2-cyanobiphenyl compound useful as an oral hypotensive agent at a low water content.

[0002]

2. Description of the Related Art In a chemical reaction, THF is widely used as a solvent, but since it is an expensive solvent, it has been studied to recover it after the reaction to reuse it.

Conventionally, as a method for obtaining anhydrous THF from water-containing THF, there is known a method in which lithium aluminum hydride is added to water-containing THF, refluxed in a nitrogen stream, and then dehydrated by distillation (Nihon Kagaku). (Ed.), “Experimental Chemistry Course (Vol. 1), 4th Edition, Maruzen, p.

However, when the anhydrous THF is recovered from the water-containing THF having a high water content after the completion of the reaction, if the above method is employed, lithium aluminum hydride reacts violently with water and ignites. There is a risk.

[0005]

DISCLOSURE OF THE INVENTION The present invention has been made in view of the above-mentioned prior art, and is a method for easily recovering THF having a low water content even if the water content of the water-containing THF is large. The purpose is to provide.

[0006]

That is, the present invention provides:
[1] (A) A water-containing organic solvent containing THF is added to a reaction solution obtained by a reaction using a Grignard reagent, and (B) an organic solvent containing THF is distilled from the obtained mixed solution. A method for recovering THF, [2] wherein a reaction solution obtained by a reaction using a Grignard reagent is unsubstituted or substituted in a solution obtained by adding manganese dioxide and trimethylchlorosilane to THF. The method for recovering THF according to the above [1], which is a reaction solution obtained by performing a coupling reaction between a phenylmagnesium chloride compound and o-chlorobenzonitrile, [3] a reaction obtained by a reaction using a Grignard reagent The solution is THF
A reaction solution obtained by performing a coupling reaction between an unsubstituted or substituted phenylmagnesium chloride compound and o-chlorobenzonitrile in a solution obtained by adding manganese dichloride to the above [1]. [4] In the step (B), water is added to a solution obtained by distilling an organic solvent containing THF from the mixed solution, and an aqueous layer containing an inorganic salt is obtained from the obtained mixed solution. Is removed by liquid separation, and the water-containing organic solvent recovered by distilling out the organic solvent portion contained in the obtained organic layer having a high water content is subjected to a water-containing organic solvent containing THF in the step (A). The method for recovering THF described in [1] above, which is used as a solvent, and [5] after pre-drying a water-containing organic solvent recovered by distilling an organic solvent portion, (A), the related THF method of recovery of the [4], wherein the use as a water-containing organic solvent containing THF.

[0007]

According to the method for recovering THF of the present invention, as described above, (A) a water-containing organic solvent containing THF is added to a reaction solution obtained by a reaction using a Grignard reagent. , (B) TH from the resulting mixed solution
By distilling out the organic solvent containing F, THF having a reduced water content can be recovered.

The present inventors have conducted intensive studies to provide a method for safely and easily recovering THF having a low water content from water-containing THF even if the water content of the water-containing THF is large. However, the reaction solution obtained by the reaction using the Grignard reagent has, surprisingly, not only a very excellent dehydration ability but also a water content as compared with the conventionally used lithium aluminum hydride. From low water content THF to high water content safely,
An entirely new fact has been found that it can be easily recovered. The present invention has been completed based on such findings.

Furthermore, the present inventors have conducted intensive studies and found that the reaction solution obtained by the reaction using the Grignard reagent was useful for producing a 2-cyanobiphenyl compound useful as an intermediate such as an oral hypotensive agent. Have been found that they can also be suitably applied.

That is, the reaction solution obtained by the reaction using the Grignard reagent is not particularly limited, but in the present invention, for example, (I) THF which is a preferable condition for the production method of a 2-cyanobiphenyl compound is used. In a solution obtained by adding manganese dioxide and trimethylchlorosilane, an unsubstituted or substituted (substituent: an alkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms) phenylmagnesium chloride compound and o
A reaction solution obtained by performing a coupling reaction with chlorobenzonitrile (hereinafter referred to as reaction solution I), and (II) a solution obtained by adding manganese dichloride to THF; A reaction solution obtained by performing a coupling reaction between a substituted (substituent: an alkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, etc.) phenylmagnesium chloride compound and o-chlorobenzonitrile (hereinafter, referred to as a reaction solution) Reaction solution II) can be suitably used.

The method for preparing the reaction solution I is as follows.
For example, the method described in Japanese Patent Application No. 10-6639 can be used. Examples of the method for preparing the reaction solution II include a method described in JP-A-6-9536.

Examples of aqueous organic solvents containing THF include:
There is no particular limitation, and those produced during various chemical reactions can be used. Examples of such a water-containing organic solvent containing THF include, after the reaction carried out by a reaction using a Grignard reagent, adding an appropriate amount of water and a pH adjuster as a post-treatment to extract the target compound, and then to concentrate the compound. And a water-containing organic solvent containing THF obtained by distillation. The organic solvent contained in the aqueous organic solvent containing THF is preferably THF alone or a mixed solvent of THF and toluene. Further, the amount of water contained in the water-containing organic solvent containing THF is preferably about 5,000 to 10,000 ppm from the viewpoint of stably obtaining, for example, THF having a low water content of 500 ppm or less.

It is necessary to separate unnecessary impurities from the water-containing organic solvent containing THF by distillation or to remove unnecessary moisture by liquid separation in advance from the viewpoint of obtaining high-purity THF. preferable.

The amount of the water-containing organic solvent containing THF cannot be determined unconditionally because the dehydration capacity varies depending on the amount of water in the water-containing organic solvent and the type of Grignard reagent. Usually, the amount of water in the water-containing organic solvent is 0.11 to 0.2 per mole.
About 2 mol is preferable from the viewpoint of obtaining THF having a low water content stably.

Next, a water-containing organic solvent containing THF is
From the mixed solution obtained by adding to the reaction solution obtained by the reaction using the Grignard reagent, TH
The organic solvent containing F is distilled off. At this time, the water contained in the water-containing organic solvent containing THF reacts with the reaction solution obtained by the reaction using the Grignard reagent, so that the organic solvent containing THF is distilled off almost in an anhydrous state. can do.

The distillation amount of the organic solvent containing THF is not particularly limited, but from the viewpoint of efficiently recovering THF,
It is preferable that the amount is as large as possible within a range that does not hinder stirring. After distilling the THF-containing organic solvent, it is desirable to leave a solvent in the reaction solution to such an extent that the reaction solution can be easily stirred. Therefore, when distilling an organic solvent containing a large amount of THF, the stirring can be facilitated.
It is preferable to add an organic solvent such as toluene to the reaction solution.

The organic solvent containing the distilled THF includes:
Although it is almost anhydrous, it can be used for various purposes, for example, a chemical reaction after the content of THF is increased by, for example, rectification.

Further, in order to further reduce unnecessary water in a water-containing organic solvent containing THF, the water content in the organic solvent is reduced by treating with a solid of inorganic salts or a high-concentration aqueous solution thereof. Can be.

As a method of removing unnecessary water from the distilled water-containing organic solvent containing THF by using inorganic salts, for example, a water-containing organic solvent containing THF is dissolved in an alkali hydroxide such as solid sodium hydroxide. , A method in which a solid alkali hydroxide such as sodium hydroxide is added to a water-containing organic solvent containing THF, and the mixture is stirred, and the resulting concentrated alkaline water is separated. Solid calcium chloride, solid magnesium sulfate Or the like is added to a water-containing organic solvent containing THF, and the mixture is stirred, and the resulting concentrated calcium chloride aqueous solution, concentrated magnesium sulfate aqueous solution and the like are separated. The temperature at which unnecessary water is removed using inorganic salts is preferably around room temperature. If the temperature is lower than room temperature, the water content can be further reduced due to the solubility of water in a solvent. .

According to the above operation, the water content in the water-containing organic solvent containing THF can be reduced by almost half.

Next, THF is recovered from the distilled organic solvent containing THF, and the THF can be recovered by a conventional method.

Further, water is added to the solution obtained by distilling the THF-containing organic solvent from the mixed solution, an aqueous layer containing an inorganic salt is removed from the obtained mixed solution by liquid separation, and then the obtained solution is separated. When the water-containing organic solvent recovered by distilling out the organic solvent portion contained in the organic layer having a high water content is used as the water-containing organic solvent containing THF,
Effective use of the THF can be achieved. When the water-containing organic solvent recovered by distilling the organic solvent portion is used as the water-containing organic solvent containing the THF, the water-containing organic solvent can be preliminarily dried beforehand using a Grignard reagent. This is preferred from the viewpoint of reducing the load on the dehydration ability of the reaction solution obtained by the above method.

As described above, according to the method for recovering THF of the present invention, THF used in a chemical reaction can be recovered with a low water content.

[0024]

Next, the present invention will be described in more detail with reference to examples, but the present invention is not limited to only these examples.

Example 1 4.73 of manganese dioxide was placed in a 1-liter flask.
g (0.054 mol), trimethylchlorosilane23.
64 g (0.217 mol) and 292.3 g of THF were charged and stirred at 40 to 45 ° C. for 3 hours. Thereafter, 18.7 g of o-chlorobenzonitrile (0.136 g) was added thereto.
Mol) and cooled to -5 to -10 ° C.

Next, 124.73 g of a THF solution of o-chlorobenzonitrile (concentration of o-chlorobenzonitrile: 60% by weight, content of o-chlorobenzonitrile: 0.544 mol) was placed in the flask. 298.8 g of a THF solution of p-methylphenylmagnesium chloride (p
-Methylphenylmagnesium chloride concentration: 42.
9% by weight, p-methylphenylmagnesium chloride content: 0.85 mol) were simultaneously added dropwise at -5 to -10 ° C over 5.5 hours, and the mixture was allowed to react for 1 hour.

After the completion of the reaction, the liquid temperature of the contents in the flask was raised to 70 to 75 ° C., and the solvent was concentrated until the liquid temperature of the contents in the flask reached 110 ° C.

Next, the obtained fraction was collected and subjected to THF 37
9.7 g were obtained.

When the obtained THF was subjected to analysis using gas chromatography (hereinafter referred to as GC analysis), the purity of THF was 94.8%, the recovery rate was 75.8%,
The water content was 176 ppm.

Next, 250 g of toluene was charged into the residue after the solvent was concentrated. 4.3% hydrochloric acid 2 previously charged in a 1-liter flask
It was dropped to 47.5 g.

The temperature of the liquid in the flask was raised to 80 to 85 ° C., and the mixture was stirred under reflux for 7 hours. Then, the aqueous layer is separated,
The organic layer was washed once with 200 g of 10% saline solution and then with 20% aqueous 5% sodium bicarbonate solution.
Washed once with 0 g.

The obtained organic layer was distilled off under reduced pressure to obtain a fraction 34.
7.1 g were recovered. When this fraction was subjected to GC analysis, the composition was 27.4% in THF and 70.5% in toluene.
Met. The recovery of THF is 20.0% and the water content is 5
000 ppm.

The THF-containing organic solvent containing water was charged into a 500-ml flask, 0.68 g of calcium chloride was added, and the mixture was stirred at 20 to 30 ° C. for 2 hours to perform dehydration. Thereafter, liquid separation was performed, and the generated aqueous layer was separated. The water content of the obtained organic layer is 1545 p.
pm.

After the completion of the dehydration, 347.1 g of a THF-containing organic solvent having the above-mentioned water content was added to the liquid obtained by concentrating the organic layer, and the organic solvent was concentrated until the internal temperature reached 110 ° C.
188.1 g of a fraction were recovered. When the obtained fraction was subjected to GC analysis, the composition was 53.1% in THF and 45.9% in toluene. The recovery of THF is 21.0%,
The water content was 189 ppm.

The obtained recovered organic solvent (188.1 g) was mixed with THF379.
7 g and a rectification operation to give a purity of 9
9.9%, water content 373ppm, purification yield 96.6%
Of THF was obtained.

The total recovery of THF was 93.5%.

From the above results, it can be seen that, according to the method of Example 1, THF having a low water content can be safely and easily recovered from THF having a high water content.

[0038]

According to the method for recovering THF of the present invention, an excellent effect is obtained in that THF having a low water content can be safely and easily recovered from THF having a high water content.

Continued on the front page (72) Inventor Katsura Tadashi, 3-1-1 Utajima, Nishiyodogawa-ku, Osaka-shi Sumika FineChem Co., Ltd. F-Chem Fine Chemicals Co., Ltd. F-term (reference) 4D056 AB19 AC03 BA03

Claims (5)

[Claims] 1. A water-containing organic solvent containing (A) tetrahydrofuran is added to a reaction solution obtained by a reaction using a Grignard reagent, and (B) an organic solvent containing tetrahydrofuran is distilled from the mixed solution obtained. A method for recovering tetrahydrofuran. 2. A reaction solution obtained by a reaction using a Grignard reagent, in a solution obtained by adding manganese dioxide and trimethylchlorosilane to tetrahydrofuran, an unsubstituted or substituted phenylmagnesium chloride compound and o-chloroform. The method for recovering tetrahydrofuran according to claim 1, which is a reaction solution obtained by performing a coupling reaction with benzonitrile. 3. A reaction solution obtained by a reaction using a Grignard reagent, a solution obtained by adding manganese dichloride to tetrahydrofuran, and an unsubstituted or substituted phenylmagnesium chloride compound and o-
The method for recovering tetrahydrofuran according to claim 1, which is a reaction solution obtained by performing a coupling reaction with chlorobenzonitrile. 4. In step (B), water is added to a solution obtained by distilling an organic solvent containing tetrahydrofuran from the mixed solution, and an aqueous layer containing an inorganic salt is separated from the obtained mixed solution by liquid separation. The water-containing organic solvent recovered by removing and removing the organic solvent part contained in the obtained organic layer having a high water content is used as a water-containing organic solvent containing tetrahydrofuran in the step (A). The method for recovering tetrahydrofuran according to claim 1. 5. After pre-drying the water-containing organic solvent recovered by distilling off the organic solvent portion, the step (A)
5. The method for recovering tetrahydrofuran according to claim 4, wherein the method is used as a water-containing organic solvent containing tetrahydrofuran.