JP2008001633A - Reduction reaction by borohydride compound in the presence of aluminum chloride using tetrahydropyran as solvent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To solve a problem in a method for reducing a carbonyl compound and a carboxylic acid derivative by a composition of a borohydride compound with an aluminum salt, and to provide a method for manufacturing an alcohol compound and the like safely and efficiently. <P>SOLUTION: In the reduction method of a carbonyl compound, a carboxylic acid derivative or the like, the same solvent can be used as a reaction solvent and an extraction solvent by using a composition comprising a borohydride compound and an aluminum salt in tetrahydropyran, whereby simplification of the reaction processes, reduction of energy costs and the like can be realized. Further, the use of low toxic tetrahydropyran as the solvent enhances safety to living organisms. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a composition containing a borohydride compound and an aluminum salt used for producing an alcohol compound or the like by reducing an organic compound such as a carbonyl compound and a carboxylic acid derivative in a tetrahydropyran solvent, and using the composition. The present invention relates to a method for producing alcohol compounds and the like.

  Boron hydride compounds are safe and stable compounds, but are known to have low reducing power. Conventionally, reduction of carbonyl compounds such as aldehyde compounds and ketone compounds, which are relatively easily reduced, in protic solvents. It was only used for the reaction.

  On the other hand, aluminum hydride compounds have strong reducing power, and even in aprotic solvents, not only carbonyl compounds but also ester compounds, carboxylic acid compounds, amide compounds, nitrile compounds, amide compounds, and lactone compounds are in the most oxidized state. It is known that the compound can be reduced to a low compound. However, while the aluminum hydride compound is excellent in reducing power, it is unstable to moisture and has a problem that it reacts explosively when water is present in the reaction system.

  For this reason, the development of compounds and compositions that do not impair the safety and stability of borohydride compounds and have a reducing power similar to aluminum hydride compounds has been carried out.

As a prior art, it is known that a compound having a strong reducing power can be obtained by using aluminum chloride in combination with a borohydride compound.
For example, Journal of industrial and engineering chemistry 47 p1560 (1955) (Non-patent Document 1) describes that aluminum borohydride can be synthesized by a salt exchange reaction between sodium borohydride and aluminum chloride.

  In J. Am. Chem. Soc., 77 p3164 (1955) (Non-patent Document 2), a composition comprising sodium borohydride and aluminum chloride in diglyme (diethylene glycol dimethyl ether) contains an ester compound and a nitrile compound. It is described that it can be reduced.

  Furthermore, J. Am. Chem. Soc., 78 p2582 (1956) (Non-patent Document 3) discloses a composition comprising 3 times molar amount of sodium borohydride and 1 time molar amount of aluminum chloride in diethylene glycol. It is described that carboxylic acid compounds, ester compounds, nitrile compounds, and lactone compounds can be reduced.

In the conventional reduction reaction using such a borohydride compound, after the reduction reaction, water is added to decompose excess hydride, and at the same time, the product is separated into an organic layer and the metal salt is separated into an aqueous layer. is necessary. However, since diglyme and diethylene glycol used as a solvent in the above non-patent documents are miscible with water, they cannot be separated easily and it is difficult to recover the produced alcohol.
In addition, when concentrating the reaction liquid and adding an extraction solvent to obtain an alcohol compound or the like produced by the reaction, high-boiling diglyme, diethylene glycol, and water having a high latent heat of evaporation are distilled off, and the extraction is different from the reaction solvent. Since a solvent must be used, there are problems in that the reaction process is complicated and energy costs are increased.

Journal of industrial and engineering chemistry 47 p1560 (1955) J. Am. Chem. Soc., 77 p3164 (1955) J. Am. Chem. Soc., 78 p2582 (1956)

  An object of the present invention is to solve the above-mentioned problems in a reduction method using a borohydride compound, and to provide a method for producing an alcohol compound and the like safely and efficiently.

  As a result of diligent efforts in view of the above problems, the present inventors have used the same reaction solvent and extraction solvent by using tetrahydropyran as the solvent in the reduction reaction using the composition containing the borohydride compound and the aluminum salt. As a result, the inventors have found that the reaction process can be simplified and energy costs can be reduced, and the present invention has been completed.

That is, the present invention relates to a method for producing the following composition and alcohol compound.
[1] A composition comprising a borohydride compound and an aluminum salt in tetrahydropyran.
[2] The composition according to 1 above, wherein the borohydride compound is one or more selected from the group consisting of sodium borohydride, potassium borohydride, and ammonium borohydride.
[3] The composition as described in 1 or 2 above, wherein the aluminum salt is aluminum chloride or aluminum bromide.
[4] A method for reducing an organic compound, which is performed using the composition according to any one of 1 to 3 above.
[5] A method for producing an alcohol compound, wherein the aldehyde compound or the ketone compound is reduced with the composition according to any one of 1 to 3 above.
[6] A method for producing an alcohol compound, wherein the ester compound is reduced with the composition according to any one of 1 to 3 above.
[7] A method for producing an alcohol compound, wherein the carboxylic acid compound is reduced with the composition according to any one of 1 to 3 above.
[8] A method for producing an alcohol compound in which a carboxylic acid chloride is reduced with the composition according to any one of 1 to 3 above.
[9] A method for producing an amine compound, wherein the amide compound is reduced with the composition according to any one of 1 to 3 above.
[10] A method for producing an amine compound, wherein a nitrile compound is reduced with the composition according to any one of 1 to 3 above.
[11] A method for producing a cyclic ether compound, wherein a lactone compound is reduced with the composition according to any one of 1 to 3 above.
[12] Using the composition according to any one of 1 to 3 above, after the reduction reaction of the compound according to any one of 5 to 11 above, water is added, and the compound produced by the reaction is transferred to the tetrahydropyran layer. The manufacturing method of the compound in any one of said 5-11 to extract.

  In the reduction method of the carbonyl compound, carboxylic acid derivative compound and the like of the present invention, the reaction solvent and the extraction solvent can be made the same by using a composition containing a borohydride compound and an aluminum salt in tetrahydropyran. Simplification of the reaction process, reduction of energy costs, etc. can be realized, and the use of tetrahydropyran with low toxicity as a solvent increases the safety to the living body.

Hereinafter, specific contents of the present invention will be described in detail.
The present invention relates to a method for reducing a carbonyl compound and a carboxylic acid derivative compound in a tetrahydropyran solvent using a composition comprising a borohydride compound and an aluminum salt.

（式中、ｐは１または２の整数を表し、Ｍはｐ価の陽イオンとなり得る金属または原子団を表す。）で表される化合物である。 [Boron hydride compound]
The borohydride compound used in the present invention has the following formula:

(Wherein p represents an integer of 1 or 2, and M represents a metal or an atomic group that can be a p-valent cation).

  When p = 1, examples of the borohydride compound in which M is a metal include lithium borohydride, sodium borohydride, and potassium borohydride. In addition, as a borohydride compound in which M can be a monovalent cation, a borohydride compound having organic ammonium (referred to as ammonium borohydride in the present application), for example, tetramethylammonium borohydride, hydrogenated Boron tetraethylammonium, borohydride tetrabutylammonium borohydride, trimethyloctylammonium borohydride, trimethylbenzylammonium borohydride and the like can be used, and among these, sodium borohydride is preferably used. As the borohydride compound in the case of p = 2, calcium borohydride, magnesium borohydride, zinc borohydride, tin borohydride and the like can be used. The case where p is 1 is more preferable.

[Aluminum salt]
The aluminum salt used in the present invention is a trivalent inorganic aluminum salt compound. Specifically, aluminum fluoride, aluminum chloride, aluminum bromide, aluminum iodide, aluminum nitrate and the like can be used. Of these, aluminum chloride is particularly preferred.

[Composition of borohydride compound and aluminum salt]
Next, the composition of a borohydride compound and an aluminum salt will be described.
The borohydride compound and the aluminum salt are dissolved or dispersed in tetrahydropyran at an arbitrary ratio.
This may be achieved by dissolving or dispersing a premixed borohydride compound and aluminum salt in tetrahydropyran, or first dispersing the borohydride compound in tetrahydropyran and then dissolving the aluminum salt, or tetrahydropyran. First, any method of dissolving the aluminum salt and then dispersing the borohydride compound may be used.
It is preferable to use 1 mol equivalent of a trivalent aluminum salt per 3 mol equivalent of a monovalent borohydride compound.

  It is not clear what composition the boron hydride compound and aluminum salt form in the tetrahydropyran (THP) solvent, but the boron hydride compound (eg, hydrogenated) in tetrahydropyran It is estimated that sodium borohydride and aluminum chloride are salt-exchanged to produce aluminum borohydride (the following reaction formula 1).

ただし、本発明はこのような反応を経ているか否かによって限定されるものではない。

However, the present invention is not limited by whether or not such a reaction has passed.

  The amount of borohydride compound used varies depending on the compound to be reduced. For example, when sodium borohydride is used as the borohydride compound, there is 4 mol of hydride per 1 mol of sodium borohydride. Therefore, when carbonyl compounds such as aldehydes and ketone compounds are reduced, an amount of at least 0.25 mol is required. . In the case of reducing the ester compound, 0.5 mol equivalent, in the case of reducing the carboxylic acid compound, 0.75 mol equivalent, in the case of reducing the carboxylic acid chloride, 0.5 mol equivalent, in the case of reducing the primary amide compound, 0. 75 mol equivalents, 0.5 mol equivalents when reducing secondary amide compounds, 0.5 mol equivalents when reducing nitrile compounds, and 0.5 mol equivalents of sodium borohydride when reducing lactone compounds are used.

  The reaction temperature can be between the melting point of tetrahydropyran (−45 ° C.) and the reflux temperature, and is preferably between 0 ° C. and 88 ° C.

  The present invention can be used for reduction reactions of various organic compounds. In general, the present invention can be applied if reduction with aluminum chloride is possible, but it can be suitably used particularly for the reduction reaction of the following compounds.

[Carbonyl compound]
The carbonyl compound used in the present invention is not particularly limited, and formaldehyde, acetaldehyde, butyraldehyde, crotonaldehyde, 3-phenylpropionaldehyde, propionaldehyde, valeraldehyde, cyclohexane sancarbaldehyde, phenylacetaldehyde, glyoxal, malonaldehyde, Aliphatic aldehyde compounds such as succinaldehyde and glutaraldehyde, benzaldehyde, anisaldehyde, p-chlorobenzaldehyde, p-methylbenzaldehyde, vanillin, 2-naphthalene aldehyde, terephthalaldehyde, phthalaldehyde, isophthalaldehyde, 1,2-naphthalene Aromatic aldehyde compounds such as carbaldehyde, acetone, methyl ethyl ketone, diethyl ketone , Isophorone, cyclopentanone, cyclohexanone, cyclohexylacetone, acetylacetone, methyl acetoacetate and other aliphatic ketone compounds, acetophenone, propiophenone, benzophenone deoxybenzoin, acetonaphthophenone, butyronaphthophenone, inden-1-one, An aromatic ketone compound such as fluoren-9-one can be used.

[Ester compound]
There is no particular limitation on the ester compound used in the present invention, methyl formate, methyl acetate, butyl acetate, methyl propionate, methyl butyrate, methyl hexanoate, methyl octylate, methyl cyclohexanecarboxylate, phenylacetic acid, ethyl acetoacetate , Aliphatic ester compounds such as dimethyl oxalate, diethyl malonate, dimethyl succinate, dimethyl maleate, diethyl glutarate, ethyl benzoate, methyl anisate, methyl 2-naphthalenecarboxylate, dimethyl terephthalate, diethyl isophthalate, Aromatic ester compounds such as dioctyl phthalate, trimethyl trimellitic acid and tetramethyl pyromellitic acid can be used.

[Carboxylic acid compound]
The carboxylic acid compound used in the present invention is not particularly limited, and formic acid, acetic acid, propion, butanoic acid, butyric acid, hexanoic acid, octylic acid, cyclohexanecarboxylic acid, phenylacetic acid, acetoacetic acid, oxalic acid, malonic acid, succinic acid Aliphatic carboxylic acid compounds such as acid, maleic acid, glutaric acid, aromatic carboxylic acid compounds such as benzoic acid, anisic acid, 2-naphthalene carboxylic acid, terephthalic acid, isophthalic acid, phthalic acid, trimellitic acid, and pyromellitic acid Etc. can be used.

[Carboxyl chloride]
There are no particular restrictions on the carboxylic acid chloride used in the present invention, formic acid chloride, acetic acid chloride, propionic acid chloride, butanoic acid chloride, butyric acid chloride, hexanoic acid chloride, octylic acid chloride, cyclohexanecarboxylic acid chloride, phenylacetic acid chloride , Acetoacetic acid chloride, oxalic acid dichloride, malonic acid dichloride, succinic acid dichloride, maleic acid dichloride, glutaric acid dichloride, and the like, benzoic acid chloride, anisic acid chloride, 2-naphthalenecarboxylic acid chloride, terephthalic acid Uses aromatic carboxylic acid compounds such as dichloride, isophthalic acid dichloride, phthalic acid dichloride, trimellitic acid trichloride, pyromellitic acid tetrachloride Rukoto can.

[Amide compound]
The amide compound used in the present invention is not particularly limited, and formic acid amide, acetic acid amide, N-methylacetic acid amide, N, N′-dimethylacetic acid amide, butyric acid amide, N-butylbutyric acid amide, N, N′— An aliphatic amide compound such as diethyl butyric acid amide, acetoacetic acid amide or oxamide, an aromatic amide compound such as benzamide, N-ethylbenzamide, N, N′-diethylbenzamide or terephthalamide can be used.

[Nitrile compound]
The nitrile compound used in the present invention is not particularly limited, and is an aliphatic nitrile compound such as acetonitrile, acrylonitrile, propionitrile, crotononitrile, valeronitrile, malonodinitrile, benzonitrile, tolunitrile, phthalonitrile, terephthalonitrile, An aromatic nitrile compound such as phthalonitrile can be used.

[Lactone compound]
The lactone compound used in the present invention is not particularly limited, and lactone compounds such as γ-butyrolactone, γ-valerolactone, δ-valerolactone, and ε-caprolactone can be used.

  In the present invention, by adding water after the reduction reaction, the inorganic substance can be extracted and separated into the aqueous layer, and the produced product such as the alcohol compound can be separated into the tetrahydropyran layer. That is, since tetrahydropyran serves as both the reaction solvent and the extraction solvent, the reaction product can be directly extracted and separated without concentrating the reaction solvent or adding a separate extraction solvent. Cost can be reduced.

（式中、Ｒ、Ｒ'及びＲ''は、それぞれ独立してアルキル基、アルケニル基、アリール基または水素原子を表す。） From the above, reaction examples applicable in the present invention can be shown below.

(In the formula, R, R ′ and R ″ each independently represents an alkyl group, an alkenyl group, an aryl group or a hydrogen atom.)

Hereinafter, the present invention will be specifically described with reference to typical examples, but the present invention is not limited to these.
In addition, in the analysis of each component in the Examples, a gas chromatography apparatus 6890N (manufactured by Agilent Technologies) was used, and a DB-1 column (manufactured by J & W Scientific, length 30 m, diameter 0.32 mm, A film thickness of 1 μm) was used.

[Example 1: Preparation of sodium borohydride-aluminum chloride composition]
A stirring bar, 1.13 g (30 mmol) of sodium borohydride, 1.33 g (10 mmol) of aluminum chloride and 30 ml of tetrahydropyran were added to an eggplant flask having a capacity of 100 ml under ice cooling, and the mixture was stirred for 1 hour. Hereinafter, this solution is abbreviated as Al (BH ₄ ) ₃ -THP solution.

[Example 2: Reduction of aldehyde]
To the Al (BH ₄ ) ₃ -THP solution prepared in Example 1, 8.65 g (65 mmol) of 3-phenylpropionaldehyde was added and reacted at room temperature for 2 hours. After the reaction, 10 ml of water was added to stop the reaction, a liquid separation operation was performed between the tetrahydropyran layer and the aqueous layer, and the formation of 3-phenylpropanol extracted in the former was confirmed by GC. The yield was 94%.

[Example 3: Reduction of ketone]
To the Al (BH ₄ ) ₃ -THP solution prepared in Example 1, 7.2 g (60 mmol) of acetophenone was added and reacted at room temperature for 4 hours. After the reaction, 10 ml of water was added to stop the reaction, and a liquid separation operation was performed between the tetrahydropyran layer and the aqueous layer, and the production of 1-phenylethanol extracted in the former was confirmed by GC. The yield was 91%.

[Example 4: Reduction of ester]
To the Al (BH ₄ ) ₃ -THP solution prepared in Example 1, ester (30 mmol) and 10 ml of tetrahydropyran were added at room temperature and reacted for 8 hours under reflux. After the reaction, 10 ml of water was added to stop the reaction, a liquid separation operation was performed between the tetrahydropyran layer and the aqueous layer, and the production of the alcohol extracted in the former was confirmed by GC. The results are shown in Table 1.

[Example 5: Reduction of carboxylic acid compound]
To the Al (BH ₄ ) ₃ -THP solution prepared in Example 1, carboxylic acid (20 mmol) and 30 ml of tetrahydropyran were added at room temperature and reacted for 8 hours under reflux. After the reaction, 10 ml of water was added to stop the reaction, a liquid separation operation was performed between the tetrahydropyran layer and the aqueous layer, and the production of the alcohol extracted in the former was confirmed by GC. The results are shown in Table 2.

[Example 6: Reduction of carboxylic acid chloride (acid chloride)]
To the Al (BH ₄ ) ₃ -THP solution prepared in Example 1, 4.2 g (30 mmol) of benzoic acid chloride was added under ice cooling and reacted at room temperature for 2 hours. After the reaction, 10 ml of water was added to stop the reaction, and a liquid separation operation was performed between the tetrahydropyran layer and the aqueous layer, and the production of benzyl alcohol extracted in the former was confirmed by GC. The yield was 74%.

[Example 7: Reduction of amide]
To the Al (BH ₄ ) ₃ -THP solution prepared in Example 1, amide (30 mmol) and 30 ml of tetrahydropyran were added at room temperature and reacted for 15 hours under reflux. After the reaction, 10 ml of water was added to stop the reaction, and a liquid separation operation was performed between the tetrahydropyran layer and the aqueous layer, and the production of the amine extracted in the former was confirmed by GC. The results are shown in Table 3.

[Example 8: Reduction of nitrile]
Nitrile (30 mmol) and 10 ml of tetrahydropyran were added to the Al (BH ₄ ) ₃ -THP solution prepared in Example 1 at room temperature and reacted for 8 hours under reflux. After the reaction, 10 ml of water was added to stop the reaction, and a liquid separation operation was performed between the tetrahydropyran layer and the aqueous layer, and the production of the amine extracted in the former was confirmed by GC. The results are shown in Table 4.

[Example 9: Lactone]
10 ml of tetrahydropyran of lactone (30 mmol) was added to the Al (BH ₄ ) ₃ -THP solution prepared in Example 1 over 1 hour under ice cooling, and the temperature was raised to room temperature over 2 hours under ice cooling over 2 hours. And allowed to react at room temperature for 8 hours. After the reaction, 10 ml of water was added to stop the reaction, and a liquid separation operation was performed between the tetrahydropyran layer and the aqueous layer, and the formation of the cyclic ether extracted in the former was confirmed by GC. The results are shown in Table 5.

[Example 10: Preparation and ester reduction of potassium borohydride-aluminum chloride composition]
A stirring bar, 1.61 g (30 mmol) of potassium borohydride, 1.33 g (10 mmol) of aluminum chloride, and 30 ml of tetrahydropyran were added to an eggplant flask having a capacity of 100 ml under ice-cooling and stirred for 1 hour. 9.2 g (60 mmol) of methyl benzoate was added and reacted for 8 hours under reflux. After the reaction, 10 ml of water was added to stop the reaction, and a liquid separation operation was performed between the tetrahydropyran layer and the aqueous layer, and the production of benzyl alcohol extracted in the former was confirmed by GC. The yield was 71%.

[Comparative Example 1: Addition of aluminum chloride, THP solvent]
A stirring bar, 1.34 g (10 mmol) of 3-phenylpropionmethyl, 0.38 g (10 mmol) of sodium borohydride, and 10 ml of tetrahydropyran were added to an eggplant flask having a volume of 30 ml, and reacted for 2 hours under reflux with vigorous stirring. When a part of the reaction solution was sampled and analyzed by GC, formation of 3-phenylpropanol was not confirmed.

[Comparative Example 2: Addition of aluminum chloride, methanol solvent]
A stirring bar, 1.34 g (10 mmol) of 3-phenylpropionmethyl, 0.38 g (10 mmol) of sodium borohydride and 10 ml of methanol were added to a eggplant flask having a volume of 30 ml, and reacted for 2 hours under reflux with vigorous stirring. The reaction solution became uniform. When a part of the reaction solution was sampled and analyzed by GC, formation of 3-phenylpropanol was not confirmed.

[Comparative Example 3: NaBH ₄ -AlCl ₃ reduction in diglyme solvent]
A stirring bar, 1.13 g (30 mmol) of sodium borohydride, 1.33 g (10 mmol) of aluminum chloride, and 30 ml of diglyme were added to an eggplant flask having a capacity of 100 ml under ice cooling, and the mixture was stirred for 1 hour. 9.2 g (60 mmol) of methyl benzoate was added and reacted for 8 hours under reflux. After the reaction, 2 ml of water was added to decompose excess lithium borohydride. The reaction solution is a mixture of water, diglyme, product, etc. In order to separate the generated benzyl alcohol, the reaction solution is distilled off with an evaporator, and then 10 ml of water and 10 ml of ethyl acetate are added to the concentrated solution for separation. It was necessary to perform an operation.

In the reduction method of the carbonyl compound, carboxylic acid derivative compound and the like of the present invention, the reaction solvent and the extraction solvent can be made the same by using a composition containing a borohydride compound and an aluminum salt in tetrahydropyran. Simplification of the reaction process, reduction of energy costs, and the like can be realized, and the use of tetrahydropyran having low toxicity as a solvent increases the safety to the living body.

Claims (12)

  A composition comprising a borohydride compound and an aluminum salt in tetrahydropyran.   The composition according to claim 1, wherein the borohydride compound is one or more selected from the group consisting of sodium borohydride, potassium borohydride, and ammonium borohydride.   The composition according to claim 1 or 2, wherein the aluminum salt is aluminum chloride or aluminum bromide.   A method for reducing an organic compound, which is performed using the composition according to claim 1.   The manufacturing method of the alcohol compound which reduces an aldehyde compound or a ketone compound with the composition in any one of Claims 1-3.   The manufacturing method of the alcohol compound which reduces an ester compound with the composition in any one of Claims 1-3.   The manufacturing method of the alcohol compound which reduces a carboxylic acid compound with the composition in any one of Claims 1-3.   The manufacturing method of the alcohol compound which reduces a carboxylic acid chloride with the composition in any one of Claims 1-3.   The manufacturing method of the amine compound which reduces an amide compound with the composition in any one of Claims 1-3.   The manufacturing method of the amine compound which reduces a nitrile compound with the composition in any one of Claims 1-3.   The manufacturing method of the cyclic ether compound which reduces a lactone compound with the composition in any one of Claims 1-3. Using the composition according to any one of claims 1 to 3, water is added after the reduction reaction of the compound according to any one of claims 5 to 11, and the compound produced by the reaction is extracted into a tetrahydropyran layer. The manufacturing method of the compound in any one of Claims 5-11.