JP5932656B2 - Nitrile production method - Google Patents

Description

  The present invention relates to a method for producing a nitrile with a high yield and a high selectivity under mild conditions.

Nitriles are organic compounds that can be converted into functional groups and are useful as synthetic raw materials for fine chemicals such as pharmaceuticals, agricultural chemicals, fragrances, and dyes.
As a method for producing such a nitrile, for example, a method using a dehydration reaction of a primary amide and a method using a dehydration reaction of an oxime are known.
As a method for producing a nitrile by dehydration reaction of a primary amide, a method using a dibutyltin oxide catalyst (see, for example, Non-Patent Document 1), a method using a ruthenium catalyst (see, for example, Non-Patent Document 2), paraformaldehyde-formic acid Methods (for example, see Non-Patent Document 3), methods using a rhenium oxo complex catalyst (for example, see Non-Patent Document 4), and the like are known.
However, these methods have insufficient catalytic activity, use highly toxic catalysts such as organotin compounds, or rare metal catalysts, or require one equivalent or more dehydrating agent for the primary amide. Or, there are problems such as complicated post-processes such as purification after nitrile synthesis and catalyst separation.

  On the other hand, as a method for producing nitrile by dehydration reaction of oxime, for example, a method of dehydrating using acetic anhydride, thionyl chloride, phosphorus pentoxide, phosphorus pentachloride or the like (for example, see Non-Patent Document 5), an acid catalyst is used. Dehydrating method (for example, see Patent Document 1), dehydrating method using an alkali metal salt or alkaline earth metal salt (for example, see Patent Document 2), dehydrating method using a heptavalent rhenium compound (for example, And Patent Document 3) are known.

Japanese Examined Patent Publication No. 2-59144 JP 2000-344723 A JP 2003-252845 A

J. et al. Org. Chem. 64, p1713, (1999) J. et al. Mol. Cat. , 58, p87, (1990) J. et al. Org. Chem. 61, p 6486, (1996) Angew. Chem. Int. Ed. , 41, p29, (2002) 83. “Fourth Edition Experimental Chemistry Course 20”, edited by The Chemical Society of Japan, published by Maruzen Co., Ltd., Organic Synthesis II, p. 451

In the method for producing nitrile by dehydration reaction of oxime, the method of Non-Patent Document 5 requires a large amount of dehydrating agent, generates a large amount of waste, and the reaction conditions are severe.
Since the method of Patent Document 1 is under a strong acidic condition, a high boiling byproduct is generated to reduce the yield, and corrosion of the apparatus or the like becomes a problem.
Since the method of Patent Document 2 performs a dehydration reaction under strong alkaline conditions, it is necessary to use an oxime that does not have a functional group that is unstable under alkaline conditions.
The method of Patent Document 3 has a problem that rhenium is a rare metal and is expensive.
In view of the above circumstances, the present invention produces an industrially advantageous nitrile by performing a dehydration reaction under mild conditions using oxime as a raw material, without discharging a large amount of waste, with high yield and high selectivity. It is an object to provide a method.

  As a result of earnest research, the present inventors have found that the above problem can be solved by performing a dehydration reaction in the presence of hydrotalcite or hydrotalcite and a transition metal compound when producing a nitrile by a dehydration reaction of oxime. I found it.

That is, the present invention is characterized in that an oxime represented by the following general formula (1) (hereinafter referred to as oxime (1)) is subjected to a dehydration reaction in the presence of hydrotalcite. This is a method for producing a nitrile represented by 2) (hereinafter referred to as nitrile (2)).
R-CH = NOH (1)
(In the formula, R is a chain or cyclic alkyl group having 3 to 20 carbon atoms, a chain or cyclic alkenyl group having 3 to 20 carbon atoms, an aryl group having 6 to 20 carbon atoms, or 7 to 20 carbon atoms. Represents an aralkyl group of
R-C≡N (2)
(Wherein R is as defined above.)

  According to the present invention, nitrile (2), which is useful as a raw material for synthesizing fine chemicals such as pharmaceuticals, agricultural chemicals, fragrances, dyes, etc., is subjected to a dehydration reaction under mild conditions using oxime (1) as a raw material. There is no waste discharge, and it can be produced industrially advantageously with high yield and high selectivity.

  The present invention is a method for producing a nitrile (2), wherein the oxime (1) is subjected to a dehydration reaction in the presence of hydrotalcite.

In the above general formulas (1) and (2), the chain alkyl group having 3 to 20 carbon atoms represented by R may be linear or branched. For example, n-propyl group, isopropyl group, n- Examples include butyl group, isobutyl group, sec-butyl group, t-butyl group, various pentyl groups, various hexyl groups, various octyl groups, various decyl groups, various dodecyl groups, various tetradecyl groups, various hexadecyl groups, various octadecyl groups, etc. It is done. Among these, a chain alkyl group having 3 to 17 carbon atoms is more preferable, and a chain alkyl group having 5 to 12 carbon atoms is more preferable. Here, “various” means a linear or branched isomer group.
Examples of the cyclic alkyl group having 3 to 20 carbon atoms represented by R include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cyclooctyl group, a cyclodecyl group, a cyclododecyl group, and an adamantyl group. Especially, a C3-C12 cyclic alkyl group is more preferable, and a C5-C10 cyclic alkyl group is still more preferable.

The chain alkenyl group having 3 to 20 carbon atoms represented by R may be linear or branched. For example, allyl group, propenyl group, various butenyl groups, various hexenyl groups, various octenyl groups, various decenyl groups, Examples include various alkenyl groups such as various dodecenyl groups, various tetradecenyl groups, various hexadecenyl groups, and various octadecenyl groups. Here, “various” means a linear isomer group or a branched isomer group. Especially, a C3-C17 chain alkenyl group is more preferable, and a C5-C12 chain alkenyl group is still more preferable.
Examples of the cyclic alkenyl group having 3 to 20 carbon atoms represented by R include a cyclopropenyl group, a cyclobutenyl group, a cyclopentenyl group, a cyclohexenyl group, a cyclooctenyl group, a cyclodecenyl group, and a cyclododecenyl group. Especially, a C3-C12 cyclic alkenyl group is more preferable, and a C5-C10 cyclic alkenyl group is still more preferable.

Examples of the aryl group having 6 to 20 carbon atoms represented by R include a phenyl group, a tolyl group, a xylyl group, and a naphthyl group. Examples of the aralkyl group having 7 to 20 carbon atoms represented by R include a benzyl group, a phenethyl group, a phenylpropyl group, and a naphthylmethyl group.
The above-described group represented by R may have a substituent, and examples of the substituent include a cyano group, a nitro group, a halogen atom, a hydroxyl group, an alkoxyl group, and an alkoxycarbonyl group.

Specific examples of oxime (1) include acetaldehyde oxime, propanal oxime, butanal oxime, pentanal oxime, hexanal oxime, decanal oxime, 2-methylpentanal oxime, 2-ethylpentanal oxime, and 2-methylhexanal. Oxime, 2-ethylhexanal oxime, 3-methoxypropanal oxime, 4-ethoxybutanal oxime, 3-acetylpropanal oxime, 4-acetylbutanal oxime, 3-ethoxycarbonylpropanal oxime, 4-methoxycarbonylbutanal Oxime, 3-phenylpropanal oxime, 2-phenyl-2-propenal oxime, 4-naphthylbutanal oxime, 2-butenal oxime, 2-pentenal oxime, -Hexenal oxime, 3,7-dimethyloct-6-enal oxime, 3,7-dimethylocta-2,6-dienal oxime, cyclopropanecarbaldehyde oxime, cyclobutanecarbaldehyde oxime, cyclopentanecarbaldehyde oxime, cyclohexane Carbaldehyde oxime, adamantane-1-carbaldehyde oxime, adamantane-2-carbaldehyde oxime, (2-methyl) adamantane-1-carbaldehyde oxime, 8- (2 ′, 6 ′, 6′-trimethyl-1′- Cyclohexen-1'-yl) -2,6-dimethyl-1,3,5,7-octatetraenecarbaldehyde oxime, benzaldehyde oxime, 2-methylbenzaldehyde oxime, 3-methylbenzaldehyde Shim, 4-methylbenzaldehyde oxime, 2,4,6-trimethylbenzaldehyde oxime, 2-acetylbenzaldehyde oxime, 3-acetylbenzaldehyde oxime, 4-acetylbenzaldehyde oxime, 2-methoxycarbonylbenzaldehyde oxime, 3-methoxycarbonylbenzaldehyde oxime, 4-methoxycarbonylbenzaldehyde oxime, 2-methoxybenzaldehyde oxime, 3-methoxybenzaldehyde oxime, 4-methoxybenzaldehyde oxime, phenylacetaldehyde oxime, 2-methylphenylacetaldehyde oxime, 3-methylphenylacetaldehyde oxime, 4-methylphenylacetaldehyde oxime, 2-acetylphenylacetaldehyde Xime, 3-acetylphenylacetaldehyde oxime, 4-acetylphenylacetaldehyde oxime, 2-methoxycarbonylphenylacetaldehyde oxime, 3-methoxycarbonylphenylacetaldehyde oxime, 4-methoxycarbonylphenylacetaldehyde oxime, 2-methoxyphenylacetaldehyde oxime, 3-methoxy Examples include phenylacetaldehyde oxime and 4-methoxyphenylacetaldehyde oxime. Among these, cyclohexanecarbaldehyde oxime is particularly preferable from the viewpoint of use of the resulting nitrile.
In the production method of the present invention, oxime (1) used as a raw material means an oxime form of aldehyde. Such oxime (1) can be obtained by reacting a corresponding aldehyde with an inorganic salt of hydroxylamine according to a conventional method.

In the production method of the present invention, hydrotalcite is present in the reaction system, and the hydrotalcite plays a role as a dehydration catalyst. Hydrotalcite is one of naturally occurring clay minerals, and for example, those having a structure represented by the following general formula (3) (hereinafter referred to as hydrotalcite (3)) are preferably used. be able to.
M ²⁺ _1-x M ³⁺ _x (OH ⁻ ) _{2 + xy} (A ⁿ⁻ ) _{y / n} (3)
^{(Wherein, M 2+} is a divalent metal ^{ion, M 3+} is a trivalent metal ^{ion, A n-is} .x showing a n-valent anion in the range of 0.1 ≦ x ≦ 0.5 A positive number, y is a positive number in the range of 0.1 ≦ y ≦ 0.5, and n is 1 or 2.)

Examples of the divalent metal ion (M ²⁺ ) in the hydrotalcite (3) include one or more of Mg ²⁺ , Ca ²⁺ , Fe ²⁺ , Zn ²⁺ and Cu ^2+. Can be mentioned. In addition, M ^<2+ > may be comprised from 1 type of metal ions, and may be comprised from 2 or more types of metal ions.
Examples of the trivalent metal ion (M ³⁺ ) in the hydrotalcite (3) include Al ³⁺ and / or Fe ³⁺ . Further, like M ²⁺ , M ³⁺ may be composed of one kind of metal ion, or may be composed of two or more kinds of metal ions.
Examples of the anion (A ⁿ⁻ ) in the hydrotalcite (3) include CO ₃ ²⁻ , Cl ⁻ , OH ⁻ , NO ₂ ⁻ , NO ₃ ⁻ and SO ₄ ²⁻ . A ⁿ⁻ may also be composed of one kind, or may be composed of any combination of two or more kinds.
In the present invention, the hydrotalcite may be a hydrate or an anhydride.

As a commercial product of hydrotalcite, “Kyoward 500SH” manufactured by Kyowa Chemical Industry Co., Ltd., “Hydrotalcite (CAS No. 12304-65-3)” manufactured by Wako Pure Chemical Industries, Ltd., and the like can be used.
The reason why hydrotalcite acts as a dehydration catalyst in the production method of the present invention is unclear, but hydrotalcite has a layer structure, and oxime (1) is chelated to this layer structure. It is presumed that the oxime is dehydrated under mild conditions by the activated CO ₃ ²⁻ etc. in the layer.

In the production method of the present invention, a transition metal compound may be further present together with the hydrotalcite. Thereby, the production | generation of nitrile (2) by the dehydration reaction of oxime (1) can be advanced smoothly.
As the transition metal compound that can be used, compounds of transition metals belonging to Group 5, Group 6 and Group 7 of the periodic table are preferable, compounds of transition metals belonging to Group 5 of the periodic table are more preferable, and vanadium compounds are particularly preferable. .
Examples of the vanadium compound include vanadium pentoxide, vanadium trioxide, vanadium tetroxide, vanadium chloride, sodium metavanadate, potassium metavanadate, ammonium metavanadate, vanadium oxide sulfate (vanadyl sulfate), vanadium chloride oxide, and vanadium bromide oxide. 1 type, or 2 or more types, such as vanadyl acetylacetonate.
When a vanadium compound is present as a transition metal compound, it is preferably pentavalent vanadium, such as sodium metavanadate.
The use ratio of the hydrotalcite and the transition metal compound is preferably hydrotalcite: transition metal compound = 1: 5 or less in terms of mass ratio from the viewpoint of smoothly proceeding the dehydration reaction, and 1: 0. More preferably within the range of 01 to 1, more preferably within the range of 1: 0.05 to 0.8, and even more preferably within the range of 1: 0.1 to 0.6. .

[Reaction conditions]
In the production method of the present invention, the dehydration reaction of oxime (1) is performed in the presence of hydrotalcite or hydrotalcite and a transition metal compound (preferably vanadium compound). ) Is preferably in the range of 0.1 to 50% by mass and more preferably in the range of 1 to 30% by mass with respect to the oxime (1) from the viewpoint of smoothly proceeding the dehydration reaction. Preferably, it is in the range of 1 to 20 mass%, more preferably in the range of 1 to 10 mass%.
Moreover, although the temperature of a dehydration reaction changes with kinds of oxime (1), the range of 30-200 degreeC is preferable normally, and the range of 80-170 degreeC is more preferable.
In the dehydration reaction, it is preferable to carry out the reaction while removing water generated as the reaction proceeds. There is no restriction | limiting in particular in the method of removing the water produced | generated by reaction. For example, (i) a method in which a solvent azeotropic with water is present and water is distilled out of the reaction system by azeotropy under the reaction conditions, (ii) a high-boiling solvent is used, and the reaction conditions are reduced in pressure. The method of distilling water out of the system etc. by this is mentioned. From the viewpoint of operability, the method (i) is preferable. In this case, as the solvent azeotropic with water, for example, aromatic hydrocarbons such as benzene, toluene and xylene, and aliphatic hydrocarbons having 5 to 10 carbon atoms such as hexane, heptane and octane can be used.
The reaction time depends on conditions such as reaction temperature, raw material and solvent type, and is usually 2 to 15 hours, preferably 4 to 10 hours.
In this way, the nitrile (2) can be obtained with high yield and high selectivity.

  Specific examples of the nitrile (2) include acetonitrile, propanenitrile, butanenitrile, pentanenitrile, hexanenitrile, decanenitrile, 2-methylpentanenitrile, 2-ethylpentanenitrile, 2-methylhexanenitrile, 2-ethylhexanenitrile. 3-methoxypropanenitrile, 4-ethoxybutanenitrile, 3-acetylpropanenitrile, 4-acetylbutanenitrile, 3-ethoxycarbonylpropanenitrile, 4-methoxycarbonylbutanenitrile, 3-phenylpropiononitrile, 2-phenylacrylonitrile, 4-naphthylbutanenitrile, 2-butenenitrile, 2-pentenenitrile, 2-hexenenitrile, 3,7-dimethyloct-6-enenitrile, 3,7-dimethylocta-2,6 Dienenitrile, cyclopropanecarbonitrile, cyclobutanecarbonitrile, cyclopentanecarbonitrile, cyclohexanecarbonitrile, adamantane-1-carbonitrile, adamantane-2-carbonitrile, (2-methyl) adamantane-1-carbonitrile, 8- ( 2 ', 6', 6'-trimethyl-1'-cyclohexen-1'-yl) -2,6-dimethyl-1,3,5,7-octatetraenecarbonitrile, benzonitrile, 2-methylbenzonitrile , 3-methylbenzonitrile, 4-methylbenzonitrile, 2,4,6-trimethylbenzonitrile, 2-acetylbenzonitrile, 3-acetylbenzonitrile, 4-acetylbenzonitrile, 2-methoxycarbonylbenzonitrile, 3- Methoxycarbonyl Indonitrile, 4-methoxycarbonylbenzonitrile, 2-methoxybenzonitrile, 3-methoxybenzonitrile, 4-methoxybenzonitrile, phenylacetonitrile, 2-methylphenylacetonitrile, 3-methylphenylacetonitrile, 4-methylphenylacetonitrile, 2- Acetylphenylacetonitrile, 3-acetylphenylacetonitrile, 4-acetylphenylacetonitrile, 2-methoxycarbonylphenylacetonitrile, 3-methoxycarbonylphenylacetonitrile, 4-methoxycarbonylphenylacetonitrile, 2-methoxyphenylacetonitrile, 3-methoxyphenylacetonitrile, 4 -Methoxyphenylacetonitrile and the like. Among these, cyclohexanecarbonitrile is particularly preferable from the viewpoint of use.

The nitrile (2) obtained by the production method of the present invention can be usually isolated and purified by a method generally used for isolation and purification of organic compounds. For example, the reaction mixture is filtered to remove hydrotalcite (3), and then the filtrate is concentrated. The concentrate can be further purified by distillation, recrystallization or the like as necessary to obtain a highly pure nitrile (2).
In addition, the hydrotalcite (3) collect | recovered by filtration above can use the at least one part or all part again in the manufacturing method of this invention as needed.

EXAMPLES Hereinafter, although an Example and a comparative example are given and this invention is demonstrated further more concretely, this invention is not limited at all by these Examples.
In addition, the following were used as hydrotalcite A and hydrotalcite B.
Hydrotalcite A: “Hydrotalcite (CAS No. 12304-65-3)” manufactured by Wako Pure Chemical Industries, Ltd.
・ Hydrotalcite B: “KYOWARD 500SH” manufactured by Kyowa Chemical Industry

Example 1
Into a 200 mL three-necked flask equipped with a nitrogen-substituted Dean-Stark water separator, 16.6 g of cyclohexanecarbaldehyde oxime (0.130 mol, containing 0.47 g of cyclohexanecarbonitrile), 54.7 g of toluene, and Hydrotalcite A (0.93 g) was charged, and the mixture was stirred for 5 hours while removing water produced by heating to 165 ° C. After completion of the reaction, hydrotalcite A was removed by filtration, and the resulting solution was quantified by gas chromatography to obtain 11.8 g (0.108 mol) of cyclohexanecarbonitrile. The conversion was 99.3%, the yield was 80.2%, and the selectivity was 80.8%.
In addition, the ratio of the hydrotalcite A with respect to the preparation cyclohexane carbaldehyde oxime was 5.6 mass%.

Example 2
Using the same apparatus as in Example 1, 18.2 g of cyclohexanecarbaldehyde oxime (0.143 mol, containing 0.52 g of cyclohexanecarbonitrile), 64.9 g of toluene, 0.93 g of hydrotalcite A, and sodium metavanadate 0.30 g was charged and stirred for 5 hours while removing water produced by heating to 140 ° C. After completion of the reaction, the solution obtained by filtering hydrotalcite A was quantified by gas chromatography to obtain 14.9 g (0.145 mol) of cyclohexanecarbonitrile. The conversion was 100%, the yield was 97.2%, and the selectivity was 97.2%.
The ratio of hydrotalcite A to the charged cyclohexanecarbaldehyde oxime was 5.1% by mass, and the mass ratio of hydrotalcite A: sodium metavanadate was about 3: 1 (1: about 0.33). .

Example 3
Using the same apparatus as in Example 1, 17.9 g of cyclohexanecarbaldehyde oxime (0.140 mol, containing 0.51 g of cyclohexanecarbonitrile), 105.9 g of xylene, 0.93 g of hydrotalcite A, and sodium metavanadate 0.30 g was charged and stirred for 5 hours while removing water produced by heating to 140 ° C. After completion of the reaction, hydrotalcite A was removed by filtration, and the resulting solution was quantified by gas chromatography to obtain 14.9 g (0.137 mol) of cyclohexanecarbonitrile. The conversion was 99.5%, the yield was 92.6%, and the selectivity was 93.1%.
The ratio of hydrotalcite A to the charged cyclohexanecarbaldehyde oxime was 5.2% by mass, and the mass ratio of hydrotalcite A: sodium metavanadate was about 3: 1 (1: about 0.33). .

Example 4
Using the same apparatus as in Example 1, 18.7 g of cyclohexanecarbaldehyde oxime (0.147 mol, containing 0.36 g of cyclohexanecarbonitrile), 137.9 g of xylene, 0.56 g of hydrotalcite B, and sodium metavanadate 0.17 g was charged and stirred for 5 hours while removing water produced by heating to 140 ° C. After completion of the reaction, hydrotalcite A was removed by filtration, and the resulting solution was quantified by gas chromatography to obtain 15.6 g (0.143 mol) of cyclohexanecarbonitrile. The conversion was 99.6%, the yield was 95.2%, and the selectivity was 95.6%.
The ratio of hydrotalcite B to the charged cyclohexanecarbaldehyde oxime was 3.0% by mass, and the mass ratio of hydrotalcite B: sodium metavanadate was about 3: 1 (1: about 0.33). .

Comparative Example 1
Using the same apparatus as in Example 1, 16.8 g of cyclohexanecarbaldehyde oxime (containing 0.132 mol, 0.53 g of cyclohexanecarbonitrile), 50.5 g of toluene, and 0.93 g of sulfuric acid were charged at 165 ° C. It stirred for 5 hours, removing the water produced | generated by heating. After completion of the reaction, the organic layer obtained by washing with water was quantified by gas chromatography to obtain 4.72 g (0.043 mol) of cyclohexanecarbonitrile. The conversion was 92.6%, the yield was 31.6%, and the selectivity was 34.1%.
In addition, the ratio of the sulfuric acid with respect to the preparation cyclohexane carbaldehyde oxime was 5.5 mass%.

  According to the production method of the present invention, nitriles useful as synthetic raw materials for fine chemicals such as pharmaceuticals, agricultural chemicals, fragrances, and dyes are dehydrated under mild conditions using oxime as a raw material, resulting in high yield and high selection. Can be produced industrially advantageously.

Claims (8)

The oxime represented by the following general formula (1) is subjected to a dehydration reaction in the presence of hydrotalcite and a transition metal compound (excluding the transition metal compound supported on hydrotalcite) , The manufacturing method of the nitrile represented by following General formula (2).
R-CH = NOH (1)
(In the formula, R is a chain or cyclic alkyl group having 3 to 20 carbon atoms, a chain or cyclic alkenyl group having 3 to 20 carbon atoms, an aryl group having 6 to 20 carbon atoms, or 7 to 20 carbon atoms. Represents an aralkyl group of
R-C≡N (2)
(Wherein R is as defined above.)   The manufacturing method of the nitrile of Claim 1 whose usage-amount of a hydrotalcite is 0.1-50 mass% with respect to the oxime represented by General formula (1).   The manufacturing method of the nitrile of Claim 1 or 2 whose oxime represented by General formula (1) is a cyclohexane carbaldehyde oxime.   The manufacturing method of the nitrile in any one of Claims 1-3 whose transition metal compound is a vanadium compound.   The manufacturing method of the nitrile in any one of Claims 1-4 whose transition metal compound is sodium metavanadate.   The manufacturing method of the nitrile in any one of Claims 1-5 whose mass ratio (hydrotalcite: transition metal compound) of a hydrotalcite and a transition metal compound is 1: 0.01-1: 1. The method for producing a nitrile according to any one of claims 1 to 6 , wherein the temperature of the dehydration reaction is 30 to 200 ° C, and water generated as the reaction proceeds is removed.   The method for producing a nitrile according to claim 7, wherein the generated water is removed by a method in which a solvent azeotropic with water is present and water is distilled out of the reaction system by azeotropy.