JPH1087619A - Production of piperidine compound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for producing a piperidine compound in high yield by completing the catalytic reduction of a pyridine base compound in the presence of a relatively small amount of a catalyst along with suppressing formation of byproducts with boiling points close to that of the aimed piperidine compound. SOLUTION: A pressure reaction vessel is charged with a pyridine base compound and stabilization-treated nickel catalyst at >=2wt.% based on the pyridine base compound to conduct a catalytic reduction of the pyridine base compound under agitation and hydrogen introduction at 140-250 deg.C while keeping a hydrogen pressure of 30-100kgf/cm<2> (2.9×10<6> to 9.8×10<6> Pa), thus obtaining the objective piperidine compound.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a method for producing piperidines by catalytic reduction of pyridine bases.

[0002]

2. Description of the Related Art Methods for producing piperidines by catalytic reduction of pyridine bases are known, and various catalysts are used in the catalytic reduction.

[0003]

Raney nickel is an inexpensive catalyst which is particularly useful, but when it is used for catalytic reduction of pyridine bases, it is difficult to complete the reaction, and the reaction is carried out under a high hydrogen pressure. However, unreacted pyridine bases remain. A large amount of Raney nickel is required to complete the reaction. Platinum catalyst, palladium catalyst,
Noble metal catalysts such as ruthenium catalysts and rhodium catalysts are also used for the catalytic reduction of pyridine bases, but these noble metal catalysts are expensive, and for example, when a ruthenium catalyst is used for the catalytic reduction of pyridine bases, the piperidine formed Amylamines in which the bond between the nitrogen atom and the carbon atom of the ring is cleaved are easily formed. Since the by-product amylamines have a boiling point close to that of the piperidines, when they are formed, it becomes difficult to recover high-purity piperidines from the reaction solution after completion of the reaction.

The present invention provides a method for producing piperidine which can solve the above-mentioned problems, that is, completes the catalytic reduction of pyridine bases with a relatively small amount of catalyst, and furthermore reduces the boiling point close to that of the target piperidine. It is an object of the present invention to provide a method capable of producing piperidines in high yield by suppressing generation of by-products having the same.

[0005]

Means for Solving the Problems The present inventor has conducted intensive studies in order to solve the above-mentioned problems. As a result, in producing piperidines by catalytic reduction of pyridine bases, a stabilized nickel catalyst (hereinafter, referred to as a stabilized nickel catalyst) which is commercially available at low cost and is easy to handle is used as a catalyst. It was found that when used, the reaction was completed with a relatively small amount of catalyst and that piperidine rings could be inhibited from being cleaved to produce piperidines in high yield, and the present invention was completed.

That is, the present invention relates to a method for producing piperidines, which comprises using a stabilized nickel catalyst as a catalyst in producing piperidines by catalytic reduction of pyridine bases.

[0007]

DESCRIPTION OF THE PREFERRED EMBODIMENTS In the present invention, it is important to use a stabilized nickel catalyst for catalytic reduction. The stabilized nickel catalyst used in the present invention is obtained by stabilizing a ignitable nickel catalyst that ignites in contact with air, and is a non-ignitable and easy-to-handle catalyst. The stabilized nickel catalyst may be one produced from a ignitable nickel catalyst by any conventionally known stabilization method. As a method of the stabilization treatment, for example, a method of oxidizing a ignitable nickel catalyst by contacting it with air in the presence of water in a gas phase or a liquid phase, or a method of converting a ignitable nickel catalyst into an inert gas such as nitrogen or carbon dioxide A method of contacting with air and oxidizing in the presence of a gas may, for example, be mentioned. Examples of the ignitable nickel catalyst used for the stabilization treatment include a catalyst obtained by reducing a nickel salt such as Raney nickel, nickel nitrate, and nickel carbonate, a catalyst obtained by decomposing nickel formate, and a nickel-manganese catalyst. And alloys of nickel and other metals, or mixtures thereof, and these may be supported on a suitable carrier such as diatomaceous earth. Further, the stabilized nickel catalyst of the present invention may contain a co-catalyst, and examples of the co-catalyst include alkaline earth metals. Stabilized nickel catalysts are readily available as commercial products. Commercially available stabilized nickel catalysts include N103, N161A, N162A and N163A.
[The above are manufactured by JGC Chemicals, Inc. Product name], SN-110,
SN-150, SN-250, SN-300, SN-7
50 [or more, manufactured by Sakai Chemical Co., Ltd.] Product Name].

The amount of the stabilized nickel catalyst used in the present invention may be usually at least 2% by weight, preferably 3 to 30% by weight, based on pyridine bases. If the use amount of the nickel catalyst is less than 2% by weight based on the pyridine base, it takes a long time to complete the reaction.

Specific examples of pyridine bases used in the present invention include pyridine, 2-methylpyridine,
-Ethylpyridine, 2-propylpyridine, 2,3-dimethylpyridine, 2,4-dimethylpyridine, 2,5-
Dimethylpyridine, 2,6-dimethylpyridine, 2-methyl-4-ethylpyridine, 2-methyl-5-ethylpyridine, 2-methyl-5-butylpyridine, 2,6-dipropylpyridine, 2,3,5 -Trimethylpyridine,
2,4,6-trimethylpyridine, 2-methyl-3-ethyl-6-propylpyridine, 3-methylpyridine,
-Methylpyridine, 3-ethylpyridine, 4-ethylpyridine, 4-propylpyridine, 4-isobutylpyridine, 4- (1-butylpentyl) pyridine, 3,4-dimethylpyridine, 3,5-dimethylpyridine, 3- Examples thereof include methyl-4-ethylpyridine, 3-ethyl-4-methylpyridine, 3,4-diethylpyridine, and 3,5-diethylpyridine. Preferably, pyridine and 2-methylpyridine, 2-ethylpyridine, 2-propylpyridine, 2,3-dimethylpyridine, 2,4-dimethylpyridine, 2,5-dimethylpyridine, 2,6-dimethylpyridine, -Methyl-4-ethylpyridine, 2
-Methyl-5-ethylpyridine, 2-methyl-5-butylpyridine, 2,6-dipropylpyridine, 2,3,5
Alkylpyridines having an alkyl group at the α-position, such as -trimethylpyridine, 2,4,6-trimethylpyridine, 2-methyl-3-ethyl-6-propylpyridine and the like.

Specific examples of the piperidine produced by the method of the present invention include piperidine, 2-methylpiperidine, 2-ethylpiperidine, 2-propylpiperidine, 2,3-dimethylpiperidine, and 2,4-dimethylpiperidine. 2,5-dimethylpiperidine, 2,6-dimethylpiperidine, 2-methyl-4-ethylpiperidine,
2-methyl-5-ethylpiperidine, 2-methyl-5
Butylpiperidine, 2,6-dipropylpiperidine,
2,3,5-trimethylpiperidine, 2,4,6-trimethylpiperidine, 2-methyl-3-ethyl-6-propylpiperidine, 3-methylpiperidine, 4-methylpiperidine, 3-ethylpiperidine, 4-ethylpiperidine , 4-propylpiperidine, 4-isobutylpiperidine, 4- (1-butylpentyl) piperidine, 3,4-
Dimethylpiperidine, 3,5-dimethylpiperidine, 3
-Methyl-4-ethylpiperidine, 3-ethyl-4-methylpiperidine, 3,4-diethylpiperidine, 3,5
-Diethylpiperidine and the like.

The reaction temperature of the catalytic reduction in the present invention is usually from 140 to 250 ° C, preferably from 150 to 210 ° C. When the reaction temperature is lower than 140 ° C., it takes a long time to complete the reaction, and when the reaction temperature is higher than 250 ° C., amylamines are easily formed. The hydrogen pressure in the catalytic reduction is usually 30 to 100 kgf / cm ² (2.9 × 10 ⁶ to
9.8 × 10 ⁶ Pa), preferably 40 to 90 kgf /
cm ² (3.9 × 10 ^{6 to} 8.8 × 10 ⁶ Pa).
If the hydrogen pressure is lower than 30 kgf / cm ² (2.9 × 10 ⁶ Pa), it takes a long time to complete the reaction, and if the hydrogen pressure is lower than 100 kgf / cm ² (2.9 × 10 ⁶ Pa).
If it is higher than kgf / cm ^{2 (9.8 × 10 6} Pa), the equipment becomes expensive and not practical.

The method of the present invention does not require a solvent, but a solvent can be used. The solvent that can be used is not particularly limited as long as it is inert to the catalytic reduction of the present invention, and examples thereof include water, ethers such as dioxane and tetrahydrofuran, and acetates.

In order to carry out the process of the present invention, for example, a pyridine base, a stabilized nickel catalyst and a solvent as required are charged into a pressurized reactor, and the above reaction temperature and hydrogen pressure are adjusted while introducing hydrogen with stirring. The reaction may be performed while keeping the temperature. When the reaction is completed, hydrogen is no longer consumed, but usually,
Further, stirring is continued at the same temperature for about 0.5 to 1 hour. In this case, unreacted pyridine bases do not remain, and piperidine is selectively produced in high yield.

According to the method of the present invention, since unreacted pyridine bases and by-products are scarcely present in the reaction solution after the completion of the reaction, a high-purity piperidine can be obtained from the reaction solution after the reaction by a simple operation. Can be obtained. For example, after the reaction is completed, the reaction solution is cooled to about room temperature, the internal pressure is returned to normal pressure, the reaction solution is filtered to remove the catalyst, and then the filtrate is easily distilled to obtain high-purity piperidine. Kind is obtained.

[0015]

EXAMPLES Next, the present invention will be described more specifically with reference to examples, but the present invention is not limited to the following examples.

Example 1 10 parts by weight of nickel nitrate hexahydrate, 2 parts by weight of water and 2 parts by weight of diatomaceous earth were mixed, dried and then roasted, and then reduced with hydrogen at about 450 ° C. did. Water is added to the obtained nickel / diatomaceous earth by spraying at 50% by weight with respect to nickel, and 80 to 90 ° C. while appropriately adding water.
The mixture was oxidized with air for 5 hours to obtain a stabilized nickel catalyst having a nickel content of 50% by weight supported on diatomaceous earth.
12 g of the obtained stabilized nickel catalyst and 400 g of 2-methylpyridine were charged into a 1-liter electromagnetic stirring type autoclave, and heated and stirred while introducing hydrogen.
The temperature was raised to 0 ° C. and kept at the same temperature for 2 hours. During the reaction, the hydrogen pressure was kept at 40 kgf / cm ² (3.9 × 10 ⁶ Pa). Thereafter, the introduction of hydrogen was terminated, the reaction solution was cooled to room temperature and returned to normal pressure, and then the reaction solution was filtered to remove the catalyst. When the obtained filtrate was analyzed by gas chromatography, the conversion of 2-methylpyridine was 100%, and the yield of 2-methylpiperidine was 98%.
No formation of 1-hexylamine or 2-hexylamine by ring cleavage was observed.

Example 2 The procedure of Example 1 was repeated, except that pyridine was used instead of 2-methylpyridine. As a result, the conversion of pyridine was 100%, and the yield of piperidine was 95%. Amylamine formation by ring cleavage was not observed.

Example 3 The same procedure as in Example 1 was carried out except that 2,6-dimethylpyridine was used instead of 2-methylpyridine. As a result, the conversion of 2,6-dimethylpyridine was 100%, and the yield of 2,6-dimethylpiperidine was 97%. No formation of 2-heptylamine by ring cleavage was observed.

Comparative Example 1 The procedure of Example 1 was repeated, except that 40 g of Raney nickel was used instead of the stabilized nickel catalyst. As a result, 2
The conversion of -methylpyridine was 95% and the yield of 2-methylpiperidine was 92%. No formation of 1-hexylamine or 2-hexylamine was observed.

Comparative Example 2 The procedure of Example 1 was repeated, except that 4 g of 5% -ruthenium / carbon was used instead of the stabilized nickel catalyst. As a result, the conversion of 2-methylpyridine was 100%, and the yield of 2-methylpiperidine was 93%. 1
-Hexylamine and 2-hexylamine total 0.3
% Had been generated.

Claims (3)

[Claims] 1. A method for producing piperidines, comprising using a stabilized nickel catalyst as a catalyst in producing piperidines by catalytic reduction of pyridine bases. 2. The pyridine base is pyridine or an alkylpyridine having an alkyl group at the α-position.
The described method. 3. The catalytic reduction is carried out at a reaction temperature of 140 to 250 ° C.
Hydrogen pressure 30-100 kgf / cm ² (2.9 × 10 ^6-
The method according to claim 1, wherein the method is performed at 9.8 × 10 ⁶ Pa).