CN1198155A - The preparation method of piperidine - Google Patents

Abstract

The present invention relates to a method for preparing piperidine compounds through the catalytic reduction reaction of pyridine base compounds, that is, the use of a relatively small amount of catalyst can promote the completion of the reaction, and can inhibit the formation of by-products close to the boiling point of the product, thereby improving The piperidine compounds were obtained in good yield. It is characterized in that a pyridine base compound is added to the high-pressure reactor, which is equivalent to more than 2% (weight) of the pyridine base compound, and a stabilized nickel catalyst is added, and the temperature is raised to 140 °C while hydrogen gas is introduced under stirring. At ~250°C, the hydrogen pressure is kept at 30-100kgf/cm ² (2.9×10 ⁶ ～9.8×10 ⁶ Pa), and the catalytic reduction reaction is carried out to prepare piperidine compounds.

Description

The preparation method of piperidine

technical field

The invention relates to a method for preparing piperidine compounds by catalytic reduction reaction of pyridine base compounds.

Background technique

The preparation of piperidines by catalytic reduction of pyridine bases is known and various catalysts are used in the catalytic reduction.

Raney nickel is a low-cost catalyst, which is particularly useful. However, if it is used as a catalyst to carry out the catalytic reduction reaction of pyridine bases, the reaction is difficult to carry out completely. Even if the reaction is carried out under high-pressure hydrogen, there will still be unreacted Pyridine base compounds, to make the reaction complete, must add excess Raney nickel. If platinum, palladium, ruthenium, rhodium and other precious metal catalysts are added, not only the price is expensive, but also for example, the chemical bond between the nitrogen and carbon atoms on the piperidine ring is easily broken by using a ruthenium catalyst to generate pentylamine compounds. The boiling point of the by-product pentylamine compound is close to that of the piperidine compound, which makes it difficult to recover the high-purity piperidine compound from the reaction solution after the reaction.

The purpose of the present invention is to provide a method for preparing piperidine compounds with high yield, which can solve the above problems, that is, adding a small amount of catalyst promotes the reduction reaction to complete, and suppresses the production of byproducts that are close to the boiling point of the product piperidine compounds. product generated.

disclosure of invention

The present inventors have carried out in-depth research to solve the above problems, and found that in the process of preparing piperidine compounds by the catalytic reduction reaction of pyridine base compounds, adding a commercially available, cheaply available, and easy-to-handle stabilization treatment An over-treated nickel catalyst (hereinafter referred to as a stabilized nickel catalyst), only using a small amount of catalyst, can promote the reaction to be carried out completely, and can suppress the cracking of the piperidine ring, thereby obtaining piperidine compounds in high yield. Thus, the present invention has been completed.

That is: the present invention relates to a preparation method of piperidine compounds, which is characterized in that in the process of preparing piperidine compounds by catalytic reduction reaction of pyridine base compounds, a stabilized nickel catalyst is used as a catalyst.

The addition of a stabilized nickel catalyst to the catalytic reduction reaction is an important aspect of the present invention.

The stabilized nickel catalyst in the present invention is obtained by stabilizing the flammable nickel catalyst that ignites in contact with air, and is a catalyst that is nonflammable and easy to handle. The stabilized nickel catalyst can be treated by any known stabilization method, such as: the flammable nickel catalyst is exposed to air oxidation in the presence of gaseous or liquid water, or in the presence of nitrogen, _CO2 and other inert gases. Existence, exposure to air oxidation methods, etc. Flammable nickel catalysts for stabilization treatment, such as: Raney nickel, catalysts obtained by the reduction of nickel salts such as nickel nitrate and nickel carbonate, catalysts obtained by the decomposition of nickel formate, alloys of nickel and other metals such as nickel-manganese, or the above A mixture of species can use diatomaceous earth as a carrier. In addition, the stabilized nickel catalyst may contain cocatalysts such as alkaline earth metals. The stabilized nickel catalyst is readily available as a commercial item. As a commercially available stabilized nickel catalyst, such as: N103, N161A, N162A, N163A [manufactured by Nikki Chemical Co., Ltd., trade name]; SN-110, SN-150, SN-250, SN-300, SN-750 [manufactured by Sakai Chemical Co., Ltd., trade name] and the like.

The amount of the stabilized nickel catalyst used in the present invention is usually more than 2% (weight) of the amount of pyridine base compound, preferably 3-30% (weight). If the amount of nickel catalyst used is less than 2% relative to the pyridine base, the time required to complete the reaction is too long.

Pyridine base compounds in the present invention, for example: pyridine, 2-picoline, 3-picoline, 4-picoline, 2-ethylpyridine, 3-ethylpyridine, 4-ethylpyridine, 2-propylpyridine, 4-propylpyridine, 4-isobutylpyridine, 4-(1-butylpentyl)pyridine, 2,3-lutidine, 2,4-lutidine, 2 , 5-lutidine, 2,6-lutidine, 3,4-lutidine, 3,5-lutidine, 2-methyl-4-ethylpyridine, 2-methyl -5-ethylpyridine, 3-methyl-4-ethylpyridine, 3-ethyl-4-methylpyridine, 3,4-diethylpyridine, 3,5-diethylpyridine, 2-methylpyridine Base-5-butylpyridine, 2,6-dipropylpyridine, 2,3,5-collidine, 2,4,6-collidine, 2-methyl-3-ethyl-6 -Propylpyridine etc. Preferred are pyridine, 2-picoline, 2,6-lutidine and other alkylpyridine compounds containing an α-position alkyl group.

The piperidine compounds prepared by the method of the present invention, for example: piperidine, 2-methylpiperidine, 3-methylpiperidine, 4-methylpiperidine, 2-ethylpiperidine, 3-ethylpiperidine Pyridine, 4-ethylpiperidine, 2-propylpiperidine, 4-propylpiperidine, 4-isobutylpiperidine, 4-(1-butylpentyl)piperidine, 2,3-dimethyl Dimethylpiperidine, 2,4-dimethylpiperidine, 2,5-dimethylpiperidine, 2,6-dimethylpiperidine, 3,4-dimethylpiperidine, 3,5-dimethylpiperidine Basepiperidine, 2-methyl-4-ethylpiperidine, 2-methyl-5-ethylpiperidine, 3-methyl-4-ethylpiperidine, 3-ethyl-4-methylpiperidine Pyridine, 3,4-diethylpiperidine, 3,5-diethylpiperidine, 2-methyl-5-butylpiperidine, 2,6-dipropylpiperidine, 2,3,5- Trimethylpiperidine, 2,4,6-trimethylpiperidine, 2-methyl-3-ethyl-6-propylpiperidine and the like.

The reaction temperature of the catalytic reduction reaction in the present invention is generally 140 to 250°C, preferably 150 to 210°C. If the reaction temperature is lower than 140° C., the time required to complete the reaction is too long; if it exceeds 250° C., pentylamine compounds are easily formed. The hydrogen pressure in the catalytic reduction reaction is generally 30 to 100kgf/cm ² (2.9×10 ⁶ to 9.8×10 ⁶ Pa), preferably 40 to 90kgf/cm ² (3.9×10 ⁶ to 8.8×10 ⁶ Pa). If the hydrogen pressure is lower than 30kgf/cm ² (2.9×10 ⁶ Pa), it will take too long to complete the reaction; if it exceeds 100kgf/cm ² (9.8×10 ⁶ Pa), expensive equipment will be required, which is impractical.

It is not necessary to use a solvent in the method of the present invention, but it is also possible if used. Usable solvents are not particularly limited as long as they are inert to the catalytic reduction, such as water, ethers such as dioxane and tetrahydrofuran, ethyl acetate, and the like.

Implement the method of the present invention, such as: add basic pyridine base compound, stabilized nickel catalyst and according to desired solvent in high-pressure reactor, under stirring, feed hydrogen while maintaining above-mentioned reaction temperature and hydrogen pressure to carry out reaction. After the reaction ends, the hydrogen is no longer consumed. Then, at the same temperature, stirring was continued for 0.5 to 1 hour. In this way, unreacted pyridine base compounds will not remain, and piperidine compounds can be selectively generated with high yield.

According to the method of the present invention, at the end of the reaction, there are almost no unreacted pyridine base compounds and by-products in the reaction liquid, and relatively high-purity piperidine compounds can be obtained by simple treatment of the reaction liquid. For example: at the end of the reaction, the reaction solution is cooled to room temperature, and after the pressure returns to normal pressure, the reaction solution is filtered to remove the catalyst, and the filtrate is distilled to obtain high-purity piperidine compounds easily.

Best form for carrying out the invention

The following examples are given to illustrate the present invention in detail, but do not limit the present invention. Example 1

10 parts by weight of nickel nitrate hexahydrate, 2 parts by weight of water, and 2 parts by weight of diatomite are mixed and dried, calcined, and then reduced by hydrogen at about 450°C to obtain nickel/diatomite. Then, through a sprayer, add water equivalent to 50% (weight) of nickel, while the temperature remains at 80 to 90° C., and oxidize in the air for 5 hours to obtain diatomaceous earth as a carrier with a nickel content of 50% (weight). Stabilized nickel catalyst.

Add 12 g of the stabilized nickel catalyst and 400 g of 2-picoline into a 1 liter electromagnetically stirred autoclave with a capacity of 1 liter, heat and stir, and heat up to 170° C. while feeding hydrogen, and keep at the same temperature for 2 hours. During the reaction, the hydrogen pressure was maintained at 40kgf/cm2 (3.9×10 ⁶ Pa). Then, the feeding of hydrogen gas was stopped, the reaction solution was cooled to room temperature, and after returning to normal pressure, the reaction solution was filtered to remove the catalyst. The result of gas chromatographic analysis is that the conversion rate of 2-methylpyridine is 100%, the yield of 2-methylpiperidine is 98%, and the by-product 1-hexylamine or 2-hexylamine generated due to ring cracking are not detected. amine. Example 2

Replace 2-picoline with pyridine, and all the other are the same as in Example 1. As a result, the conversion rate of pyridine was 100%, the yield of piperidine was 95%, and the by-product pentylamine due to ring cleavage was not detected. Example 3

Replace 2-picoline with 2,6-lutidine, and the rest are the same as in Example 1. As a result, the conversion rate of 2,6-lutidine was 100%, the yield of 2,6-dimethylpiperidine was 97%, and the by-product 2-heptylamine due to ring cleavage was not detected. Comparative example 1

Replace the stabilized nickel catalyst with 40 g of Raney nickel, and the rest are the same as in Example 1. As a result, the conversion rate of 2-methylpyridine was 95%, the yield of 2-methylpiperidine was 92%, and no by-product 1-hexylamine or 2-hexylamine was detected. Comparative example 2

Replace the stabilized nickel catalyst with 5% ruthenium/carbon 4g, and the rest are the same as in Example 1. As a result, the conversion rate of 2-methylpyridine was 100%, the yield of 2-methylpiperidine was 93%, and the total of by-products 1-hexylamine and 2-hexylamine was 0.3%.

Claims (3)

1, a kind of method for preparing piperidines is characterized in that, is obtained by the catalytic reduction reaction of pyridine bases compound, and the stabilization nickel catalyzator of crossing with stabilization treatment is as catalyzer.

2, the method for claim 1, wherein said pyridine bases compound is pyridine or the alkyl pyridine compounds that contains α position alkyl.

3, method as claimed in claim 1 or 2, wherein, carrying out the catalytic reduction reaction temperature is 140～250 ℃, hydrogen-pressure is 30～100kgf/cm ², promptly 2.9 * 10 ⁶～9.8 * 10 ⁶Pa.