A method for catalytic synthesis of cycloheximide

Abstract

The present invention relates to a method for catalytically synthesizing cycloheximide, comprising the following steps: in the presence of a selective hydrogenation amination catalyst, adding a raw material, adiponitrile, and a solvent to a high-pressure reactor and stirring uniformly; then sealing the reactor to test air tightness; introducing hydrogen into the reactor for replacement, exhausting other gases, introducing hydrogen, heating reaction, and obtaining cycloheximide; wherein the selective amination hydrogenation catalyst is a nitrogen source using 2-methylimidazole as a matrix, and an active metal Ni and a carrier activated carbon are combined with the catalyst; mechanical ball milling and pyrolysis are used to finally obtain a catalyst having a mass content of Ni of 8 to 18%. The present invention uses adiponitrile as a starting material, is cheap and readily available, has a simple catalyst preparation method, can be synthesized at low catalyst dosages, is easily separated after the reaction, can be recycled multiple times, and has good industrial application prospects.

Description

Technical Field

[0001] The invention relates to the technical field of organic chemical industry, in particular to a method for catalytically synthesizing cycloheximide, and in particular to a process for synthesizing cycloheximide by hydrogenating adiponitrile and performing a cyclization reaction based on a nickel catalyst. Background Art

[0002] Cycloheximine, also known as hexamethyleneimine (ACH), is an important organic synthesis intermediate widely used in pesticides, pharmaceutical intermediates, and in fiber, textile, and rubber products, among other fields. Cycloheximine, as a pesticide intermediate, can be used to synthesize a variety of carbamate herbicides, most notably the systemic selective herbicide cypermethrin. It is also used in the synthesis of some heterocyclic fungicides. In medicine, a world patent (W09945006) reports the use of cycloheximine to synthesize a series of heteroaryl homopiperidine derivatives, which have the potential to nourish nerves and prevent immune disorders in the nervous system. Another patent (CN1213303A) describes a method for enhancing sphincter function using drugs containing phenylcycloheximine derivatives. Its wide range of applications encompasses numerous industrial sectors.

[0003] Among existing technologies, patent (CN107739318A) discloses a method for producing cycloheximide using caprolactam. Melted caprolactam and high-purity hydrogen are placed in a reactor at high temperature. A reduction reaction is then carried out in the presence of a catalyst and white oil at a temperature of 180°C to 260°C and a pressure of 10 kg / cm3. The traces of the reactor column can produce a cycloheximide product with a content of approximately 90%. Because the crude product obtained in the system exists in gaseous form and mixes with unreacted hydrogen, multiple separation steps, including condensation, compression, and reboiling, are required. This makes product separation difficult, the reaction system is heated to a high temperature, and the process flow is lengthy.

[0004] Patent (US4786727) also describes a process for producing cycloheximide by reacting caprolactam with hydrogen under the action of Cu, Cr, and Al catalysts. The reaction proceeds efficiently at a reaction temperature of 200°C and a hydrogen pressure of approximately 10 bar, achieving a yield of approximately 60% to 80% for the synthesis of cycloheximide. Patent (CN107739318A) also discloses a process and apparatus for preparing a key intermediate of cycloheximide using a caprolactam liquid phase method. The raw materials caprolactam and ammonia react under the catalysis of phosphoric acid or a phosphate at a temperature of 260-280°C for a reaction time of 0.5-2 hours, but the caprolactam conversion rate is only 48% to 65%. These methods have practical problems such as high catalyst requirements, harsh reaction conditions, and the high cost of the caprolactam raw material, resulting in a high cost for the final product, cycloheximide.

[0005] As subsequent research progressed, a patent (CN114426520B) provided a process for producing cycloheximide by reacting adipaldehyde or its acetal as a starting material with hydrogen and ammonia. The reaction system employed a noble metal, Ru, as an active metal, in combination with one or more of the modifying metals Pt, Ag, Pd, Co, Cu, and Sn, supported on an oxide support such as TiO2 or Al2O3. Under a hydrogen pressure of 1.0 MPa to 4.0 MPa, a reaction temperature of 100°C to 300°C, and a reaction time of 6.0 h, the Ru-containing supported catalyst catalyzed the reaction of adipaldehyde or its acetal with hydrogen and ammonia, producing cycloheximide in a yield of approximately 90%. While the use of noble metals makes the catalytic hydrogenation process more efficient, noble metal catalysts are also expensive, and their reusability is a concern in industrial applications. Therefore, there is an urgent need to develop catalytic systems with low or even no noble metals.

[0006] In the present invention, the method for synthesizing cycloheximide uses cheap and readily available adiponitrile as the starting material for the reaction and nickel as the active metal for catalysis. The system adopts an atomically efficient and environmentally friendly reduction method.

[0007] Beatty et al. discovered that ruthenium complexes are highly active in the hydrogenation of adiponitrile. (RICHARD, BEATTY, AND, et al. Process for the preparation of ruthenium hydrogenation catalysts and products thereof [J]. Journal of Molecular Catalysis A Chemical.) Using RuHCl(H2)(PCy3)2 as the catalyst, adiponitrile conversion reached 96%, with the majority being the semi-hydrogen product, while selectivity for cycloheximide was only 32%. At a reaction temperature of 60°C, a hydrogen pressure of 0.86 MPa, and a reaction time of 2.3 hours, the catalyst achieved 96% conversion of adiponitrile, with the majority being the semi-hydrogen product.

[0008] Y.Cesteros et al. found that the main products of adiponitrile hydrogenation on SrO / Ni catalyst were cycloheximide and other cyclization products. (Y.Cesteros, R.Fernandez, J.Estelle, et al., Characterization and catalytic properties of several La / Ni and Sr / Ni solids, Applied Catalysis A.) Using SrO / gNi catalyst, when atmospheric pressure, 443K, H 2 / AND (molar ratio) is 300 and space velocity is 1500h -1When the conversion of adiponitrile is 100%, the selectivity of cycloheximide is 36%.

[0009] In summary, cycloheximide, as an important intermediate, is widely used in various fields. Given that one of the main goals of modern catalysis is cleanliness and efficiency, developing industrial technologies for producing cycloheximide that utilize readily available raw materials, a short process flow, low equipment costs, environmentally friendly, reusable, and low-cost technologies is a direction that warrants further research and has important practical significance. Summary of the Invention

[0010] The object of the present invention is to provide a synthetic method for cyclohexyl imine. Improvements have been made to the problems in the prior art, such as the high cost of raw materials leading to rising product costs, a complex synthesis process, a large number of by-products, and the poor repeatability of homogeneous noble metal catalysts. The synthetic method provided by the present invention uses the nitrile compound adiponitrile as a starting raw material, which is cheaper and more readily available, has a higher degree of unsaturation in its nitrile functional group, and the intermediate product of partial hydrogenation is more active. A catalyst system based on nickel as an active metal is centrally designed, in which non-precious metal nickel is linked to a cheap and renewable carrier / ligand. This is used to study and improve the efficient and accurate selectivity of the target product, cyclohexyl imine. The reaction is carried out under relatively mild conditions, has better economic benefits, and the preparation process of the catalyst is simple, with a stable multiple recovery effect.

[0011] The technical solution of the present invention is: a method for catalytically synthesizing cyclohexylimine, characterized in that: in the presence of a selective hydrogenation hydrogenation catalyst, raw materials adiponitrile and a solvent are added together into a high-pressure reactor and stirred evenly; the reactor is then sealed and the airtightness is tested; hydrogen is introduced into the well-sealed reactor for displacement, and after other gases are exhausted, hydrogen at a certain pressure is introduced, and heating reaction is carried out to obtain a hydrogenation hydrogenation product cyclohexylimine; wherein the selective hydrogenation hydrogenation catalyst uses 2-methylimidazole as a nitrogen source as a matrix, and an active metal Ni and a carrier activated carbon are combined with the catalyst; mechanical ball milling and thermal decomposition are performed to finally obtain a carbon and nitrogen-containing Ni-based catalyst, wherein the mass content of Ni is 8-18%.

[0012] Preferably, the above-mentioned Ni-based catalyst is prepared by the following method: a nickel-containing compound, 2-methylimidazole, and an activated carbon carrier are added to a planetary ball mill in proportion, and then a solvent and wear-resistant balls are added, and the ball milling is adjusted to a suitable speed; after the ball milling is completed, the mixture is taken out and vacuum dried; after the solvent evaporates, the mixture is placed in a muffle furnace for pretreatment to obtain a Ni-based catalyst precursor; the precursor is then further reduced under H2 conditions to obtain a supported Ni-based catalyst; and the mixture is sealed and stored for reaction.

[0013] Preferably, the nickel-containing compound is nickel acetate or nickel nitrate; the solvent is deionized water; and the material of the wear-resistant balls is zirconium oxide or stainless steel.

[0014] Preferably, the molar ratio of the nickel-containing compound to 2-methylimidazole is 1:(1-5); the mass ratio of the molar amount of the nickel-containing compound to the activated carbon carrier is 0.02-0.15 mmol / mg; the mass ratio of the added amount of water to the nickel-containing compound is (2-5):1; and the mass ratio of the wear-resistant ball to the nickel-containing compound is (4-13):1.

[0015] The preferred ball milling process is as follows: first, high-speed ball milling is performed at a speed of 220 to 260 r / min for 10 to 20 min, and then the speed is adjusted to 160 to 180 r / min for 5 to 6 h; the pretreatment temperature is 500 to 600° C., and the pretreatment time is 3 to 5 h; the reduction temperature is 400 to 500° C., and the reduction time is 2 to 3 h.

[0016] Preferably, the solvent is cyclohexane, tetrahydrofuran or isopropanol.

[0017] Preferably, the volume ratio of the added molar amount of adiponitrile to the solvent is 0.5-2 mmol / mL; the amount of catalyst added is 9%-28% of the mass of adiponitrile; the pressure of the introduced hydrogen is 0.5-1.5 MPa; the heating reaction temperature is 140-180° C.; and the heating reaction time is 3-8 hours.

[0018] The reaction formula of the above-mentioned catalytic synthesis of cycloheximide is:

[0019]

[0020] After the reaction, the reactor was removed and cooled to room temperature. Samples were taken and analyzed for conversion and selectivity using gas chromatography. The collected samples were also analyzed by GC-MS using Agilent, and the resulting liquid fractions were sequenced to identify the products. The reaction liquid was filtered to separate the catalyst. The separated catalyst was then washed, dried, and reused.

[0021] The invention selects adiponitrile, a cheap and readily available nitrile compound, as a starting raw material for synthesizing cycloheximide. The reaction system avoids using a homogeneous noble metal catalyst, and combines non-noble metal Ni with a cheap and renewable carrier / ligand. Based on a balanced coordination structure between imidazole and nickel ions in the binding process, a nitrogen-doped carbon-supported nickel metal catalyst is synthesized by mechanical ball milling and thermal decomposition to exhibit a high conversion rate of adiponitrile and high selectivity for the product cycloheximide. Compared with a homogeneous catalyst, the nickel-based catalyst cannot be recovered after the reaction. The nickel-based catalyst used in the reaction process can be prepared on a larger scale, has high catalyst activity, and a more efficient hydrogenation process. The catalyst can be reused multiple times without significant loss of catalytic effect.

[0022] Reaction mechanism of the catalytic process:

[0023] Based on the research on the mechanism of nitrile hydrogenation reaction, the main catalytic processes of adiponitrile hydrogenation to cycloheximide are: a) adiponitrile is adsorbed on the active metal sites on the catalyst surface

[0024] b) Hydrogen is adsorbed on the active metal sites on the catalyst surface

[0025] c) Surface active metal sites catalyze the reaction of adiponitrile with hydrogen

[0026] d) The product is desorbed from the catalyst surface and released into the solvent

[0027] Beneficial effects:

[0028] 1) The synthesis process avoids the use of expensive caprolactam as raw material, provides a readily available and inexpensive nitrile compound adiponitrile, and reduces the cost of the product cycloheximide. 2) The catalytic system combines the non-precious metal Ni with a cheap and renewable carrier / ligand, resulting in a simple catalyst preparation process and high activity. 3) Multi-step synthesis is avoided, reducing the overall production cost. 4) The reaction can be efficiently catalyzed under relatively mild conditions and is easy to separate after the reaction. 5) The problem of difficult recycling of homogeneous catalysts is avoided, and the prepared nickel catalyst has high activity, stability, and can be recycled for multiple reactions. DETAILED DESCRIPTION

[0029] Example 1:

[0030] 30 mmol of nickel acetate tetrahydrate, 30 mmol of 2-methylimidazole, 0.2 g of activated carbon, 30 g of zirconium oxide wear-resistant balls, and 8 mL of water were added to a planetary ball mill; high-speed ball milling was performed at 220 r / min for 15 min, and then the speed was adjusted to 160 r / min and uniform ball milling was performed for 5 h; after the ball milling was completed, the mixture was taken out and vacuum dried; after the solvent evaporated, the mixture was placed in a muffle furnace for pretreatment at 600°C for 3 h to obtain a Ni-based catalyst precursor; the precursor was then further reduced under H2 conditions at 500°C for 3 h with a heating rate of 5°C / min to obtain a Ni-based catalyst C1 with a Ni content of 17.4 wt%; and the mixture was sealed and stored for reaction.

[0031] Example 2:

[0032] 20 mmol of nickel acetate tetrahydrate, 40 mmol of 2-methylimidazole, 0.2 g of activated carbon, 30 g of zirconium oxide wear-resistant balls, and 8 mL of water were added to a planetary ball mill; high-speed ball milling was performed at 220 r / min for 15 min, and then the speed was adjusted to 160 r / min and uniform ball milling was performed for 5 h; after the ball milling was completed, the mixture was taken out and vacuum dried; after the solvent evaporated, the mixture was placed in a muffle furnace for pretreatment at 600°C for 3 h to obtain a Ni-based catalyst precursor; the precursor was then reduced under H2 conditions at 500°C for 3 h, with a heating rate of 5°C / min; a Ni-based catalyst C2 with a Ni content of 13.9 wt% was obtained; and the mixture was sealed and stored for reaction.

[0033] Example 3:

[0034] 15 mmol of nickel acetate tetrahydrate, 45 mmol of 2-methylimidazole, 0.2 g of activated carbon, 30 g of zirconium oxide wear-resistant balls, and 8 mL of water were added to a planetary ball mill; high-speed ball milling was performed at 220 r / min for 15 min, and then the speed was adjusted to 160 r / min and uniform ball milling was performed for 5 h; after the ball milling was completed, the mixture was taken out and vacuum dried; after the solvent evaporated, the mixture was placed in a muffle furnace for pretreatment at 600°C for 3 h to obtain a Ni-based catalyst precursor; the precursor was then reduced under H2 conditions at 500°C for 3 h, with a heating rate of 5°C / min; a Ni-based catalyst C3 with a Ni content of 11.5 wt% was obtained; and the mixture was sealed and stored for reaction.

[0035] Example 4:

[0036] 10 mmol of nickel acetate tetrahydrate, 50 mmol of 2-methylimidazole, 0.2 g of activated carbon, 30 g of zirconium oxide wear-resistant balls, and 8 mL of water were added to a planetary ball mill; high-speed ball milling was performed at 220 r / min for 15 min, and then the speed was adjusted to 160 r / min for uniform ball milling for 5 h; after the ball milling was completed, the mixture was taken out and vacuum dried; after the solvent evaporated, the mixture was placed in a muffle furnace for pretreatment at 600°C for 3 h to obtain a Ni-based catalyst precursor; the precursor was then reduced under H2 conditions at 500°C for 3 h with a heating rate of 5°C / min to obtain a Ni-based catalyst C4 with a Ni content of 8.6 wt%; and the mixture was sealed and stored for reaction.

[0037] Example 5:

[0038] 20 mmol of nickel acetate tetrahydrate, 40 mmol of 2-methylimidazole, 0.5 g of activated carbon, 30 g of zirconium oxide wear-resistant balls, and 10 mL of water were added to a planetary ball mill; high-speed ball milling was performed at 220 r / min for 15 min, and then the speed was adjusted to 160 r / min and uniform ball milling was performed for 5 h; after the ball milling was completed, the mixture was taken out and vacuum dried; after the solvent evaporated, the mixture was placed in a muffle furnace for pretreatment at 600°C for 3 h to obtain a Ni-based catalyst precursor; the precursor was then reduced under H2 conditions at 500°C for 3 h with a heating rate of 5°C / min to obtain a Ni-based catalyst C5 with a Ni content of 13.4 wt%; and the mixture was sealed and stored for reaction.

[0039] Example 6:

[0040] 20 mmol of nickel acetate tetrahydrate, 40 mmol of 2-methylimidazole, 1.0 g of activated carbon, 30 g of zirconium oxide wear-resistant balls, and 10 mL of water were added to a planetary ball mill; high-speed ball milling was performed at 220 r / min for 15 min, and then the speed was adjusted to 160 r / min and uniform ball milling was performed for 5 h; after the ball milling was completed, the mixture was taken out and vacuum dried; after the solvent evaporated, the mixture was placed in a muffle furnace for pretreatment at 600°C for 3 h to obtain a Ni-based catalyst precursor; the precursor was then reduced under H2 conditions at 500°C for 3 h with a heating rate of 5°C / min to obtain a Ni-based catalyst C6 with a Ni content of 12.7 wt%; and the mixture was sealed and stored for reaction.

[0041] Example 7:

[0042] 20 mmol of nickel acetate tetrahydrate, 40 mmol of 2-methylimidazole, 0.2 g of activated carbon, 30 g of zirconium oxide wear-resistant balls, and 8 mL of water were added to a planetary ball mill; high-speed ball milling was performed at 220 r / min for 15 min, and then the speed was adjusted to 160 r / min and uniform ball milling was performed for 5 h; after the ball milling was completed, the mixture was taken out and vacuum dried; after the solvent evaporated, the mixture was placed in a muffle furnace for pretreatment at 500°C for 5 h to obtain a Ni-based catalyst precursor; the precursor was then reduced under H2 conditions at 400°C for 2 h with a heating rate of 5°C / min to obtain a Ni-based catalyst C7 with a Ni content of 13.9 wt%; and the mixture was sealed and stored for reaction.

[0043] Example 8:

[0044] 20 mmol of nickel acetate tetrahydrate, 40 mmol of 2-methylimidazole, 0.2 g of activated carbon, 30 g of zirconium oxide wear-resistant balls, and 8 mL of water were added to a planetary ball mill; high-speed ball milling was performed at 260 r / min for 20 min, and then the speed was adjusted to 180 r / min and uniform ball milling was performed for 6 h; after the ball milling was completed, the mixture was taken out and vacuum dried; after the solvent evaporated, the mixture was placed in a muffle furnace for pretreatment at 600°C for 3 h to obtain a Ni-based catalyst precursor; the precursor was then reduced under H2 conditions at 500°C for 3 h, with a heating rate of 5°C / min; a Ni-based catalyst C8 with a Ni content of 13.9 wt% was obtained; and the mixture was sealed and stored for reaction.

[0045] Example 9:

[0046] 15 mmol of nickel acetate tetrahydrate, 45 mmol of 2-methylimidazole, 0.2 g of activated carbon, 30 g of zirconium oxide wear-resistant balls, and 10 mL of water were added to a planetary ball mill; high-speed ball milling was performed at 260 r / min for 20 min, and then the speed was adjusted to 180 r / min and uniform ball milling was performed for 6 h; after the ball milling was completed, the mixture was taken out and vacuum dried; after the solvent evaporated, the mixture was placed in a muffle furnace for pretreatment at 500°C for 3 h to obtain a Ni-based catalyst precursor; the precursor was then reduced under H2 conditions at 400°C for 3 h with a heating rate of 5°C / min to obtain a Ni-based catalyst C9 with a Ni content of 11.5 wt%; and the mixture was sealed and stored for reaction.

[0047] Example 10:

[0048] 108.14 mg (1.0 mmol) of adiponitrile, 2.0 mL of cyclohexane, and 20 mg of catalyst C1 were added to a high-pressure reactor; the reactor was sealed after stirring and tested for airtightness; hydrogen was introduced for displacement; after exhausting other gases in the reactor, 1.5 MPa of H2 was introduced; the reaction system was heated at 180°C for 5 h; after the reaction was completed, the reactor was removed and cooled to room temperature; the reaction liquid was separated from the catalyst, sampled, and subjected to chromatographic analysis; the adiponitrile conversion was 91%, and the cycloheximide selectivity was 92%.

[0049] Example 11:

[0050] 108.14 mg (1.0 mmol) of adiponitrile, 2.0 mL of cyclohexane, and 20 mg of catalyst C2 were added to a high-pressure reactor; the reactor was sealed after stirring evenly and tested for airtightness; hydrogen was introduced for displacement; after exhausting other gases in the reactor, 1.5 MPa of H2 was introduced; the reaction system was heated at 180°C for 5 hours; after the reaction was completed, the reactor was taken out and cooled to room temperature; the reaction liquid and the catalyst were separated, and the separated catalyst was washed and dried for use (named R1); the reaction liquid was sampled and subjected to chromatographic detection; the adiponitrile conversion rate was 100%, and the cycloheximide selectivity was 98%.

[0051] Example 12:

[0052] 108.14 mg (1.0 mmol) of adiponitrile, 2.0 mL of cyclohexane, and 20 mg of catalyst C3 were added to a high-pressure reactor; the reactor was sealed after stirring and tested for airtightness; hydrogen was introduced for displacement; after exhausting other gases in the reactor, 1.5 MPa of H2 was introduced; the reaction system was heated at 180°C for 5 h; after the reaction was completed, the reactor was removed and cooled to room temperature; the reaction liquid was separated from the catalyst, sampled, and subjected to chromatographic analysis; the adiponitrile conversion rate was 96%, and the cycloheximide selectivity was 97%.

[0053] Example 13:

[0054] 108.14 mg (1.0 mmol) of adiponitrile, 2.0 mL of cyclohexane, and 20 mg of catalyst C4 were added to a high-pressure reactor; the reactor was sealed after stirring evenly and tested for airtightness; hydrogen was introduced for displacement; after exhausting other gases in the reactor, 1.5 MPa of H2 was introduced; the reaction system was heated at 180°C for 5 h; after the reaction was completed, the reactor was removed and cooled to room temperature; the reaction liquid and the catalyst were separated; the reaction liquid was sampled and subjected to chromatographic analysis; the adiponitrile conversion rate was 88%, and the cycloheximide selectivity was 85%.

[0055] Example 14:

[0056] 108.14 mg (1.0 mmol) of adiponitrile, 2.0 mL of cyclohexane, and 20 mg of catalyst C5 were added to a high-pressure reactor; the reactor was sealed after stirring and tested for airtightness; hydrogen was introduced for displacement; after exhausting other gases in the reactor, 1.5 MPa of H2 was introduced; the reaction system was heated at 180°C for 5 h; after the reaction was completed, the reactor was removed and cooled to room temperature; the reaction liquid and the catalyst were separated; the reaction liquid was sampled and subjected to chromatographic analysis; the adiponitrile conversion rate was 96%, and the cycloheximide selectivity was 94%.

[0057] Example 15:

[0058] 108.14 mg (1.0 mmol) of adiponitrile, 2.0 mL of cyclohexane, and 20 mg of catalyst C6 were added to a high-pressure reactor; the reactor was sealed after stirring and tested for airtightness; hydrogen was introduced for displacement; after exhausting other gases in the reactor, 1.5 MPa of H2 was introduced; the reaction system was heated at 180°C for 5 h; after the reaction was completed, the reactor was removed and cooled to room temperature; the reaction liquid and the catalyst were separated; the reaction liquid was sampled and subjected to chromatographic analysis; the adiponitrile conversion rate was 95%, and the cycloheximide selectivity was 92%.

[0059] Example 16:

[0060] 108.14 mg (1.0 mmol) of adiponitrile, 2.0 mL of cyclohexane, and 20 mg of catalyst C7 were added to a high-pressure reactor; the reactor was sealed after stirring and tested for airtightness; hydrogen was introduced for displacement; after exhausting other gases in the reactor, 1.5 MPa of H2 was introduced; the reaction system was heated at 180°C for 5 h; after the reaction was completed, the reactor was removed and cooled to room temperature; the reaction liquid was separated from the catalyst, and the reaction liquid was sampled and subjected to chromatographic analysis; the adiponitrile conversion rate was 99%, and the cycloheximide selectivity was 93%.

[0061] Example 17:

[0062] 108.14 mg (1.0 mmol) of adiponitrile, 2.0 mL of cyclohexane, and 20 mg of catalyst C8 were added to a high-pressure reactor; the reactor was sealed after stirring evenly and tested for airtightness; hydrogen was introduced for displacement; after exhausting other gases in the reactor, 1.5 MPa of H2 was introduced; the reaction system was heated at 180°C for 5 h; after the reaction was completed, the reactor was removed and cooled to room temperature; the reaction liquid and the catalyst were separated, the reaction liquid was sampled, and chromatographic analysis was performed; the adiponitrile conversion rate was 100%, and the cycloheximide selectivity was 97%.

[0063] Example 18:

[0064] 108.14 mg (1.0 mmol) of adiponitrile, 2.0 mL of cyclohexane, and 20 mg of catalyst C9 were added to a high-pressure reactor; the reactor was sealed after stirring evenly and tested for airtightness; hydrogen was introduced for displacement; after exhausting other gases in the reactor, 1.5 MPa of H2 was introduced; the reaction system was heated at 180°C for 5 h; after the reaction was completed, the reactor was removed and cooled to room temperature; the reaction liquid was separated from the catalyst, and the reaction liquid was sampled and subjected to chromatographic analysis; the adiponitrile conversion rate was 98%, and the cycloheximide selectivity was 94%.

[0065] Example 19:

[0066] 324.42 mg (3.0 mmol) of adiponitrile, 2.0 mL of cyclohexane, and 30 mg of catalyst C2 were added to a high-pressure reactor; the reactor was sealed after stirring evenly and tested for airtightness; hydrogen was introduced for displacement; after exhausting other gases in the reactor, 1.5 MPa of H2 was introduced; the reaction system was heated at 180°C for 5 h; after the reaction was completed, the reactor was removed and cooled to room temperature; the reaction liquid and the catalyst were separated; the reaction liquid was sampled and subjected to chromatographic analysis; the adiponitrile conversion rate was 99%, and the cycloheximide selectivity was 98%.

[0067] Example 20:

[0068] 324.42 mg (3.0 mmol) of adiponitrile, 2.0 mL of cyclohexane, and 30 mg of catalyst C3 were added to a high-pressure reactor; the reactor was sealed after stirring and tested for airtightness; hydrogen was introduced for displacement; after exhausting other gases in the reactor, 1.5 MPa of H2 was introduced; the reaction system was heated at 180°C for 5 h; after the reaction was completed, the reactor was removed and cooled to room temperature; the reaction liquid and the catalyst were separated; the reaction liquid was sampled and subjected to chromatographic analysis; the adiponitrile conversion rate was 95%, and the cycloheximide selectivity was 92%.

[0069] Example 21:

[0070] 540.7 mg (5.0 mmol) of adiponitrile, 3.0 mL of cyclohexane, and 50 mg of catalyst C2 were added to a high-pressure reactor; the reactor was sealed after stirring evenly and tested for airtightness; hydrogen was introduced for displacement; after exhausting other gases in the reactor, 1.5 MPa of H2 was introduced; the reaction system was heated at 180°C for 5 h; after the reaction was completed, the reactor was removed and cooled to room temperature; the reaction liquid and the catalyst were separated; the reaction liquid was sampled and subjected to chromatographic analysis; the adiponitrile conversion rate was 100%, and the cycloheximide selectivity was 96%.

[0071] Example 22:

[0072] 108.14 mg (1.0 mmol) of adiponitrile, 2.0 mL of isopropanol, and 20 mg of catalyst C2 were added to a high-pressure reactor; the reactor was sealed after stirring and tested for airtightness; hydrogen was introduced for displacement; after exhausting other gases in the reactor, 1.5 MPa of H2 was introduced; the reaction system was heated at 180°C for 5 h; after the reaction was completed, the reactor was removed and cooled to room temperature; the reaction liquid and the catalyst were separated; the reaction liquid was sampled and subjected to chromatographic analysis; the adiponitrile conversion rate was 99%, the cycloheximide selectivity was 76%, and the selectivity of cycloheximide and 6-aminocapronitrile was 88%.

[0073] Example 23:

[0074] 108.14 mg (1.0 mmol) of adiponitrile, 2.0 mL of cyclohexane, and 20 mg of catalyst C2 were added to a high-pressure reactor; the reactor was sealed after stirring evenly and tested for airtightness; hydrogen was introduced for displacement; after exhausting other gases in the reactor, 1.5 MPa of H2 was introduced; the reaction system was heated at 180°C for 4 h; after the reaction was completed, the reactor was removed and cooled to room temperature; the reaction liquid and the catalyst were separated; the reaction liquid was sampled and subjected to chromatographic analysis; the adiponitrile conversion rate was 100%, and the cycloheximide selectivity was 92%.

[0075] Example 24:

[0076] 108.14 mg (1.0 mmol) of adiponitrile, 2.0 mL of cyclohexane, and 30 mg of catalyst C2 were added to a high-pressure reactor; the reactor was sealed after stirring evenly and tested for airtightness; hydrogen was introduced for displacement; after exhausting other gases in the reactor, 1.5 MPa of H2 was introduced; the reaction system was heated at 180°C for 3 h; after the reaction was completed, the reactor was removed and cooled to room temperature; the reaction liquid and the catalyst were separated; the reaction liquid was sampled and subjected to chromatographic analysis; the adiponitrile conversion rate was 98%, and the cycloheximide selectivity was 94%.

[0077] Example 25:

[0078] 108.14 mg (1.0 mmol) of adiponitrile, 2.0 mL of cyclohexane, and 20 mg of catalyst C2 were added to a high-pressure reactor; the reactor was sealed after stirring evenly and tested for airtightness; hydrogen was introduced for displacement; after exhausting other gases in the reactor, 1.0 MPa of H2 was introduced; the reaction system was heated at 180°C for 6 h; after the reaction was completed, the reactor was removed and cooled to room temperature; the reaction liquid and the catalyst were separated; the reaction liquid was sampled and subjected to chromatographic analysis; the adiponitrile conversion rate was 100%, and the cycloheximide selectivity was 93%.

[0079] Example 26:

[0080] 108.14 mg (1.0 mmol) of adiponitrile, 2.0 mL of cyclohexane, and 30 mg of catalyst C2 were added to a high-pressure reactor; the reactor was sealed after stirring evenly and tested for airtightness; hydrogen was introduced for displacement; after exhausting other gases in the reactor, 0.5 MPa of H2 was introduced; the reaction system was heated at 180°C for 8 h; after the reaction was completed, the reactor was removed and cooled to room temperature; the reaction liquid and the catalyst were separated; the reaction liquid was sampled and subjected to chromatographic analysis; the adiponitrile conversion rate was 91%, and the cycloheximide selectivity was 87%.

[0081] Example 27:

[0082] 108.14 mg (1.0 mmol) of adiponitrile, 2.0 mL of cyclohexane, and 15 mg of catalyst C2 were added to a high-pressure reactor; the reactor was sealed after stirring evenly and tested for airtightness; hydrogen was introduced for displacement; after exhausting other gases in the reactor, 1.5 MPa of H2 was introduced; the reaction system was heated at 180°C for 5 h; after the reaction was completed, the reactor was removed and cooled to room temperature; the reaction liquid and the catalyst were separated; the reaction liquid was sampled and subjected to chromatographic analysis; the adiponitrile conversion rate was 97%, and the cycloheximide selectivity was 95%.

[0083] Example 28:

[0084] 108.14 mg (1.0 mmol) of adiponitrile, 2.0 mL of cyclohexane, and 10 mg of catalyst C2 were added to a high-pressure reactor; the reactor was sealed after stirring evenly and tested for airtightness; hydrogen was introduced for displacement; after exhausting other gases in the reactor, 1.5 MPa of H2 was introduced; the reaction system was heated at 180°C for 6 h; after the reaction was completed, the reactor was removed and cooled to room temperature; the reaction liquid and the catalyst were separated; the reaction liquid was sampled and subjected to chromatographic analysis; the adiponitrile conversion rate was 98%, and the cycloheximide selectivity was 92%.

[0085] Example 29:

[0086] 108.14 mg (1.0 mmol) of adiponitrile, 2.0 mL of cyclohexane, and 20 mg of catalyst C2 were added to a high-pressure reactor; the reactor was sealed after stirring evenly and tested for airtightness; hydrogen was introduced for displacement; after exhausting other gases in the reactor, 1.5 MPa of H2 was introduced; the reaction system was heated at 170°C for 5 h; after the reaction was completed, the reactor was removed and cooled to room temperature; the reaction liquid and the catalyst were separated; the reaction liquid was sampled and subjected to chromatographic analysis; the adiponitrile conversion rate was 99%, and the cycloheximide selectivity was 95%.

[0087] Example 30:

[0088] 108.14 mg (1.0 mmol) of adiponitrile, 2.0 mL of cyclohexane, and 20 mg of catalyst C2 were added to an autoclave; after stirring, the autoclave was sealed and tested for airtightness. Hydrogen was introduced to displace the gas; after exhausting all other gases in the autoclave, 1.5 MPa of H2 was introduced. The reaction system was heated at 150°C for 8 hours. After the reaction was completed, the autoclave was removed and cooled to room temperature; the reaction liquid and catalyst were separated; the reaction liquid was sampled and analyzed by chromatography. The adiponitrile conversion was 99%, and the cycloheximide selectivity was 91%. Catalyst R1, washed and dried in Example 11, was reused. The process flow was consistent with the implementation plan, and the catalyst recovery and use are shown in the following table.

[0089] Recycling times Cycloheximide yield 1 97％ 2 95％ 3 95％ 4 93％ 5 92％

Claims

1. A method for catalytic synthesis of cycloheximide, characterized in that: In the presence of a selective hydrogenation and amination catalyst, the raw material adiponitrile and a solvent are added to a high-pressure reactor and stirred uniformly, wherein the solvent is cyclohexane or isopropanol; the reactor is then sealed and tested for airtightness; hydrogen is introduced into the reactor for displacement, and after other gases are exhausted, hydrogen is introduced, and the reaction is heated to obtain cycloheximide; wherein the selective amination and hydrogenation catalyst is prepared by the following method, which specifically comprises the following steps: adding a nickel-containing compound, 2-methylimidazole, and an activated carbon carrier in a planetary ball mill at a molar ratio of the nickel-containing compound to 2-methylimidazole of 1: (1-5) and a mass ratio of the molar amount of the nickel-containing compound to the activated carbon carrier of 0.02-0.15 mmol / mg, then adding a solvent and wear-resistant balls, and adjusting the speed for ball milling; after the ball milling is completed, taking out the mixture and vacuum drying it, and after the solvent evaporates, placing the mixture in a furnace for pretreatment to obtain a Ni-based catalyst precursor, and then continuing to reduce the precursor under H2 conditions to obtain a Ni content of 8-18 % supported Ni-based catalyst; wherein the volume ratio of the raw material adiponitrile to the solvent is 0.5-2 mmol / mL; the amount of catalyst added is 9%-28% of the mass of adiponitrile; the pressure of the introduced hydrogen is 0.5-1.5 MPa; the temperature of the heating reaction is 140-180°C; the heating reaction time is 3-8 hours; the nickel-containing compound is nickel acetate or nickel nitrate; the solvent added during ball milling is deionized water; the ball milling process is as follows: first, high-speed ball milling at a speed of 220-260 r / min for 10-20 minutes and then adjusted to 160-180 r / min for 5-6 hours; the pretreatment temperature is 500-600°C, the pretreatment time is 3-5 hours; the reduction temperature is 400-500°C, and the reduction time is 2-3 hours.

2. The method according to claim 1, wherein: The material of the wear-resistant balls is zirconia or stainless steel.

3. The method according to claim 1, wherein: The mass ratio of the added amount of deionized water to the nickel-containing compound is (2~5):1; the mass ratio of the wear-resistant ball to the nickel-containing compound is (4~13):1.

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