Steroid hormone double-bond selective hydrogenation catalyst as well as preparation process and application thereof

Abstract

The invention provides a steroid hormone double-bond selective hydrogenation catalyst as well as a preparation process and application thereof, and belongs to the technical field of catalysts. The preparation process of the hydrogenation catalyst comprises the following steps: (1) preparing a carrier loaded with an active metal: dispersing the carrier in a cerium-containing metal salt ethanol solution, stirring, and carrying out suction filtration, drying and temperature programming roasting after stirring to prepare the carrier loaded with the active metal; (2) loading a bimetal carrier: dipping the active metal-loaded carrier in the precursor solution, carrying out ultrasonic-assisted dipping, and then dropwise adding an alkali solution to adjust the pH value of the solution so as to obtain a bimetal-loaded carrier solution; and (3) reduction: slowly dropwise adding a reducing agent solution into the solution, and after reduction is completed, separating, washing and carrying out vacuum drying to obtain the catalyst. The preparation process is green and safe, and the prepared catalyst can be used for selective hydrogenation reaction of steroid hormone double bonds and has relatively high selectivity and conversion rate.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of organic catalytic hydrogenation, in particular to a steroid hormone double bond selective hydrogenation catalyst and its preparation process and use. BACKGROUND

[0002] Steroid compounds are a kind of drugs named by chemical structure, which refer to compounds containing "cyclopentane and polyhydrogen phenanthrene" mother nucleus structure in molecular structure, with the characteristics of small molecular weight and large lipid solubility. This characteristic makes it easy to enter cells and produce a series of changes. It occupies an important position in the chemical system and is the second largest class of drugs next to antibiotics. The earliest steroid compounds were mainly extracted from natural organisms. With the rapid increase in demand for steroid hormone drugs, artificial synthesis is gradually being adopted. According to the properties of downstream products, steroid hormone drugs can be divided into corticosteroids, sex hormones, progestogens and others. Steroid hormone drugs play an important role in regulating the body, including improving protein metabolism, restoring and enhancing physical strength, and can also be used in the fields of contraception, tocolysis and anesthesia. The market for steroid hormone drugs is developing rapidly, among which sex hormones and reproductive system drugs and corticosteroids occupy the first place, so the development of steroid hormone drugs is one of the recent development directions and focuses of the pharmaceutical industry.

[0003] Patents CN101177443A, CN101362789A, CN102212099A and CN101717422A, etc. have all studied the preparation process of steroid drugs, but these preparation methods all have the same reaction shortcomings: the reaction products are sensitive to temperature and difficult to control, and the yield of the products is low.

[0004] Patents CN103386301A, CN106582757A and CN119954881A all disclose preparation methods for steroid hormone drugs and related intermediates, and the catalysts used are prepared and developed, but the preparation process of the catalysts is not easy to control, which has certain limitations on industrial safety and industrial scale. SUMMARY

[0005] Based on the above technical purposes, the present application provides a steroid hormone double bond selective hydrogenation catalyst and its preparation process and use. The preparation process is green and safe, and the prepared catalyst can be used for selective hydrogenation of steroid hormone double bonds, with high selectivity and conversion rate.

[0006] In a first aspect, a preparation process of a steroid hormone double bond selective hydrogenation catalyst is provided, comprising the following steps: Step (1) loading active metal carrier: disperse the carrier in a cerium metal salt ethanol solution and stir, then filter, dry and program temperature calcine to obtain a carrier loaded with active metal; Step (2) loading bimetallic carrier: Preparation of precursor solution: prepare a precursor solution of palladium salt and auxiliary metal salt; Impregnate the active metal-loaded carrier in the precursor solution, ultrasonic-assisted impregnation, then drop alkali solution to adjust the pH of the solution, and obtain the bimetallic carrier solution; Step (3) reduction: slowly drop the reducing agent solution into the bimetallic carrier solution, continue stirring after the drop is completed, separate the filter cake by suction filtration, wash the filter cake until the conductivity meets the requirements, and vacuum dry to obtain the catalyst.

[0007] In some embodiments, the carrier is selected from alumina, activated carbon, and silica. The carrier is spherical alumina, activated carbon, or silica with a diameter of 1-5 mm, or strip-shaped alumina, activated carbon, or silica with a size of 1-10 mm relative to the carrier.

[0008] In some embodiments, the concentration of the cerium-containing metal salt ethanol solution is 0.08-0.12 mol / L, preferably 0.08 mol / L, 0.09 mol / L, 0.1 mol / L, 0.11 mol / L, 0.12 mol / L, and any one of the ranges formed by any two of the above values.

[0009] In some embodiments, the cerium-containing metal salt is cerous nitrate or cerium chloride.

[0010] In some embodiments, the molar mass ratio of cerium atoms to the carrier in the cerium-containing metal salt ethanol solution is 0.008-0.012 mol / g, preferably 0.008 mol / g, 0.009 mol / g, 0.01 mol / g, 0.011 mol / g, 0.012 mol / g, and any one of the ranges formed by any two of the above values.

[0011] In some embodiments, in step (1), the drying is at 90-100°C for 20-24 h.

[0012] In some embodiments, in step (1), the programmed temperature roasting is as follows: Step one: increase the temperature from room temperature to 100-120°C at a rate of 2-5°C / min, and keep the temperature at 120°C for 1 h; Step two: increase the temperature from 120°C to 400-450°C at a rate of 1-5°C / min, and keep the temperature at 450°C for 2 h.

[0013] In some embodiments, in step (1), the programmed temperature roasting is as follows: Step one: increase the temperature from room temperature to 120°C at a rate of 2°C / min, and keep the temperature at 120°C for 1 h; Step two: increase the temperature from 120°C to 450°C at a rate of 5°C / min, and keep the temperature at 450°C for 2 h.

[0014] In some embodiments, the concentration of the palladium salt in the precursor solution is 0.1-0.5 mol / L, preferably 0.1 mol / L, 0.2 mol / L, 0.3 mol / L, 0.4 mol / L, 0.5 mol / L, and any one of the ranges formed by any two of the above values. The concentration of the co-metal salt in the precursor solution is 0.1-0.5 mol / L, preferably 0.1 mol / L, 0.2 mol / L, 0.3 mol / L, 0.4 mol / L, 0.5 mol / L, and any one of the ranges formed by any two of the above values.

[0015] In some embodiments, the molar ratio of palladium atoms of the palladium salt to cerium atoms in the ethanol solution of the cerium-containing metal salt is (3-15):(8-12), preferably 3:8, 1:4, 1:2, 5:8, 1:1, 5:4, 15:8, 3:2, 5:4, and any one of the ranges formed by any two of the above values.

[0016] In some embodiments, the molar ratio of palladium of the palladium salt to co-metal of the co-metal salt is (1-5):(1-5), preferably 1:1, 1:2, 1:3, 1:4, 1:5, 5:1, 5:2, 5:3, 5:4, and any one of the ranges formed by any two of the above values.

[0017] In some embodiments, the palladium salt is palladium acetate, palladium chloride, palladium chlorate, or sodium tetrachloropalladate.

[0018] In some embodiments, the co-metal salt is lanthanum nitrate, lanthanum chloride, magnesium chloride, or magnesium nitrate.

[0019] In some embodiments, the ultrasonic-assisted impregnation refers to an impregnation assisted by an ultrasonic frequency of 35-45 kHz for 25-35 min, preferably the ultrasonic frequency is 35 kHz, 40 kHz, 45 kHz, and any one of the ranges formed by any two of the above values; preferably the impregnation time is 25 min, 30 min, 35 min, and any one of the ranges formed by any two of the above values.

[0020] In some embodiments, the base is one of potassium hydroxide, sodium hydroxide, aqueous ammonia, sodium carbonate, potassium carbonate, sodium bicarbonate, and ethylenediamine, and the adjusted pH is 8-11.

[0021] In some embodiments, the reducing agent is sodium formate, triethylamine, sodium borohydride, potassium borohydride, hydrazine hydrate, or formaldehyde.

[0022] In some embodiments, the molar mass ratio of the reducing agent to the carrier is 0.01-0.05 mol / g, preferably 0.01 mol / g, 0.02 mol / g, 0.03 mol / g, 0.04 mol / g, 0.05 mol / g, and any one of the ranges defined by any two of the above values.

[0023] In some embodiments, the electrical conductivity is ≤200 us / cm, preferably less than 100 us / cm, 120 us / cm, 140 us / cm, 150 us / cm, 160 us / cm, 180 us / cm, 200 us / cm, and any one of the ranges defined by any two of the above values.

[0024] In some embodiments, the solvent is deionized water, methanol or ethanol.

[0025] In some embodiments, the vacuum drying is at 60-100℃ for 12-24h, preferably the temperature is 60℃, 70℃, 80℃, 90℃, 100℃, and any one of the ranges defined by any two of the above values; preferably the time is 12h, 14h, 16h, 18h, 20h, 22h, 24h, and any one of the ranges defined by any two of the above values.

[0026] In a second aspect, a hydrogenation catalyst is provided, which is prepared by the method of the present application.

[0027] In a third aspect, the use of the hydrogenation catalyst of the present application in the selective hydrogenation of the double bond of a steroid hormone compound is provided, which use comprises mixing the hydrogenation catalyst of the present application, the steroid hormone compound and an organic solvent, introducing hydrogen gas, and separating the product after the reaction.

[0028] In some embodiments, the steroid hormone compound comprises one of the intermediates of finasteride F9 (I-1), dienol ketone acetate (II-1), 6-methylene-pregn-4-ene-17a-ol-3,20-dione-17-acetate (III-1), the structures of which are shown below: .

[0029] In some embodiments, the temperature of the reaction is 0-50℃, the pressure is 0.1-1.5MPa, and the reaction time is 2.5h-40h. Preferably, the temperature is 0℃, 10℃, 20℃, 30℃, 40℃, 50℃, and any one of the ranges formed by any two of the above values. Preferably, the pressure is 0.1MPa, 0.2MPa, 0.3MPa, 0.4MPa, 0.5MPa, 0.6MPa, 0.7MPa, 0.8MPa, 0.9MPa, 1MPa, 1.1MPa, 1.2MPa, 1.3MPa, 1.4MPa, 1.5MPa, and any one of the ranges formed by any two of the above values. Preferably, the reaction time is 2.5h, 3h, 5h, 10h, 15h, 20h, 25h, 30h, 35h, 40h, and any one of the ranges formed by any two of the above values.

[0030] In some embodiments, the organic solvent is glacial acetic acid or ethanol.

[0031] In some embodiments, the mass ratio of the organic solvent to the steroid hormone compound is (10-100):1, preferably 10:1, 20:1, 30:1, 40:1, 50:1, 60:1, 70:1, 80:1, 90:1, 100:1, and any one of the ranges formed by any two of the above values.

[0032] In some embodiments, the mass ratio of the hydrogenation catalyst to the steroid hormone compound is (5-10):20, preferably 1:4, 2:5, 1:2, and any one of the ranges formed by any two of the above values.

[0033] Catalytic reaction mechanism: after the carrier is pretreated with a Ce-containing metal salt and then subjected to temperature programmed calcination, a carrier-CeO2 structure can be constructed in the pore structure of the carrier. When the palladium metal is loaded, the palladium metal particles can be anchored at the carrier-CeO2 structure through the carrier interface effect, directional preparation is achieved, the electronic effect of the palladium metal is controlled by adding the auxiliary metals magnesium and lanthanum, directional double bond hydrogenation is achieved, and high selectivity of the catalyst is achieved.

[0034] Compared with the prior art, one of the technical solutions has the following advantages or beneficial effects: The present application effectively solves the problem of competitive adsorption of palladium and cerium by loading cerium on the carrier first, sintering, and then loading palladium and auxiliary metals, thereby achieving step-by-step loading control. The adoption of temperature programmed calcination is conducive to the formation of cerium oxide nanoparticles. The carrier loaded with bimetallic is prepared by distribution impregnation, thereby improving the uniformity of palladium distribution. The adoption of a mild reduction system reduces the problem of palladium particle aggregation caused by high-temperature hydrogen reduction, and effectively controls the average particle size of the metal.

[0035] The present application prepares a hydrogenation catalyst with high activity, high selectivity and long service life. The catalyst of the present application shows excellent catalytic performance in selective hydrogenation reaction of double bond of steroid hormone compounds, which can significantly improve the yield and purity of target product, and reduce the energy consumption and cost of reaction. When the catalyst is applied to the hydrogenation of steroid hormone compounds, the conversion rate is >99%, the selectivity of target product is >99%, and it can be used for more than 50 times. BRIEF DESCRIPTION OF DRAWINGS

[0036] Figure 1 The electron microscope image of catalyst A prepared in Example 1, in which the metal nanoparticle size is 3-5 nm.

[0037] TERMINOLOGY Certain embodiments of the present application now will be described in detail with reference to examples illustrated in the accompanying structures and chemical formulas. The present application intends to cover all alternatives, modifications and equivalents thereof which are included in the scope of the present application as defined by the claims. One skilled in the art will recognize that many methods and materials similar or equivalent to those described herein can be used in the practice of the present application. The present application is in no way limited to the methods and materials described herein. In the event of a conflict between the incorporated documents, patents and similar materials and the present application, including but not limited to defined terms, term application, described techniques, etc., the present application controls.

[0038] It should be further recognized that certain of the features of the present application, described in detail herein in the context of a number of separate embodiments, can also be provided in combination in a single embodiment. Conversely, various features of the present application, described in the context of a single embodiment, can also be provided separately or in any appropriate subcombination. It is therefore intended that the present application be considered as encompassing all such variations, modifications and equivalents as can fall within the scope of the appended claims.

[0039] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. All patents and publications referred to in this application are incorporated herein by reference in their entirety.

[0040] In the description of the specification, the description of the terms "one embodiment", "some embodiments", "example", "specific example", or "some examples" and the like means that the specific features, structures, materials or characteristics described in connection with the embodiment or example are included in at least one embodiment or example of the present application. In the specification, the illustrative description of the above terms does not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any appropriate manner in any one or more embodiments or examples. In addition, the skilled person in the art can combine and combine the features of the embodiments or examples in the specification without contradiction.

[0041] Unless specifically indicated otherwise, the description "each independently" and "each independently" and "independently" as used throughout this application and in the claims is intended to function as a broad limitation in reference to multiple related groups. Broadly stated, "each independently" means that each occurrence of the group is independent of the other occurrences of the group. Stated another way, the description "each independently" is intended to mean that the recited symbol can occur with any of the listed options, and that the occurrence of the recited symbol with one option does not exclude the occurrence of the recited symbol with another option in a different group.

[0042] The terms "optionally," "optional," or "any," "any," when used in a description of an event or circumstance, means that the event or circumstance can or can not occur, and that the description includes instances where the event or circumstance occurs and instances where it does not. For example, "optionally substituted" means that the substitution can or can not be present.

[0043] The term "each independently" in combination with "any," for example, "each independently any of...," means that the recited symbol can or can not be substituted with any of the listed options, and that the occurrence of the recited symbol with one option does not exclude the occurrence of the recited symbol with another option in a different group. DETAILED DESCRIPTION

[0044] The following presents a simplified summary of different embodiments or examples in order to provide a basic understanding of the application. This summary is not an extensive overview of the application. It is not intended to identify key / critical elements of the application or to delineate the scope of the application. Its sole purpose is to present some embodiments of the application in a simplified form as a prelude to the more detailed description that is presented later.

[0045] In the description of the specification, the description of the terms "one embodiment", "some embodiments", "an example", "a specific example", or "some examples" and the like means that the specific feature, structure, material or characteristic being described is included in at least one embodiment or example of the application. The illustrative description of these terms in the specification does not necessarily refer to the same embodiment or example. Moreover, the description of such terms is intended to cover any and all combinations of one or more of the described features, structures, materials or characteristics. In addition, the description of the specification is not intended to be limiting of the application. The terms "comprising", "including", "containing" and "having" are intended to be inclusive and mean that there can be additional

[0046] In order to make the purposes, technical solutions and advantages of the present application clearer, the following further describes the present application in combination with embodiments. The specific embodiments described herein are only used to explain the present application and do not constitute any limitation on the present application. In addition, in the following description, the description of well-known structures and technologies is omitted to avoid unnecessary confusion of the concept of the present disclosure. Such structures and technologies are also described in many publications.

[0047] The reagents used in the present application can be purchased from the market or prepared by the method described in the present application.

[0048] Example 1 Preparation of catalyst Step (1) Support loaded with active metal: 1 g of activated carbon support was dispersed in 0.08-0.12 mol / L cerium metal salt ethanol solution (10 mL) and stirred for 1-5 h, then filtered under suction, and the solid was dried at 90°C for 24 h, and then transferred to a rotary furnace in an atmosphere, and calcined under a nitrogen atmosphere by programmed temperature rising: Step one: from room temperature to 120°C at a rate of 2°C / min, and kept at 120°C for 1 h; Step two: from 120°C to 450°C at a rate of 5°C / min, and kept at 450°C for 2 h, to obtain a support loaded with active metal; Step (2) Support loaded with bimetal: Preparation of precursor solution: PdCl2 and La(NO3)3 were dissolved in 10 mL of water to prepare a precursor solution, wherein the concentration of the palladium salt in the precursor solution was 0.1 mol / L, and the concentration of the auxiliary metal salt in the precursor solution was 0.1 mol / L; 1 g of the support loaded with active metal was immersed in 30 mL of the precursor solution, and assisted with ultrasonic frequency of 40 kHz for 30 min, then 0.5 mol / L NaOH solution was added dropwise to adjust the pH of the solution to 10, to obtain a support loaded with bimetal; Step (3) Reduction: a reducing agent NaBH4 solution was prepared by dissolving NaBH4 in water to obtain a 0.1 mol / L reducing agent NaBH4 solution; 10 mL of the reducing agent NaBH4 solution was slowly added dropwise to the foregoing solution, after the reducing agent NaBH4 solution was completely added, the reduction reaction was continued to stir at 30°C for 12 h, then the filter cake was separated by filtration, washed with 10 mL of deionized water for three times, and washed until the conductivity met the requirements, and then vacuum dried at 60-100°C for 12-24 h, to obtain the catalyst.

[0049] The preparation conditions of the catalyst are shown in Table 1: Table 1 Changes in the preparation conditions of the catalyst

[0050] In this example, the active metal Ce was pre-loaded on the support, and after programmed temperature rising calcination, Pd and auxiliary metal were further loaded, to realize reduction of competitive loading, and through ultrasonic assisted immersion and reduction of the reducing agent at normal temperature and pressure, the metal particles were highly uniformly dispersed, so that the particle size of the metal particles loaded on the support was in the nanometer level, as shown in Table 2. Figure 1 As shown in Table 2, the metal nanoparticle size of the catalyst A prepared in Example 1-1 was 3-5 nm.

[0051] Example 2 Preparation of catalyst Step (1) active metal loaded carrier: 1 g of carrier was dispersed in 0.1 mol / L cerous nitrate ethanol solution (10 mL) and stirred for 2 h, then filtered under suction, and the solid was dried at 90°C for 24 h, and then transferred into a rotary furnace in an atmosphere, and calcined at a programmed temperature under nitrogen atmosphere: stage one: from room temperature to 120°C at a rate of 2°C / min, and kept at 120°C for 1 h; stage two: from 120°C to 450°C at a rate of 5°C / min, and kept at 450°C for 2 h, to obtain an active metal loaded carrier; Step (2) bimetal loaded carrier: Preparation of precursor solution: a palladium salt and an auxiliary metal salt were dissolved in 10 mL of water to prepare a precursor solution, wherein the concentration of the palladium salt in the precursor solution was 0.1-0.5 mol / L, and the concentration of the auxiliary metal salt in the precursor solution was 0.1-0.5 mol / L; 1 g of the active metal loaded carrier was immersed in 30 mL of the precursor solution, and assisted with ultrasonic frequency of 35-45 kHz for 25-35 min, then 0.5 mol / L alkali solution was added dropwise to adjust the pH of the solution to 10, to obtain a bimetal loaded carrier solution; Step (3) reduction: a reducing agent was dissolved in water to prepare a 0.1 mol / L reducing agent solution; 10 mL of the reducing agent solution was slowly added dropwise into the foregoing solution, and after the reducing agent solution was completely added, the reduction reaction was continued to stir at 30°C for 12 h, then the filter cake was separated by filtration, washed with 10 mL of deionized water for three times, and washed until the conductivity met the requirements, and then dried at 80°C under vacuum for 18 h, to obtain a catalyst.

[0052] The preparation conditions of the catalysts are shown in Table 2: Table 2 Changes in the preparation conditions of the catalysts

[0053] Comparative Example 1 The difference from Example 1-1 is that in step (1), the active metal loaded carrier was prepared by directly calcining at 450°C for 3 h, and the remaining steps were consistent with those of Example 1-1, to obtain catalyst a.

[0054] Comparative Example 2 The difference from Example 1-1 is that the cerium metal salt containing ethanol solution and the precursor solution were mixed and then assisted with ultrasonic immersion, and the remaining steps were consistent with those of Example 1-1, to obtain catalyst b.

[0055] Comparative Example 3 The difference from Example 1-1 is that the bimetallic-loaded carrier solution is filtered and dried to obtain a bimetallic-loaded carrier, which is further reduced at 500 DEG C for 30 min using pure H2, the H2 flow rate is controlled at 50 mL / min, and is maintained for 4 h, the rest is consistent with the steps of Example 1-1, to obtain the catalyst c.

[0056] Comparative Example 4 The catalyst is 5wt% palladium on carbon, which is named as catalyst d.

[0057] Application Example 1 In a pressure bottle, 2g of the steroid hormone compound I-1, 20g of glacial acetic acid and 0.9g of the catalyst A are put in, hydrogen is introduced after replacement, the reaction temperature is 0 DEG C-50 DEG C, the hydrogen pressure is 0.1-1.5Mpa, and the reaction is carried out for 2.5h, HPLC analysis detection, and the conversion rate and selectivity of the product are calculated. The reaction conditions and results are shown in Table 2.

[0058] Preparation of finasteride F9 Chemical formula:

[0059] Table 2 Screening of hydrogenation reaction conditions

[0060] As can be seen from Table 2, under the hydrogen pressure of 0.4MPa and the reaction temperature of 30 DEG C, the conversion rate and selectivity effect and cost of the hydrogenation reaction are the best, and the subsequent test conditions are explored by considering the comprehensive consideration. The hydrogenation reaction is carried out by using the catalyst prepared by the application, the hydrogen pressure requirement is reduced to 0.1-1.5MPa, the industrial applicability and safety production are increased.

[0061] Application Example 2 In a pressure bottle, 2g of the steroid hormone compound I-1, 20g of glacial acetic acid and 0.9g of the catalyst are put in, hydrogen is introduced after replacement, the reaction temperature is 30 DEG C, the hydrogen pressure is 0.4Mpa, and the reaction is carried out for 2-10h, HPLC analysis detection, and the conversion rate and selectivity of the product are calculated. The reaction conditions and results are shown in Table 3.

[0062] Table 3 Screening of hydrogenation reaction conditions

[0063] As can be seen from Table 3, under the hydrogen pressure of 0.4MPa and the reaction temperature of 30 DEG C, the conversion rate and selectivity effect and cost of the hydrogenation reaction are the best, and the subsequent test conditions are explored by considering the comprehensive consideration. The hydrogenation reaction is carried out by using the catalyst prepared by the application, the hydrogen pressure requirement is reduced to 0.1-1.5MPa, the industrial applicability and safety production are increased.

[0064] Application Example 3 In a pressure bottle, 2 g of the steroid hormone compound I-1, a solvent and a catalyst A were put in, hydrogen was introduced after replacement, the reaction temperature was 30℃, the hydrogen pressure was 0.4 MPa, and the reaction was carried out for 2.5 h. HPLC analysis was performed to calculate the conversion rate and selectivity of the product. The reaction conditions and results are shown in Table 4.

[0065] Table 4. Condition screening of hydrogenation reaction

[0066] As can be seen from Table 4, the different solvents have little effect on the conversion rate and selectivity, and the increase of the solvent ratio leads to the decrease of the conversion rate and selectivity. The increase of the catalyst amount has little effect on the conversion rate, but the decrease of the catalyst amount is not conducive to the conversion rate and selectivity.

[0067] Application Example 4 Based on the condition screening of Application Examples 1-3, the best reaction conditions of Application Example 4 were obtained as follows: In a pressure bottle, 2 g of the steroid hormone compound, 20 g of glacial acetic acid and 0.9 g of catalyst A were put in, hydrogen was introduced after replacement, the reaction temperature was 30℃, the hydrogen pressure was 0.4 MPa, and the reaction was carried out for 2.5 h. HPLC analysis was performed to calculate the conversion rate and selectivity of the product. After the catalyst was used for 50 times, HPLC analysis was performed to calculate the conversion rate and selectivity of the product. The reaction conditions and results are shown in Table 5.

[0068] The preparation reaction formula of 6-methylenepregn-4-ene-17α-ol-3,20-dione-17-acetate (abbreviated as methylene product) for preparing medroxyprogesterone acetate is as follows:

[0069] The chemical formula of dienolone acetate for preparing pregnenolone acetate is as follows:

[0070] Table 5. Hydrogenation reaction conditions and results

[0071] As shown in Table 5, the catalysts of the application examples were used to realize the selective hydrogenation of the double bond of the steroid hormone compound, and the conversion rate of the obtained product was >99%, and the selectivity was >99%. After 50 times of use, the hydrogenation product with high conversion rate and high selectivity was still obtained, and the catalytic activity was almost not decreased, and the catalyst stability was good.

[0072] Comparative Examples 5, 6 and 7 used different catalysts from the preparation process of the application examples for hydrogenation catalysis, and the conversion rate and selectivity of the obtained product were significantly lower than those of the application examples.

[0073] Comparative Example 8, Comparative Example 9 and Comparative Example 10 are catalyzed by 5wt% palladium-carbon, and the conversion rate and selectivity of the obtained product is low, and the conversion rate and selectivity are obviously reduced after 50 times of reuse.

[0074] In conclusion, the hydrogenation catalyst prepared by the embodiment of the present application has excellent catalytic performance in the selective hydrogenation reaction of the double bond of the steroid hormone compound, and can significantly improve the conversion rate and selectivity of the target product, and reduce the energy consumption and cost of the reaction.

[0075] The method of the present application has been described by preferred embodiments, and the related personnel can obviously modify or appropriately change and combine the method and application described herein to realize and apply the present application technology within the content, spirit and scope of the present application. The skilled in the art can refer to the content herein to appropriately improve the process parameters. It is particularly pointed out that all similar replacements and modifications are obvious to the skilled in the art, and they are considered to be included in the present application.

Claims

1. A preparation process for a steroid hormone-based double bond selective hydrogenation catalyst, characterized in that, Includes the following steps: Step (1) Support for loading active metals: Disperse the support in an ethanol solution containing cerium metal salt and stir. After stirring, filter, dry, and calcine at a programmed temperature to obtain the support for loading active metals. Step (2) Loading bimetallic substrate: Preparation of precursor solution: Prepare precursor solution by mixing palladium salt and auxiliary metal salt; The support loaded with active metals was immersed in a precursor solution, and the immersion was assisted by ultrasound. Then, an alkaline solution was added dropwise to adjust the pH of the solution to obtain a support solution loaded with bimetals. Step (3) Reduction: The reducing agent solution is slowly added dropwise to the aforementioned solution. After all the solution has been added, stirring is continued, and the filter cake is obtained by vacuum filtration. The filter cake is washed and dried under vacuum to obtain the catalyst.

2. The preparation process according to claim 1, characterized in that, The carrier is selected from alumina, activated carbon, and silicon dioxide; And / or, the concentration of the cerium-containing metal salt ethanol solution is 0.08-0.12 mol / L; And / or, the cerium-containing metal salt is cerium nitrate or cerium chloride; And / or, the molar mass ratio of cerium atoms to the support in the cerium-containing metal salt ethanol solution is 0.008-0.012 mol / g; And / or, in step (1), the drying is performed at 90-100°C for 20-24 hours.

3. The preparation process according to claim 1, characterized in that, In step (1), the programmed temperature rise calcination is as follows: Step 1: the temperature is increased from room temperature to 100-120℃ at a rate of 2-5℃ / min, and held at 120℃ for 1h; Step 2: the temperature is increased from 120℃ to 400-450℃ at a rate of 1-5℃ / min, and held at 450℃ for 2h.

4. The preparation process according to claim 1, characterized in that, The concentration of the palladium salt in the precursor solution is 0.1-0.5 mol / L, and the concentration of the auxiliary metal salt in the precursor solution is 0.1-0.5 mol / L; And / or, the molar ratio of palladium atoms in the palladium salt to cerium atoms in the cerium-containing metal salt ethanol solution is (3-15):(8-12); And / or, the molar ratio of palladium in the palladium salt to the auxiliary metal in the auxiliary metal salt is (1-5):(1-5).

5. The preparation process according to claim 1, characterized in that, The palladium salt is palladium acetate, palladium chloride, palladium chlorate, or sodium tetrachloropalladium. And / or, the auxiliary metal salt is lanthanum nitrate, lanthanum chloride, magnesium chloride, or magnesium nitrate; And / or, the ultrasonic-assisted impregnation refers to impregnation at an ultrasonic frequency of 35-45 kHz for 25-35 minutes.

6. The preparation process according to claim 1, characterized in that, The alkali is one of potassium hydroxide, sodium hydroxide, ammonia, sodium carbonate, potassium carbonate, sodium bicarbonate, and ethylenediamine, and the adjusted pH is 8-11.

7. The preparation process according to claim 1, characterized in that, The reducing agent is sodium formate, triethylamine, sodium borohydride, potassium borohydride, hydrazine hydrate, or formaldehyde; And / or, the molar mass ratio of the reducing agent to the carrier is 0.01-0.05 mol / g; And / or, the solvent is deionized water, methanol or ethanol; And / or, the vacuum drying is performed at 60-100℃ for 12-24 hours.

8. A hydrogenation catalyst, characterized in that, It is prepared by the method described in any one of claims 1 to 7.

9. Use of a hydrogenation catalyst prepared by the method of any one of claims 1 to 7 in the selective hydrogenation reaction of double bonds in steroid hormone compounds, the use comprising: The hydrogenation catalyst, steroid hormone compound, and organic solvent are mixed, and hydrogen gas is introduced to carry out the reaction. After the reaction is completed, the product is separated.

10. The use according to claim 9, characterized in that, The steroid hormone compounds include one of the compounds shown in the following structures: ； And / or, the reaction temperature is 0℃-50℃, the pressure is 0.1-1.5MPa, and the reaction time is 2.5h-40h; And / or, the organic solvent is glacial acetic acid or ethanol; And / or, the mass ratio of the organic solvent to the steroid hormone compound is (10-100):1; And / or, the mass ratio of the hydrogenation catalyst to the steroid hormone compound is (5-10):20.

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