Molybdenum catalyst and preparation and application thereof

Abstract

The invention relates to a molybdenum catalyst and a preparation method and application thereof. The method comprises the following steps: by taking ammonium heptamolybdate as a molybdenum source, trithiocyanuric acid as a sulfur source and activated carbon as a carrier, dispersing by ball milling, and calcining and loading in a nitrogen atmosphere to obtain the catalyst with molybdenum disulfide loaded on the activated carbon. The catalyst can be recovered through centrifugation and filtration and has excellent cycle stability. According to the method, a dexlansoprazole by-product (a mixture mainly containing levolansoprazole) is taken as a substrate, under the action of a molybdenum catalyst, hydrogen is introduced as a reducing agent, and the by-product can be reduced into the lansoprazole thioether (a synthetic precursor of dexlansoprazole) in a high-selectivity manner. In addition, racemic lansoprazole can be directly used as a substrate, high-selectivity reduction into lansoprazole thioether (a dexlansoprazole synthesis precursor) can be realized under the action of the same molybdenum catalyst, and the raw material application range of the process is further widened. The method solves the industrial problem that byproducts cannot be efficiently recycled in the existing dexlansoprazole synthesis process, has the advantages of simple reaction process, easiness in product separation and catalyst recyclability, and has a good industrial application prospect.

Description

Technical Field

[0001] This invention relates to a molybdenum catalyst, its preparation and application, and more particularly to a supported molybdenum disulfide catalyst, its preparation method, and its application in the catalytic hydrogenation reduction of lansoprazole substrate to prepare lansoprazole sulfide. Background Technology

[0002] Dexlansoprazole is a benzimidazole derivative proton pump inhibitor that blocks gastric acid secretion by irreversibly inhibiting H+ / K+-ATPase in gastric parietal cells. The U.S. FDA approved this drug, manufactured by Takeda Pharmaceutical Company of Japan, on January 30, 2009, for the treatment of erosive esophagitis, gastroesophageal reflux disease-related heartburn, and peptic ulcers.

[0003]

[0004] Dextrorotatory lansoprazole is the dextrorotatory optical isomer of lansoprazole, and its structural formula is shown in Formula 1. Dextrorotatory lansoprazole exhibits significantly better acid-suppressing activity than its racemic counterpart. With the increasing emphasis on green, low-cost, and resource-recyclable industrial synthesis, it has become a key research focus in the pharmaceutical and chemical industries. Research on efficient and low-cost catalysts and process routes is increasingly focusing on issues such as high selectivity, low toxicity, and recyclability. Currently, the industrial synthesis of dextrorotatory lansoprazole mainly relies on two core routes: Route 1 is the chiral resolution of the racemic lansoprazole. This route uses the racemic lansoprazole as a raw material, and achieves the separation of the dextrorotatory and levorotatory isomers through chiral reagent-induced crystallization or column chromatography, thereby obtaining dextrorotatory lansoprazole. For example, the solvent crystallization method disclosed in Chinese patent document CN1478086A uses a mixed solvent of ethyl acetate and toluene combined with n-hexane or heptane as the reaction solvent to separate the (R)- or (S)-lansoprazole enantiomers. The byproducts generated by this route are usually directly discarded, resulting in a waste of pharmaceutical intermediates and increasing environmental costs and pollution risks. Route 2 uses lansoprazole sulfide as a key precursor and directs the asymmetric oxidation reaction of a chiral catalytic system to generate dexlansoprazole, which is currently a widely used synthetic route, as shown in Formula 2. In related studies such as Chinese patent document CN104177336A (Chinese Journal of Medicinal Chemistry, 2016, 26(2):136-138), transition metal catalysts (such as titanium or vanadium complexes) are often used in its process system. The technical limitations of this route are also prominent. The catalytic system is highly sensitive to moisture, and the water content of the reaction system must be strictly controlled and a low temperature environment must be maintained. This leads to limitations in industrial production. In addition, a certain amount of byproducts such as levlansoprazole will still be generated during the oxidation process, which can only be discharged with waste liquid or waste residue, exacerbating resource consumption and environmental pressure. At present, there are few reports on the recovery technology of dexlansoprazole byproducts. In the existing technology, the hydrogenation reduction of sulfoxide compounds mostly relies on noble metal catalysts. In summary, the development of a highly efficient non-precious metal catalyst that can catalytically reduce and recover dexlansoprazole synthesis byproducts, directly convert racemic lansoprazole, recover it as lansoprazole sulfide, and then oxidize it to high-value dexlansoprazole in a green process has significant application prospects.

[0005] In 2025, Pengyao You et al. found that phosphate-modified Pt / TiO2 catalysts exhibited excellent activity in the hydrodeoxygenation of sulfoxide to sulfide. However, the use of toluene as a solvent could lead to environmental and cost issues, and toluene's volatility and potential pollution if not handled properly. The use of the precious metal Pt in this catalyst significantly increases industrial costs, hindering industrial production. (J.Am.Chem.Soc.2025,DOI:10.1021 / jacs.5c09850). In 2020, Kaiyue Yao et al. found that nitrogen-doped carbon-supported cobalt-molybdenum bimetallic catalysts showed excellent catalytic performance in the hydrodeoxygenation of sulfoxide to sulfide. However, the preparation of this catalyst requires ZIF-67 as a precursor, introducing a molybdenum source via a dual-solvent method and undergoing pyrolysis at a specific temperature, making the preparation process relatively complex. Furthermore, the optimal solvent is methanol, increasing recovery costs and hindering industrial recovery. (GreenChem., 2020, DOI: 10.1039 / c9gc02465d) In 2014, Takato Mitsudome et al. found that TiO2-supported Ru nanoparticle catalysts exhibited excellent activity and selectivity in the hydrodeoxygenation of sulfoxide to sulfide under ambient pressure and H2 atmosphere. However, the Ru used in this catalyst is still a precious metal, which significantly increases the cost of industrial production, and the catalyst recovery is difficult, which is not conducive to industrial production. (AngewandteChemie, 2014, DOI: 10.1002 / ange.201403425)

[0006] In 2016, Zhang Chaofeng et al. reported the preparation of oxygen-doped MoS2 catalyst (O-MoS2) via an incomplete sulfidation reduction method, using ammonium molybdate as a precursor. The reaction was carried out under hydrothermal conditions at 180℃ for 24 hours, followed by centrifugation, washing, and vacuum drying of the MoS2 catalyst (Applied Catalysis A: General, 2016, 525: 85-93). However, this catalyst exhibited low activity and could not be used for the hydrogenation of sulfoxides to obtain sulfides.

[0007] In 2016, Li Yulong et al. discovered that dexlansoprazole could be synthesized via asymmetric oxidation using isopropyl titanate and L-(+)-diethyl tartrate as a catalytic system. This reaction required strict temperature control between -5 and 0°C, was sensitive to moisture which could affect catalytic efficiency, and required multi-step recrystallization using acetone and water, isopropanol and n-hexane, making solvent recovery difficult. This resulted in high costs and complex operation for industrial scale-up. (Chinese Journal of Medicinal Chemistry, 2016, 26(2):136-138). In 2014, Xu Liqun et al. discovered that dexlansoprazole could be synthesized via asymmetric oxidation of cumene hydroperoxide with 2-mercaptobenzimidazole and 2-chloromethyl-3-methyl-4-(2,2,2-trifluoroethoxy)pyridine hydrochloride as raw materials, followed by condensation to obtain an intermediate thioether, and then a vanadium-tartrate catalyzed cumene hydroperoxide. This method required column chromatography for separation and purification, was cumbersome in post-processing, and was costly for industrial scale-up, making it unsuitable for industrial production. (Chemical and Biological Engineering, 2014, 31(4):26-28). In 2013, Yu Xiaoling et al. found that 4-chloro-2,3-dimethylpyridine-N-oxide was used as the starting material. After acylation, hydrolysis, chlorination, substitution, and asymmetric oxidation, a key intermediate was obtained, which was then substituted with trifluoroethanol to synthesize dexlansoprazole. This method requires multiple extractions with ammonia to adjust the pH value in the asymmetric oxidation post-treatment. The use of potassium tert-butoxide must be strictly controlled during the reaction to avoid water interference. The solvent system is complex and it is difficult to carry out large-scale production. (Modern Drugs and Clinical, 2013, 28(5):661-664). In 2012, Ge Zhixin et al. found that R- and S-lansoprazole were synthesized by asymmetric oxidation, using tetraisopropyl titanium and diethyl tartrate as the catalytic system to perform chiral oxidation of the thioether intermediate. The catalytic system of this method is highly sensitive to moisture, requiring precise control of the water content. Furthermore, sulfone byproducts are easily generated during the reaction, necessitating multiple pH adjustments and solvent extraction in post-processing. This limited process adaptability hinders large-scale production. (Pharmaceutical Progress, 2012, 36(7):325-327). Chinese patent document CN104177336A reports a method for synthesizing dexlansoprazole via asymmetric oxidation using a vanadium-tartrate ester catalytic system. This method requires chiral separation and purification via column chromatography after the oxidation reaction, and the conversion rate is low. It requires recrystallization using multiple solvents such as acetonitrile, acetone, and n-hexane, resulting in high costs and limited operational efficiency in industrial scale-up, and also easily causing environmental pollution. Chinese patent document CN1478086A reports a method for separating (R)- or (S)-lansoprazole enantiomers using solvent crystallization. This method preferably uses a mixture of ethyl acetate and toluene as the reaction solvent, combined with n-hexane or heptane. Summary of the Invention

[0008] The purpose of this invention is to provide a cheap, simple, and efficient molybdenum catalyst to overcome the shortcomings of the prior art. Another purpose of this invention is to provide a method for preparing the above-mentioned catalyst. A further purpose of this invention is its application in the catalytic hydrogenation reduction of lansoprazole substrate to prepare lansoprazole sulfide, that is, a method for preparing lansoprazole sulfide using this molybdenum catalyst.

[0009] The technical solution of the present invention is: a molybdenum catalyst, characterized in that: activated carbon is used as a carrier, molybdenum disulfide is used as an active component, and molybdenum disulfide is loaded on the surface and in the pores of the activated carbon, wherein the loading mass of the active component molybdenum disulfide is 35% to 37% of the total mass of the catalyst.

[0010] The present invention also provides a method for preparing the above-mentioned molybdenum catalyst, characterized in that: molybdenum disulfide is obtained by sulfidation reaction of molybdenum source and sulfur source, and then dispersed by ball milling with activated carbon and calcined for loading. The specific steps are as follows: molybdenum source, sulfur source, solvent and activated carbon are weighed in proportion and added to ball mill jar. The ball mill jar is placed in a ball mill and dispersed by ball milling to obtain a uniform mixture. After drying, it is placed in a tube furnace and calcined under nitrogen atmosphere. After cooling, the supported molybdenum catalyst MoS2@AC is obtained.

[0011] Preferably, the molybdenum source is ammonium heptamolybdate, ammonium octamolybdate, or sodium molybdate; the sulfur source is trithiocyanate, thiourea, or thioacetamide.

[0012] The preferred molar ratio of molybdenum source to sulfur source is 1:(3-12); the solvent is deionized water (the amount of solvent is sufficient to dissolve both molybdenum source and sulfur source); the mass ratio of activated carbon to molybdenum source is 1-2:1.

[0013] The preferred ball milling speed is 150-160 r / min, and the ball milling time is 3-10 h; the calcination temperature is 400℃-800℃, and the calcination time is 2-4 h.

[0014] This invention also provides the application of the above-mentioned supported molybdenum disulfide catalyst in the catalytic hydrogenation reduction of lansoprazole substrate to prepare lansoprazole sulfide. The specific steps are as follows: lansoprazole substrate, solvent and molybdenum catalyst are added to a container, followed by the introduction of hydrogen gas and heating to obtain lansoprazole sulfide.

[0015] Preferably, the lansoprazole substrate is racemic lansoprazole or a dextro-lansoprazole byproduct; the solvent is ethanol, tert-butanol, or 1,4-dioxane, and the mass of the solvent added is 0.4 to 1 times that of the substrate; the mass of the molybdenum catalyst added is 5% to 15% of the mass of the lansoprazole substrate. The reaction is carried out under a hydrogen atmosphere, preferably with the hydrogen pressure controlled at 1 to 2 MPa.

[0016] The preferred temperature for the heating reaction is 25–60°C; the preferred heating time is 3–5 hours.

[0017] The principle of this invention is shown in Equation 3:

[0018]

[0019] Beneficial effects:

[0020] This invention provides a simple, inexpensive, and efficient method for preparing a molybdenum catalyst, and a method for using this catalyst to catalytically hydrogenate and reduce dexlansoprazole byproducts (a mixture mainly composed of levonorlansoprazole) to prepare lansoprazole sulfide (a precursor of dexlansoprazole). The MoS2@AC catalyst used in this invention uses non-precious metal molybdenum as the active center and activated carbon as the support. The preparation process employs ball milling dispersion and calcination under a nitrogen atmosphere. This MoS2 catalyst exhibits high reactivity and excellent stability. After the reaction, it can be rapidly separated by centrifugation or filtration and recycled after simple treatment. The entire process utilizes a non-precious metal MoS2@AC catalyst, achieving resource recycling of dexlansoprazole byproducts. The lansoprazole sulfide obtained from the reduction can be directly reused in the resynthesis of dexlansoprazole, reducing resource waste and environmental pollution caused by byproduct disposal, and lowering the raw material cost of dexlansoprazole production. It shows significant promise for industrial application. Furthermore, the process has low equipment requirements and low cost, making it suitable for industrial production. Attached Figure Description

[0021] Figure 1 The images show the XRD (X-ray diffraction) patterns of the MoS2@AC catalyst materials prepared in Examples 1-4, where the horizontal axis represents the diffraction angle (2θ) and the vertical axis represents the diffraction intensity; the black characteristic line represents catalyst A, the red characteristic line represents catalyst B, the blue characteristic line represents catalyst C, and the green characteristic line represents catalyst D. Detailed Implementation

[0022] Example 1: Preparation of Catalyst A. 1.23 g of ammonium heptamolybdate, 0.531 g of trithiocyanate, 5 mL of deionized water, and 1.23 g of activated carbon (activated carbon to molybdenum source mass ratio 1:1) were added to a planetary ball mill jar along with wear-resistant balls. The ball speed was set to 160 r / min, and ball milling was performed for 5 hours. After ball milling, the mixture was dried in an oven and then calcined at 600 °C for 2 hours in a tube furnace under a nitrogen atmosphere to obtain MoS2@AC catalyst A (molar ratio of molybdenum source to sulfur source 1:3). The loading of the active component, molybdenum disulfide, in the catalyst was 35.8% (mass fraction). Its XRD pattern corresponds to… Figure 1The black characteristic line, when compared with the standard XRD pattern of MoS2, indicates that catalyst A is a less-layered MoS2 catalyst. In the spectrum, PDF#17-0744-MoS2 is the standard diffraction peak reference for molybdenum disulfide, and PDF#05-0508-MoO3 and PDF#25-1366-Mo2N are the standard peak references for MoO3 and Mo2N, respectively. The experimentally prepared catalyst showed no obvious impurity peaks, demonstrating the excellent purity of the molybdenum disulfide active component.

[0023] Example 2: Preparation of Catalyst B. 1.23 g of ammonium heptamolybdate, 1.062 g of trithiocyanate, 5 mL of deionized water, and 2.46 g of activated carbon (activated carbon to molybdenum source mass ratio 2:1) were added to a planetary ball mill jar along with wear-resistant balls. The ball speed was set to 160 r / min, and milling was performed for 5 hours. After milling, the mixture was dried in an oven and then calcined at 600 °C for 2 hours in a tube furnace under a nitrogen atmosphere to obtain MoS2@AC catalyst B (molar ratio of molybdenum source to sulfur source 1:6). The loading of the active component, molybdenum disulfide, in the catalyst was 35.8% (mass fraction). Its XRD pattern corresponds to… Figure 1 The red characteristic line, when compared with the standard XRD pattern of MoS2, indicates that this catalyst is a few-layer MoS2 catalyst, and its active site exposure is better than that of catalyst A.

[0024] Example 3: Preparation of Catalyst C. 1.23 g of ammonium heptamolybdate, 1.593 g of trithiocyanate, 5 mL of deionized water, and 2 g of activated carbon (activated carbon to molybdenum source mass ratio 1.6:1) were added to a planetary ball mill jar along with wear-resistant balls. The ball speed was set to 160 r / min, and ball milling was performed for 5 hours. After ball milling, the mixture was dried in an oven and then calcined at 600 °C for 2 hours in a tube furnace under a nitrogen atmosphere to obtain MoS2@AC catalyst C (molar ratio of molybdenum source to sulfur source 1:9). The loading of the active component, molybdenum disulfide, in the catalyst was 35.8% (mass fraction). Its XRD pattern corresponds to… Figure 1 The blue characteristic line, when compared with the standard XRD pattern of MoS2, indicates that this catalyst is a highly dispersed few-layer MoS2 catalyst, and the uniformity of the active component loading is the best among the series of catalysts.

[0025] Example 4: Preparation of Catalyst D. 1.23 g of ammonium heptamolybdate, 2.124 g of trithiocyanate, 5 mL of deionized water, and 2 g of activated carbon (activated carbon to molybdenum source mass ratio 1.6:1) were added to a planetary ball mill jar along with wear-resistant balls. The ball speed was set to 160 r / min, and ball milling was performed for 5 hours. After ball milling, the mixture was dried in an oven and then calcined at 600 °C for 2 hours in a tube furnace under a nitrogen atmosphere to obtain MoS2@AC catalyst D (molar ratio of molybdenum source to sulfur source 1:12). The loading of the active component, molybdenum disulfide, in the catalyst was 35.8% (mass fraction). Its XRD pattern corresponds to... Figure 1The green characteristic line, when compared with the standard XRD pattern of MoS2, indicates that this catalyst is a highly dispersed few-layer MoS2 catalyst, but it still possesses stable catalytic active sites.

[0026] Example 5: Preparation of catalyst E. 1.1 g of ammonium octamolybdate, 1.593 g of trithiocyanate, 5 mL of deionized water, and 2 g of activated carbon (mass ratio of activated carbon to molybdenum source 1.6:1) were added to a planetary ball mill jar along with wear-resistant balls. The ball speed was set to 150 r / min, and the mixture was ball-milled for 10 hours. After ball milling, the mixture was dried in an oven and then calcined at 400 °C for 4 hours in a tube furnace under a nitrogen atmosphere to obtain MoS2@AC catalyst E (molar ratio of molybdenum source to sulfur source 1:10). The loading of the active component molybdenum disulfide in the catalyst was 36.5% (mass fraction).

[0027] Example 6: Preparation of catalyst F. 1.69 g of sodium molybdate, 1.593 g of trithiocyanate, 5 mL of deionized water, and 2 g of activated carbon (molybdenum source to molybdenum mass ratio 1.6:1) were added to a planetary ball mill jar along with wear-resistant balls. The ball speed was set to 150 r / min, and milling was performed for 3 hours. After milling, the mixture was dried in an oven and then calcined in a tube furnace at 800 °C for 3 hours under a nitrogen atmosphere to obtain MoS2@AC catalyst F (molar ratio of molybdenum source to sulfur source 1:9). The loading of the active component, molybdenum disulfide, in the catalyst was 35.7% (mass fraction). Comparative Example 1: Preparation of catalyst G (hydrothermal method control). 1.23 g of ammonium heptamolybdate, 2.28 g of thiourea, 35 mL of deionized water, and 2 g of activated carbon (mass ratio of activated carbon to molybdenum source 1.6:1) were added to a hydrothermal reactor and reacted at 200 °C for 10 hours. After the reaction was completed, the mixture was washed with water, filtered, and dried in an oven to obtain MoS2@AC catalyst G (molar ratio of molybdenum source to sulfur source 1:6). The loading of molybdenum disulfide, the active component in the catalyst, was 35.8% (mass fraction).

[0028] Comparative Application Example 1: 369 g (1 mol) of dextrolansoprazole byproduct (total mass 369 g, calculated by total mass), 2 MPa hydrogen gas, 400 mL of ethanol (density 0.789 g / mL at 25°C, mass 315.6 g, 0.855 times the mass of the substrate), and 50 g of catalyst G prepared according to Control Method 1 (control group, molar ratio of molybdenum source to sulfur source 1:6) were stirred at 60°C for 5 hours. After the reaction, the molybdenum catalyst was separated by filtration, extracted with ethyl acetate, the organic phases were combined, and the solvent was evaporated under reduced pressure to obtain 240 g of lansoprazole sulfide, yield 65%.

[0029] Comparative Application Example 2: 369 g (1 mol) of dextrolansoprazole byproduct (total mass 369 g, calculated by total mass), 2 MPa hydrogen gas, 400 mL of ethanol (density 0.789 g / mL at 25°C, mass 315.6 g, 0.855 times the substrate mass), and 50 g of commercially available MoS2 catalyst were reacted at 60°C with stirring for 5 hours. After the reaction, the molybdenum catalyst was separated by filtration, extracted with ethyl acetate, and the organic phases were combined. The solvent was evaporated under reduced pressure to obtain 214 g of lansoprazole sulfide, yield 58%.

[0030] Application Example 1: 369 g (1 mol) of racemic lansoprazole (by total mass), 2 MPa of hydrogen gas, 400 mL of ethanol (density 0.789 g / mL at 25°C, mass 315.6 g, 0.855 times the mass of the substrate), and 50 g of catalyst C (molar ratio of molybdenum source to sulfur source 1:9) prepared according to Example 3 were added to a reaction vessel and stirred at 60°C for 5 hours. After the reaction was completed, the molybdenum catalyst was separated by filtration, extracted with ethyl acetate, the organic phases were combined, and the solvent was evaporated under reduced pressure to obtain 328 g of lansoprazole sulfide, with a yield of 93%.

[0031] Application Example 2: 369 g (1 mol) of dextro-lansoprazole byproduct (total mass 369 g, of which levonorhanazole accounts for 70% by total mass), 2 MPa hydrogen gas, 400 mL of ethanol (density 0.789 g / mL at 25°C, mass 315.6 g, 0.855 times the mass of the substrate) and 50 g of catalyst C (molar ratio of molybdenum source to sulfur source 1:9) prepared according to Example 3 were added to a reaction vessel. The mixture was stirred at 60°C for 5 hours. After the reaction was completed, the molybdenum catalyst was separated by filtration, extracted with ethyl acetate, and the organic phases were combined. The solvent was evaporated under reduced pressure to obtain 314 g of lansoprazole sulfide, with a yield of 89%.

[0032] Application Example 3: 369 g (1 mol) of dextro-lansoprazole byproduct (total mass 369 g, of which levo-lansoprazole accounts for 85% by total mass), 2 MPa hydrogen gas, 400 mL of ethanol (density 0.789 g / mL at 25°C, mass 315.6 g, 0.855 times the mass of the substrate) and 50 g of catalyst C (molar ratio of molybdenum source to sulfur source 1:9) prepared according to Example 3 were added to a reaction vessel. The mixture was stirred at 60°C for 5 hours. After the reaction was completed, the molybdenum catalyst was separated by filtration, extracted with ethyl acetate, and the organic phases were combined. The solvent was evaporated under reduced pressure to obtain 321 g of lansoprazole sulfide, with a yield of 91%.

[0033] Application Example 4: 369 g (1 mol) of dextro-lansoprazole byproduct (total mass 369 g, of which 85% is levonorhanil, calculated by total mass), 2 MPa hydrogen gas, 400 mL of ethanol (density 0.789 g / mL at 25°C, mass 315.6 g, 0.855 times the mass of the substrate) and 50 g of catalyst E (molar ratio of molybdenum source to sulfur source 1:10) prepared according to Example 5 were added to a reaction vessel. The mixture was stirred at 60°C for 5 hours. After the reaction, the molybdenum catalyst was separated by filtration, extracted with ethyl acetate, and the organic phases were combined. The solvent was evaporated under reduced pressure to obtain 318 g of lansoprazole sulfide, with a yield of 90%.

[0034] Application Example 5: 369 g (1 mol) of dextro-lansoprazole byproduct (total mass 369 g, of which levo-lansoprazole accounts for 85% by total mass), 2 MPa hydrogen gas, 400 mL of ethanol (density 0.789 g / mL at 25°C, mass 315.6 g, 0.855 times the mass of the substrate) and 50 g of catalyst F prepared according to Example 6 (molar ratio of molybdenum source to sulfur source 1:9) were added to a reaction vessel, and the mixture was stirred at 60°C for 5 hours. After the reaction was completed, the molybdenum catalyst was separated by filtration, extracted with ethyl acetate, the organic phases were combined, and the solvent was evaporated under reduced pressure to obtain 315 g of lansoprazole sulfide, with a yield of 89%.

[0035] Application Example 6: 369 g (1 mol) of levlansoprazole (calculated by total mass) was added to the reaction vessel, the reaction time was changed to 3 hours, and the remaining operations were performed as described in Application Example 1, yielding 247 g of lansoprazole sulfide, with a yield of 70%.

[0036] Application Example 7: The amount of hydrogen added was changed to 1 MPa, and the remaining operations were performed as described in Application Example 1, resulting in 265 g of lansoprazole sulfide with a yield of 75%.

[0037] Application Example 8: The amount of hydrogen added was changed to 1.5 MPa, and the remaining operations were performed as described in Application Example 1, yielding 314 g of lansoprazole sulfide with a yield of 89%.

[0038] Application Example 9: Ethanol was replaced with 1,4-dioxane, and the remaining operations were performed as described in Application Example 1, to obtain 222g of lansoprazole sulfide, with a yield of 63%.

[0039] Application Example 10: The amount of ethanol added was changed to 200 mL (density 0.789 g / mL at 25°C, mass 157.8 g, which is 0.428 times the mass of the substrate), and the remaining operations were performed as described in Application Example 1, to obtain 222 g of lansoprazole sulfide, with a yield of 63%.

[0040] Application Example 11: The amount of ethanol added was changed to 300 mL (density at 25°C 0.789 g / mL, mass 236.7 g, which is 0.641 times the mass of the substrate), and the remaining operations were performed as described in Application Example 1, to obtain 300 g of lansoprazole sulfide, with a yield of 85%.

[0041] Application Example 12: The amount of catalyst added was changed to 18.5 g (5% of the substrate), and the remaining operations were performed as described in Application Example 1, yielding 233 g of lansoprazole sulfide, with a yield of 66%.

[0042] Application Example 13: The amount of catalyst added was changed to 36.9 g (10% of the substrate), and the remaining operations were performed as described in Application Example 1, yielding 268 g of lansoprazole sulfide, with a yield of 76%.

[0043] Application Example 14: The amount of catalyst added was changed to 48g (13% of the substrate), and the remaining operations were performed as described in Application Example 1, yielding 279g of lansoprazole sulfide, with a yield of 79%.

[0044] Application Example 15: The amount of catalyst added was changed to 50 g (14% of the substrate), and the remaining operations were performed as described in Application Example 1, yielding 328 g of lansoprazole sulfide in 93% yield.

[0045] Application Example 16: The reaction temperature was changed to 25°C, and the remaining operations were performed as described in Application Example 1, yielding 261g of lansoprazole sulfide, with a yield of 74%.

[0046] Application Example 17: The reaction temperature was changed to 60°C, and the remaining operations were performed as described in Application Example 1, yielding 328g of lansoprazole sulfide with a yield of 93%.

[0047] Application Example 18: 369 g (1 mol) of dextrolansoprazole byproduct (total mass 369 g, calculated by total mass), 2 MPa hydrogen gas, 400 mL of ethanol (density 0.789 g / mL at 25°C, mass 315.6 g, 0.855 times the mass of the substrate), and 50 g of catalyst A (molar ratio of molybdenum source to sulfur source 1:3) prepared according to Example 1 were stirred at 60°C for 5 hours. After the reaction was completed, the molybdenum catalyst was separated by filtration, extracted with ethyl acetate, the organic phases were combined, and the solvent was evaporated under reduced pressure to obtain 278 g of lansoprazole sulfide, yield 73%.

[0048] Application Example 19: 369 g (1 mol) of dexlansoprazole byproduct (total mass 369 g, calculated by total mass), 2 MPa hydrogen gas, 400 mL of ethanol (density 0.789 g / mL at 25°C, mass 315.6 g, 0.855 times the mass of the substrate), and 50 g of catalyst B (molar ratio of molybdenum source to sulfur source 1:6) prepared according to Example 2 were stirred at 60°C for 5 hours. After the reaction was completed, the molybdenum catalyst was separated by filtration, extracted with ethyl acetate, the organic phases were combined, and the solvent was evaporated under reduced pressure to obtain 286 g of lansoprazole sulfide, yield 81%.

[0049] Application Example 20: 369 g (1 mol) of dextrolansoprazole byproduct (total mass 369 g, calculated by total mass), 2 MPa hydrogen gas, 400 mL of ethanol (density 0.789 g / mL at 25°C, mass 315.6 g, 0.855 times the mass of the substrate), and 50 g of catalyst C (molar ratio of molybdenum source to sulfur source 1:9) prepared according to Example 3 were stirred at 60°C for 5 hours. After the reaction was completed, the molybdenum catalyst was separated by filtration, extracted with ethyl acetate, the organic phases were combined, and the solvent was evaporated under reduced pressure to obtain 328 g of lansoprazole sulfide, yield 93%.

[0050] Application Example 21: 369 g (1 mol) of dextrolansoprazole byproduct (total mass 369 g, calculated by total mass), 2 MPa hydrogen gas, 400 mL of ethanol (density 0.789 g / mL at 25°C, mass 315.6 g, 0.855 times the mass of the substrate), and 50 g of catalyst D (molar ratio of molybdenum source to sulfur source 1:12) prepared according to Example 4 were stirred at 60°C for 5 hours. After the reaction was completed, the molybdenum catalyst was separated by filtration, extracted with ethyl acetate, the organic phases were combined, and the solvent was evaporated under reduced pressure to obtain 265 g of lansoprazole sulfide, yield 75%.

[0051] Application Example 22: The catalyst washed and dried after the reaction in Application Example 20 was reused. The results are shown in Table 1.

[0052] Table 1:

[0053] The process flow is consistent with the implementation case, and the catalyst recovery and utilization are shown in the table below:

[0054] Number of recyclings Lansoprazole sulfide yield (%) 1 88％ 2 86％ 3 90％ 4 87％ 5 85％ 6 71％ 7 63％

[0055] Furthermore, the application scope of the MoS2@AC catalyst for the catalytic recovery of dexlansoprazole byproducts provided in this invention is not limited, but is only used as an application example. It exhibits universal catalytic effects on the catalytic hydrodeoxygenation reactions of sulfoxide compounds.

Claims

1. A molybdenum catalyst, characterized in that: Activated carbon is used as a carrier, and molybdenum disulfide is used as the active component. Molybdenum disulfide is loaded on the surface and in the pores of the activated carbon, and the loading mass of the active component molybdenum disulfide is 35% to 37% of the total mass of the catalyst.

2. A method for preparing the molybdenum catalyst as described in claim 1, characterized in that: Molybdenum disulfide is obtained by sulfidation reaction of molybdenum source and sulfur source, and then dispersed by ball milling with activated carbon and calcined for loading. The specific steps are as follows: weigh molybdenum source, sulfur source, solvent and activated carbon in proportion, add them to ball mill jar, place the ball mill jar in ball mill, disperse by ball milling to obtain a uniform mixture, dry it, and then place it in a tube furnace for calcination under nitrogen atmosphere. After cooling, a supported molybdenum catalyst is obtained.

3. The method as described in claim 2, characterized in that: The molybdenum source is ammonium heptamolybdate, ammonium octamolybdate, or sodium molybdate; the sulfur source is trithiocyanate, thiourea, or thioacetamide.

4. The method as described in claim 2, characterized in that: The molar ratio of molybdenum source to sulfur source is 1:(3-12); The solvent is deionized water; the mass ratio of activated carbon to molybdenum source is 1 to 2:

1.

5. The method as described in claim 2, characterized in that: The ball milling speed is 150-160 r / min, and the milling time is 3-10 h; the calcination temperature is 400℃-800℃, and the calcination time is 2-4 h.

6. The use of the molybdenum catalyst as described in claim 1 in the catalytic hydrogenation reduction of lansoprazole substrate to prepare lansoprazole sulfide.

7. The application as described in claim 6, wherein the specific steps are as follows: lansoprazole substrate, solvent and molybdenum catalyst are added to a container, followed by the introduction of hydrogen gas and heating to react and obtain lansoprazole sulfide.

8. The application as described in claim 7, characterized in that... The lansoprazole substrate is racemic lansoprazole or a dextro-lansoprazole byproduct; the solvent is ethanol, tert-butanol, or 1,4-dioxane, and the mass of the solvent added is 0.4 to 1 times that of the substrate; the mass of the molybdenum catalyst added is 5% to 15% of the mass of the lansoprazole substrate.

9. The application as described in claim 7, characterized in that: The reaction was carried out in a hydrogen atmosphere, and the hydrogen pressure in the system was controlled at 1–2 MPa.

10. The application as described in claim 7, characterized in that: The temperature for the heating reaction is 25–60℃; the heating reaction time is 3–5 hours.

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