A method for synthesizing tropisetron
High-purity tropisetron was directly synthesized by catalyzing the reaction of indole and tropine with a Pd single-atom catalyst at room temperature. This solved the problems of heterogeneous reaction and low purity in existing technologies, and realized an efficient and environmentally friendly tropisetron synthesis that is suitable for industrial production.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2025-07-04
- Publication Date
- 2026-04-07
AI Technical Summary
Existing methods for synthesizing tropisetron suffer from problems such as heterogeneous reaction, high temperature requirements, complex post-processing, numerous byproducts, low purity, difficulty in meeting pharmacopoeia standards, and heavy metal residues. Furthermore, traditional catalysts result in slow reaction rates and low yields.
Indole and tropane were reacted in solvents such as water at room temperature using a Pd single-atom catalyst and an oxidant. The CH bond of indole was directly activated by the Pd single-atom catalyst to synthesize tropisetron. The catalyst was directly filtered after the reaction to avoid heavy metal contamination and to obtain a high-purity product.
It achieves a high yield (close to 98%) of high-purity tropisetron, simplifies the process, meets pharmacopoeia standards, is suitable for industrial production, and avoids column chromatography operations and waste generation.
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Abstract
Description
Technical Field
[0001] This invention relates to the field of drug synthesis, specifically a method for synthesizing tropisetron. Background Technology
[0002] Tropisetron is a white solid that is sensitive to light and air. Common formulations include tablets, oral solutions, and injections. It is an antiemetic and antinausea medication, highly effective in preventing and treating nausea and vomiting induced by cancer chemotherapy.
[0003] Tropisetron is a highly potent and selective 5-HT3 receptor antagonist. It selectively inhibits the excitation of presynaptic 5-HT3 receptors in the peripheral nervous system during this reflex, thereby blocking the vomiting reflex. This drug is a highly selective inhibitor of 5-HT3 receptors in both peripheral neurons and the central nervous system, exerting a central antiemetic effect. It is also effective in treating vomiting induced by chemotherapy and radiotherapy.
[0004] Existing synthetic methods generally use indole-3-carboxylic acid as a raw material, which reacts with acyl chloride reagents such as oxalyl chloride and thionyl chloride to generate an acyl chloride intermediate—indolecarboxyl chloride. Tropine alcohol reacts with n-butyllithium or a strong base such as sodium hydroxide or sodium ethoxide to obtain the metal salt of tropine alcohol, which then reacts with indolecarboxyl chloride to prepare tropisetron.
[0005] Subsequent improvements to the synthesis method have been developed. For example, in an inert solvent, indole-3-carboxylic acid is reacted with tropine alcohol in the presence of 1,3-dimethyl-2-chloroimidazoline chloride and an organic base at room temperature for 12–24 h. After cooling, filtration, and washing, tropisetron is prepared. This process avoids the use of oxalyl chloride, n-butyllithium, tetrahydrofuran, etc., as it does not employ an acylation step. However, the preparation of the condensing agent 1,3-dimethyl-2-chloroimidazoline chloride requires the use of highly toxic phosgene.
[0006] For example, direct esterification involves using aromatic organic sulfonic acid compounds as catalysts in an inert solvent to directly esterify indole-3-carboxylic acid and tropine alcohol to prepare tropisetron. The reaction temperature is 50–150 °C, and the reaction time is 2–35 h. This process employs a one-step esterification mechanism, but the reaction is heterogeneous, which is not conducive to a complete reaction. Furthermore, continuous dehydration is required during the reaction, making the process complex. The dehydration materials used, such as molecular sieves, are difficult to handle. The high reaction temperature may cause decomposition of the target product, leading to increased impurities and reduced purity. Post-reaction treatment requires acid-base adjustment, making the process complex and unsuitable for industrial application.
[0007] Another example is the mixed anhydride method: In an inert solvent, C2-C4 aliphatic halocarboxylic acids are used as catalysts, and C2-C4 aliphatic halocarboxylic acid anhydrides are used as activating agents to activate indole-3-carboxylic acid into mixed anhydrides. Then, a tropisetron solution dissolved in an inert solvent is added dropwise to carry out a condensation reaction. However, C2-C4 aliphatic halocarboxylic acids and their anhydrides have certain chemical reactivity. Therefore, in actual production, the stability and cost of raw materials are significant challenges.
[0008] Therefore, in order to overcome the above problems, it is necessary to change the raw materials and design new synthetic routes, such as the homogeneous Pd-catalyzed carbonylation coupling reaction of indole and tropine alcohol (Organic Letters, 2012, 14(16): 4130-4133.). However, the problems with homogeneous Pd catalysts are: (1) I2 must be used first to generate the iodinated product before Pd reaction occurs. 0 (1) The oxidative addition reaction is followed by the addition of K2CO3 after the reaction, resulting in KI waste residue. (2) It is not applicable to NH substrates and can only synthesize N-CH3 substituted tropisetron analogs, not NH tropisetron. (3) When homogeneous Pd catalysts are used in drug synthesis processes, special consideration should be given to whether the residue of heavy metal Pd in the product complies with the pharmacopoeia regulations. Therefore, the post-treatment process of column chromatography is commonly used in homogeneous catalytic systems to remove Pd catalysts and achieve the purpose of separating tropisetron. However, column chromatography is time-consuming and material-intensive, and is not conducive to large-scale drug production.
[0009] Furthermore, commercially available Pd / C and other multiphase nanocatalysts suffer from slow reaction rates (nanoparticles have lower reaction rates than single atoms, Chemical reviews, 2020, 120(21): 11986-12043. AppliedCatalysis B: Environmental, 2020, 264: 118502.). When using Pd / C and other catalysts to catalyze the oxidative carbonylation, the esterification rate is slow, the conversion rate is low, and there are many byproducts, which reduces the quality of tropisetron and makes it difficult to meet the purity requirements of tropisetron compounds in the current pharmacopoeia. Summary of the Invention
[0010] In view of this, the technical problem to be solved by the present invention is to provide a method for synthesizing tropisetron. The method provided by the present invention can synthesize high-purity tropisetron with high yield, simple method and no waste residue generated after reaction.
[0011] This invention provides a method for synthesizing tropisetron, comprising the following steps:
[0012] In the presence of a Pd single-atom catalyst and an oxidant, indole, carbon monoxide, and tropine alcohol are reacted in a solvent to yield tropisetron.
[0013] The Pd single-atom catalyst of the present invention comprises a support and Pd single atoms supported on the support; wherein the mass fraction of the Pd single atoms supported on the support is 0.1% to 0.5%, preferably 0.2% to 0.4%, and more preferably 0.3%. The support of the present invention is selected from activated carbon, iron oxide, alumina, cerium oxide, zirconium oxide, titanium oxide, manganese oxide, or silicon dioxide, preferably activated carbon.
[0014] The Pd single-atom catalyst of this invention is prepared by the following method:
[0015] S1) Stir the EDTA solution containing Pd ions and the support together until the solvent evaporates completely, and then dry to obtain the precursor of the Pd single-atom catalyst.
[0016] S2) The precursor of the Pd single-atom catalyst obtained in step S1) is calcined to obtain the Pd single-atom catalyst.
[0017] This invention first mixes a Pd-ion-containing EDTA solution with the support until the solvent completely evaporates, then dries to obtain a precursor for a Pd single-atom catalyst. Specifically, a Pd salt and an EDTA salt are mixed to obtain a Pd-ion-containing EDTA solution. The support is then added to the Pd-ion-containing EDTA solution and mixed until the solvent completely evaporates, then dried to obtain the precursor for a Pd single-atom catalyst. In some embodiments of this invention, Pd(NO3)2·2H2O and EDTA-2Na are mixed to obtain a Pd-ion-containing EDTA solution. The support is then added to the mixed Pd-ion-containing EDTA solution and stirred until the solvent completely evaporates, then dried to obtain the precursor for a Pd single-atom catalyst. The concentration of the Pd-ion-containing EDTA solution in this invention is 5 mg / mL to 15 mg / mL. The amount of the support used in this invention is 400 mg to 600 mg, preferably 500 mg. The stirring temperature in this invention is 90℃ to 100℃.
[0018] After obtaining the precursor of the Pd single-atom catalyst, this invention calcines the precursor to obtain the Pd single-atom catalyst. Specifically, the precursor is calcined under a protective gas atmosphere to obtain the Pd single-atom catalyst. The protective gas atmosphere is selected from one or more of nitrogen, helium, neon, or argon. The calcination temperature is 500℃~700℃, the calcination time is 2 h~4 h, and the heating rate is 4℃ / min~6℃ / min, preferably 5℃ / min.
[0019] The method for synthesizing tropisetron provided by this invention, based on the action of the Pd single-atom catalyst, exhibits excellent selectivity for indole, an NH substrate, and can synthesize tropisetron with NH substituents. This solves the problem in existing technologies that can only synthesize N-CH3-substituted tropisetron analogs using 1-methylindole, an N-CH3 substrate, as a starting material. Furthermore, the tropisetron synthesized by this invention has a yield close to 98%, and its purity fully meets the standards for use in the Chinese Pharmacopoeia. The synthesis method is also simple. In addition, by optimizing the coordination structure of the Pd single-atom catalyst and maintaining the positive valence state of Pd, this invention can directly activate the CH bond at the 3-position of indole without the need for the addition of I2 and K2CO3, and no waste residue is generated after the reaction.
[0020] The method for synthesizing tropisetron provided by this invention first involves reacting indole, carbon monoxide, and tropine alcohol in a solvent under the presence of a Pd single-atom catalyst and an oxidant. Specifically, indole, carbon monoxide, tropine alcohol, the Pd single-atom catalyst, and the oxidant are mixed in a solvent, carbon monoxide is introduced into the mixture, and the reaction is carried out by heating.
[0021] This invention involves reacting indole, carbon monoxide, and tropine in a solvent under the influence of a Pd single-atom catalyst and an oxidant. The reaction temperature is 20°C to 120°C, and the reaction time is 1 h to 12 h. The carbon monoxide pressure is 1 atm to 10 atm; the molar ratio of indole to tropine is 1:(1 to 1.5); the amount of oxidant is 100% to 300% of the molar amount of indole; the amount of Pd single-atom catalyst is 30 mg / mmol to 50 mg / mmol based on the molar amount of indole; and the amount of solvent is 2 mL / mmol to 5 mL / mmol based on the molar amount of indole. The oxidant is selected from one or more of hydrogen peroxide, oxygen, p-benzoquinone, peracetic acid, 2,2,6,6-tetramethyl-1-piperidine, and tert-butylhydrogen peroxide; in one embodiment, the oxidant is selected from 30% hydrogen peroxide. The solvent used in this invention is selected from one or more of water, dimethyl carbonate (DMC), 1,4-dioxane, tetrahydrofuran (THF), dimethyl sulfoxide (DMSO), dimethylformamide (DMF), and toluene. Compared with traditional methods, the tropisetron synthesis method provided by this invention can use water as a solvent, hydrogen peroxide as an oxidant, and can carry out the reaction in a normal pressure carbon monoxide atmosphere, synthesizing the target product in one step. The preparation method is faster, more efficient, environmentally friendly, and milder.
[0022] This invention, involving the reaction of indole, carbon monoxide, and tropine in a solvent under the presence of a Pd single-atom catalyst and an oxidant, further includes: filtering the resulting reaction solution, removing the solvent from the filtrate, and obtaining tropisetron. Specifically, the reaction solution is filtered to remove the solid Pd single-atom catalyst, and the resulting filtrate is washed with dichloromethane to obtain a washing liquid. The filtrate and washing liquid are combined, and the combined solution is dehydrated with anhydrous sodium sulfate, the solvent is evaporated, and the solution is vacuum dried to obtain tropisetron. This invention directly filters the solid catalyst after the reaction, avoiding contamination of the product by the heavy metal Pd. It eliminates the need for column chromatography separation, and the product purity meets the standards of the Chinese Pharmacopoeia. The Pd single-atom catalyst can be recycled, making it more advantageous for industrial production than homogeneous catalysts.
[0023] This invention provides a method for synthesizing tropisetron. Compared with traditional methods, the synthetic route provided by this invention is more efficient, faster, more environmentally friendly, milder, and more selective. Based on the action of the Pd single-atom catalyst, it exhibits good selectivity for indole, an NH substrate, enabling the synthesis of tropisetron with NH substituents. This solves the problem that existing technologies can only synthesize N-CH3-substituted tropisetron analogs using 1-methylindole, an N-CH3 substrate, as a starting material. The yield of tropisetron synthesized by this invention is close to 98%, and traditional column chromatography is not required. The product purity meets the standards of the Chinese Pharmacopoeia. The high yield and simplified purification process facilitate large-scale industrial production. Furthermore, by optimizing the coordination structure of the Pd single-atom catalyst and maintaining the positive valence state of Pd, this invention can directly activate the CH bond at the 3-position of indole without the need for external I2 and K2CO3, and no waste is generated after the reaction. Attached Figure Description
[0024] Figure 1 This is a high-angle annular dark-field scanning transmission electron microscope image of the 0.3% Pd / NC single-atom catalyst prepared in Example 1 of the present invention.
[0025] Figure 2 The above is the 1H NMR spectrum of the tropisetron product synthesized in Example 1 of this invention;
[0026] Figure 3 The image shows the carbon NMR spectrum of the tropisetron product synthesized in Example 1 of this invention. Detailed Implementation
[0027] This invention discloses a method for synthesizing tropisetron. Those skilled in the art can refer to this document and appropriately modify the process parameters to achieve the desired result. It should be particularly noted that all similar substitutions and modifications are obvious to those skilled in the art and are considered to be included in this invention. The method and application of this invention have been described through preferred embodiments. Those skilled in the art can clearly modify or appropriately change and combine the method and application described herein without departing from the content, spirit, and scope of this invention to realize and apply the technology of this invention.
[0028] The present invention will be further described below with reference to the embodiments:
[0029] Example 1
[0030] Palladium single-atom catalysts were prepared according to the following steps:
[0031] Step S1: Prepare a Pd-EDTA solution of a certain concentration by mixing Pd(NO3)2·2H2O and EDTA-2Na. Add activated carbon powder to the Pd-EDTA solution and stir until the solvent evaporates completely. Then dry the remaining material to obtain the precursor of the palladium single-atom catalyst. In step S1, the concentration of the Pd-EDTA solution is 10 mg / mL, the amount of activated carbon powder used is 500 mg, and the stirring temperature is 95 ℃.
[0032] Step S2: The precursor of the palladium single-atom catalyst is calcined at high temperature to obtain a 0.3% Pd / NC single-atom catalyst. In step S2, the atmosphere for high-temperature calcination is nitrogen, the calcination temperature is 600 °C, the heating rate is 5 °C / min, and the time is 3 h.
[0033] The structure of the 0.3% Pd / NC single-atom catalyst prepared above was analyzed. For example... Figure 1 As shown, Figure 1 This is a high-angle annular dark-field scanning transmission electron microscope (HAADF-STEM) image of the 0.3% Pd / NC single-atom catalyst prepared in Example 1 of this invention. Figure 1 It is evident that the palladium element in the 0.3% Pd / NC single-atom catalyst provided in this application is dispersed on the carbon support in the form of single atoms.
[0034] The performance of the 0.3% Pd / NC single-atom catalyst prepared above was tested. Specifically, the effect of the 0.3% Pd / NC single-atom catalyst prepared above on the synthesis of tropisetron using indole, carbon monoxide, and tropine alcohol as reactants was tested. The synthetic route is as follows:
[0035]
[0036] The specific process for the synthesis of tropisetron using a palladium single-atom catalyst is as follows:
[0037] First, 117 mg (1 mmol) of indole and 141 mg (1 mmol) of tropine were added to the reaction flask, followed by 40 mg of 0.3% Pd / NC single-atom catalyst, 2 mL of water, and 204 μL of 30% hydrogen peroxide solution (2 mmol H2O2). Then, the air in the reaction flask was purged and carbon monoxide (1 atm) was introduced. A balloon was attached to the flask and the flask was sealed. A magnetic stirrer was turned on, and the reaction was carried out in a water bath at 80 °C for 6 h. After the reaction was stopped, the reaction solution was filtered to remove the solid-phase catalyst, washed with dichloromethane (20 mL × 2), and the filtrate and washings were combined. Anhydrous sodium sulfate was added to remove water, and the mixture was filtered again. The solvent was evaporated and the product was dried under vacuum to obtain 0.978 mmol of pure tropisetron, with a yield of 97.8%. 1 H NMR and 13 The C NMR data are as follows:
[0038] 1 H NMR (500 MHz, CHLOROFORM-D) δ 10.22 (s, 1H), 8.26 – 8.21 (m, 1H), 7.84 (s, 1H), 7.40 (dd, J = 6.3, 3.0 Hz, 1H), 7.29 – 7.22 (m, 2H), 5.28 (t, J= 5.5 Hz, 1H), 3.21 (s, 2H), 2.34 (s, 3H), 2.32 – 2.25 (m, 2H), 2.18 – 2.06(m, 4H), 1.94 (d, J = 14.0 Hz, 2H);
[0039] 13 C NMR (126 MHz, CHLOROFORM-D) δ 164.83, 136.54, 131.28, 126.11,123.19, 122.01, 121.21, 111.86, 108.89, 66.51, 59.95, 40.20, 36.51, 26.01.
[0040] like Figure 2 and Figure 3 As shown, Figure 2 This is the 1H NMR spectrum of the tropisetron product synthesized in Example 1 of this invention. Figure 3 The image shows the carbon NMR spectrum of the tropisetron product synthesized in Example 1 of this invention.
[0041] Example 2
[0042] Palladium single-atom catalysts were prepared using the same method as in Example 1, except that activated carbon was replaced with CeO2, ultimately yielding a 0.3% Pd / CeO2 single-atom catalyst.
[0043] The synthesis of tropisetron using palladium single-atom catalyst was carried out according to the synthetic route of Example 1, and the specific process is as follows:
[0044] First, 117 mg (1 mmol) of indole and 141 mg (1 mmol) of tropine were added to the reaction flask, followed by 40 mg of 0.3% Pd / CeO2 single-atom catalyst, 2 mL of water, and 204 μL of 30% hydrogen peroxide solution (2 mmol H2O2). Then, the air in the reaction flask was purged and carbon monoxide (1 atm) was introduced. A balloon was attached to the mouth of the flask and sealed. The magnetic stirrer was turned on, and the reaction was carried out in a water bath at 80 °C for 6 h. After the reaction was stopped, the reaction solution was filtered to remove the solid catalyst, washed with dichloromethane (20 mL × 2), and the filtrate and washing solution were combined. Anhydrous sodium sulfate was added to remove water, and the mixture was filtered again. The solvent was evaporated and the solution was dried under vacuum to obtain 0.951 mmol of pure tropisetron compound, with a yield as high as 95.1%.
[0045] Example 3
[0046] Using the 0.3% Pd / NC single-atom catalyst prepared in Example 1, tropisetron was synthesized via palladium single-atom catalyst according to the synthetic route of Example 1. The specific process is as follows:
[0047] First, 117 mg (1 mmol) of indole and 141 mg (1 mmol) of tropine were added to the reaction flask, followed by 40 mg of 0.3% Pd / NC single-atom catalyst, 2 mL of water, and 180 mg (1 mmol) of tert-butyl hydrogen peroxide. The air in the reaction flask was then purged and carbon monoxide (1 atm) was introduced. A balloon was attached to the flask and the flask was sealed. A magnetic stirrer was turned on, and the reaction was carried out in a water bath at 80 °C for 6 h. After the reaction was stopped, the reaction solution was filtered to remove the solid catalyst. The solution was washed with dichloromethane (20 mL × 2), and the filtrate and washings were combined. Anhydrous sodium sulfate was added to remove water, and the solution was filtered again. The solvent was evaporated and the solution was dried under vacuum to obtain 0.965 mmol of pure tropisetron, with a yield of 96.5%.
[0048] Example 4
[0049] Using the 0.3% Pd / NC single-atom catalyst prepared in Example 1, tropisetron was synthesized via palladium single-atom catalyst according to the synthetic route of Example 1. The specific process is as follows:
[0050] First, 117 mg (1 mmol) of indole and 141 mg (1 mmol) of tropine were added to the reaction flask, followed by 40 mg of 0.3% Pd / NC single-atom catalyst, 2 mL of toluene, and 204 μL of 60% hydrogen peroxide solution (2 mmol H2O2). The air in the reaction flask was then purged and carbon monoxide (1 atm) was introduced. A balloon was attached to the flask and the flask was sealed. A magnetic stirrer was turned on, and the reaction was carried out in a water bath at 80 °C for 6 h. After the reaction was stopped, the reaction solution was filtered to remove the solid catalyst, washed with dichloromethane (20 mL × 2), and the filtrate and washings were combined. Anhydrous sodium sulfate was added to remove water, and the mixture was filtered again. The solvent was evaporated and the solution was dried under vacuum to obtain 0.964 mmol of pure tropisetron, with a yield of 96.4%.
[0051] Comparative Example 1
[0052] The performance of the homogeneous (CH3COO)2Pd catalyst was tested. Specifically, the effect of the homogeneous (CH3COO)2Pd catalyst on the synthesis of tropanesetron using indole, carbon monoxide, and tropine as reactants was tested. The synthetic route is as follows:
[0053]
[0054] The specific process for the synthesis of tropanesetron catalyzed by the homogeneous (CH3COO)2Pd catalyst is as follows:
[0055] First, 117 mg (1 mmol) of indole and 141 mg (1 mmol) of tropine were added to the reaction flask, followed by 4 mL of 5 mmol / mL (CH3COO)2Pd catalyst, 2 mL of water, and 204 μL of 30% hydrogen peroxide solution (2 mmol H2O2). Then, the air in the reaction flask was purged and carbon monoxide (1 atm) was introduced. A balloon was attached to the flask and the flask was sealed. The magnetic stirrer was turned on, and the reaction was carried out in a water bath at 80 °C for 6 h. After the reaction was stopped, the organic phase was washed with dichloromethane, and the tropisetron organic solution was separated by column chromatography. The solvent was removed by rotary evaporation and the solution was dried under vacuum to obtain 0.05 mmol of pure tropisetron compound, with a yield of only 5%.
[0056] Comparative Example 2
[0057] Performance tests were conducted on the 10% nano-Pd / C catalyst. Specifically, the test focused on the effect of the 10% nano-Pd / C catalyst on the synthesis of tropisetron using indole, carbon monoxide, and tropine as reactants. The synthetic route is as follows:
[0058]
[0059] The process of synthesizing tropisetron using a 10% nano-Pd / C catalyst includes:
[0060] First, 117 mg (1 mmol) of indole and 141 mg (1 mmol) of tropine were added to the reaction flask, followed by 40 mg of 10% nano-Pd / C catalyst, 2 mL of water, and 204 μL of 30% hydrogen peroxide solution (2 mmol H2O2). The air in the reaction flask was then purged and carbon monoxide (1 atm) was introduced. A balloon was attached to the flask and the flask was sealed. A magnetic stirrer was turned on, and the reaction was carried out in a water bath at 80 °C for 6 h. After the reaction was stopped, the reaction solution was filtered to remove the solid catalyst, washed with dichloromethane (20 mL × 4), and the filtrate and washings were combined. Anhydrous sodium sulfate was added to remove water, and the mixture was filtered again. The solvent was evaporated and the solution was dried under vacuum to obtain 0.386 mmol of pure tropisetron, with a yield of only 38.6%.
[0061] By comparing the above examples, it can be found that in Examples 1-4, the yield of tropisetron synthesized using palladium single-atom catalysts was higher than 95%. When using a homogeneous (CH3COO)2Pd catalyst, the yield of tropisetron was only 5%. Furthermore, when using a 10% Pd / C heterogeneous nanocatalyst, the amount of dichloromethane washing solution increased significantly, and the yield of tropisetron was only 38.6%.
[0062] The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and inventive concept of the present invention, should be covered within the scope of protection of the present invention.
Claims
1. A method for synthesizing tropisetron, characterized in that, Includes the following steps: In the presence of a Pd single-atom catalyst and an oxidant, indole, carbon monoxide, and tropine alcohol are reacted in a solvent to yield tropisetron. The Pd single-atom catalyst was prepared by the following method: S1) Stir the EDTA solution containing Pd ions and the support together until the solvent evaporates completely, and then dry to obtain the precursor of the Pd single-atom catalyst. S2) The precursor of the Pd single-atom catalyst obtained in step S1) is calcined in a protective gas atmosphere to obtain the Pd single-atom catalyst. The oxidant is selected from one or more of hydrogen peroxide, oxygen, p-benzoquinone, peracetic acid, and tert-butyl hydroperoxide.
2. The synthesis method according to claim 1, characterized in that, The Pd single-atom catalyst includes a support and Pd single atoms supported on the support. The mass fraction of the Pd single atom loaded on the support is 0.1% to 0.5%.
3. The synthesis method according to claim 2, characterized in that, The carrier is selected from activated carbon, iron oxide, aluminum oxide, cerium oxide, zirconium oxide, titanium oxide, manganese oxide, or silicon dioxide.
4. The synthesis method according to claim 1, characterized in that, In step S1), the concentration of the EDTA solution containing Pd ions is 5 mg / mL to 15 mg / mL.
5. The synthesis method according to claim 1, characterized in that, In step S1), the stirring temperature is 90℃~100℃; In step S2), the calcination temperature is 500℃~700℃, and the calcination time is 2 h~4 h.
6. The synthesis method according to claim 1, characterized in that, The carbon monoxide pressure is 1 atm to 10 atm; The molar ratio of indole to tropine is 1:(1~1.5); The amount of the oxidant used is 100% to 300% of the amount of indole. The amount of the Pd single-atom catalyst used, based on the amount of indole, is 30 mg / mmol to 50 mg / mmol. The amount of solvent used is 2 mL / mmol to 5 mL / mmol, based on the amount of indole.
7. The synthesis method according to claim 1, characterized in that, The solvent is selected from one or more of water, dimethyl carbonate, 1,4-dioxane, tetrahydrofuran, dimethyl sulfoxide, dimethylformamide, and toluene.
8. The synthesis method according to claim 1, characterized in that, The reaction temperature is 20℃~120℃, and the reaction time is 1 h~12 h.
9. The synthesis method according to claim 1, characterized in that, After the reaction, the process also includes: filtering the reaction solution obtained after the reaction, removing the solvent from the filtrate obtained after filtration, and obtaining tropisetron.