阅读说明：本技术 一种莫西沙星合成用催化剂的制备方法 (Preparation method of catalyst for synthesis of moxifloxacin ) 是由 王昭文 翟康 张磊 李岳锋 闫江梅 万克柔 曾永康 张之翔 于 2019-10-13 设计创作，主要内容包括：本发明公开了一种莫西沙星合成用催化剂的制备方法,所述催化剂包括活性炭,负载在活性炭上的助剂元素的氧化物,以及负载在活性炭上的活性组分Pd；所述助剂元素为Si、Al或Zr；催化剂的制备方法包括：一、制备活性炭载体；二、氧化物改性活性炭载体；三、浸渍吸附活性组分钯,制备催化剂。本发明通过在活性炭上优先吸附助剂元素氧化物,改变催化剂表面的酸碱性,增强了催化剂抗氮毒化能力,同时活性组分钯与助剂元素氧化物之间具有较强的结合能力,避免了因活性组分金属流失引起的催化剂性能下降,采用乙二醇水溶液作为浸渍溶剂,更易控制活性组分在载体上的分布深度,形成具有抗毒性的蛋白型分布,提高催化剂的稳定性。(The invention discloses a preparation method of a catalyst for synthesizing moxifloxacin, wherein the catalyst comprises activated carbon, an oxide of an auxiliary element loaded on the activated carbon, and an active component Pd loaded on the activated carbon; the auxiliary agent element is Si, Al or Zr; the preparation method of the catalyst comprises the following steps: firstly, preparing an active carbon carrier; secondly, modifying an active carbon carrier by using an oxide; and thirdly, dipping and adsorbing active component palladium to prepare the catalyst. According to the invention, the auxiliary element oxide is preferentially adsorbed on the activated carbon, so that the acidity and alkalinity of the surface of the catalyst are changed, the nitrogen poisoning resistance of the catalyst is enhanced, meanwhile, the active component palladium and the auxiliary element oxide have stronger binding capacity, the performance reduction of the catalyst caused by the loss of active component metal is avoided, and the glycol aqueous solution is used as an impregnation solvent, so that the distribution depth of the active component on the carrier is more easily controlled, the protein distribution with toxicity resistance is formed, and the stability of the catalyst is improved.)

1. A preparation method of a catalyst for synthesizing moxifloxacin is characterized in that the catalyst comprises activated carbon, an oxide of an auxiliary element loaded on the activated carbon, and an active component Pd loaded on the activated carbon; the auxiliary element is Si, Al or Zr, and the mass of the auxiliary element is 1-3% of that of the activated carbon; the mass percentage of an active component Pd in the catalyst is 5%;

the preparation method of the catalyst comprises the following steps:

step one, placing activated carbon in a hydrogen peroxide solution, stirring for 2-4 h, filtering, washing trapped matters to be neutral by deionized water, and drying to obtain an activated carbon carrier;

dissolving soluble salt of an auxiliary element in deionized water, adding the activated carbon carrier obtained in the step one into the solution to obtain slurry, adjusting the pH value of the slurry to be 5-6, carrying out hydrothermal treatment on the slurry after the pH value is adjusted, cooling to room temperature, carrying out suction filtration to obtain a filter cake, and drying the filter cake to obtain a modified activated carbon carrier;

dissolving sodium chloropalladite in an ethylene glycol aqueous solution with the mass concentration of 10-30%, adding the modified activated carbon carrier in the step two, stirring for 1-2 h at the temperature of 30-40 ℃, adjusting the pH value of a system to 6.5-7.5 by using an alkaline solution, and stabilizing for 0.5-1 h; and dropwise adding formic acid into the stabilized system, stirring for 1-3 h, cooling to room temperature, filtering to obtain a filter cake, washing the filter cake with water until no chloride ion remains, and obtaining the catalyst for synthesizing moxifloxacin.

2. The preparation method of the catalyst for moxifloxacin synthesis according to claim 1, wherein the mass concentration of hydrogen peroxide in the step one is 5% -10%, and the stirring temperature is 15-30 ℃.

3. The method for preparing a catalyst for moxifloxacin synthesis according to claim 1, wherein the particle size of the activated carbon in the first step is 200-400 meshes, and the specific surface area of the activated carbon is 800m²/g～1500m²/g。

4. The method for preparing a moxifloxacin synthesis catalyst according to claim 1, wherein the soluble salt of the auxiliary agent element in the second step is sodium silicate, aluminum nitrate and zirconium nitrate.

5. The method for preparing a moxifloxacin synthesis catalyst according to claim 1, wherein the reagent used for adjusting the pH value in step two is hydrochloric acid or sodium hydroxide aqueous solution.

6. The method for preparing a catalyst for moxifloxacin synthesis according to claim 1, wherein the temperature of the hydrothermal treatment in the second step is 150-200 ℃ and the time is 2-4 h.

7. The method for preparing a catalyst for moxifloxacin synthesis according to claim 1, wherein the alkali solution in step three is sodium carbonate solution, sodium bicarbonate solution or sodium hydroxide solution.

8. The method for preparing a moxifloxacin synthesis catalyst according to claim 1, wherein the volume of formic acid in step three is 3-8 times of the mass of Pd, wherein the unit of mass is g, and the unit of volume is mL.

Technical Field

The invention belongs to the technical field of precious metal catalyst preparation, and particularly relates to a preparation method of a catalyst for synthesizing moxifloxacin.

Background

Moxifloxacin, with the chemical name of 1-cyclopropyl-7- [ (S, S) -2, 8-diazabicyclo [4.3.0] -nonan-8-yl ] -6-fluoro-8-methoxy-1, 4-dihydro-4-oxo-3-quinolinecarboxylic acid, is a fourth generation broad spectrum fluoroquinolone antibacterial drug developed by German Bayer company and marketed in Germany in 1999, and is clinically used for treating chronic obstructive pulmonary disease, acute bacterial nasosinusitis and skin and soft tissue infection, has strong antibacterial activity, wide antibacterial spectrum and is not easy to generate drug resistance, and enters ten-year-old mass-market antibiotic drugs in the world in 2002. In the next half year of 2002, moxifloxacin is on the market in China, and in 2004, the medicine enters the national medical insurance catalogue, so that the market demand for the medicine is increased year by year. Therefore, the moxifloxacin serving as a new generation quinolone antibacterial drug has good economic value and wide market prospect.

In the industrial synthesis route of moxifloxacin, a Pd/C catalyst is used in the synthesis process of a key intermediate of moxifloxacin. The palladium-carbon catalyst is an excellent hydrogenation and hydrogenolysis catalyst, is widely used in the process of medicament synthesis, has the advantages of small dosage, environmental protection and the like, but has high price and greatly limits the production cost of moxifloxacin medicaments, so that the good activity, selectivity and mechanical property of the catalyst are the keys related to the production cost of moxifloxacin. The literature reports that the reaction performance and the applicability of the palladium-carbon catalyst for synthesizing moxifloxacin can be improved by selecting coconut shell carbon with higher mechanical strength, 10% of the palladium-carbon catalyst needs to be supplemented each time in the application process, the yield of a target product of 97% -98% can be realized, and the catalyst can be repeatedly used for 4 times.

Disclosure of Invention

The technical problem to be solved by the invention is to provide a preparation method of a catalyst for synthesizing moxifloxacin aiming at the defects of the prior art. The method uses hydrogen peroxide to treat the activated carbon carrier, not only can increase oxygen-containing groups on the surface of the activated carbon, but also is beneficial to subsequent metal oxide modification and reaming effect, thereby being beneficial to diffusion mass transfer of reactant molecules on the surface of the catalyst; the palladium-carbon is modified by preferentially adsorbing the auxiliary element oxide on the active carbon, and the silicon oxide, the aluminum oxide or the zirconium oxide changes the acidity and alkalinity of the surface of the catalyst, enhances the nitrogen poisoning resistance of the catalyst, has stronger binding capacity between the active component palladium and the oxide, avoids the performance reduction of the catalyst caused by the loss of the active component metal, and further improves the reaction performance and the applicability of the catalyst.

In order to solve the technical problems, the invention adopts the technical scheme that: a preparation method of a catalyst for synthesizing moxifloxacin is characterized in that the catalyst comprises activated carbon, an oxide of an auxiliary element loaded on the activated carbon, and an active component Pd loaded on the activated carbon; the auxiliary element is Si, Al or Zr, and the mass of the auxiliary element is 1-3% of that of the activated carbon; the mass percentage of an active component Pd in the catalyst is 5%;

the preparation method of the catalyst comprises the following steps:

step one, placing activated carbon in a hydrogen peroxide solution, stirring for 2-4 h, filtering, washing trapped matters to be neutral by deionized water, and drying to obtain an activated carbon carrier;

dissolving soluble salt of an auxiliary element in deionized water, adding the activated carbon carrier obtained in the step one into the solution to obtain slurry, adjusting the pH value of the slurry to be 5-6, carrying out hydrothermal treatment on the slurry after the pH value is adjusted, cooling to room temperature, carrying out suction filtration to obtain a filter cake, and drying the filter cake to obtain a modified activated carbon carrier;

dissolving sodium chloropalladite in an ethylene glycol aqueous solution with the mass concentration of 10-30%, adding the modified activated carbon carrier in the step two, stirring for 1-2 h at the temperature of 30-40 ℃, adjusting the pH value of a system to 6.5-7.5 by using an alkaline solution, and stabilizing for 0.5-1 h; and dropwise adding formic acid into the stabilized system, stirring for 1-3 h, cooling to room temperature, filtering to obtain a filter cake, washing the filter cake with water until no chloride ion remains, and obtaining the catalyst for synthesizing moxifloxacin.

The preparation method of the catalyst for synthesizing moxifloxacin is characterized in that the mass concentration of hydrogen peroxide in the step one is 5% -10%, and the stirring temperature is 15-30 ℃.

The preparation method of the catalyst for synthesizing moxifloxacin is characterized in that in the step one, the granularity of the activated carbon is 200-400 meshes, and the specific surface area of the activated carbon is 800m²/g～1500m²/g。

The preparation method of the catalyst for synthesizing moxifloxacin is characterized in that soluble salts of the auxiliary elements in the second step are sodium silicate, aluminum nitrate and zirconium nitrate.

The preparation method of the catalyst for synthesizing moxifloxacin is characterized in that a reagent used for adjusting the pH value in the second step is hydrochloric acid or a sodium hydroxide aqueous solution.

The preparation method of the catalyst for synthesizing moxifloxacin is characterized in that the temperature of the hydrothermal treatment in the step two is 150-200 ℃, and the time is 2-4 hours.

The preparation method of the catalyst for synthesizing moxifloxacin is characterized in that the alkali liquor in the step three is a sodium carbonate solution, a sodium bicarbonate solution or a sodium hydroxide solution.

The preparation method of the catalyst for synthesizing moxifloxacin is characterized in that the volume of formic acid in the step three is 3-8 times of the mass of Pd, wherein the unit of mass is g, and the unit of volume is mL.

Compared with the prior art, the invention has the following advantages:

1. the invention uses hydrogen peroxide to treat the activated carbon carrier, which can increase oxygen-containing groups on the surface of the activated carbon, is beneficial to subsequent metal oxide modification and reaming action, thereby being beneficial to the diffusion and mass transfer of reactant molecules on the surface of the catalyst.

2. According to the invention, the auxiliary element oxide is preferentially adsorbed on the active carbon, and the palladium carbon is modified by the silicon oxide, the aluminum oxide or the zirconium oxide, so that the acidity and alkalinity of the surface of the catalyst are changed, the nitrogen poisoning resistance of the catalyst is enhanced, meanwhile, the active component palladium and the oxide have stronger binding capacity, and the performance reduction of the catalyst caused by the loss of the active component metal is avoided, thereby improving the reaction performance and the applicability of the catalyst.

3. The method adopts the ethylene glycol aqueous solution as the dipping solvent, and the dipping temperature and time are optimized, so that the distribution depth of the active components on the carrier is easier to control, and the protein distribution with antitoxic property is formed, thereby improving the stability of the catalyst.

4. The catalyst prepared by the method can be used for synthesis reaction of moxifloxacin, and has good reaction performance and high stability.

The technical solution of the present invention is further described in detail by the following examples.

Detailed Description