阅读说明：本技术 一种盐酸米诺环素合成用铑炭催化剂的制备方法 (Preparation method of rhodium-carbon catalyst for synthesizing minocycline hydrochloride ) 是由 李岳锋 张之翔 曾永康 万克柔 曾利辉 王昭文 张鹏 陈丹 闫江梅 于 2019-10-24 设计创作，主要内容包括：本发明公开了一种盐酸米诺环素合成用铑炭催化剂的制备方法,该催化剂包括载体以及分散于载体上的铑纳米颗粒,所述载体为在微波条件下经氢氧化钠水溶液处理的粉状活性炭,催化剂中铑的质量百分含量为5％。本发明采用一锅法制备,通过引入螯合剂提高铑炭催化剂活性,通过微波加热适当降低催化剂活性,在保证催化剂活性的同时,提高了催化剂的选择性。制备的催化剂应用于盐酸米诺环素合成中脱羟基步骤,具有高选择性,能够有效降低副反应脱水杂质的生成,提高目标产物盐酸山环素的收率,对于降低盐酸米诺环素的生产成本并提高产品品质有重要意义。(The invention discloses a preparation method of a rhodium-carbon catalyst for synthesizing minocycline hydrochloride, which comprises a carrier and rhodium nanoparticles dispersed on the carrier, wherein the carrier is powdered activated carbon treated by a sodium hydroxide aqueous solution under a microwave condition, and the mass percentage of rhodium in the catalyst is 5%. The invention adopts a one-pot method for preparation, improves the activity of the rhodium-carbon catalyst by introducing a chelating agent, properly reduces the activity of the catalyst by microwave heating, and improves the selectivity of the catalyst while ensuring the activity of the catalyst. The prepared catalyst is applied to the step of dehydroxylation in minocycline hydrochloride synthesis, has high selectivity, can effectively reduce the generation of side reaction dehydration impurities, improves the yield of the target product of the minocycline hydrochloride, and has important significance for reducing the production cost of the minocycline hydrochloride and improving the product quality.)

1. The preparation method of the rhodium-carbon catalyst for synthesizing minocycline hydrochloride is characterized in that the catalyst comprises a carrier and rhodium nanoparticles dispersed on the carrier, wherein the carrier is powdered activated carbon treated by a sodium hydroxide aqueous solution under a microwave condition, and the mass percentage of rhodium in the catalyst is 5%;

the preparation method of the catalyst comprises the following steps:

step one, the granularity is 200-400 meshes, and the specific surface area is 800m²/g～1000m²Refluxing wood charcoal/g with sodium hydroxide aqueous solution for 2-4 h under microwave heating condition, washing with pure water until pH is 7.0-8.0, and drying to obtain pretreated activated carbon;

dissolving rhodium trichloride in pure water at the temperature of 80-100 ℃ to obtain a solution A; dissolving a chelating agent in pure water at the temperature of 80-100 ℃ to obtain a solution B; pouring the solution B into the solution A under the condition of stirring, diluting with pure water at the temperature of 80-100 ℃, and stabilizing for 20-40 min to obtain an active component solution;

pulping the pretreated activated carbon in the step one by using pure water, and stirring to obtain slurry;

step four, dropwise adding the active component solution in the step two into the slurry in the step three, and stabilizing for 2-4 h;

step five, dropwise adding the sodium borohydride aqueous solution into the slurry stabilized in the step four, wherein the dropwise adding time is 0.5-2 h, and the slurry is stabilized for 1-3 h after the dropwise adding is finished, so as to obtain catalyst slurry; under the microwave heating condition, the catalyst slurry is heated to 70-100 ℃ and stabilized for 1-5 h, and finally cooled to normal temperature, filtered, and the intercepted substances are washed until no chloride ion exists, so that the rhodium-carbon catalyst is obtained.

2. The preparation method of the rhodium-carbon catalyst for minocycline hydrochloride synthesis according to claim 1, wherein the mass concentration of the aqueous solution of sodium hydroxide in the first step is 3-10%.

3. The preparation method of the rhodium-carbon catalyst for synthesizing minocycline hydrochloride according to claim 1, wherein the microwave heating temperature in the first step is 80-100 ℃.

4. The method for preparing the rhodium-carbon catalyst for synthesizing minocycline hydrochloride according to claim 1, wherein the chelating agent in the second step is sodium oxalate, o-hydroxybenzoic acid, ascorbic acid or disodium ethylenediamine tetraacetic acid, and the amount of the chelating agent is 3-10 times of that of the rhodium.

5. The preparation method of the rhodium-carbon catalyst for synthesizing minocycline hydrochloride according to claim 4, characterized in that the amount of the chelating agent is 4-6 times of the amount of the rhodium substance.

6. The preparation method of the rhodium-carbon catalyst for synthesizing minocycline hydrochloride according to claim 1, wherein the stirring time in the third step is 1-10 h.

7. The preparation method of the rhodium-carbon catalyst for synthesizing minocycline hydrochloride according to claim 6, characterized in that the stirring time is 2-5 h.

8. The preparation method of the rhodium-carbon catalyst for synthesizing minocycline hydrochloride according to claim 1, wherein the dripping time in the fourth step is 0.5-3 h.

9. The preparation method of the rhodium-carbon catalyst for synthesizing minocycline hydrochloride according to claim 8, characterized in that the dripping time is 1-2 h.

10. The preparation method of the rhodium-carbon catalyst for synthesizing minocycline hydrochloride according to claim 1, characterized in that in the fifth step, under the microwave heating condition, the catalyst slurry is heated to 80-90 ℃ and stabilized for 2-4 h.

Technical Field

The invention belongs to the technical field of precious metal catalyst preparation, and particularly relates to a preparation method of a rhodium-carbon catalyst for minocycline hydrochloride synthesis.

Background

Minocycline Hydrochloride (MINO, Minocycline Hydrochloride), also known as: the hydrochloride of two methylamine tetracycline, medemycin, originally by the United states Lederle company developed on the market of the new generation of four ring antibiotic, chemical name: 4S- (4a,4aa,5aa,12aa) -4, 7-bis (dimethylamino) -1,4,4a,5,5a,6,11,12 a-octahydro-3, 10,12,12 a-tetrahydroxy-1, 11-dioxo-2-naphthacene carboxamide hydrochloride. The antibacterial activity of the medicine on gram-positive bacteria is 2-4 times stronger than that of first generation tetracycline, and the medicine has the advantages of high efficiency, broad spectrum, low effective dose, rapid oral absorption, wide in-vivo distribution, long acting, low drug resistance rate and the like, and is one of the varieties with the best curative effect in tetracycline antibiotics.

Compared with other tetracycline antibiotics, minocycline hydrochloride has many advantages, but the production and application of minocycline hydrochloride are greatly limited by factors such as complex synthesis process, low synthesis and extraction yield, many byproducts and the like. The synthesis route of minocycline hydrochloride comprises three steps in four-step reaction, wherein a noble metal catalyst is used for catalytic hydrogenation. The second step dehydroxylation reaction is the most difficult step in the whole minocycline synthesis process, and the hydroxyl on the C-6 position is easily dehydrated with the hydrogen on the C-5a position under high pressure and acidic conditions to form an intramolecular dehydration product while the hydroxyl on the C-6 position is removed. The side reaction phenomenon is serious, and the yield of the dehydroxylation reaction is greatly influenced. The activity of palladium and platinum in the noble metal catalyst is high, the activity of ruthenium is poor and the use condition is harsh. The rhodium-carbon catalyst used in the reaction has the defects of poor catalyst selectivity, high dehydrated impurities and low yield of a target product, and is a key factor influencing the synthesis cost and the product quality of minocycline hydrochloride.

CN 109847741A relates to a method for catalyzing olefin hydroformylation reaction to generate branched chain aldehyde and olefine aldehyde, a brand new reaction path is realized by applying a prepared monoatomic dispersion type rhodium catalyst, the olefin hydroformylation reaction and aldol condensation reaction are connected in series under the condition of no additional acid and alkali, and branched chain aldehyde and olefine aldehyde products are generated by olefin and synthesis gas in one step. The catalyst shows higher catalytic activity and stability in the reaction. Has the obvious advantages of low economic and environmental cost, easy separation of products, simple post-treatment, and the like. CN 106861684B relates to a titanium oxide supported sub-nanometer rhodium catalyst, which is applied to the oxidation elimination of trace carbon monoxide (CO) in an ultralow temperature environment and the low-temperature catalytic decomposition of a liquid unit Ammonium Dinitramide (ADN) aerospace propellant. CN 107051552B relates to a magnetic carbon nanotube supported rhodium catalyst, wherein a carbon nanotube is magnetized by modifying the carbon nanotube with ferric chloride, and the catalyst obtained by loading rhodium on the magnetic carbon nanotube is applied to nitrile butadiene hydrogenation and has the advantages of good double bond selectivity, good applicability and good magnetism and easiness in recovery. CN 103055854B relates to a rhodium carbon catalyst for olefin hydroformylation, the invention adopts a colloid method to prepare rhodium colloid, then the rhodium colloid is loaded on active carbon, and the rhodium carbon catalyst is obtained by reduction again.

The Wangchun Master thesis "research on minocycline hydrochloride synthesis process" (2017, Zhejiang university) investigated in detail the performance control of different rhodium carbons of catalyst manufacturers at home and abroad, but did not relate to the specific development research on the rhodium carbon process.

In view of the above, no special research on the rhodium-carbon catalyst dedicated for the dehydroxylation step in minocycline hydrochloride synthesis has been found in the prior published patents and documents, and only the use effect is described.

Disclosure of Invention

The invention aims to solve the technical problem of providing a preparation method of a rhodium-carbon catalyst for synthesizing minocycline hydrochloride aiming at the defects of the prior art. The method adopts a one-pot method for preparation, the activity of the rhodium-carbon catalyst is improved by introducing a chelating agent, the activity of the catalyst is properly reduced by microwave heating, the selectivity of the catalyst is improved while the activity of the catalyst is ensured, the prepared catalyst is applied to a dehydroxylation step in minocycline hydrochloride synthesis, has high selectivity, can effectively reduce the generation of side reaction dehydrated impurities, improves the yield of a target product of the minocycline hydrochloride, and has important significance for reducing the production cost of the minocycline hydrochloride and improving the product quality.

In order to solve the technical problems, the invention adopts the technical scheme that: the preparation method of the rhodium-carbon catalyst for synthesizing minocycline hydrochloride is characterized in that the catalyst comprises a carrier and rhodium nanoparticles dispersed on the carrier, wherein the carrier is powdered activated carbon treated by a sodium hydroxide aqueous solution under a microwave condition, and the mass percentage of rhodium in the catalyst is 5%;

the preparation method of the catalyst comprises the following steps:

step one, the granularity is 200-400 meshes, and the specific surface area is 800m²/g～1000m²Refluxing wood charcoal/g with sodium hydroxide aqueous solution for 2-4 h under microwave heating condition, washing with pure water until pH is 7.0-8.0, and drying to obtain pretreated activated carbon;

dissolving rhodium trichloride in pure water at the temperature of 80-100 ℃ to obtain a solution A; dissolving a chelating agent in pure water at the temperature of 80-100 ℃ to obtain a solution B; pouring the solution B into the solution A under the condition of stirring, diluting with pure water at the temperature of 80-100 ℃, and stabilizing for 20-40 min to obtain an active component solution;

pulping the pretreated activated carbon in the step one by using pure water, and stirring to obtain slurry;

step four, dropwise adding the active component solution in the step two into the slurry in the step three, and stabilizing for 2-4 h;

step five, dropwise adding the sodium borohydride aqueous solution into the slurry stabilized in the step four, wherein the dropwise adding time is 0.5-2 h, and the slurry is stabilized for 1-3 h after the dropwise adding is finished, so as to obtain catalyst slurry; under the condition of microwave heating, the catalyst slurry is heated to 70-100 ℃ and stabilized for 1-5 h, and finally cooled to normal temperature, filtered, and the intercepted matters are washed until no chloride ion exists, so that the rhodium-carbon catalyst is obtained.

The preparation method of the rhodium-carbon catalyst for synthesizing minocycline hydrochloride is characterized in that in the first step, the mass concentration of the sodium hydroxide aqueous solution is 3-10%.

The preparation method of the rhodium-carbon catalyst for synthesizing minocycline hydrochloride is characterized in that the microwave heating temperature in the first step is 80-100 ℃.

The preparation method of the rhodium-carbon catalyst for synthesizing minocycline hydrochloride is characterized in that in the second step, the chelating agent is sodium oxalate, o-hydroxybenzoic acid, ascorbic acid or disodium ethylene diamine tetraacetate, and the amount of the chelating agent is 3-10 times of that of the rhodium substance.

The preparation method of the rhodium-carbon catalyst for synthesizing minocycline hydrochloride is characterized in that the amount of the chelating agent is 4-6 times of that of the rhodium substance.

The preparation method of the rhodium-carbon catalyst for synthesizing minocycline hydrochloride is characterized in that the stirring time in the step three is 1-10 hours.

The preparation method of the rhodium-carbon catalyst for synthesizing minocycline hydrochloride is characterized in that the stirring time is 2-5 hours.

The preparation method of the rhodium-carbon catalyst for synthesizing minocycline hydrochloride is characterized in that the dripping time in the fourth step is 0.5-3 h.

The preparation method of the rhodium-carbon catalyst for synthesizing minocycline hydrochloride is characterized in that the dripping time is 1-2 h.

The preparation method of the rhodium-carbon catalyst for synthesizing minocycline hydrochloride is characterized in that in the fifth step, under the microwave heating condition, the catalyst slurry is heated to 80-90 ℃ and is stabilized for 2-4 hours.

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

1. the invention adopts a one-pot method for preparation, improves the activity of the rhodium-carbon catalyst by introducing a chelating agent, properly reduces the activity of the catalyst by microwave heating, and improves the selectivity of the catalyst while ensuring the activity of the catalyst.

2. The chelating agent is introduced during the preparation of the active component solution to form the macromolecular chelate of rhodium metal, so that the rhodium is uniformly dispersed on the outer surface of the active carbon, and the utilization rate of the metal rhodium is improved in the reaction, thereby improving the activity of the catalyst.

3. The invention utilizes the uniformity of microwave heating to treat the reduced rhodium carbon catalyst at a certain temperature, so that rhodium nano particles grow up properly, and the purposes of properly reducing the activity of the catalyst and improving the selectivity of the catalyst are achieved.

4. The preparation method is simple and easy to control, and improves the selectivity of the catalyst while ensuring the activity of the catalyst. The catalyst prepared by the invention is applied to the step of dehydroxylation in minocycline hydrochloride synthesis, has high selectivity, can effectively reduce the generation of side reaction dehydration impurities, improves the yield of the target product of the minocycline hydrochloride, and has important significance for reducing the production cost of the minocycline hydrochloride and improving the product quality.

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

Detailed Description