Catalyst for doxycycline synthesis and preparation method and application thereof

Abstract

The invention discloses a catalyst for doxycycline synthesis. The catalyst comprises an activated carbon carrier and a metal component loaded on the activated carbon carrier, the metal components comprise palladium, rhodium and auxiliary metal, the mass percentage content of the palladium in the catalyst is 1%-5%, the mass percentage content of the rhodium in the catalyst is 0.1%-0.3%, the mass percentage content of the auxiliary metal in the catalyst is 0.2%-0.5%, and the auxiliary metal is one or two of zinc and barium. In addition, the invention also discloses a preparation method and application of the catalyst. When the catalyst is used in doxycycline synthesis, the yield of doxycycline sulfo salt in the hydrogenation step exceeds 70%, and the catalyst has the advantages of being small in precious metal consumption, low in catalyst feeding amount, fast in reaction, high in product purity and low in cost.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and specifically relates to a catalyst for synthesizing doxycycline and a preparation method and application thereof. Background Art

[0002] Doxycycline is a tetracycline antibiotic, mainly used to treat respiratory, urinary and biliary tract infections caused by sensitive bacteria. It has the characteristics of long-acting, high efficiency, rapid effect, low toxicity, low dosage and few side effects. It has obvious antibacterial advantages over other tetracycline antibiotics and has a long life cycle.

[0003] In the domestic market, doxycycline (i.e., doxycycline) is mostly produced using dehydrated oxytetracycline as the raw material. 11α-chloro-6-methylidene oxytetracycline p-toluenesulfonate is catalytically hydrogenated to remove 11α-chlorine and reduce 6-methylidene to methyl under the action of palladium-carbon catalyst, and then salified with 5-sulfosalicylic acid to obtain 6-deoxyoxytetracycline sulfosalicylate, which is then aminated and hydrochlorinated to obtain doxycycline hydrochloride. The reaction process is as follows:

[0004]

[0005] The intermediate 11α-chloro-6-methylidene oxytetracycline toluenesulfonate is hydrogenated under the catalytic action of the catalyst. Since there is a chiral carbon atom when the 6-methylidene is reduced to a methyl group, a β-configuration by-product will also be produced. Therefore, in the synthesis process of doxycycline, selective hydrogenation has very high requirements on the activity and selectivity of the catalyst. The mass yield of the sulfonate salt in the hydrogenation step, that is, the selectivity of the catalyst directly affects the yield of the target product. Dehydrated oxytetracycline is selectively hydrogenated to obtain doxycycline sulfonate with a theoretical mass yield of 102%. In current industrial production, the yield of the above sulfonate salt is 64-66%, and the β isomer is ~8%. The above reaction has extremely high requirements on the selectivity of the catalyst. The catalyst, as the core material of the reaction, determines the selectivity and yield of the target product. Chinese patent CN110918121B discloses a hydrogenation catalyst for doxycycline production, a preparation method and application thereof, and proposes that the catalyst is composed of

[0006] PdCl2 and polystyrene loading material are composed, and the polystyrene loading material is terminally modified with polystyrene as a carrier, with straight-chain alkane triazole as a linking group, and with a nitrogen-containing ligand as a modifying group. Chinese patent CN102086165B discloses an application of a Pd catalyst in the production of doxycycline hydrogenation process, by selecting polyvinyl chloride polyethylene polyamine loaded palladium complex (pvc-pp-Pd) as a catalyst for hydrogenation. These two catalyst carriers are special and have high production costs. Chinese patent CN115532254B discloses a preparation method of a palladium-carbon catalyst for doxycycline production, a carbon carrier obtained by ethanol soaking, carbonization, activation, hot water beating and filtering and leaching, and then an eggshell-type palladium-carbon catalyst is obtained by loading palladium by impregnation, and the catalyst needs to synthesize a well-developed shell channel, and the inner core channel is small and less carbon carrier, and the stable synthesis of the carbon carrier is greatly affected by wood raw materials. Therefore, it is urgent to develop a catalyst with high activity and selectivity, low cost, and easy production. Summary of the invention

[0007] The technical problem to be solved by the present invention is to provide a catalyst for doxycycline synthesis in view of the above-mentioned deficiencies of the prior art. In the synthesis of doxycycline, the catalyst has a yield of more than 70% of doxycycline sulfonate in the hydrogenation step, and has the characteristics of less precious metal usage, low catalyst feed amount, fast reaction, high product purity and low cost.

[0008] In order to solve the above technical problems, the technical solution adopted by the present invention is: a catalyst for synthesizing doxycycline, characterized in that it includes an activated carbon carrier and a metal component loaded on the activated carbon carrier; the metal components are palladium, rhodium and a promoter metal, the mass percentage of palladium in the catalyst is 1% to 5%, the mass percentage of rhodium is 0.1% to 0.3%, the mass percentage of the promoter metal is 0.2% to 0.5%, and the promoter metal is one or both of zinc and barium.

[0009] Furthermore, the present invention provides a method for preparing the above catalyst, characterized in that it comprises the following steps:

[0010] Step 1, placing activated carbon in a pretreatment liquid to obtain an activated carbon slurry; placing a soluble salt solution of a metal promoter in the activated carbon slurry, stirring and mixing for 2h to 6h at room temperature, heating to boiling, cooling, filtering, and drying to obtain an activated carbon carrier loaded with a metal promoter; the pretreatment liquid is a mixed solution of p-toluenesulfonic acid and sodium pyrophosphate;

[0011] Step 2: placing a complexing agent in a palladium salt and rhodium salt solution, stirring for 1 h to 3 h at a temperature of 40° C. to 60° C., and cooling to obtain a mixed solution containing metal components; the mass of the complexing agent is 1 to 5 times the mass of palladium, and the complexing agent is malonic acid or succinic acid;

[0012] Step 3: Mix the activated carbon carrier loaded with the auxiliary metal in step 1 with the mixed solution containing the metal component in step 2, and stir at a temperature of 30° C. to 60° C. for 8 h to 24 h to obtain a catalyst precursor slurry;

[0013] Step 4: Adjust the pH of the catalyst precursor slurry in step 3 to alkaline with alkali solution, add formaldehyde solution for reduction, filter to obtain a retentate, wash the retentate with deionized water until there is no chloride ion, and obtain a catalyst for doxycycline synthesis.

[0014] The above method is characterized in that the activated carbon in step 1 is powdered activated carbon, and the specific surface area of ​​the activated carbon is 1000m 2 / g~1800m 2 / g; the average particle size of the activated carbon is 15μm to 35μm.

[0015] The above method is characterized in that the mass of the pretreatment liquid in step one is 8 to 15 times the mass of the activated carbon; the mass percentage of p-toluenesulfonic acid in the pretreatment liquid is 0.02% to 0.08%, and the mass percentage of sodium pyrophosphate is 0.1% to 0.8%.

[0016] The above method is characterized in that the mass percentage of the auxiliary metal in the soluble salt solution of the auxiliary metal in step 1 is 5% to 10%.

[0017] The above method is characterized in that the palladium salt and rhodium salt solution in step 2 is an aqueous solution containing palladium salt and rhodium salt, the palladium salt is chloropalladic acid or sodium chloropalladate, and the rhodium salt is rhodium trichloride.

[0018] The above method is characterized in that the alkali solution in step 4 is a sodium carbonate solution with a mass fraction of 10% to 20% or a sodium hydroxide solution with a mass fraction of 10% to 20%, and the pH is adjusted to 9 to 12.

[0019] The above method is characterized in that the reduction temperature in step 4 is 70°C to 90°C and the time is 2h to 4h.

[0020] The above method is characterized in that the mass of the formaldehyde solution in step 4 is 10 to 20 times the mass of palladium.

[0021] Furthermore, the present invention provides an application of the above-mentioned catalyst for synthesizing doxycycline in catalyzing the hydrogenation of 11α-chloro-6-methyleneoxytetracycline p-toluenesulfonate to synthesize doxycycline.

[0022] Compared with the prior art, the present invention has the following advantages:

[0023] 1. The catalyst for doxycycline synthesis of the present invention comprises an activated carbon carrier and a metal component supported on the activated carbon carrier, wherein the metal component is palladium, rhodium and a promoter metal. In the synthesis of doxycycline, the catalyst has a doxycycline sulfonate yield of more than 70% in the hydrogenation step, and has the characteristics of low precious metal usage, low catalyst feed amount, fast reaction, high product purity and low cost.

[0024] 2. In the catalyst for synthesizing doxycycline of the present invention, activated carbon treated with a pretreatment solution is used as a carrier and then loaded with a metal. The active functional groups on the surface of the carrier are doped with heteroatoms, and a complexing agent is used to induce the activated carbon to serve as a selective adsorption center on the surface of the activated carbon to achieve effective adsorption and dispersion of the metal components, thereby making the catalyst have higher catalytic activity and anti-toxic stability.

[0025] 3. The catalyst preparation method of the present invention comprises the steps of treating activated carbon with a pretreatment solution, loading an auxiliary metal as a carrier, and then loading palladium and rhodium to prepare a catalyst, which can enhance the interaction between the metal and the carrier, and the competitive adsorption and electron transfer between the metals, thereby improving the selectivity of the catalyst.

[0026] 4. The catalyst preparation method of the present invention can obtain a catalyst with a certain dispersion depth of active metals, and realize the control of the valence distribution of the active metals, thereby realizing a highly efficient catalyst for the synthesis of doxycycline.

[0027] 5. The catalyst metal dosage for synthesizing doxycycline of the present invention is small, the process is simple and easy to operate, and the cost is low.

[0028] The technical solution of the present invention is further described in detail below in conjunction with embodiments. DETAILED DESCRIPTION

[0029] The present invention is further described below in conjunction with specific embodiments, so as to more clearly explain the advantages of the present invention. The embodiments described are only exemplary and do not constitute any limitation to the scope of the present invention.

[0030] Example 1

[0031] The catalyst for synthesizing doxycycline in this embodiment includes an activated carbon carrier and a metal component supported on the activated carbon carrier. The activated carbon is powdered activated carbon, and the specific surface area of ​​the activated carbon is 1000 m 2 / g; the average particle size of the activated carbon is 15μm; the metal components are palladium, rhodium and auxiliary metal zinc, the mass percentage of palladium in the catalyst is 5%, the mass percentage of rhodium is 0.3%, and the mass percentage of auxiliary metal zinc is 0.5%.

[0032] The preparation method of the catalyst comprises the following steps:

[0033] Step 1, placing 9.42g of activated carbon in 76g of pretreatment liquid to obtain activated carbon slurry; placing a zinc nitrate solution containing 0.05g of zinc in the activated carbon slurry, stirring and mixing at room temperature for 6h, heating to boiling, cooling, filtering, and drying to obtain an activated carbon carrier loaded with metal; the pretreatment liquid is a mixed solution of p-toluenesulfonic acid and sodium pyrophosphate, wherein the mass percentage of p-toluenesulfonic acid is 0.08%, and the mass percentage of sodium pyrophosphate is 0.8%; the mass percentage of zinc in the zinc nitrate solution is 5%;

[0034] Step 2: dissolving chloropalladic acid containing 0.5 g of palladium and rhodium trichloride containing 0.03 g of rhodium in deionized water, adding 0.5 g of malonic acid, stirring at 60° C. for 1 h, and cooling to obtain a mixed solution containing metal components;

[0035] Step 3: Mix the activated carbon carrier loaded with the auxiliary metal in step 1 with the mixed solution containing the metal component in step 2, and stir at 30° C. for 24 hours to obtain a catalyst precursor slurry;

[0036] Step 4: Adjust the pH value of the catalyst precursor slurry in step 3 to 12 with a 10% sodium hydroxide solution by mass, add 5g of formaldehyde solution, stir at 90°C for 4h for reduction, filter to obtain a retentate, wash the retentate with deionized water until there is no chloride ion, and obtain a catalyst for the synthesis of doxycycline.

[0037] Example 2

[0038] The catalyst for synthesizing doxycycline in this embodiment includes an activated carbon carrier and a metal component supported on the activated carbon carrier. The activated carbon is powdered activated carbon, and the specific surface area of ​​the activated carbon is 1400 m 2 / g; the average particle size of the activated carbon is 20μm; the metal components are palladium, rhodium and auxiliary metal barium, the mass percentage of palladium in the catalyst is 3%, the mass percentage of rhodium is 0.2%, and the mass percentage of auxiliary metal barium is 0.3%.

[0039] The preparation method of the catalyst comprises the following steps:

[0040] Step 1, placing 9.65g of activated carbon in 110g of pretreatment liquid to obtain activated carbon slurry; placing a barium nitrate solution containing 0.03g of barium in the activated carbon slurry, stirring and mixing at room temperature for 4h, heating to boiling, cooling, filtering, and drying to obtain an activated carbon carrier loaded with metal; the pretreatment liquid is a mixed solution of p-toluenesulfonic acid and sodium pyrophosphate, the mass percentage of p-toluenesulfonic acid is 0.05%, and the mass percentage of sodium pyrophosphate is 0.45%; the mass percentage of barium in the barium nitrate solution is 7.5%;

[0041] Step 2: dissolving chloropalladic acid containing 0.3 g of palladium and rhodium trichloride containing 0.02 g of rhodium in deionized water, adding 1.5 g of succinic acid, stirring at 50° C. for 2 h, and cooling to obtain a mixed solution containing metal components;

[0042] Step 3: Mix the activated carbon carrier loaded with the auxiliary metal in step 1 with the mixed solution containing the metal component in step 2, and stir at 40° C. for 16 hours to obtain a catalyst precursor slurry;

[0043] Step 4: Adjust the pH value of the catalyst precursor slurry in step 3 to 10 with a 15% sodium hydroxide solution by mass, add 4.5g formaldehyde solution, stir at 80°C for 3h for reduction, filter to obtain a retentate, wash the retentate with deionized water until there is no chloride ion, and obtain a catalyst for the synthesis of doxycycline.

[0044] Example 3

[0045] The catalyst for synthesizing doxycycline in this embodiment includes an activated carbon carrier and a metal component supported on the activated carbon carrier. The activated carbon is powdered activated carbon, and the specific surface area of ​​the activated carbon is 1800 m 2 / g; the average particle size of the activated carbon is 35μm; the metal components are palladium, rhodium, auxiliary metals zinc and barium, the mass percentage of palladium in the catalyst is 1%, the mass percentage of rhodium is 0.1%, the mass percentage of auxiliary metal zinc is 0.1%, and the mass percentage of auxiliary metal barium is 0.1%.

[0046] The preparation method of the catalyst comprises the following steps:

[0047] Step 1, placing 9.87g of activated carbon in 148g of pretreatment liquid to obtain activated carbon slurry; placing a mixed solution of barium nitrate and zinc nitrate containing 0.01g of barium and 0.01g of zinc in the activated carbon slurry, stirring and mixing at room temperature for 2h, heating to boiling, cooling, filtering, and drying to obtain an activated carbon carrier loaded with metal promoters; the pretreatment liquid is a mixed solution of p-toluenesulfonic acid and sodium pyrophosphate, the mass percentage of p-toluenesulfonic acid is 0.02%, and the mass percentage of sodium pyrophosphate is 0.1%; the mass percentage of barium and zinc in the mixed solution of barium nitrate and zinc nitrate is 10%;

[0048] Step 2: dissolving chloropalladic acid containing 0.1 g of palladium and rhodium trichloride containing 0.01 g of rhodium in deionized water, adding 0.3 g of malonic acid, stirring at 60° C. for 1 h, and cooling to obtain a mixed solution containing metal components;

[0049] Step 3: Mix the activated carbon carrier loaded with the auxiliary metal in step 1 with the mixed solution containing the metal component in step 2, and stir at 60° C. for 8 hours to obtain a catalyst precursor slurry;

[0050] Step 4: Adjust the pH value of the catalyst precursor slurry in step 3 to 9 with a 20% sodium carbonate solution by mass, add 2.0 g of formaldehyde solution, stir at 70° C. for 4 h for reduction, filter, and obtain a retentate. Wash the retentate with deionized water until there is no chloride ion, and obtain a catalyst for doxycycline synthesis.

[0051] Example 4

[0052] The catalyst for synthesizing doxycycline in this embodiment includes an activated carbon carrier and a metal component supported on the activated carbon carrier. The activated carbon is powdered activated carbon, and the specific surface area of ​​the activated carbon is 1600 m 2 / g; the average particle size of the activated carbon is 25μm; the metal components are palladium, rhodium and auxiliary metal zinc, the mass percentage of palladium in the catalyst is 1.5%, the mass percentage of rhodium is 0.15%, and the mass percentage of auxiliary metal zinc is 0.3%.

[0053] The preparation method of the catalyst comprises the following steps:

[0054] Step 1, placing 9.805g of activated carbon in 100g of pretreatment liquid to obtain activated carbon slurry; placing a zinc nitrate solution containing 0.03g of zinc in the activated carbon slurry, stirring and mixing at room temperature for 3h, heating to boiling, cooling, filtering, and drying to obtain an activated carbon carrier loaded with metal promoters, wherein the pretreatment liquid is a mixed solution of p-toluenesulfonic acid and sodium pyrophosphate, the mass percentage of p-toluenesulfonic acid is 0.03%, and the mass percentage of sodium pyrophosphate is 0.3%; the mass percentage of zinc in the zinc nitrate solution is 8%;

[0055] Step 2: dissolving chloropalladic acid containing 0.15 g of palladium and rhodium trichloride containing 0.015 g of rhodium in deionized water, adding 0.75 g of succinic acid, stirring at 50° C. for 2 h, and cooling to obtain a mixed solution containing metal components;

[0056] Step 3: Mix the activated carbon carrier loaded with the auxiliary metal in step 1 with the mixed solution containing the metal component in step 2, and stir at 40° C. for 12 hours to obtain a catalyst precursor slurry;

[0057] Step 4: Adjust the pH value of the catalyst precursor slurry in step 3 to 11 with a 15% sodium hydroxide solution by mass, add 2.25g formaldehyde solution, stir at 80°C for 3h for reduction, filter to obtain a retentate, wash the retentate with deionized water until there is no chloride ion, and obtain a catalyst for doxycycline synthesis.

[0058] Example 5

[0059] The catalyst for synthesizing doxycycline in this embodiment includes an activated carbon carrier and a metal component supported on the activated carbon carrier; the activated carbon is powdered activated carbon, and the specific surface area of ​​the activated carbon is 1500 m 2 / g; the average particle size of the activated carbon is 18μm; the metal components are palladium, rhodium and auxiliary metal barium, the mass percentage of palladium in the catalyst is 2%, the mass percentage of rhodium is 0.3%, and the mass percentage of auxiliary metal barium is 0.4%.

[0060] The preparation method of the catalyst comprises the following steps:

[0061] Step 1, placing 9.73g of activated carbon in 140g of pretreatment liquid to obtain activated carbon slurry; placing a barium nitrate solution containing 0.04g of barium in the activated carbon slurry, stirring and mixing at room temperature for 3h, heating to boiling, cooling, filtering, and drying to obtain an activated carbon carrier loaded with metal; the pretreatment liquid is a mixed solution of p-toluenesulfonic acid and sodium pyrophosphate, wherein the mass percentage of p-toluenesulfonic acid is 0.05%, and the mass percentage of sodium pyrophosphate is 0.4%; the mass percentage of barium in the barium nitrate solution is 8%;

[0062] Step 2: dissolving sodium chloropalladate containing 0.2 g of palladium and rhodium trichloride containing 0.03 g of rhodium in deionized water, adding 0.6 g of malonic acid, stirring at 40° C. for 3 h, and cooling to obtain a mixed solution containing metal components;

[0063] Step 3: Mix the activated carbon carrier loaded with the auxiliary metal in step 1 with the mixed solution containing the metal component in step 2, and stir at 60° C. for 10 hours to obtain a catalyst precursor slurry;

[0064] Step 4: Adjust the pH value of the catalyst precursor slurry in step 3 to 9.5 with a sodium carbonate solution having a mass fraction of 15%, add 3 g of formaldehyde solution, stir for 2 h at 90° C. for reduction, filter, and obtain a retentate. Wash the retentate with deionized water until there is no chloride ion, and obtain a catalyst for the synthesis of doxycycline.

[0065] Comparative Example 1

[0066] This comparative example investigates the effect of the carrier pretreatment method on the catalyst performance.

[0067] This comparative example is the same as Example 4, except that in step 1, 9.805 g of activated carbon is placed in 100 g of pure water to obtain activated carbon slurry.

[0068] Comparative Example 2

[0069] This comparative example investigates the effect of the carrier pretreatment method on the catalyst performance.

[0070] This comparative example is the same as Example 4, except that: in step 1, 9.805 g of activated carbon is placed in 100 g of pretreatment liquid to obtain activated carbon slurry; the pretreatment liquid is a p-toluenesulfonic acid solution, and the mass percentage of p-toluenesulfonic acid is 0.03%.

[0071] Comparative Example 3

[0072] This comparative example investigates the effect of the carrier pretreatment method on the catalyst performance.

[0073] This comparative example is the same as Example 4, except that: in step 1, 9.805 g of activated carbon is placed in 100 g of pretreatment liquid to obtain activated carbon slurry; the pretreatment liquid is a solution of sodium pyrophosphate, and the mass percentage of sodium pyrophosphate is 0.3%.

[0074] Comparative Example 4

[0075] This comparative example investigates the effect of promoter metals on catalyst performance.

[0076] This comparative example is the same as Example 4, except that in step 1, the activated carbon slurry is heated to boiling, cooled, filtered, and dried to obtain an activated carbon carrier.

[0077] Comparative Example 5

[0078] This comparative example investigates the effect of the complexing agent on the catalyst performance.

[0079] This comparative example is the same as Example 4, except that 0.75 g of succinic acid is not added in step 2.

[0080] Comparative Example 6

[0081] This comparative example investigates the effect of metallic rhodium on the performance of the catalyst.

[0082] This comparative example is the same as Example 4, except that: in step 1, 9.82 g of activated carbon is placed in 100 g of pretreatment liquid to obtain activated carbon slurry; the pretreatment liquid is a mixed solution of p-toluenesulfonic acid and sodium pyrophosphate, the mass percentage of p-toluenesulfonic acid is 0.03%, and the mass percentage of sodium pyrophosphate is 0.3%; in step 2, chloropalladic acid containing 0.15 g of palladium is dissolved in deionized water, 0.75 g of succinic acid is added, and the mixture is stirred at 50° C. for 2 h, cooled, and a mixed solution containing metal components is obtained.

[0083] Performance Evaluation

[0084] The catalysts of Examples 1 to 5 of the present invention and Comparative Examples 1 to 6 were used to synthesize doxycycline, and the catalyst performance was evaluated. The specific method was as follows: in a stainless steel autoclave, 60 mL of ethanol, 60 mL of pure water, 0.02 g of methylthiouracil, 0.2 mL of quinoline, 0.1 mL of pyridine, 20 g of 11α-chloro-6-methoxyoxytetracycline p-toluenesulfonate and 1.2 g of the catalyst described in Example 4 (dry basis, other catalysts are converted according to the metal palladium content) were added, the autoclave was sealed, the air in the reactor was replaced with nitrogen three times, and then replaced with hydrogen three times, the temperature was raised to 50°C, hydrogen was continuously introduced until the hydrogen pressure was 0.6 MPa, the reaction was carried out for 4 hours, the reaction was stopped after the reaction was completed, the catalyst was filtered to remove, the sulfonate was precipitated, the mass yield was calculated after constant weight, and then a sample was taken for analysis by liquid chromatography. The results are shown in Table 1.

[0085] Table 1 Performance evaluation results

[0086] project Mass yield (%) β-isomer (%) Metacycline (%) Example 1 70.24 6.81 0.13 Example 2 71.53 6.88 0.10 Example 3 72.86 6.79 0.14 Example 4 73.38 6.63 0.11 Example 5 73.12 6.75 0.13 Comparative Example 1 58.21 8.34 0.43 Comparative Example 2 64.21 7.52 0.39 Comparative Example 3 60.32 7.84 0.41 Comparative Example 4 65.26 7.63 0.28 Comparative Example 5 66.58 7.14 0.32 Comparative Example 6 68.24 7.15 0.22

[0087] It can be clearly seen from Table 1 that the catalyst of the present invention has high activity, the yield of doxycycline sulfonate can reach up to 73.38%, and the β isomer is 6.63%, which is significantly higher than 58.21% to 68.24% of Comparative Examples 1 to 6, and the impurities are lower than 7.14% to 8.34% of Comparative Examples 1 to 6. It shows that the catalyst of the present invention has high reactivity and selectivity in catalyzing the synthesis of doxycycline. The present invention uses Pd-Rh loaded on a pretreated activated carbon carrier added with auxiliary metals Zn and Ba as a catalyst, and has significantly improved reactivity and selectivity in the catalytic synthesis of doxycycline as a reaction catalyst. The activated carbon is treated with a mixed solution of p-toluenesulfonic acid and sodium pyrophosphate and auxiliary metals Zn and Ba are added as carriers, Pd-Rh is adsorbed with a complexing agent, and formaldehyde is reduced, giving the catalyst significantly improved reaction performance.

[0088] The above is only a preferred embodiment of the present invention and does not limit the present invention in any way. Any simple modification, change and equivalent structural change made to the above embodiment according to the technical essence of the invention still falls within the protection scope of the technical solution of the present invention.

Claims

1. A catalyst for the synthesis of doxycycline, characterized in that: The catalyst comprises an activated carbon carrier and a metal component loaded on the activated carbon carrier; the metal component comprises palladium, rhodium and an auxiliary metal, the mass percentage of palladium in the catalyst is 1% to 5%, the mass percentage of rhodium is 0.1% to 0.3%, the mass percentage of the auxiliary metal is 0.2% to 0.5%, and the auxiliary metal is one or two of zinc and barium.

2. A method for preparing the catalyst as claimed in claim 1, characterized in that: The following steps are involved: Step 1, placing activated carbon in a pretreatment liquid to obtain an activated carbon slurry; placing a soluble salt solution of a metal promoter in the activated carbon slurry, stirring and mixing for 2h to 6h at room temperature, heating to boiling, cooling, filtering, and drying to obtain an activated carbon carrier loaded with a metal promoter; the pretreatment liquid is a mixed solution of p-toluenesulfonic acid and sodium pyrophosphate; Step 2: placing a complexing agent in a palladium salt and rhodium salt solution, stirring for 1 h to 3 h at a temperature of 40° C. to 60° C., and cooling to obtain a mixed solution containing metal components; the mass of the complexing agent is 1 to 5 times the mass of palladium, and the complexing agent is malonic acid or succinic acid; Step 3: Mix the activated carbon carrier loaded with the auxiliary metal in step 1 with the mixed solution containing the metal component in step 2, and stir at a temperature of 30° C. to 60° C. for 8 h to 24 h to obtain a catalyst precursor slurry; Step 4: Adjust the pH of the catalyst precursor slurry in step 3 to alkaline with alkali solution, add formaldehyde solution for reduction, filter to obtain a retentate, wash the retentate with deionized water until there is no chloride ion, and obtain a catalyst for doxycycline synthesis.

3. The method according to claim 2, characterized in that The activated carbon in step 1 is powdered activated carbon, and the specific surface area of ​​the activated carbon is 1000m 2 / g~1800m 2 / g; the average particle size of the activated carbon is 15μm to 35μm.

4. The method according to claim 2, characterized in that: The mass of the pretreatment liquid in step 1 is 8 to 15 times the mass of the activated carbon; the mass percentage of p-toluenesulfonic acid in the pretreatment liquid is 0.02% to 0.08%, and the mass percentage of sodium pyrophosphate is 0.1% to 0.8%.

5. The method according to claim 2, characterized in that: The mass percentage of the auxiliary metal in the soluble salt solution of the auxiliary metal in step 1 is 5% to 10%.

6. The method according to claim 2, characterized in that The palladium salt and rhodium salt solution in step 2 is an aqueous solution containing palladium salt and rhodium salt, the palladium salt is chloropalladic acid or sodium chloropalladate, and the rhodium salt is rhodium trichloride.

7. The method according to claim 2, characterized in that The alkali solution in step 4 is a sodium carbonate solution with a mass fraction of 10% to 20% or a sodium hydroxide solution with a mass fraction of 10% to 20%, and the pH is adjusted to 9 to 12.

8. The method according to claim 2, characterized in that: The reduction temperature in step 4 is 70° C. to 90° C., and the time is 2 h to 4 h.

9. The method according to claim 2, characterized in that: The mass of the formaldehyde solution in step 4 is 10 to 20 times the mass of palladium.

10. Use of the catalyst for synthesizing doxycycline as claimed in claim 1 in catalyzing the hydrogenation of 11α-chloro-6-methyleneoxytetracycline p-toluenesulfonate to synthesize doxycycline.

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