Preparation and application of carbobenzoxy deprotection catalyst

Abstract

The invention relates to preparation and application of a carbobenzoxy deprotection catalyst. Ultra-small nano anatase titanium oxide with a high surface area and multiple oxygen vacancies is adopted as a carrier, precious metal palladium is adopted as an active component, the palladium loading capacity is 0.1%-5% (mass percent), the high-dispersion palladium catalyst is prepared through a deposition-precipitation method, and the catalyst has the advantages of being high in conversion rate, selectivity and yield in a carbobenzoxy deprotection reaction, low in cost and the like. And the cycling stability is good. The catalyst innovatively adopts ultra-small nano anatase titanium oxide with high surface area and multiple oxygen vacancies as a carrier, precious metal palladium can be highly dispersed, the catalyst is resistant to high-temperature oxidation, the preparation process is simple, raw materials are easy to obtain, and the catalyst has good application prospects.

Description

Technical Field

[0001] The present invention belongs to the preparation of noble metal catalysts and their application in the field of benzyloxycarbonyl deprotection, and specifically relates to a noble metal palladium catalyst for the deprotection reaction of N-benzyloxycarbonylaniline. Palladium is highly dispersed on the ultra-small nano anatase titanium oxide support with a high surface area and multiple oxygen vacancies, and serves as the catalytic active center, showing high catalytic activity for the benzyloxycarbonyl deprotection reaction. Background Art

[0002] Organic macromolecules have a variety of functional groups. Usually, during the experiment, reactions need to occur at specific functional groups or positions to obtain the target product. In order not to react with other functional groups and generate more by-products, it is necessary to protect the positions and functional groups that do not participate in the reaction in advance. Such introduced groups are protection groups. The benzyloxycarbonyl (Cbz) group is usually used to protect amino and hydroxyl groups during organic synthesis and is very stable under relatively mild acidic and basic conditions. The catalytic hydrogenation method is a commonly used method for the deprotection of benzyloxycarbonyl.

[0003] In 2015, Prakash R et al. (Tetrahedron Letters, 2015, 56, 2067 - 2070) used Pd / C (10 wt%) as a catalyst, with sodium borohydride and methanol as the hydrogen transfer agent and solvent, to conduct the de-Cbz protection experiment on benzyloxycarbonylaniline. Finally, a yield of 98% could be obtained. The hydrogen transfer agent could obtain a faster reaction rate, but the hydrogen transfer reagent was expensive and not green and environmentally friendly, and was not suitable for industrial production. Moreover, the loading and usage amount of the Pd / C catalyst were both as high as 10%, and no recycling test was carried out, resulting in a high cost. In 2020, Tsuyoshi Yamada et al. (ChemCatChem, 2020, 12, 4052.) prepared 2 wt% Pd / CLM and 2 wt% Pd / CLP catalysts and applied them to the selective hydrogenation of organic compounds and the deprotection of catalytic aromatic N-Cbz. Reacting at 25 °C for 24 h in the presence of methanol and hydrogen, 86% - 92% of the deprotected product was obtained. This process had a long reaction time, and the usage amount (1%) and loading amount (2 wt%) of palladium were high, resulting in a high cost. In 2020, Yuta et al. (ACSOmega, 2020, 5, 2699−2709) used Pd / C and Nb2O5 / C in combination for the debenzylcarbonyl protection reaction. When exploring the substrate, quantitative deprotection of N-benzyloxycarbonylaniline was carried out. Adding 10 wt% Pd / C (1%) and 10 wt% Nb2O5 / C (1%) in a hydrogen environment (balloon) and reacting for 30 min could achieve complete conversion. However, when the researchers carried out a recycling test on this catalyst, they found that the selectivity and conversion rate of the catalyst decreased after 3 cycles, and the recycling stability was not good.

[0004] In the current research, the catalyst for catalytic hydrogenation of benzyloxycarbonyl deprotection is mainly palladium-carbon catalyst. Due to the weak interaction between the carbon carrier and palladium in the palladium-carbon catalyst, palladium cannot be well dispersed, the overall particle size is relatively large, and the utilization rate of palladium atoms is low. This leads to the need to use a high loading amount of palladium catalyst (5wt%-10wt%) during use. The extensive use of palladium-carbon will increase the cost, making it difficult to apply palladium-carbon in industrial production. Therefore, studying a suitable carrier to keep palladium in a highly dispersed state to obtain a higher utilization rate of palladium atoms, preparing a catalyst with a low noble metal loading amount and usage amount, and being able to be recycled multiple times, with high conversion rate and yield, is the key to reducing the cost of N-benzyloxycarbonylaniline de-Cbz protection.

[0005] The present invention innovatively uses ultra-small nanosized anatase titanium oxide with high specific surface area and multiple oxygen vacancies as the carrier, which can highly disperse noble metal palladium. In the reaction of N-benzyloxycarbonylaniline deprotection to form aniline, not only the complete conversion of raw materials is achieved, but also when the catalyst loading amount is 2wt% and the usage amount is 0.2‰, the yield is as high as over 90%, and it can be recycled more than 12 times. Generally speaking, the catalyst preparation process of the present invention is simple, the catalyst structure is stable, resistant to high-temperature oxidation, and has the characteristics of high conversion rate, high selectivity, high yield, and good cycle stability, and has good application prospects. Summary of the Invention

[0006] The purpose of the present invention is to provide a high-dispersion palladium catalyst supported on ultra-small nanosized anatase titanium oxide with high specific surface area and multiple oxygen vacancies for benzyloxycarbonyl deprotection reaction and its preparation. This catalyst not only has a low noble metal palladium loading amount and less usage amount, and the ratio of catalyst palladium to substrate is in the range of 0.1‰-10‰, but also in the reaction of N-benzyloxycarbonylaniline de-Cbz, it can achieve 100% conversion rate and a yield of over 90%, and can be recycled more than 12 times. That is, this catalyst has the advantages of high activity, high yield, high selectivity, and good cycle stability, effectively reducing the cost of N-benzyloxycarbonylaniline de-Cbz protection.

[0007] The purpose of the present invention is achieved through the following technical solutions: A high-dispersion palladium catalyst supported on ultra-small nanosized anatase titanium oxide with high specific surface area and multiple oxygen vacancies for benzyloxycarbonyl deprotection reaction and its preparation. The catalyst uses self-made ultra-small nanosized anatase titanium oxide as the carrier and noble metal palladium as the active component, wherein the content of noble metal palladium is 0.1% - 5% (mass percentage) of the total amount of the catalyst.

[0008] A preparation method of the palladium catalyst supported on ultra-small nanosized anatase titanium oxide as described above, specifically including the following steps: Preparation of ultra-small nanosized anatase titanium oxide carrier: The support is prepared by the sol-gel method. The additive is dissolved and reserved. Solvent and titanium source are added to a beaker and stirred evenly at room temperature for 5 min to 30 min. The prepared additive solution is added to form a sol. It is placed in a fume hood for aging for 5 h to 48 h. After aging, it is dried at 50 °C to 80 °C for 5 h to 48 h. The obtained solid is ground into powder, and then calcined at 300 °C to 600 °C for 1 h to 5 h to obtain a yellow powder. And the obtained powder is reduced at 100 °C to 500 °C for 1 h to 5 h in a hydrogen atmosphere to obtain an ultrasmall nanocrystalline anatase titanium oxide support with more oxygen vacancies.

[0009] In the above steps, the additive is one or a mixture of more of ammonium acid, 1,3-propanediamine, diethylenetriamine, ammonium oxalate, triethanolamine, ammonium chloride, ammonium bicarbonate and tetramethylammonium hydroxide; the solvent is one or a mixture of more of methanol, ethanol, isopropanol and ethylene glycol; the titanium source is one or a mixture of more of titanium tetrachloride, isopropyl titanate and tetrabutyl titanate.

[0010] Preparation of ultrasmall nanocrystalline anatase titanium oxide supported noble metal palladium catalyst: The above ultrasmall nanocrystalline anatase titanium oxide support is put into deionized water, a palladium precursor is added and stirred at room temperature for 1 h to 24 h. A precipitant is added to adjust the solution to alkaline, and stirring is continued for 5 h to 24 h. It is filtered, washed, dried at 50 °C to 100 °C for 8 h to 24 h, and reduced in a tubular furnace with hydrogen at 20 mL / min to 50 mL / min, at 200 °C to 500 °C for 1 h to 4 h, with a heating rate of 2 °C / min to 10 °C / min to obtain a palladium supported catalyst powder.

[0011] In the above steps, the precipitant is one or a mixture of more of sodium hydroxide, potassium hydroxide, sodium carbonate and sodium bicarbonate; the palladium precursor is one or a mixture of more of palladium chloride, palladium nitrate and palladium acetate.

[0012] Application of an ultrasmall nanocrystalline anatase titanium oxide supported palladium catalyst as described above in the benzyloxycarbonyl deprotection reaction.

[0013] The specific application is as follows: Raw material N-benzyloxycarbonylaniline and a quantitative catalyst are added to the inner lining of a reaction kettle, a certain amount of methanol is added as a solvent, and they are stirred and mixed evenly. The inner lining is transferred into the reaction kettle, nitrogen is filled and discharged 3 times to exhaust the air in the kettle, and then hydrogen is filled and discharged 3 times. The final pressure of hydrogen in the reaction kettle is maintained at 0.4 MPa. It is heated to 20 °C to 50 °C and reacted for 1 h to 10 h. After the reaction ends, the product is obtained. After the reaction solution is collected and fixed in volume, a high performance liquid chromatograph and a reverse phase chromatographic column are used to analyze the concentrations of the raw materials and products in the reaction solution by the standard curve method.

[0014] The catalyst whose activity has decreased after being recycled more than 12 times is regenerated. Specifically: The reaction solution containing the catalyst is centrifuged, and the obtained precipitate is centrifugally washed with a solvent 2 to 5 times, dried at room temperature to 120 °C for 1 h to 48 h, and then heat-treated at 100 °C to 300 °C for 0.5 h to 8 h to obtain a regenerated catalyst. The regenerated ultra-small nano-anatase titanium oxide supported palladium catalyst can still maintain its activity in the above-mentioned benzyloxycarbonyl deprotection reaction.

[0015] The solvent in the above steps is one or a mixture of acetonitrile, water, N,N-dimethylformamide, tetrahydrofuran, ethyl acetate, ethanol or methanol. The heat treatment is a heat treatment by mixing one or more of air, static air, hydrogen, or an inert atmosphere.

[0016] The present invention innovatively uses ultra-small nano-anatase titanium oxide with a high surface area and multiple oxygen vacancies as a carrier, changes the interaction between the metal and the carrier, improves the dispersion of metallic palladium, and enhances the catalytic reaction performance. In the benzyloxycarbonyl deprotection reaction, it not only has high catalytic activity, achieves high yield and high selectivity under the conditions of a loading amount of only 2 wt% and a dosage of 0.2‰, and still maintains high activity after 12 cycles, but also the catalyst can be regenerated. It is a novel high-efficiency and low-loading benzyloxycarbonyl deprotection catalyst; the catalyst raw materials are easily available and the process is simple, with good application prospects, and is expected to be applied to the industrial large-scale production of deprotecting N-benzyloxycarbonylaniline to aniline. Description of the Drawings

[0017] Figure 1 It is the reaction formula for the deprotection of N-benzyloxycarbonylaniline.

[0018] Figure 2 It is the XRD pattern of the TiO2 support in Example 1.

[0019] Figure 3 It is the Raman spectrum of the TiO2 support in Example 1.

[0020] Figure 4 It is the XPS spectrum of O1s in the TiO2 support and the Pd / TiO2 catalyst in Example 1.

[0021] Figure 5 It is the HAADF image and particle size distribution of Pd nanoparticles in the Pd / TiO2 catalyst in Example 1.

[0022] Figure 6 It is the cyclic stability diagram of the reaction test of the Pd / TiO2 catalyst in Example 8. Detailed Embodiments

[0023] The present invention will be further described in detail below in conjunction with the description of the drawings and the detailed embodiments.

[0024] Example 1 Preparation of 2 wt% Palladium Catalyst Supported on Ultra-Small Nano-Anatase Titanium Oxide and Benzyloxycarbonyl Deprotection Reaction Preparation of ultra-small nano-anatase titanium oxide support: Add 4 ml of titanium tetrachloride to 10 ml of isopropanol and stir for 10 min; add 1 ml of ammonium chloride aqueous solution (18.4 wt%), and stir vigorously for 1 h; age at room temperature for 24 h and dry at 60 °C for 12 h; after drying, grind thoroughly. Place the powder in a muffle furnace and calcine at 500 °C for 1 h at a heating rate of 5 °C / min, and reduce the obtained powder in a hydrogen atmosphere at 350 °C for 1 h to obtain a nitrogen-doped titanium oxide support with more oxygen vacancies, denoted as Ti-Cl. Characterization and analysis were performed by XRD, Raman, and XPS. See specifically Figure 2 , 3, 4, and it was found that the diffraction peaks of anatase-type titanium oxide appeared. Calculated by the Scherrer formula, its particle size was 10 nm. It can be seen from XPS that the titanium oxide support is rich in oxygen vacancies.

[0025] Preparation of 2 wt% palladium catalyst: Disperse 0.5 g of the above support in 200 mL of water, stir for 30 minutes, add 1.02 mL of palladium chloride aqueous solution (concentration: 10 mg Pd / mL), stir for 1 h, add sodium hydroxide aqueous solution (concentration: 10 wt%), adjust the pH = 9 - 10, react overnight, filter and wash, dry at 60 °C for 12 h. Then place the obtained powder in a tubular furnace, reduce it at 200 °C for 2 h with a hydrogen flow rate of 30 mL / min and a heating rate of 5 °C / min to obtain a catalyst with a palladium loading of 2.0 wt.%, denoted as Pd / Ti-Cl. At the same time, the filtrate was recovered and elemental analysis tests were carried out. No palladium was detected, indicating that all the fed palladium was loaded on the support without loss, that is, the actual palladium loading was consistent with the theoretical feeding amount. Characterization by HAADF and particle size analysis, see specifically Figure 5 , the average particle size of palladium is 1.3 nm, and palladium is highly dispersed.

[0026] Benzyloxycarbonyl deprotection reaction test: Take 1.0000 g of N-benzyloxycarbonylaniline, 0.0100 g of the catalyst, and 5 ml of methanol and place them in the inner lining of the reaction kettle. After stirring and dispersing evenly, put the inner lining of the reaction kettle into the reaction kettle, fill and discharge nitrogen three times, then fill with hydrogen to 0.4 Mpa, react at 30 °C for 1 h. After the reaction, release the gas, collect and fix the volume of the reaction solution, and analyze the concentrations of the raw materials and products in the reaction solution by the standard curve method using a high-performance liquid chromatograph and a reverse-phase chromatographic column. The mobile phase is water and acetonitrile. The yield of the Pd / Ti-Cl catalyst in the above reaction was calculated to be 95.6%.

[0027] Example 2 Preparation of 2 wt% Palladium Catalyst Supported on Ultra-Small Nano-Anatase Titanium Oxide and Benzyloxycarbonyl Deprotection Reaction Preparation of ultra-small nanosized anatase titanium oxide support: Same as Example 1, except that in this example, the titanium precursor used for the preparation of the ultra-small nanosized anatase titanium oxide support is isopropyl titanate. The remaining support preparation process is the same as that in Example 1, denoted as Ti-C3. Through XRD, Raman and XPS characterization and analysis, the figures are similar to those in Example 1, showing diffraction peaks of anatase titanium oxide and being rich in oxygen vacancies.

[0028] Preparation of 2 wt% palladium catalyst: The catalyst preparation is the same as that in Example 1, and the prepared palladium catalyst is denoted as Pd / Ti-C3. At the same time, the filtrate is recovered and elemental analysis tests are carried out. No palladium is detected, indicating that all the fed palladium is loaded on the support without loss, that is, the actual loading amount of palladium is consistent with the theoretical feeding amount. Through HAADF characterization and particle size analysis, the figures are the same as those in Example 1, and palladium is highly dispersed.

[0029] Benzyl carbamate deprotection reaction test: The reaction test is the same as that in Example 1, and the calculated yield is 94.1%.

[0030] Preparation of 2 wt% palladium catalyst supported on ultra-small nanosized anatase titanium oxide and benzyl carbamate deprotection reaction in Example 3 Preparation of ultra-small nanosized anatase titanium oxide support: Same as Example 1, except that in this example, the titanium precursor used for the preparation of the ultra-small nanosized anatase titanium oxide support is tetrabutyl titanate. The remaining support preparation process is the same as that in Example 1, denoted as Ti-C4. Through XRD, Raman and XPS characterization and analysis, the figures are similar to those in Example 1, showing diffraction peaks of anatase titanium oxide and being rich in oxygen vacancies.

[0031] Preparation of 2 wt% palladium catalyst: The catalyst preparation is the same as that in Example 1, and the prepared palladium catalyst is denoted as Pd / Ti-C4. At the same time, the filtrate is recovered and elemental analysis tests are carried out. No palladium is detected, indicating that all the fed palladium is loaded on the support without loss, that is, the actual loading amount of palladium is consistent with the theoretical feeding amount. Through HAADF characterization and particle size analysis, the figures are the same as those in Example 1, and palladium is highly dispersed.

[0032] Benzyl carbamate deprotection reaction test: The reaction test is the same as that in Example 1, and the calculated yield is 92.2%.

[0033] Preparation of 2 wt% palladium catalyst supported on ultra-small nanosized anatase titanium oxide and benzyl carbamate deprotection reaction in Example 4 Preparation of ultra-small nanosized anatase titanium oxide support: Same as Example 1, except that in this example, the additive ammonium salt for preparing the carrier is ammonium nitrate, and the titanium precursor used is isopropyl titanate. The remaining process for preparing the carrier is the same as that in Example 1, denoted as Ti-C3-N1. Through XRD, Raman, and XPS characterization and analysis, the figures are similar to those in Example 1, showing anatase titanium oxide diffraction peaks and being rich in oxygen vacancies.

[0034] Preparation of 2 wt% palladium catalyst: The preparation of the catalyst is the same as that in Example 1; the prepared palladium catalyst is denoted as Pd / Ti-C3-N1. Meanwhile, the filtrate is recovered and subjected to elemental analysis test. No palladium is detected, indicating that all the fed palladium is loaded on the carrier without loss, that is, the actual loading amount of palladium is consistent with the theoretical feeding amount. Through HAADF characterization and particle size analysis, the figures are the same as those in Example 1, and palladium is highly dispersed.

[0035] Test for benzyloxycarbonyl deprotection reaction: The reaction test is the same as that in Example 1, and the calculated yield is 92.1%.

[0036] Preparation of 2 wt% palladium catalyst supported on ultra-small nano-anatase titanium oxide and benzyloxycarbonyl deprotection reaction in Example 5 Preparation of ultra-small nano-anatase titanium oxide carrier: Same as Example 1, except that in this example, the additive ammonium salt for preparing the carrier is ammonium bicarbonate; the titanium precursor used is isopropyl titanate; the remaining process for preparing the carrier is the same as that in Example 1, denoted as Ti-C3-N2. Through XRD, Raman, and XPS characterization and analysis, the figures are similar to those in Example 1, showing anatase titanium oxide diffraction peaks and being rich in oxygen vacancies.

[0037] Preparation of 2 wt% palladium catalyst: The preparation of the catalyst is the same as that in Example 1, and the prepared palladium catalyst is denoted as Pd / Ti-C3-N2. Meanwhile, the filtrate is recovered and subjected to elemental analysis test. No palladium is detected, indicating that all the fed palladium is loaded on the carrier without loss, that is, the actual loading amount of palladium is consistent with the theoretical feeding amount. Through HAADF characterization and particle size analysis, the figures are the same as those in Example 1, and palladium is highly dispersed.

[0038] Test for benzyloxycarbonyl deprotection reaction: The reaction test is the same as that in Example 1, and the calculated yield is 91.5%.

[0039] Preparation of 2 wt% palladium catalyst supported on ultra-small nano-anatase titanium oxide and benzyloxycarbonyl deprotection reaction in Example 6 Preparation of ultra-small nano-anatase titanium oxide: Same as Example 1, except that in this example, the ammonium salt used in the preparation of the carrier is tetramethylammonium hydroxide; the titanium precursor used is isopropyl titanate, and the rest of the carrier preparation process is the same as that in Example 1, denoted as Ti-C3-N3. Through XRD, Raman, and XPS characterization and analysis, the graphs are similar to those in Example 1, showing anatase titanium oxide diffraction peaks and being rich in oxygen vacancies.

[0040] Preparation of 2 wt% palladium catalyst: The catalyst preparation is the same as that in Example 1, and the prepared palladium catalyst is denoted as Pd / Ti-C3-N3. At the same time, the filtrate is recovered and elemental analysis tests are carried out. No palladium is detected, indicating that all the fed palladium is loaded on the carrier without loss, that is, the actual loading amount of palladium is consistent with the theoretical feeding amount. Through HAADF characterization and particle size analysis, the graphs are the same as those in Example 1, and palladium is highly dispersed.

[0041] Benzyl carbamate deprotection reaction test: The reaction test is the same as that in Example 1, and the calculated yield is 89.6%.

[0042] Preparation of 2 wt% palladium catalyst supported on ultrasmall nano-anatase titanium oxide and benzyl carbamate deprotection reaction in Example 7 Preparation of ultrasmall nano-anatase titanium oxide carrier: Same as Example 1, except that in this example, the reduction temperature during carrier preparation is 250 °C, and the rest of the carrier preparation process is the same as that in Example 1, denoted as Ti-Cl-250. Through XRD, Raman, and XPS characterization and analysis, the graphs are similar to those in Example 1, showing anatase titanium oxide diffraction peaks and being rich in oxygen vacancies.

[0043] Preparation of 2 wt% palladium catalyst: The catalyst preparation is the same as that in Example 1, and the prepared palladium catalyst is denoted as Pd / Ti-Cl-250. At the same time, the filtrate is recovered and elemental analysis tests are carried out. No palladium is detected, indicating that all the fed palladium is loaded on the carrier without loss, that is, the actual loading amount of palladium is consistent with the theoretical feeding amount. Through HAADF characterization and particle size analysis, the graphs are the same as those in Example 1, and palladium is highly dispersed.

[0044] Benzyl carbamate deprotection reaction test: The reaction test is the same as that in Example 1, and the calculated yield is 93.3%.

[0045] Preparation of 2 wt% palladium catalyst supported on ultrasmall nano-anatase titanium oxide and benzyl carbamate deprotection reaction in Example 8 Preparation of ultrasmall nano-anatase titanium oxide carrier: Same as Example 1, except that in this example, the reduction temperature during the preparation of the carrier is 400 °C, and the remaining process of preparing the carrier is the same as that in Example 5, denoted as Ti-Cl-400. Through XRD, Raman and XPS characterization and analysis, the figures are similar to those in Example 1, showing anatase titanium oxide diffraction peaks and being rich in oxygen vacancies.

[0046] Preparation of 2 wt% palladium catalyst: The preparation of the catalyst is the same as that in Example 1, except that in this example, the pH is adjusted to 12 - 13, and the prepared palladium catalyst is denoted as Pd / Ti-Cl-400. At the same time, the filtrate is recovered and elemental analysis tests are carried out. No palladium is detected, indicating that all the fed palladium is loaded on the carrier without loss, that is, the actual loading amount of palladium is consistent with the theoretical feeding amount. Through HAADF characterization and particle size analysis, the figures are the same as those in Example 1, and palladium is highly dispersed.

[0047] Test of benzyloxycarbonyl deprotection reaction: The reaction test is the same as that in Example 1, and the calculated yield is 96.8%.

[0048] Centrifuge the above reaction solution, wash the obtained precipitate twice with ethanol and methanol alternately, dry it in a vacuum oven at 60 °C for 12 h, and then reduce it with hydrogen at 200 °C for 2 h. The obtained catalyst is denoted as re-Pd / Ti-Cl-400. Repeat the benzyloxycarbonyl deprotection reaction test of re-Pd / Ti-Cl-400, and the calculated yield is 95.9%. The cyclic test was repeated 12 times, and the test results are as Figure 6 .

[0049] Preparation of 2 wt% palladium catalyst supported on ultra-small nano-anatase titanium oxide and benzyloxycarbonyl deprotection reaction Preparation of ultra-small nano-anatase titanium oxide carrier: The preparation of the carrier is the same as that in Example 1. Through XRD, Raman and XPS characterization and analysis, the figures are similar to those in Example 1, showing anatase titanium oxide diffraction peaks, with a particle size of 10 nm and being rich in oxygen vacancies.

[0050] Preparation of 2 wt% palladium catalyst: The preparation of the catalyst is the same as that in Example 1, except that in this example, the palladium precursor used in the preparation of the catalyst is palladium nitrate; the precipitating agent added is potassium hydroxide, and the prepared catalyst is denoted as Pd-N-K / Ti-Cl. At the same time, the filtrate is recovered and elemental analysis tests are carried out. No palladium is detected, indicating that all the fed palladium is loaded on the carrier without loss, that is, the actual loading amount of palladium is consistent with the theoretical feeding amount. Through HAADF characterization and particle size analysis, the figures are the same as those in Example 1, and palladium is highly dispersed.

[0051] Test of benzyloxycarbonyl deprotection reaction: The reaction test was the same as in Example 1, and the calculated yield was 95.5%.

[0052] Example 10 Preparation of 2wt% Palladium Catalyst Supported on Ultra-small Nano Anatase Titanium Oxide and Benzyloxycarbonyl Deprotection Reaction Preparation of ultra-small nano anatase titanium oxide support: The support was prepared in the same way as in Example 1. Through XRD, Raman and XPS characterization and analysis, the figures were similar to those in Example 1, showing anatase titanium oxide diffraction peaks, with a particle size of 10 nm and rich in oxygen vacancies.

[0053] Preparation of 2wt% palladium catalyst: The catalyst was prepared in the same way as in Example 1, except that in this example, the palladium precursor used for catalyst preparation was palladium acetate; the precipitating agent added was sodium bicarbonate, and the prepared catalyst was denoted as Pd-A-CH / Ti-Cl. At the same time, the filtrate was recovered and elemental analysis was carried out. No palladium was detected, indicating that all the fed palladium was loaded on the support without loss, that is, the actual loading amount of palladium was consistent with the theoretical feeding amount. Through HAADF characterization and particle size analysis, the figures were the same as in Example 1, and palladium was highly dispersed.

[0054] Benzyloxycarbonyl deprotection reaction test: The reaction test was the same as in Example 1, and the calculated yield was 91.9%.

[0055] Example 11 Preparation of 2wt% Palladium Catalyst Supported on Ultra-small Nano Anatase Titanium Oxide and Benzyloxycarbonyl Deprotection Reaction Preparation of ultra-small nano anatase titanium oxide support: The support was prepared in the same way as in Example 1. Through XRD, Raman and XPS characterization and analysis, the figures were similar to those in Example 1, showing anatase titanium oxide diffraction peaks, with a particle size of 10 nm and rich in oxygen vacancies.

[0056] Preparation of 2wt% palladium catalyst: The catalyst was prepared in the same way as in Example 1, except that in this example, the catalyst reduction temperature was 300 °C, and the prepared catalyst was denoted as Pd-300 / Ti-Cl. At the same time, the filtrate was recovered and elemental analysis was carried out. No palladium was detected, indicating that all the fed palladium was loaded on the support without loss, that is, the actual loading amount of palladium was consistent with the theoretical feeding amount. Through HAADF characterization and particle size analysis, the figures were the same as in Example 1, and palladium was highly dispersed.

[0057] Benzyloxycarbonyl deprotection reaction test: The reaction test was the same as in Example 1, and the calculated yield was 90.8%.

[0058] Example 12 Preparation of 2wt% Palladium Catalyst Supported on Ultra-small Nano Anatase Titanium Oxide and Benzyloxycarbonyl Deprotection Reaction Preparation of ultrasmall nanosized anatase titanium oxide support: The support was prepared in the same manner as in Example 1. Through XRD, Raman and XPS characterization and analysis, the figures were similar to those in Example 1, showing anatase titanium oxide diffraction peaks, with a particle size of 10 nm and rich in oxygen vacancies.

[0059] Preparation of 2 wt% palladium catalyst: The catalyst was prepared in the same manner as in Example 1, except that in this example, the catalyst reduction temperature was 500 °C, and the prepared catalyst was denoted as Pd-500 / Ti-Cl. At the same time, the filtrate was recovered and elemental analysis tests were carried out. No palladium was detected, indicating that all the fed palladium was loaded on the support without loss, that is, the actual loading amount of palladium was consistent with the theoretical feeding amount. Through HAADF characterization and particle size analysis, the figures were the same as those in Example 1, and palladium was highly dispersed.

[0060] Test of benzyloxycarbonyl deprotection reaction: The reaction test was the same as in Example 1, and the calculated yield was 92.1%.

[0061] Preparation of 0.1 wt% palladium catalyst supported on ultrasmall nanosized anatase titanium oxide and benzyloxycarbonyl deprotection reaction in Example 13 Preparation of ultrasmall nanosized anatase titanium oxide support: The support was prepared in the same manner as in Example 1. Through XRD, Raman and XPS characterization and analysis, the figures were similar to those in Example 1, showing anatase titanium oxide diffraction peaks, with a particle size of 10 nm and rich in oxygen vacancies.

[0062] Preparation of 0.5 wt% palladium catalyst: The catalyst preparation process was the same as in Example 1; the difference was that in this example, an ultrasmall nanosized anatase titanium oxide supported palladium catalyst with a loading amount of 0.1 wt% was prepared, and the prepared catalyst was denoted as Pd-0.1 / Ti-Cl. At the same time, the filtrate was recovered and elemental analysis tests were carried out. No palladium was detected, indicating that all the fed palladium was loaded on the support without loss, that is, the actual loading amount of palladium was consistent with the theoretical feeding amount. Through HAADF characterization and particle size analysis, the figures were the same as those in Example 1, and palladium was highly dispersed.

[0063] Test of benzyloxycarbonyl deprotection reaction: The reaction test was the same as in Example 1, and the calculated yield was 71.6%.

[0064] Test of benzyloxycarbonyl deprotection reaction of commercial palladium on carbon: The test of N-benzyloxycarbonylaniline debenzylcarbonyl protection reaction was the same as in Example 1. The calculated yield of the Pd / C catalyst in the above reaction was 88.6% Centrifuge the above-mentioned palladium-carbon reaction solution. The obtained precipitate is washed twice with ethanol and methanol alternately, and then dried in a vacuum oven at 60 °C for 12 h. The obtained catalyst is denoted as re-Pd / C-1. Repeat the test of the benzyloxycarbonyl deprotection reaction of re-Pd / C-1, and the calculated yield is 45.6%.

[0065] Repeat the above treatment process and the test of the benzyloxycarbonyl deprotection reaction. The yield in the second cycle is 28.9%.

[0066] Take the catalyst after the first cycle of treatment, reduce it with hydrogen at 200 °C for 2 h to obtain a regenerated catalyst, denoted as re-Pd / C. Repeat the test of the benzyloxycarbonyl deprotection reaction, and the calculated yield of the re-Pd / C catalyst in the above reaction is 40.4%.

[0067] Preparation of XC-72 supported noble metal 2wt% palladium catalyst and benzyloxycarbonyl deprotection reaction: The catalyst preparation process is the same as that in Example 1. The obtained catalyst is denoted as Pd / XC-72. At the same time, the filtrate is recovered and elemental analysis is carried out. No palladium is detected, indicating that all the fed palladium is loaded on the support without loss, that is, the actual loading amount of palladium is consistent with the theoretical feeding amount.

[0068] The test of the benzyloxycarbonyl deprotection reaction is the same as that in Example 1. The calculated yield of the Pd / XC-72 catalyst in the above reaction is 80.9%.

[0069] Centrifuge the above-mentioned Pd / XC-72 reaction solution. The obtained precipitate is washed twice with ethanol and methanol alternately, and then dried in a vacuum oven at 60 °C for 12 h. The obtained catalyst is denoted as re-Pd / XC-72-1. Repeat the test of the benzyloxycarbonyl deprotection reaction of re-Pd / XC-72-1, and the calculated yield is 50.5%.

[0070] Repeat the above treatment process and the test of the benzyloxycarbonyl deprotection reaction. The yield in the second cycle is 20.9%.

[0071] Take the catalyst after the first cycle of treatment, reduce it with hydrogen at 200 °C for 2 h in a tubular furnace to obtain a regenerated catalyst, denoted as re-Pd / XC-72. Repeat the test of the benzyloxycarbonyl deprotection reaction, and the calculated yield of the re-Pd / XC-72 catalyst in the above reaction is 45.3%.

[0072] The above content is a further detailed description of the present invention in combination with specific embodiments. It cannot be considered that the specific implementation of the present invention is only limited to these descriptions. For those of ordinary skill in the technical field to which the present invention belongs, without departing from the concept of the present invention, simple modifications and substitutions made should be regarded as belonging to the protection scope of the present invention.

Claims

1. A preparation and application of a benzyloxycarbonyl deprotection palladium catalyst, characterized in that: The benzyloxycarbonyl deprotection reaction is: The raw material N-benzyloxycarbonylaniline and the quantitative catalyst are added to the lining of the reactor, a certain amount of methanol is added as a solvent, and the mixture is stirred and mixed evenly; the lining is transferred to the reactor, nitrogen is charged and discharged 3 times to discharge the air in the reactor, and then hydrogen is charged and discharged 3 times, and the final pressure of hydrogen in the reactor is maintained at 0.4MPa; it is heated to 20℃~50℃, reacted for 1h~10h, and the product is obtained after the reaction is completed. The reaction conversion rate and yield are obtained by HPLC test. The catalyst uses ultra-small nano-rutile titanium oxide with high specific surface area and multiple oxygen vacancies as a carrier and precious metal palladium as an active component. The loading amount of the palladium is as low as 0.1wt%~5wt% of the total catalyst. The invented catalyst palladium to substrate ratio is within the range of 0.1‰-10‰, and 100% conversion rate, more than 90% yield, and the number of cycles is up to more than 12 times.

2. According to claim 1, the preparation method of the catalyst carrier is as follows: The carrier is prepared by a sol-gel method. The additive is dissolved and set aside. A solvent and a titanium source are added to a beaker and stirred evenly at room temperature for 5 minutes to 30 minutes. The prepared additive solution is added to form a sol. The carrier is placed in a fume hood for aging for 5 hours to 48 hours. After the aging, it is dried at 50°C to 80°C for 5 hours to 48 hours. The obtained solid is ground into powder, and then calcined at 300°C to 600°C for 1 hour to 5 hours to obtain a yellow powder. The obtained powder is reduced at 100°C to 500°C in a hydrogen atmosphere for 1 hour to 5 hours to obtain an ultra-small nano-anatase titanium oxide carrier containing more oxygen vacancies.

3. The method for preparing a carrier according to claim 2, characterized in that: The additive is a mixture of one or more of ammonium nitrate, 1,3-propylenediamine, diethylenetriamine, ammonium oxalate, triethanolamine, ammonium chloride, ammonium bicarbonate and tetramethylammonium hydroxide; The solvent is a mixture of one or more of methanol, ethanol, isopropanol and ethylene glycol; The titanium source is a mixture of one or more of titanium tetrachloride, isopropyl titanate and tetrabutyl titanate.

4. The method for preparing the catalyst according to claim 1 is a sedimentation precipitation method, characterized in that: The following steps are involved: The ultrasmall nano-anatase titanium oxide carrier is placed in deionized water, a palladium precursor is added and stirred at room temperature for 1 h~24 h, a precipitant is added to adjust the solution to alkalinity, stirring is continued for 5 h~24 h, filtered and washed, dried at 50°C~100°C for 8 h~24 h, and reduced in a tubular furnace with 20 mL / min~50 mL / min hydrogen, 200°C~500°C for 1 h~4 h, and a heating rate of 2°C / min~10°C / min to obtain a loaded palladium catalyst powder.

5. The method for preparing a catalyst according to claim 4, characterized in that: The precipitant is a mixture of one or more of sodium hydroxide, potassium hydroxide, sodium carbonate and sodium bicarbonate; The palladium precursor is a mixture of one or more of palladium chloride, palladium nitrate and palladium acetate.

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