Preparation method of benzyl carbazate

Abstract

The invention provides a preparation method of benzyl carbazate, and belongs to the technical field of organic synthesis. The method comprises the following steps: reacting methyl carbazate with benzyl alcohol under the action of a catalyst to prepare benzyl carbazate; the catalyst is a metal organic framework immobilized lipase composite catalyst. The prepared catalyst can greatly improve the reaction activity and increase the yield of products under the synergistic effect of multi-metal coordinated catalysis and organic alkali and lipase, meanwhile, the reaction condition is mild, the preparation method is simple, no pollutant is generated in the reaction, and the catalyst is more environmentally friendly and efficient.

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis, and in particular to a method for preparing benzyl carbazate. Background Art

[0002] Benzyl carbazate is an important organic intermediate that can be used to prepare plant protection agents (such as indoxacarb) and transaminase inhibitors, and has a wide range of uses in the synthesis of pesticides and medicines. A patent reported that dimethyl carbonate (DMC) and benzyl alcohol were used for complete ester exchange reaction to obtain dibenzyl carbonate, which was then reacted with hydrated cake to obtain benzyl carbamate, but the yield of this process was only 50%, and the synthesis route was long and the product purity was low.

[0003] The English name of benzyl carbazate is benzyl carbazate, the molecular formula is C8H10N2O2, the molecular weight is 166.18, CAS number: 5331-43-1, this substance is seriously harmful to the eyes. The structural formula of benzyl carbazate is as follows: .

[0004] Chinese patent 201410055938.3 (synthesis method of benzyl hydrazinecarboxylate) discloses a synthesis method of benzyl hydrazinecarboxylate, which mainly records: a synthesis method of benzyl hydrazinecarboxylate, which comprises the following steps: a) dissolving hydrazine hydrate in a solvent and adding a base; b) adding benzyl chloroformate dropwise under the condition of controlling the reaction temperature to be between -20°C and 80°C; c) subjecting the obtained crude product to a salt-forming reaction and removing impurities; and d) dissociating the obtained salt with a base to obtain pure benzyl hydrazinecarboxylate. It is simple to operate, has good safety, high yield and low production cost, thus meeting the large demand for the key intermediate benzyl hydrazinecarboxylate in the mass production of the new pesticide indoxacarb and other fine chemical products.

[0005] Chinese Patent No. 200810031026.7 (Synthesis Method of Benzyl Hydrazate) discloses a synthesis method of benzyl hydrazinecarboxylate, which mainly records: a one-step process for synthesizing benzyl hydrazinecarboxylate, wherein dimethyl carbonate is reacted with hydrazine hydrate to form an intermediate product methyl hydrazinecarboxylate, and benzyl alcohol is directly added to react in one step under the action of a catalyst without separation and purification to obtain benzyl hydrazinecarboxylate. The invention has the advantages of using a one-step process for synthesizing benzyl hydrazinecarboxylate, having the characteristics of simple process, high product yield and high purity, low production cost, etc., and solves the problem that the raw material methyl hydrazinecarboxylate is not produced in China and is monopolized in the foreign market and is expensive. Summary of the invention

[0006] The purpose of the present invention is to provide a preparation method of benzyl carbazate, which can greatly improve the activity of the reaction and the yield of the product under the coordinated catalysis of multiple metals, the synergistic effect of organic base and lipase. At the same time, the reaction conditions are mild, the preparation method is simple, and no pollutants are generated in the reaction, which is more green, environmentally friendly and efficient.

[0007] The technical solution of the present invention is achieved in this way: The invention provides a method for preparing benzyl hydrazinecarboxylate. Methyl hydrazinecarboxylate and benzyl alcohol react under the action of a catalyst to prepare benzyl hydrazinecarboxylate. The catalyst is a metal organic framework fixed lipase composite catalyst.

[0008] As a further improvement of the present invention, the molar ratio of methyl carbazate to benzyl alcohol is 1.1-1.2:1, the reaction temperature is 120-130° C., and the reaction time is 3-5 h.

[0009] As a further improvement of the present invention, the added amount of the catalyst is 1-2 wt % of the total mass of the system.

[0010] As a further improvement of the present invention, the preparation method of the catalyst is as follows: S1. Preparation of metal organic framework: zinc nitrate is added to DMF, terephthalic acid is dissolved in DMF, the two solutions are mixed evenly, added to a polytetrafluoroethylene-lined autoclave, heated and stirred to react, cooled to room temperature, filtered, washed, and dried to obtain a metal organic framework; S2. Preparation of magnetic metal organic framework: adding metal organic framework to water, adding ferric chloride and ferrous chloride, adding ammonia water dropwise under inert gas protection, heating and stirring to react, filtering, calcining, washing, and drying to obtain magnetic metal organic framework; S3. Metal oxide doping: adding a magnetic metal organic framework to water, adding lanthanum nitrate and cerium nitrate, impregnating, separating with a magnet, and calcining to obtain a doped magnetic metal organic framework; S4. Organic base modification: adding the doped magnetic metal organic framework into water, adding dopamine hydrochloride and a catalyst, heating and stirring to react, separating with a magnet, washing, and drying to obtain a modified doped magnetic metal organic framework; S5. Lipase immobilization: Add lipase into water, add NHS and EDC, stir to activate, add modified doped magnetic metal organic framework, stir to react, separate with a magnet, wash, dry, and obtain a catalyst.

[0011] As a further improvement of the present invention, the molar ratio of zinc nitrate to terephthalic acid in step S1 is 2-3:4, the temperature of the heating and stirring reaction is 105-115° C., and the time is 44-52 hours.

[0012] As a further improvement of the present invention, the mass ratio of the metal organic framework, ferric chloride, ferrous chloride and ammonia water in step S2 is 10:3.2-3.3:1.25-1.3:4-6, the temperature of the heating and stirring reaction is 80-90°C, the time is 3-5h, and the calcination temperature is 450-550°C, and the time is 2-3h.

[0013] As a further improvement of the present invention, in step S3, the mass ratio of the magnetic metal organic framework, lanthanum nitrate and cerium nitrate is 100:1-2:1-2, the impregnation time is 1-2h, the calcination temperature is 450-550°C, and the time is 1-2h.

[0014] As a further improvement of the present invention, the mass ratio of the doped magnetic metal organic framework, dopamine hydrochloride and catalyst in step S4 is 10:2-3:0.5-1, the catalyst is a Tris-HCl solution with a pH of 8.5-9.5, the temperature of the heating and stirring reaction is 35-45°C, and the time is 3-5h.

[0015] As a further improvement of the present invention, the lipase in step S5 is porcine pancreatic lipase and high temperature resistant lipase, the mass ratio of which is 10:4-7, the mass ratio of the lipase, NHS, EDC, and modified doped magnetic metal organic framework is 2-3:0.5-1:0.3-0.5:10, the stirring activation time is 0.5-1h, and the stirring reaction time is 10-12h.

[0016] The present invention further provides a catalyst, the preparation method of which comprises the following steps: S1. Preparation of metal organic framework: add 2-3 molar equivalents of zinc nitrate into DMF, dissolve 4 molar equivalents of terephthalic acid in DMF, mix the two solutions evenly, add them into a polytetrafluoroethylene-lined autoclave, heat to 105-115°C, stir to react for 44-52h, cool to room temperature, filter, wash, and dry to obtain a metal organic framework; S2. Preparation of a magnetic metal organic framework: add 10 parts by weight of a metal organic framework to water, add 3.2-3.3 parts by weight of ferric chloride and 1.25-1.3 parts by weight of ferrous chloride, add 4-6 parts by weight of aqueous ammonia dropwise under inert gas protection, heat to 80-90° C., stir to react for 3-5 hours, filter, calcine at 450-550° C. for 2-3 hours, wash, and dry to obtain a magnetic metal organic framework; S3. Metal oxide doping: 10 parts by weight of a magnetic metal organic framework was added to water, 0.1-0.2 parts by weight of lanthanum nitrate and 0.1-0.2 parts by weight of cerium nitrate were added, and the mixture was immersed for 1-2 hours, separated by a magnet, and calcined at 450-550° C. for 1-2 hours to obtain a doped magnetic metal organic framework; S4. Organic base modification: 10 parts by weight of a doped magnetic metal organic framework is added to water, 2-3 parts by weight of dopamine hydrochloride and 0.5-1 parts by weight of a catalyst are added, heated to 35-45°C, stirred for reaction for 3-5h, separated by a magnet, washed, and dried to obtain a modified doped magnetic metal organic framework; The catalyst is a Tris-HCl solution with a pH of 8.5-9.5; S5. Lipase immobilization: 2-3 parts by weight of lipase were added to water, 0.5-1 parts by weight of NHS and 0.3-0.5 parts by weight of EDC were added, and the mixture was activated by stirring at room temperature for 0.5-1h, 10 parts by weight of the modified doped magnetic metal organic framework was added, and the reaction was stirred for 10-12h, separated by a magnet, washed, and dried to obtain a catalyst; The lipase is porcine pancreatic lipase and thermostable lipase, and the mass ratio is 10:4-7.

[0017] The present invention has the following beneficial effects: The present invention uses methyl carbazate and benzyl alcohol to replace each other to prepare benzyl carbazate, and the synthesis route is as follows: ; However, the raw materials used in this route are relatively safe and suitable for operation, but the reaction yield is low and the production cost is high, which is not suitable for industrial production.

[0018] Therefore, the present invention develops a reaction catalyst using a Zn metal organic framework as a carrier. On the one hand, it has the advantages of porosity, large specific surface area, regular structure, controllability, and easy functionalization, which is convenient for the subsequent loading of lipase and metal oxides. At the same time, Zn also has good catalytic activity for the reaction.

[0019] The present invention deposits magnetic ferrosoferric oxide on the surface of the prepared metal organic framework, which can improve the activity of the catalytic reaction on the one hand, and at the same time, make the catalyst magnetic, which is convenient for subsequent preparation and separation as well as separation after the reaction, and provides more convenience for regeneration.

[0020] The surface of the invention is doped with lanthanum metal lanthanum and rare earth metal cerium, and the multi-metal synergistic effect of metal ions can improve the catalytic activity; after the surface is modified with organic base polydopamine, on the one hand, the loading amount of lipase can be increased, and on the other hand, the organic base also has a good catalytic effect on the reaction, which greatly improves the reaction yield.

[0021] Lipase is an effective and safe biocatalyst that catalyzes transesterification reactions to form fatty acid esters during the production and utilization of food oils. Compared with acid-base chemical catalysts, which have harsh reaction conditions, are prone to corrosion of reaction equipment, and have the problems of "three wastes", the biocatalytic method using lipase meets the needs of green production, has mild reaction conditions, high selectivity, and can reduce resource waste.

[0022] The catalyst prepared by the present invention can greatly improve the activity of the reaction and the yield of the product under the synergistic effect of multi-metal coordinated catalysis, organic base and lipase. At the same time, the reaction conditions are mild, the preparation method is simple, and the reaction does not generate pollutants, which is more green, environmentally friendly and efficient. DETAILED DESCRIPTION

[0023] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0024] Porcine pancreatic lipase, 30,000 U / g, was purchased from Shanghai Yuanye Biotechnology Co., Ltd.; thermostable lipase, 100,000 U / g, was purchased from Jiangsu Caiwei Biotechnology Co., Ltd.

[0025] NHS——N-hydroxysuccinimide, EDC——1-ethyl-(3-dimethylaminopropyl)carbodiimide, DMF——N,N-dimethylformamide.

[0026] Preparation Example 1 Preparation of Catalyst The method comprises the following steps: S1. Preparation of metal organic framework: 0.2 mol zinc nitrate was added to 200 mL DMF, 0.4 mol terephthalic acid was dissolved in 200 mL DMF, the two solutions were mixed evenly, added to a polytetrafluoroethylene-lined autoclave, heated to 105°C, stirred for reaction for 44 hours, cooled to room temperature, filtered, washed, and dried to obtain a metal organic framework; S2. Preparation of magnetic metal organic framework: 10 g metal organic framework was added to 500 mL water, 3.2 g ferric chloride and 1.25 g ferrous chloride were added, 4 g ammonia water was added dropwise under nitrogen protection, heated to 80 ° C, stirred for 3 h, filtered, calcined at 450 ° C for 2 h, washed, and dried to obtain a magnetic metal organic framework; S3. Metal oxide doping: 10 g of magnetic metal organic framework was added to 200 mL of water, 0.1 g of lanthanum nitrate and 0.1 g of cerium nitrate were added, immersed for 1 h, separated by a magnet, and calcined at 450 ° C for 1 h to obtain a doped magnetic metal organic framework; S4. Organic base modification: 10 g of doped magnetic metal organic framework was added to 200 mL of water, 2 g of dopamine hydrochloride and 0.5 g of catalyst were added, heated to 35°C, stirred for reaction for 3 h, separated by magnet, washed, and dried to obtain a modified doped magnetic metal organic framework; The catalyst is a Tris-HCl solution with a pH of 8.5; S5. Lipase immobilization: 2 g of lipase was added to 200 mL of water, 0.5 g of NHS and 0.3 g of EDC were added, and the mixture was activated by stirring at room temperature for 0.5 h, and 10 g of modified doped magnetic metal organic framework was added, and the reaction was stirred for 10 h, separated by a magnet, washed, and dried to obtain a catalyst; The lipase is porcine pancreatic lipase and thermostable lipase, with a mass ratio of 10:4.

[0027] Preparation Example 2 Preparation of Catalyst The method comprises the following steps: S1. Preparation of metal organic framework: 0.3 mol zinc nitrate was added to 200 mL DMF, 0.4 mol terephthalic acid was dissolved in 200 mL DMF, the two solutions were mixed evenly, added to a polytetrafluoroethylene-lined autoclave, heated to 115°C, stirred for reaction for 52 hours, cooled to room temperature, filtered, washed, and dried to obtain a metal organic framework; S2. Preparation of magnetic metal organic framework: 10 g metal organic framework was added to 500 mL water, 3.3 g ferric chloride and 1.3 g ferrous chloride were added, 6 g ammonia water was added dropwise under nitrogen protection, heated to 90 ° C, stirred for 5 h, filtered, calcined at 550 ° C for 3 h, washed, and dried to obtain a magnetic metal organic framework; S3. Metal oxide doping: 10 g of magnetic metal organic framework was added to 200 mL of water, 0.2 g of lanthanum nitrate and 0.2 g of cerium nitrate were added, immersed for 2 h, separated by a magnet, and calcined at 550 ° C for 2 h to obtain a doped magnetic metal organic framework; S4. Organic base modification: 10 g of doped magnetic metal organic framework was added to 200 mL of water, 3 g of dopamine hydrochloride and 1 g of catalyst were added, heated to 45°C, stirred for reaction for 5 h, separated by magnet, washed, and dried to obtain a modified doped magnetic metal organic framework; The catalyst is a Tris-HCl solution with a pH of 9.5; S5. Lipase immobilization: 3 g of lipase was added to 200 mL of water, 1 g of NHS and 0.5 g of EDC were added, and the mixture was activated by stirring at room temperature for 1 h. 10 g of modified doped magnetic metal organic framework was added, and the reaction was stirred for 12 h. The catalyst was separated by a magnet, washed, and dried to obtain a catalyst. The lipase is porcine pancreatic lipase and thermostable lipase, with a mass ratio of 10:7.

[0028] Preparation Example 3 Preparation of Catalyst The method comprises the following steps: S1. Preparation of metal organic framework: 0.25 mol zinc nitrate was added to 200 mL DMF, 0.4 mol terephthalic acid was dissolved in 200 mL DMF, the two solutions were mixed evenly, added to a polytetrafluoroethylene-lined autoclave, heated to 110°C, stirred for reaction for 48 hours, cooled to room temperature, filtered, washed, and dried to obtain a metal organic framework; S2. Preparation of magnetic metal organic framework: 10 g metal organic framework was added to 500 mL water, 3.24 g ferric chloride and 1.26 g ferrous chloride were added, 5 g ammonia water was added dropwise under nitrogen protection, heated to 85 ° C, stirred for 4 h, filtered, calcined at 500 ° C for 2.5 h, washed, and dried to obtain a magnetic metal organic framework; S3. Metal oxide doping: 10 g of magnetic metal organic framework was added to 200 mL of water, 0.15 g of lanthanum nitrate and 0.15 g of cerium nitrate were added, and the mixture was immersed for 1.5 h, separated by a magnet, and calcined at 500 °C for 1.5 h to obtain a doped magnetic metal organic framework; S4. Organic base modification: 10 g of doped magnetic metal organic framework was added to 200 mL of water, 2.5 g of dopamine hydrochloride and 0.7 g of catalyst were added, heated to 40°C, stirred for reaction for 4 h, separated by magnet, washed, and dried to obtain a modified doped magnetic metal organic framework; The catalyst is a Tris-HCl solution with a pH of 9; S5. Lipase immobilization: 2.5 g lipase was added to 200 mL water, 0.6 g NHS and 0.4 g EDC were added, and the mixture was activated by stirring at room temperature for 1 h. 10 g modified doped magnetic metal organic framework was added, and the reaction was stirred for 11 h. The catalyst was separated by magnet, washed and dried to obtain a catalyst. The lipase is porcine pancreatic lipase and thermostable lipase, with a mass ratio of 10:5.

[0029] Preparation Example 4 Compared with Preparation Example 3, the difference is that the lipase is a single porcine pancreatic lipase.

[0030] Preparation Example 5 Compared with Preparation Example 3, the difference is that the lipase is a single high temperature resistant lipase.

[0031] Comparative Preparation Example 1 Compared with Preparation Example 3, the difference is that step S2 is not performed.

[0032] The details are as follows: S1. Preparation of metal organic framework: 0.25 mol zinc nitrate was added to 200 mL DMF, 0.4 mol terephthalic acid was dissolved in 200 mL DMF, the two solutions were mixed evenly, added to a polytetrafluoroethylene-lined autoclave, heated to 110°C, stirred for reaction for 48 hours, cooled to room temperature, filtered, washed, and dried to obtain a metal organic framework; S2. Metal oxide doping: 10 g of metal organic framework was added to 200 mL of water, 0.15 g of lanthanum nitrate and 0.15 g of cerium nitrate were added, and the mixture was immersed for 1.5 h, separated by a magnet, and calcined at 500 °C for 1.5 h to obtain a doped metal organic framework; S3. Organic base modification: 10 g of the doped metal organic framework was added to 200 mL of water, 2.5 g of dopamine hydrochloride and 0.7 g of catalyst were added, heated to 40°C, stirred for reaction for 4 h, separated by a magnet, washed, and dried to obtain a modified doped metal organic framework; The catalyst is a Tris-HCl solution with a pH of 9; S4. Lipase immobilization: 2.5 g of lipase was added to 200 mL of water, 0.6 g of NHS and 0.4 g of EDC were added, and the mixture was activated by stirring at room temperature for 1 h. 10 g of the modified doped metal organic framework was added, and the reaction was stirred for 11 h. The catalyst was separated by a magnet, washed, and dried to obtain a catalyst. The lipase is porcine pancreatic lipase and thermostable lipase, with a mass ratio of 10:5.

[0033] Comparative Preparation Example 2 Compared with Preparation Example 3, the difference is that lanthanum nitrate is not added in step S3.

[0034] The details are as follows: S3. Metal oxide doping: 10 g of magnetic metal organic framework was added into 200 mL of water, and 0.3 g of cerium nitrate was added, and the mixture was immersed for 1.5 h, separated by a magnet, and calcined at 500° C. for 1.5 h to obtain a doped magnetic metal organic framework.

[0035] Comparative Preparation Example 3 Compared with Preparation Example 3, the difference is that cerium nitrate is not added in step S3.

[0036] The details are as follows: S3. Metal oxide doping: 10 g of magnetic metal organic framework was added into 200 mL of water, and 0.3 g of lanthanum nitrate was added, and the mixture was immersed for 1.5 h, separated by a magnet, and calcined at 500 °C for 1.5 h to obtain a doped magnetic metal organic framework.

[0037] Comparative Preparation Example 4 Compared with Preparation Example 3, the difference is that step S3 is not performed.

[0038] The details are as follows: S1. Preparation of metal organic framework: 0.25 mol zinc nitrate was added to 200 mL DMF, 0.4 mol terephthalic acid was dissolved in 200 mL DMF, the two solutions were mixed evenly, added to a polytetrafluoroethylene-lined autoclave, heated to 110°C, stirred for reaction for 48 hours, cooled to room temperature, filtered, washed, and dried to obtain a metal organic framework; S2. Preparation of magnetic metal organic framework: 10 g metal organic framework was added to 500 mL water, 3.24 g ferric chloride and 1.26 g ferrous chloride were added, 5 g ammonia water was added dropwise under nitrogen protection, heated to 85 ° C, stirred for 4 h, filtered, calcined at 500 ° C for 2.5 h, washed, and dried to obtain a magnetic metal organic framework; S3. Organic base modification: 10 g of magnetic metal organic framework was added to 200 mL of water, 2.5 g of dopamine hydrochloride and 0.7 g of catalyst were added, heated to 40°C, stirred for reaction for 4 h, separated by magnet, washed and dried to obtain a modified magnetic metal organic framework; The catalyst is a Tris-HCl solution with a pH of 9; S4. Lipase immobilization: 2.5 g of lipase was added to 200 mL of water, 0.6 g of NHS and 0.4 g of EDC were added, and the mixture was activated by stirring at room temperature for 1 h. 10 g of the modified magnetic metal organic framework was added, and the reaction was stirred for 11 h. The catalyst was separated by a magnet, washed, and dried to obtain a catalyst. The lipase is porcine pancreatic lipase and thermostable lipase, with a mass ratio of 10:5.

[0039] Comparative Preparation Example 5 Compared with Preparation Example 3, the difference is that step S4 is not performed.

[0040] The details are as follows: S1. Preparation of metal organic framework: 0.25 mol zinc nitrate was added to 200 mL DMF, 0.4 mol terephthalic acid was dissolved in 200 mL DMF, the two solutions were mixed evenly, added to a polytetrafluoroethylene-lined autoclave, heated to 110°C, stirred for reaction for 48 hours, cooled to room temperature, filtered, washed, and dried to obtain a metal organic framework; S2. Preparation of magnetic metal organic framework: 10 g metal organic framework was added to 500 mL water, 3.24 g ferric chloride and 1.26 g ferrous chloride were added, 5 g ammonia water was added dropwise under nitrogen protection, heated to 85 ° C, stirred for 4 h, filtered, calcined at 500 ° C for 2.5 h, washed, and dried to obtain a magnetic metal organic framework; S3. Metal oxide doping: 10 g of magnetic metal organic framework was added to 200 mL of water, 0.15 g of lanthanum nitrate and 0.15 g of cerium nitrate were added, and the mixture was immersed for 1.5 h, separated by a magnet, and calcined at 500 °C for 1.5 h to obtain a doped magnetic metal organic framework; S4. Lipase immobilization: 2.5 g lipase was added to 200 mL water, 0.6 g NHS and 0.4 g EDC were added, and the mixture was activated by stirring at room temperature for 1 h. 10 g doped magnetic metal organic framework was added, and the reaction was stirred for 11 h. The catalyst was separated by a magnet, washed and dried to obtain a catalyst. The lipase is porcine pancreatic lipase and thermostable lipase, with a mass ratio of 10:5.

[0041] Comparative Preparation Example 6 Compared with Preparation Example 3, the difference is that step S5 is not performed.

[0042] The details are as follows: S1. Preparation of metal organic framework: 0.25 mol zinc nitrate was added to 200 mL DMF, 0.4 mol terephthalic acid was dissolved in 200 mL DMF, the two solutions were mixed evenly, added to a polytetrafluoroethylene-lined autoclave, heated to 110°C, stirred for reaction for 48 hours, cooled to room temperature, filtered, washed, and dried to obtain a metal organic framework; S2. Preparation of magnetic metal organic framework: 10 g metal organic framework was added to 500 mL water, 3.24 g ferric chloride and 1.26 g ferrous chloride were added, 5 g ammonia water was added dropwise under nitrogen protection, heated to 85 ° C, stirred for 4 h, filtered, calcined at 500 ° C for 2.5 h, washed, and dried to obtain a magnetic metal organic framework; S3. Metal oxide doping: 10 g of magnetic metal organic framework was added to 200 mL of water, 0.15 g of lanthanum nitrate and 0.15 g of cerium nitrate were added, and the mixture was immersed for 1.5 h, separated by a magnet, and calcined at 500 °C for 1.5 h to obtain a doped magnetic metal organic framework; S4. Organic base modification: add 10g of doped magnetic metal organic framework into 200mL of water, add 2.5g of dopamine hydrochloride and 0.7g of catalyst, heat to 40°C, stir and react for 4h, separate with a magnet, wash and dry to obtain a modified doped magnetic metal organic framework, which is the catalyst; The catalyst is a Tris-HCl solution with a pH of 9.

[0043] Test Example 1 N2 low temperature physical adsorption-desorption test: The specific surface area of ​​the catalysts prepared in Preparation Examples 1-5 or Comparative Preparation Examples 1-6 was tested using a fully automatic physical / chemical adsorption analyzer. The results are shown in Table 1.

[0044] Table 1 Group <![CDATA[Specific surface area (m 2 / g)]]> Preparation Example 1 227.5 Preparation Example 2 229.6 Preparation Example 3 230.4 Preparation Example 4 220.5 Preparation Example 5 217.8 Comparative Preparation Example 1 174.6 Comparative Preparation Example 2 210.3 Comparative Preparation Example 3 208.5 Comparative Preparation Example 4 200.7 Comparative Preparation Example 5 185.9 Comparative Preparation Example 6 213.8 It can be seen from the above table that the catalysts prepared in Preparation Examples 1-3 of the present invention have a relatively high specific surface area.

[0045] Example 1 This embodiment provides a method for preparing benzyl carbazate, and the synthetic route is as follows: ; Preparation method: 1.1 mol of methyl hydrazinecarboxylate and 1 mol of benzyl alcohol were mixed, and the catalyst prepared in Preparation Example 1 was added, wherein the amount of the catalyst added was 1 wt% of the total mass of the system, and the mixture was stirred and heated to 90°C. Methanol was continuously evaporated during the reaction. The temperature was raised to 120°C, and the reaction was kept warm for 3 hours. The mixture was cooled to room temperature, and the catalyst was separated by a magnet. The filtrate was subjected to reduced pressure distillation to remove benzyl alcohol and residual methanol. The substrate was then cooled to obtain a light yellow solid, which was recrystallized from ethyl acetate to obtain pure benzyl hydrazinecarboxylate with a melting point of 68-71°C.

[0046] Example 2 This embodiment provides a method for preparing benzyl hydrazine carboxylate: 1.2 mol of methyl hydrazinecarboxylate and 1 mol of benzyl alcohol were mixed, and the catalyst prepared in Preparation Example 2 was added, wherein the amount of the catalyst added was 2 wt% of the total mass of the system, and the mixture was stirred and heated to 90°C. Methanol was continuously evaporated during the reaction. The temperature was raised to 130°C, and the reaction was kept warm for 5 hours. The mixture was cooled to room temperature, and the catalyst was separated by a magnet. The filtrate was subjected to reduced pressure distillation to remove benzene, methanol and residual methanol. The substrate was then cooled to obtain a light yellow solid, which was recrystallized from ethyl acetate to obtain pure benzyl hydrazinecarboxylate with a melting point of 68-71°C.

[0047] Example 3 This embodiment provides a method for preparing benzyl hydrazine carboxylate: 1.15 mol of methyl hydrazinecarboxylate and 1 mol of benzyl alcohol were mixed, and the catalyst prepared in Preparation Example 3 was added, wherein the amount of the catalyst added was 1.5 wt% of the total mass of the system, and the mixture was stirred and heated to 90°C. Methanol was continuously evaporated during the reaction. The temperature was raised to 125°C, and the reaction was kept warm for 4 hours. The mixture was cooled to room temperature, and the catalyst was separated by a magnet. The filtrate was subjected to reduced pressure distillation to remove benzyl alcohol and residual methanol. The substrate was then cooled to obtain a light yellow solid, which was recrystallized from ethyl acetate to obtain pure benzyl hydrazinecarboxylate with a melting point of 68-71°C.

[0048] Comparative Examples 1-6 Compared with Example 3, the difference is that the catalyst is prepared by Comparative Preparation Examples 1-6.

[0049] Comparative Example 7 Compared with Example 3, the difference is that the catalyst is sodium carbonate (separated by filtration).

[0050] Test Example 1 The methods in Examples 1-5 of the present invention and Comparative Examples 1-7 were evaluated, and the results are shown in Table 2.

[0051] Table 2 Group Benzyl carbazate purity (%) Yield of benzyl carbazate (%) Example 1 99.79 95.2 Example 2 99.80 94.8 Example 3 99.82 95.9 Example 4 99.22 89.5 Example 5 99.10 90.4 Comparative Example 1 99.75 91.4 Comparative Example 2 98.37 90.6 Comparative Example 3 98.25 89.2 Comparative Example 4 97.05 86.3 Comparative Example 5 98.47 82.1 Comparative Example 6 98.04 85.7 Comparative Example 7 96.29 65.7 As can be seen from the above table, the benzyl carbazate prepared by the method in Examples 1-3 of the present invention has high purity and high yield.

[0052] Test Example 2 After the catalysts in Examples 1-5 or Comparative Examples 1-7 were separated, the catalytic reaction was repeated 10 times, and the reaction result of the 10th time was evaluated. The results are shown in Table 3.

[0053] Table 3 Group Benzyl carbazate purity (%) Yield of benzyl carbazate (%) Example 1 99.32 92.2 Example 2 99.35 92.8 Example 3 99.42 93.9 Example 4 98.42 78.9 Example 5 97.04 76.5 Comparative Example 1 99.02 86.8 Comparative Example 2 97.25 80.5 Comparative Example 3 97.31 78.4 Comparative Example 4 95.67 70.2 Comparative Example 5 96.05 67.5 Comparative Example 6 96.56 71.0 Comparative Example 7 91.84 34.8 It can be seen from the above table that the catalysts in Examples 1-3 of the present invention have good repeated catalytic activity.

[0054] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for preparing benzyl carbazate, characterized in that: Benzyl hydrazine carboxylate is prepared by reacting methyl hydrazine carboxylate with benzyl alcohol under the action of a catalyst; the catalyst is a metal organic framework fixed lipase composite catalyst.

2. The preparation method according to claim 1, characterized in that: The molar ratio of methyl carbazate to benzyl alcohol is 1.1-1.2:1, the reaction temperature is 120-130° C., and the reaction time is 3-5 hours.

3. The preparation method according to claim 1, characterized in that: The amount of the catalyst added is 1-2 wt% of the total mass of the system.

4. The preparation method according to claim 1, characterized in that: The preparation method of the catalyst is as follows: S1. Preparation of metal organic framework: zinc nitrate is added to DMF, terephthalic acid is dissolved in DMF, the two solutions are mixed evenly, added to a polytetrafluoroethylene-lined autoclave, heated and stirred to react, cooled to room temperature, filtered, washed, and dried to obtain a metal organic framework; S2. Preparation of magnetic metal organic framework: adding metal organic framework to water, adding ferric chloride and ferrous chloride, adding ammonia water dropwise under inert gas protection, heating and stirring to react, filtering, calcining, washing, and drying to obtain magnetic metal organic framework; S3. Metal oxide doping: adding a magnetic metal organic framework to water, adding lanthanum nitrate and cerium nitrate, impregnating, separating with a magnet, and calcining to obtain a doped magnetic metal organic framework; S4. Organic base modification: adding the doped magnetic metal organic framework into water, adding dopamine hydrochloride and a catalyst, heating and stirring to react, separating with a magnet, washing, and drying to obtain a modified doped magnetic metal organic framework; S5. Lipase immobilization: Add lipase into water, add NHS and EDC, stir to activate, add modified doped magnetic metal organic framework, stir to react, separate with a magnet, wash, dry, and obtain a catalyst.

5. The preparation method according to claim 4, characterized in that: In step S1, the molar ratio of zinc nitrate to terephthalic acid is 2-3:4, the temperature of the heating and stirring reaction is 105-115° C., and the time is 44-52 hours.

6. The preparation method according to claim 4, characterized in that: In step S2, the mass ratio of the metal organic framework, ferric chloride, ferrous chloride and ammonia water is 10:3.2-3.3:1.25-1.3:4-6, the temperature of the heating and stirring reaction is 80-90°C, the time is 3-5h, and the calcination temperature is 450-550°C, and the time is 2-3h.

7. The preparation method according to claim 4, characterized in that: In step S3, the mass ratio of the magnetic metal organic framework, lanthanum nitrate and cerium nitrate is 100:1-2:1-2, the impregnation time is 1-2 hours, the calcination temperature is 450-550° C., and the time is 1-2 hours.

8. The preparation method according to claim 4, characterized in that: In step S4, the mass ratio of the doped magnetic metal organic framework, dopamine hydrochloride and catalyst is 10:2-3:0.5-1, the catalyst is a Tris-HCl solution with a pH of 8.5-9.5, the temperature of the heating and stirring reaction is 35-45° C., and the time is 3-5 hours.

9. The preparation method according to claim 4, characterized in that: The lipase in step S5 is porcine pancreatic lipase and thermostable lipase, the mass ratio of which is 10:4-7, the mass ratio of the lipase, NHS, EDC and modified doped magnetic metal organic framework is 2-3:0.5-1:0.3-0.5:10, the stirring activation time is 0.5-1h, and the stirring reaction time is 10-12h.

10. A catalyst, characterized in that The preparation method comprises the following steps: S1. Preparation of metal organic framework: add 2-3 molar equivalents of zinc nitrate into DMF, dissolve 4 molar equivalents of terephthalic acid in DMF, mix the two solutions evenly, add them into a polytetrafluoroethylene-lined autoclave, heat to 105-115°C, stir to react for 44-52h, cool to room temperature, filter, wash, and dry to obtain a metal organic framework; S2. Preparation of a magnetic metal organic framework: add 10 parts by weight of a metal organic framework to water, add 3.2-3.3 parts by weight of ferric chloride and 1.25-1.3 parts by weight of ferrous chloride, add 4-6 parts by weight of aqueous ammonia dropwise under inert gas protection, heat to 80-90° C., stir to react for 3-5 hours, filter, calcine at 450-550° C. for 2-3 hours, wash, and dry to obtain a magnetic metal organic framework; S3. Metal oxide doping: 10 parts by weight of a magnetic metal organic framework was added to water, 0.1-0.2 parts by weight of lanthanum nitrate and 0.1-0.2 parts by weight of cerium nitrate were added, and the mixture was immersed for 1-2 hours, separated by a magnet, and calcined at 450-550° C. for 1-2 hours to obtain a doped magnetic metal organic framework; S4. Organic base modification: 10 parts by weight of a doped magnetic metal organic framework is added to water, 2-3 parts by weight of dopamine hydrochloride and 0.5-1 parts by weight of a catalyst are added, heated to 35-45°C, stirred for reaction for 3-5h, separated by a magnet, washed, and dried to obtain a modified doped magnetic metal organic framework; The catalyst is a Tris-HCl solution with a pH of 8.5-9.5; S5. Lipase immobilization: 2-3 parts by weight of lipase were added to water, 0.5-1 parts by weight of NHS and 0.3-0.5 parts by weight of EDC were added, and the mixture was activated by stirring at room temperature for 0.5-1h, 10 parts by weight of the modified doped magnetic metal organic framework was added, and the reaction was stirred for 10-12h, separated by a magnet, washed, and dried to obtain a catalyst; The lipase is porcine pancreatic lipase and thermostable lipase, and the mass ratio is 10:4-7.