Method for catalytic synthesis of 3-nitro pyrazole by metalloporphyrin

Abstract

The application discloses a method for synthesizing 3-nitro pyrazole by catalysis of metal porphyrin, and belongs to the technical field of organic synthesis and biomimetic catalysis. The application solves the problem that although the 3-nitro pyrazole synthesized by the oxidation method has a certain yield, the time cost and the post-processing cost cannot be saved. The application establishes a green catalytic oxidation system, uses 3-amino pyrazole as raw material, uses hydrogen peroxide or tert-butyl hydroperoxide as an oxidant, avoids the fact that the waste liquid contains various inorganic ions, solves the problem of high waste liquid treatment cost, uses metal porphyrin as a catalyst, improves the oxidation capacity of the oxidant, has the potential of efficiently catalyzing the oxidation of 3-amino pyrazole, and the yield reaches 50% in 0.5 h at room temperature. The reaction condition is mild, the time is short, high temperature and high pressure are not needed, the process is safe and green, and the process is easy to industrialize. The application has important significance for the popularization and application of 3-nitro pyrazole.

Description

TECHNICAL FIELD

[0001] The present application relates to a kind of metal porphyrin catalytic synthesis 3-nitro pyrazole synthesis method, belong to organic synthesis, biomimetic catalysis technical field. BACKGROUND

[0002] 3-nitro pyrazole is an important compound, can be used for synthesis multiple geliatin and conai feni etc. Variety of drugs, can also be used as raw material synthesis pyrazole energetic material 3, 4-dinitro pyrazole etc. Currently 3-nitro pyrazole synthesis is mainly cyclization method, rearrangement method and oxidation method.

[0003] The existing literature (Verbruggen, R. 《Cycloadditions with 2-Chloro-1-Nitroethylene》. 1975, 29(8): 350-352) uses diazomethane and chloronitroethylene as raw materials to synthesize 3-nitropyrazole through cyclization reaction. This method is simple to operate, but has problems such as poor stability of diazomethane, poor process safety, etc., which limits its application. Literature (Janssen, J.W.A.M., et al. 《Pyrazoles. XII. Preparation of 3(5)-nitropyrazoles by thermal rearrangement of N-nitropyrazoles》. The Journal of Organic Chemistry, 38.10 (1973): 1777-1782) and (Cui-Ping LI. 《Synthesis of 3-Nitropyrazole》. Dyestuffs and coloration, 2004. (3): 168-169) successively use pyrazole as raw material, nitrate at No. 1 through mixed acid to form N-NO2, and then heat rearrangement in high-boiling organic solvents such as benzonitrile, anisole, n-octanol, etc. to obtain 3-nitropyrazole. Although this process has high yield, it still has problems such as easy sublimation of intermediate N-nitropyrazole, high toxicity of rearrangement solvent, and long reaction time. In order to solve the problems of easy sublimation of N-nitropyrazole and high toxicity of solvent in the above process, literature (Tong Zhike, Wang Mingya, Chen Jun, et al. 《Process optimization of hydrothermal synthesis of 3-nitropyrazole》. Powder and Explosives, 2023, 46(11): 965-970) uses a hydrothermal kettle as the reaction container and xylene as the thermal rearrangement solvent instead of organic solvents such as benzonitrile, anisole, n-octanol, etc. in the original process, so that the rearrangement yield reaches 100%, and the sublimation of N-nitropyrazole is avoided by using a hydrothermal kettle. However, the high-pressure process still has problems such as difficult scaling up. Compared with cyclization and rearrangement methods, oxidation method has the advantage of being more mild.The method for synthesizing 3-nitro pyrazole by the amino oxidation method reported in the literature is potassium monopersulfate (Oxone) oxidation method. In the literature (Zhao XX, Zhang JC, Li SH, Yang QP, Li YC, Pang SP. A green and facile approach for synthesis of nitro heteroaromatics in water. Organic Process Research & Development. 2014 Jul 18; 18 (7): 886-90), 3-amino pyrazole is used as a substrate, and 3-nitro pyrazole is obtained after 18 h of reaction at 40 DEG C by potassium monopersulfate oxidation. The oxidation method has the problems of long reaction time and K. + , SO4 2- and other inorganic ions, resulting in high treatment cost, environmental pollution and other problems. Although the method has a certain yield, it cannot save time cost and post-treatment cost. SUMMARY

[0004] The present application provides a method for synthesizing 3-nitro pyrazole by metal porphyrin catalysis to overcome the technical defects of the prior art.

[0005] To solve the above technical problems, the present application realizes the following technical scheme:

[0006] The purpose of the present application is to provide a method for synthesizing 3-nitro pyrazole by metal porphyrin catalysis. The method is to dissolve 3-amino pyrazole in a solvent to form a 3-amino pyrazole solution, then add a metal porphyrin catalyst, an oxidizing agent and a ligand, and perform extraction, reduced pressure distillation and chromatographic separation steps after reaction at room temperature for a certain time to obtain 3-amino pyrazole.

[0007] Further limited, the structural formula of the metal porphyrin catalyst is:

[0008]

[0009] Wherein, M is one of Fe, Mn, Co, Mg, Ni, Cu and Zn, and R is one of carboxyl, alkyl, hydroxyl, alkoxy, nitro and halogen.

[0010] Further limited, the solvent is one of water, dichloromethane, 1, 2-dichloromethane, trichloromethane, dimethyl sulfoxide, N, N-dimethylformamide, tetrahydrofuran, 1, 4-dioxane, acetonitrile and acetone.

[0011] Further limited, the concentration of the 3-amino pyrazole solution is (0.1-10) g / L.

[0012] Further limitation, the oxidant is one of hydrogen peroxide, tert-butyl hydroperoxide.

[0013] Further limitation, the ligand is one of imidazole, 1-methylimidazole, phenol, pyridine, thiophene, 2-mercaptobenzoic acid.

[0014] Further limitation, the metalloporphyrin catalyst is used in an amount of (2.5x10 -5 )~(5x10 -4 ) molar equivalents of 3-aminopyrazole.

[0015] Further limitation, the oxidant is used in an amount of 2~4 molar equivalents of 3-aminopyrazole.

[0016] Further limitation, the ligand is used in an amount of 0.2~0.6 molar equivalents of 3-aminopyrazole.

[0017] Further limitation, the reaction time is 0.3~24h.

[0018] The beneficial effects of the present application are:

[0019] The present application establishes an efficient and mild oxidation system with metalloporphyrin as catalyst. Tert-butyl hydroperoxide and hydrogen peroxide are used to replace common oxidants such as potassium monopersulfate, avoiding the presence of various inorganic ions in the waste liquid, solving the problem of high cost of waste liquid treatment, and the products after decomposition of the oxidant are green and environmentally friendly, harmless to the environment and human body, and low in cost; at the same time, with metalloporphyrin as catalyst, the low catalytic amino oxidation activity of tert-butyl hydroperoxide and hydrogen peroxide is improved, and the metalloporphyrin can also react with the oxidant to generate high-valent metal oxide compounds with higher activity, thereby improving the oxidation capacity of the oxidant, so the oxidation system with metalloporphyrin as catalyst has the potential to efficiently catalyze the oxidation of 3-aminopyrazole, and the yield can reach 50% in only 0.5h at room temperature, saving time and cost; the oxidation system established by the present application is green and safe, the reaction conditions are mild, high temperature and high pressure are not required, and the operation is simple, which has important potential for industrial application. BRIEF DESCRIPTION OF DRAWINGS

[0020] Figure 1 The mass spectrum of 3-nitropyrazole prepared in Example 1 is shown in the following figure ([M+H] + : 114.04);

[0021] Figure 2 The nuclear magnetic hydrogen spectrum of 3-nitropyrazole prepared in Example 1 is shown in the following figure. DETAILED DESCRIPTION

[0022] In order to make the above-mentioned purposes, features and advantages of the present application more obvious and easy to understand, the specific embodiments of the present application will be described in detail below with reference to the description examples.

[0023] In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present application. However, it will be apparent to one skilled in the art that the present application can be practiced without the specific details set forth in this description. In other instances, well-known methods have not been described in detail in order not to unnecessarily obscure aspects of the present application.

[0024] Second, the "one embodiment" or "an embodiment" as used herein means a specific implementation, or a specific combination of features, structures, or characteristics that can be included in at least one implementation of the present application. The various embodiments presented in this description are not necessarily mutually exclusive as specific manifestations of the present application can be made in a wide variety of contexts to adapt the application for the particular situation at hand.

[0025] The experimental methods used in the following examples are all conventional methods unless otherwise specified. The materials, reagents, methods and instruments used are all conventional materials, reagents, methods and instruments in the art unless otherwise specified, and can be obtained by commercial channels by those skilled in the art.

[0026] The synthetic route of the metalloporphyrin catalytic synthesis of 3-nitro pyrazole is as follows:

[0027]

[0028] The synthetic route of the metalloporphyrin catalyst in the present application is as follows:

[0029]

[0030] Example 1

[0031] Preparation of metalloporphyrin catalyst:

[0032] (1) Preparation of porphyrazine: dissolve p-substituted benzaldehyde (0.08 mol) in 300 mL of propionic acid, heat to 141℃, then add freshly distilled pyrrole (5.56 mL, 0.08 mol) dropwise into the reaction system, control the drop to be completed in 2 min, the solution gradually turns brown-black, control the temperature to be 131℃, react for 0.5 h, cool and stand for a period of time, then purple solid is precipitated, directly filter, wash the solid obtained by filtration with anhydrous ethanol until the color is light purple, and air dry to obtain porphyrazine;

[0033] (2) Preparation of iron(III)-tetra(4-methylphenyl)chlorin (metal porphyrin catalyst): The porphyrin obtained in (1) (0.063 mmol) was dissolved in 5 mL of N,N-dimethylformamide (DMF) with iron chloride (2.51 mmol), and the reaction solution was cooled to room temperature after being reacted at 120°C for 2 h. The unreacted iron chloride was removed by filtration, and the DMF was spin-dried. Extraction was performed using 10 mL of a solution of dichloromethane (DCM) and H2O in a volume ratio of 1:1, and the DCM phase was collected. After spin-drying, iron(III)-tetra(4-methylphenyl)chlorin was obtained, and its structure is as follows:

[0034]

[0035] wherein M is Fe, and R is methoxy.

[0036] Preparation of 3-nitropyrazole:

[0037] In a 50 mL single-neck flask, 3-aminopyrazole (0.25 mmol, 20 mg) was dissolved in 20 mL of carbonate buffer (pH = 10.6), and then iron(III)-tetra(4-methylphenyl)chlorin (2.5 x 10 -5 mmol, 1.9 mg), t-butyl hydroperoxide (2 mmol, 275 μL), and 1-methylimidazole ligand (0.1 mmol, 8.3 μL) were sequentially added. After being reacted at room temperature for 24 h, methanol was added to dilute the product obtained in the reaction to a concentration of 1000 ppm, and then liquid chromatography was used for quantitative detection. The conversion rate of 3-aminopyrazole was 86.9%, and the yield of 3-nitropyrazole was 26.9%. The structure of the 3-nitropyrazole product was characterized by nuclear magnetic resonance hydrogen spectrum testing, and its structure is as follows: 1 H NMR (600 MHz, MeOD) δ 7.81 and δ 6.95 are two Hs on the pyrazole ring. The mass spectrum of the 3-nitropyrazole product was detected, and the molecular weight of 3-nitropyrazole was 113.02. The peak in the mass spectrum was 114.04, i.e., [M+H] + was 114.04, indicating that 3-nitropyrazole was successfully prepared in this embodiment.

[0038] Example 2

[0039] Preparation of metal porphyrin catalyst:

[0040] (1) Preparation of porphyrin: Dissolve p-substituted benzaldehyde (0.08 mol) in 300 mL propionic acid, heat to 141 °C, then add freshly distilled pyrrole (5.56 mL, 0.08 mol) dropwise into the reaction system, control the dropwise addition to be completed in 2 min, the solution gradually turns brown-black, control the temperature to be 131 °C, react for 0.5 h, after cooling and standing for a period of time, purple solid is precipitated, directly filter, wash the solid obtained by filtration with anhydrous ethanol until the color is light purple, and air dry to obtain porphyrin;

[0041] (2) Preparation of iron (III) -tetra (4-methylphenyl) chlorin porphyrin (metal porphyrin catalyst): Dissolve the porphyrin obtained in (1) (0.063 mmol) and iron chloride (2.51 mmol) in 5 mL N, N-dimethylformamide (DMF), react at 120 °C for 2 h, then cool the reaction solution to room temperature, remove the unreacted iron chloride by filtration, spin dry the DMF, extract with 10 mL of a solution of dichloromethane (DCM) and H2O in a volume ratio of 1:1, collect the DCM phase, and spin dry to obtain iron (III) -tetra (4-methylphenyl) chlorin porphyrin, which has the same structure as the metal porphyrin catalyst in Example 1.

[0042] 3-nitro pyrazole preparation:

[0043] In a 50 mL single-neck flask, 3-amino pyrazole (0.25 mmol, 20 mg) is dissolved in 20 mL acetonitrile, then iron (III) -tetra (4-methylphenyl) chlorin porphyrin (2.5 x 10 -5 mmol, 1.9 mg), tert-butyl hydroperoxide (0.75 mmol, 103 μL), 1-methyl imidazole ligand (0.1 mmol, 8.3 μL) are sequentially added, after reacting at room temperature for 0.5 h, methanol is added to dilute the product obtained in the reaction to a concentration of 1000 ppm, then liquid chromatography is used for quantification, and it is detected that the conversion rate of 3-amino pyrazole is 99.0%, and the yield of 3-nitro pyrazole is 34.8%.

[0044] Example 3

[0045] Preparation of metal porphyrin catalyst:

[0046] (1) Preparation of porphyrin: Dissolve p-substituted benzaldehyde (0.08 mol) in 300 mL propionic acid, heat to 141 °C, then add freshly distilled pyrrole (5.56 mL, 0.08 mol) dropwise into the reaction system, control the dropwise addition to be completed in 2 min, the solution gradually turns brown-black, control the temperature to be 131 °C, react for 0.5 h, after cooling and standing for a period of time, purple solid is precipitated, directly filter, wash the solid obtained by filtration with anhydrous ethanol until the color is light purple, and air dry to obtain porphyrin;

[0047] (2) Preparation of iron(III)-tetra(4-methylphenyl)chlorin (metal porphyrin catalyst): The porphyrin obtained in (1) (0.063 mmol) was dissolved in 5 mL of N,N-dimethylformamide (DMF) with iron chloride (2.51 mmol), and the reaction solution was cooled to room temperature after being reacted at 120°C for 2 h. The unreacted iron chloride was removed by filtration, and the DMF was spin-dried. Extraction was performed using 10 mL of a solution of dichloromethane (DCM) and H2O in a volume ratio of 1:1, and the DCM phase was collected. After spin-drying, iron(III)-tetra(4-methylphenyl)chlorin was obtained, which had the same structure as the metal porphyrin catalyst in Example 1.

[0048] 3-nitropyrazole

[0049] In a 50 mL single-neck flask, 3-aminopyrazole (0.25 mmol, 20 mg) was dissolved in 20 mL of dichloromethane, and then iron(III)-tetra(4-methylphenyl)chlorin (2.5 x 10 -5 mmol, 1.9 mg), t-butyl hydroperoxide (0.75 mmol, 103 μL), and 1-methylimidazole ligand (0.1 mmol, 8.3 μL) were sequentially added. After being reacted at room temperature for 0.5 h, the resulting product was diluted to a concentration of 1000 ppm using methanol, and then quantified using liquid chromatography. It was detected that the conversion rate of 3-aminopyrazole was 99.6%, and the yield of 3-nitropyrazole was 44.8%.

[0050] Example 4

[0051] Preparation of metal porphyrin catalyst

[0052] (1) Preparation of porphyrin: p-substituted benzaldehyde (0.08 mol) was dissolved in 300 mL of propionic acid, and then freshly distilled pyrrole (5.56 mL, 0.08 mol) was added dropwise to the reaction system while controlling the temperature to be 141°C. The solution was gradually changed to brown black, and the temperature was controlled to be 131°C. After being reacted for 0.5 h, a purple solid was precipitated after being cooled and left to stand for a while. The solid material obtained by filtration was washed with anhydrous ethanol until the color was light purple, and then air-dried to obtain porphyrin.

[0053] (2) Preparation of iron(III)-tetra(4-methylphenyl)chlorin (metal porphyrin catalyst): The porphyrin obtained in (1) (0.063 mmol) was dissolved in 5 mL of N,N-dimethylformamide (DMF) with iron chloride (2.51 mmol) and the reaction was carried out at 120°C for 2 h. The reaction solution was cooled to room temperature and unreacted iron chloride was removed by filtration. The DMF was evaporated and extraction was carried out using 10 mL of a solution of dichloromethane (DCM) and H2O (1:1 by volume). The DCM phase was collected and evaporated to obtain iron(III)-tetra(4-methylphenyl)chlorin, which has the same structure as the metal porphyrin catalyst of Example 1.

[0054] 3-nitropyrazole preparation:

[0055] In a 50 mL single-neck flask, 3-aminopyrazole (0.25 mmol, 20 mg) was dissolved in 20 mL of dichloromethane, and then iron(III)-tetra(4-methylphenyl)chlorin (6.25 x 10 -6 mmol, 0.47 mg), t-butyl hydroperoxide (0.75 mmol, 103 μL), and 1-methylimidazole ligand (0.1 mmol, 8.3 μL) were sequentially added. The reaction was carried out at room temperature for 0.5 h, and then methanol was added to dilute the product to a concentration of 1000 ppm. The conversion of 3-aminopyrazole was 96.6% and the yield of 3-nitropyrazole was 40.3% as determined by liquid chromatography.

[0056] Example 5

[0057] Preparation of metal porphyrin catalyst:

[0058] (1) Preparation of porphyrin: p-substituted benzaldehyde (0.08 mol) was dissolved in 300 mL of propionic acid, and the temperature was raised to 141°C. Freshly distilled pyrrole (5.56 mL, 0.08 mol) was added dropwise over 2 min, and the solution gradually turned brown-black. The temperature was controlled at 131°C, and the reaction was carried out for 0.5 h. After cooling and standing for some time, purple solid was precipitated, which was directly filtered. The solid obtained by filtration was washed with anhydrous ethanol until the color was light purple. The solid was air-dried to obtain porphyrin.

[0059] (2) Preparation of iron(III)-tetra(4-methylphenyl)chlorin (metal porphyrin catalyst): The porphyrin obtained in (1) (0.063 mmol) was dissolved in 5 mL of N,N-dimethylformamide (DMF) with iron chloride (2.51 mmol) and the reaction was carried out at 120°C for 2 h. After cooling to room temperature, the unreacted iron chloride was removed by filtration and the DMF was evaporated. Extraction was carried out using 10 mL of dichloromethane (DCM) and H2O (1:1 by volume) and the DCM phase was collected. After evaporation, iron(III)-tetra(4-methylphenyl)chlorin was obtained, which had the same structure as the metal porphyrin catalyst of Example 1.

[0060] Preparation of 3-nitropyrazole:

[0061] In a 50 mL single-necked flask, 3-aminopyrazole (0.25 mmol, 20 mg) was dissolved in 20 mL of dichloromethane, and then iron(III)-tetra(4-methylphenyl)chlorin (1.25 x 10 -4 mmol, 9.5 mg), t-butyl hydroperoxide (0.75 mmol, 103 μL), and 1-methylimidazole ligand (0.1 mmol, 8.3 μL) were added in sequence. After reaction at room temperature for 0.5 h, the resulting product was diluted with methanol to a concentration of 1000 ppm and quantified by liquid chromatography. The conversion of 3-aminopyrazole was 98.9% and the yield of 3-nitropyrazole was 45.5%.

[0062] Example 6

[0063] Preparation of metal porphyrin catalyst:

[0064] (1) Preparation of porphyrin: p-substituted benzaldehyde (0.08 mol) was dissolved in 300 mL of propionic acid and heated to 141°C. Freshly distilled pyrrole (5.56 mL, 0.08 mol) was added dropwise over 2 min, and the solution gradually turned brown-black. The temperature was controlled at 131°C and the reaction was carried out for 0.5 h. After cooling and standing for some time, purple solid was precipitated and was directly filtered. The solid obtained by filtration was washed with anhydrous ethanol until the color was light purple. After air-drying, porphyrin was obtained.

[0065] (2) Preparation of iron(III)-tetra(4-methylphenyl)chlorin (metal porphyrin catalyst): The porphyrin obtained in (1) (0.063 mmol) was dissolved in 5 mL of N,N-dimethylformamide (DMF) with iron chloride (2.51 mmol), and the reaction solution was cooled to room temperature after being reacted at 120°C for 2 h. The unreacted iron chloride was removed by filtration, and the DMF was spin-dried. Extraction was performed using 10 mL of a solution of dichloromethane (DCM) and H2O in a volume ratio of 1:1, and the DCM phase was collected. After spin-drying, iron(III)-tetra(4-methylphenyl)chlorin was obtained, which had the same structure as the metal porphyrin catalyst in Example 1.

[0066] 3-nitro-pyrazole preparation:

[0067] In a 50 mL single-neck flask, 3-amino-pyrazole (0.25 mmol, 20 mg) was dissolved in 20 mL of dichloromethane, and then iron(III)-tetra(4-methylphenyl)chlorin (2.5 x 10 -5 mmol, 1.9 mg), t-butyl hydroperoxide (0.75 mmol, 103 μL), and 1-methylimidazole ligand (0.1 mmol, 8.3 μL) were sequentially added. After being reacted at room temperature for 24 h, the reaction product was diluted to a concentration of 1000 ppm using methanol, and then quantified using liquid chromatography. It was detected that the conversion rate of 3-amino-pyrazole was 99.1%, and the yield of 3-nitro-pyrazole was 43.3%.

[0068] Example 7

[0069] Preparation of metal porphyrin catalyst:

[0070] (1) Preparation of porphyrin: p-substituted benzaldehyde (0.08 mol) was dissolved in 300 mL of propionic acid, and then freshly distilled pyrrole (5.56 mL, 0.08 mol) was added dropwise to the reaction system while controlling the temperature to be 141°C. The solution was gradually changed to brown black, and the temperature was controlled to be 131°C for 0.5 h. After being cooled and left to stand for a while, a purple solid was precipitated, which was directly filtered. The solid obtained by filtration was washed with anhydrous ethanol until the color was light purple, and then air-dried to obtain porphyrin.

[0071] (2) Preparation of iron(III)-tetra(4-methylphenyl)chlorin (metal porphyrin catalyst): The porphyrin obtained in (1) (0.063 mmol) was dissolved in 5 mL of N,N-dimethylformamide (DMF) with iron chloride (2.51 mmol), and the reaction solution was cooled to room temperature after being reacted at 120°C for 2 h. The unreacted iron chloride was removed by filtration, and the DMF was spin-dried. Extraction was performed using 10 mL of a solution of dichloromethane (DCM) and H2O in a volume ratio of 1:1, and the DCM phase was collected. After spin-drying, iron(III)-tetra(4-methylphenyl)chlorin was obtained, which had the same structure as the metal porphyrin catalyst in Example 1.

[0072] 3-nitro-pyrazole preparation:

[0073] In a 50 mL single-neck flask, 3-amino-pyrazole (0.25 mmol, 20 mg) was dissolved in 20 mL of dichloromethane, and then iron(III)-tetra(4-methylphenyl)chlorin (2.5 x 10 -5 mmol, 1.9 mg), t-butyl hydroperoxide (0.75 mmol, 103 μL), and imidazole ligand (0.1 mmol, 6.8 mg) were sequentially added. After being reacted at room temperature for 0.5 h, methanol was added to dilute the resulting product to a concentration of 1000 ppm, and liquid chromatography was performed to quantify the product. It was detected that the conversion rate of 3-amino-pyrazole was 99.9%, and the yield of 3-nitro-pyrazole was 46.8%.

[0074] Example 8

[0075] Preparation of metal porphyrin catalyst:

[0076] (1) Preparation of porphyrin: p-substituted benzaldehyde (0.08 mol) was dissolved in 300 mL of propionic acid, and the temperature was raised to 141°C. Then, freshly distilled pyrrole (5.56 mL, 0.08 mol) was added dropwise to the reaction system over 2 min. The solution gradually changed to brown black, and the temperature was controlled at 131°C. After being reacted for 0.5 h, a purple solid was precipitated after being cooled and left to stand for some time. The solid obtained by filtration was washed with anhydrous ethanol until the color became light purple, and then it was air-dried to obtain porphyrin.

[0077] (2) Preparation of iron(III)-tetra(4-methylphenyl)porphyrin chloride (metal porphyrin catalyst): The porphin (0.063 mmol) obtained in (1) was dissolved in 5 mL of N,N-dimethylformamide (DMF) with iron chloride (2.51 mmol), and the reaction was carried out at 120°C for 2 hours. After the reaction solution was cooled to room temperature, unreacted iron chloride was removed by filtration, and the DMF was evaporated. Extraction was carried out using 10 mL of a solution of dichloromethane (DCM) and H2O in a volume ratio of 1:1, and the DCM phase was collected. After evaporation, iron(III)-tetra(4-methylphenyl)porphyrin chloride was obtained, which had the same structure as the metal porphyrin catalyst in Example 1.

[0078] 3-nitropyrazole

[0079] In a 50 mL single-neck flask, 3-aminopyrazole (0.25 mmol, 20 mg) was dissolved in 20 mL of dichloromethane, and then iron(III)-tetra(4-methylphenyl)porphyrin chloride (2.5 x 10 -5 mmol, 1.9 mg), t-butyl hydroperoxide (0.75 mmol, 103 μL), and phenol ligand (0.1 mmol, 9.4 mg) were sequentially added. After the reaction was carried out at room temperature for 0.5 hours, the resulting product was diluted to a concentration of 1000 ppm using methanol, and then quantified using liquid chromatography. It was detected that the conversion rate of 3-aminopyrazole was 92.4%, and the yield of 3-nitropyrazole was 21.4%.

[0080] Example 9

[0081] Preparation of metal porphyrin catalyst

[0082] (1) Preparation of porphin: p-bromosubstituted benzaldehyde (0.08 mol) was dissolved in 300 mL of propionic acid, and then freshly distilled pyrrole (5.56 mL, 0.08 mol) was added dropwise to the reaction system while the temperature was controlled at 141°C. The solution gradually changed to brown black, and the temperature was controlled at 131°C for 0.5 hours. After the reaction was carried out, a purple solid was precipitated after the solution was cooled and left to stand for some time. The solid was directly filtered, and then washed with anhydrous ethanol until the color of the solid was light purple. After air-drying, porphin was obtained.

[0083] (2) Preparation of iron(III)-tetra(4-bromophenyl)porphyrin chloride (metal porphyrin catalyst): The porphin (0.063 mmol) obtained in (1) was dissolved in 5 mL of N,N-dimethylformamide (DMF) with iron chloride (2.51 mmol), and the reaction was carried out at 120°C for 2 hours. After the reaction solution was cooled to room temperature, unreacted iron chloride was removed by filtration, and the DMF was evaporated. Extraction was carried out using 10 mL of a solution of dichloromethane (DCM) and H2O in a volume ratio of 1:1, and the DCM phase was collected. After evaporation, iron(III)-tetra(4-methylphenyl)porphyrin chloride was obtained, which had the same structure as the metal porphyrin catalyst in Example 1.

[0084]

[0085] wherein M is Fe and R is bromo.

[0086] Preparation of 3-nitro pyrazole:

[0087] Into a 50 mL single neck flask, 3-aminopyrazole (0.25 mmol, 20 mg) was dissolved in 20 mL dichloromethane, then iron (III)-tetra(4-bromophenyl) porphyrin chloride (2.5 x 10 -5 mmol, 1.9 mg), tert-butyl hydroperoxide (0.75 mmol, 103 μL), 1-methylimidazole ligand (0.1 mmol, 8.3 μL) were added successively. After 0.5 h at room temperature, methanol was added to dilute the product to a concentration of 1000 ppm. The conversion of 3-aminopyrazole was 98.8% and the yield of 3-nitro pyrazole was 45.5% as determined by liquid chromatography.

[0088] Example 10

[0089] Preparation of metalloporphyrin catalyst:

[0090] (1) Preparation of porphyrazine: p-trifluoromethyl benzaldehyde (0.08 mol) was dissolved in 300 mL propionic acid, and the temperature was raised to 141 °C. Freshly distilled pyrrole (5.56 mL, 0.08 mol) was added dropwise over 2 min. The solution gradually turned brown-black. The temperature was controlled at 131 °C, and the reaction was allowed to proceed for 0.5 h. After cooling and standing for some time, purple solid precipitated. The solid was filtered directly, washed with anhydrous ethanol until the color was light purple, and air-dried to obtain porphyrazine.

[0091] (2) Preparation of iron (III)-tetra(4-trifluoromethylphenyl) porphyrin chloride (metalloporphyrin catalyst): porphyrazine (0.063 mmol) obtained in (1) and iron chloride (2.51 mmol) were dissolved in 5 mL N,N-dimethylformamide (DMF), and the reaction was allowed to proceed at 120 °C for 2 h. The reaction solution was cooled to room temperature, and unreacted iron chloride was removed by filtration. The DMF was evaporated, and extraction was performed with 10 mL of a solution of dichloromethane (DCM) and H2O (1:1 by volume). The DCM phase was collected, and the iron (III)-tetra(4-trifluoromethylphenyl) porphyrin chloride was obtained after evaporation. The structure is as follows:

[0092]

[0093] wherein M is Fe and R is trifluoromethyl.

[0094] Preparation of 3-nitro pyrazole:

[0095] In a 50 mL single neck flask, 3-aminopyrazole (0.25 mmol, 20 mg) was dissolved in 20 mL of dichloromethane, then iron (III) -tetra (4-trifluoromethylphenyl) porphyrin chloride (2.5 x 10 -5 mmol, 1.9 mg), tert-butyl hydroperoxide (0.75 mmol, 103 μL), 1-methylimidazole ligand (0.1 mmol, 8.3 μL) were added successively. After 0.5 h reaction at room temperature, the reaction product was diluted to a concentration of 1000 ppm with methanol and quantified by liquid chromatography. The conversion of 3-aminopyrazole was 99.31% and the yield of 3-nitropyrazole was 50.0%.

[0096] Comparative Example 1

[0097] In a 50 mL single neck flask, 3-aminopyrazole (0.25 mmol, 20 mg) was dissolved in 20 mL of dichloromethane, then m-chloroperbenzoic acid (0.75 mmol, 0.152 g) was added. After 0.5 h reaction at room temperature, the sample was diluted to a concentration of 1000 ppm with methanol and quantified by liquid chromatography. The conversion of 3-aminopyrazole was 94.6% and the yield of 3-nitropyrazole was 21.1%.

[0098] The above description is merely preferred specific embodiments of the application. However, the protection scope of the application is not limited to this. Any person skilled in the art, according to the technical range disclosed in the application and the inventive concept, can make equivalent replacements or changes, which should be covered in the protection scope of the application.

Claims

1. A method for the catalytic synthesis of 3-nitro pyrazoles with metalloporphyrins, characterized in that, The method comprises dissolving 3-aminopyrazole in a solvent to form a 3-aminopyrazole solution, then adding a metal porphyrin catalyst, an oxidant, a ligand, performing extraction, vacuum distillation and chromatographic separation after reaction at room temperature for a certain time, and obtaining 3-nitropyrazole. The metal porphyrin catalyst has a structural formula as follows: In the formula, M is Fe, and R is alkoxy or halogen. The oxidant is one of hydrogen peroxide and tert-butyl hydroperoxide. The ligand is one of imidazole, 1-methyl imidazole and phenol.

2. The method of claim 1, wherein, The solvent is one of dichloromethane, trichloromethane, dimethyl sulfoxide, N,N-dimethylformamide, tetrahydrofuran, 1,4-dioxane, acetonitrile, acetone and carbonate buffer solution.

3. The method of claim 1, wherein, The concentration of the 3-aminopyrazole solution is (0.1-10) g / L.

4. The method of claim 1, wherein, The metalloporphyrin catalyst was used in 2.5 x 10 -5 ) to 5 x 10 -4 ) molar equivalents relative to the 3-aminopyrazole.

5. The method of claim 1, wherein, The amount of the oxidant is 2-4 molar equivalents of 3-aminopyrazole.

6. The method of claim 1, wherein, The amount of the ligand is 0.2-0.6 molar equivalents of 3-aminopyrazole.

7. The method of claim 1, wherein, The reaction time is 0.3-24 h.

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