Method for catalytically synthesizing 3-nitropyrazole by metalloporphyrin

Abstract

The invention discloses a method for catalytically synthesizing 3-nitropyrazole by metalloporphyrin, and belongs to the technical field of organic synthesis and biomimetic catalysis. The method solves the problem that the time cost and the post-treatment cost cannot be saved although the 3-nitropyrazole synthesized by an oxidation method has a certain yield. A green catalytic oxidation system is established, 3-aminopyrazole is used as a raw material, hydrogen peroxide or tert-butyl hydroperoxide is used as an oxidizing agent, waste liquid is prevented from containing various inorganic ions, the problem of high waste liquid treatment cost is solved, metalloporphyrin is used as a catalyst, the oxidizing capacity of the oxidizing agent is improved, and the method is suitable for industrial production. The potential of efficiently catalyzing oxidation of 3-aminopyrazole is achieved, and the yield reaches 50% at the room temperature within 0.5 h; the method is mild in reaction condition, short in time, free of high temperature and high pressure, safe and green in process and easy for industrial production, and has important significance on popularization and application of 3-nitropyrazole.

Description

Technical Field

[0001] The invention relates to a method for synthesizing 3-nitropyrazole by catalyzing metalloporphyrin, and belongs to the technical field of organic synthesis and bionic catalysis. Background Art

[0002] 3-Nitropyrazole is an important compound that can be used to synthesize various drugs such as doglitin and conafenib, and can also be used as a raw material to synthesize pyrazole energetic materials such as 3,4-dinitropyrazole. Currently, the synthesis of 3-nitropyrazole is mainly carried out by cyclization, rearrangement and oxidation.

[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. The method is simple to operate, but has the problems of poor stability of the raw material diazomethane and poor process safety, which limits its application; the literature (Janssen, JWAM, 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 L I. "Synthesis of 3-Nitropyrazole". Dyestuffs and coloration, 2004. (3): 168-169) pyrazole is used as a raw material, and N-NO2 is formed at the 1 position through mixed acid nitration, and then heated in a high-boiling point organic solvent such as benzonitrile, anisole, and n-octanol to rearrange to obtain 3-nitropyrazole. Although this process has a high yield, it still has problems such as the easy sublimation of the intermediate product N-nitropyrazole, the high toxicity of the rearrangement solvent, and the long reaction time. In order to solve the problem that N-nitropyrazole is easy to sublime and the solvent is highly toxic in the above process, the literature (Tong Zhike, Wang Mingya, Chen Jun, et al. "Process Optimization of Hydrothermal Synthesis of 3-Nitropyrazole". Journal of Explosives and Propellants, 2023, 46 (11): 965-970) uses a hydrothermal kettle as a reaction vessel and xylene as a thermal rearrangement solvent to replace the original process of benzonitrile, anisole, octanol and other organic solvents, 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 of this process still has problems such as difficulty in amplification. Compared with the cyclization method and the rearrangement method, the oxidation method has the advantage of being milder.The method for synthesizing 3-nitropyrazole by amino oxidation method reported in the literature is potassium monopersulfate (Oxone) oxidation method. 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 JμL 18; 18(7): 886-90) uses 3-aminopyrazole as a substrate and reacts with potassium monopersulfate at 40°C for 18 hours to obtain 3-nitropyrazole. The oxidation method has the disadvantages of long reaction time and K contained in the waste liquid. + 、SO4 2- The presence of various inorganic ions leads to high processing costs and environmental pollution. Although it has a certain yield, it cannot save time and post-processing costs. Summary of the invention

[0004] In order to overcome the technical defects of the existing oxidation method for synthesizing 3-nitropyrazole, the present invention provides a method for synthesizing 3-nitropyrazole by catalysis of metalloporphyrin.

[0005] In order to solve the above technical problems, the present invention is implemented through the following technical solutions:

[0006] The invention aims to provide a method for synthesizing 3-nitropyrazole by metalloporphyrin catalysis. The method comprises the following steps: dissolving 3-aminopyrazole in a solvent to form a 3-aminopyrazole solution, subsequently adding a metalloporphyrin catalyst, an oxidant and a ligand, reacting at room temperature for a certain period of time, performing extraction, reduced pressure distillation and chromatographic separation steps to obtain 3-aminopyrazole.

[0007] Further defined, the structural formula of the metalloporphyrin 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] It is further defined that the solvent is one of water, dichloromethane, 1,2-dichloromethane, chloroform, dimethyl sulfoxide, N,N-dimethylformamide, tetrahydrofuran, 1,4-dioxane, acetonitrile and acetone.

[0011] It is further defined that the concentration of the 3-aminopyrazole solution is (0.1-10) g / L.

[0012] It is further defined that the oxidant is one of hydrogen peroxide and tert-butyl hydroperoxide.

[0013] It is further defined that the ligand is one of imidazole, 1-methylimidazole, phenol, pyridine, thiophene, and 2-mercaptobenzoic acid.

[0014] It is further defined that the amount of metalloporphyrin catalyst is (2.5×10 -5 )~(5×10 -4 ) molar equivalent.

[0015] It is further defined that the amount of the oxidant used is 2 to 4 molar equivalents of 3-aminopyrazole.

[0016] It is further defined that the amount of the ligand used is 0.2 to 0.6 molar equivalent of 3-aminopyrazole.

[0017] It is further defined that the reaction time is 0.3 to 24 hours.

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

[0019] The present invention establishes an efficient and mild oxidation system with metal porphyrin as a catalyst. Tert-butyl hydroperoxide and hydrogen peroxide are used to replace common oxidants such as potassium monopersulfate, so as to avoid the waste liquid from containing a variety of inorganic ions, solve the problem of high waste liquid treatment cost, and the product after the oxidant is decomposed is green and environmentally friendly, harmless to the environment and human body, and has low cost; at the same time, metal porphyrin is used as a catalyst, and its low catalytic amino oxidation activity is improved when tert-butyl hydroperoxide and hydrogen peroxide have weak oxidation ability, and metal porphyrin can also react with the oxidant to generate a more active high-valent metal oxide compound, thereby improving the oxidation ability of the oxidant, so the oxidation system with metal porphyrin as a catalyst has the potential of efficiently catalyzing the oxidation of 3-aminopyrazole, and the yield can reach 50% in only 0.5h at room temperature, saving time cost; the oxidation system established by the present invention is green and safe, with mild reaction conditions, no need for high temperature and high pressure, simple operation, and important potential for industrial application. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 The mass spectrum ([M+H] + :114.04);

[0021] Figure 2 This is the H NMR spectrum of 3-nitropyrazole prepared in Example 1. DETAILED DESCRIPTION

[0022] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the specific implementation methods of the present invention are described in detail below in conjunction with the embodiments of the specification.

[0023] In the following description, many specific details are set forth to facilitate a full understanding of the present invention, but the present invention may also be implemented in other ways different from those described herein, and those skilled in the art may make similar generalizations without violating the connotation of the present invention. Therefore, the present invention is not limited to the specific embodiments disclosed below.

[0024] Secondly, the term "one embodiment" or "embodiment" as used herein refers to a specific feature, structure, or characteristic that may be included in at least one implementation of the present invention. The term "in one embodiment" that appears in different places in this specification does not necessarily refer to the same embodiment, nor does it refer to a separate or selective embodiment that is mutually exclusive with other embodiments.

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

[0026] The synthetic route of the metalloporphyrin-catalyzed synthesis of 3-nitropyrazole of the present invention is as follows:

[0027]

[0028] The synthetic route of the metal porphyrin catalyst in the present invention is as follows:

[0029]

[0030] Example 1

[0031] Preparation of Metalloporphyrin Catalysts:

[0032] (1) Preparation of porphine: 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. The solution gradually turned brown-black and the temperature was controlled to be 131°C. The reaction was continued for 0.5 h. After cooling and standing for a period of time, a purple solid precipitated. The solid was directly filtered and washed with anhydrous ethanol until it turned light purple. The solid was air-dried to obtain porphine.

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

[0034]

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

[0036] Preparation of 3-nitropyrazole:

[0037] 3-Aminopyrazole (0.25 mmol, 20 mg) was added to a 50 mL single-mouth bottle and dissolved in 20 mL carbonate buffer (pH = 10.6), and then iron (III)-tetrakis (4-methylphenyl) porphyrin chloride (2.5 × 10 -5 mmol, 1.9 mg), tert-butyl hydroperoxide (2 mmol, 275 μL), 1-methylimidazole ligand (0.1 mmol, 8.3 μL), react at room temperature for 24 hours, add methanol to dilute the product to a concentration of 1000 ppm, and then use liquid chromatography for quantitative detection. The conversion rate of 3-aminopyrazole is 86.9%, and the yield of 3-nitropyrazole is 26.9%. The 3-nitropyrazole product is tested by nuclear magnetic hydrogen spectrum, and its structural characterization is as follows: 1 H NMR (600 MHz, MeOD) δ7.81 and δ6.95 are two H on the pyrazole ring. The 3-nitropyrazole product was detected by mass spectrometry. The molecular weight of 3-nitropyrazole was 113.02. The peak in the mass spectrum was 114.04, that is, [M+H] + The molecular weight of the reaction mixture was 114.04, indicating that 3-nitropyrazole was successfully prepared in this example.

[0038] Example 2

[0039] Preparation of Metalloporphyrin Catalysts:

[0040] (1) Preparation of porphine: 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. The solution gradually turned brown-black and the temperature was controlled to be 131°C. The reaction was continued for 0.5 h. After cooling and standing for a period of time, a purple solid precipitated. The solid was directly filtered and washed with anhydrous ethanol until it turned light purple. The solid was air-dried to obtain porphine.

[0041] (2) Preparation of iron (III)-tetrakis (4-methylphenyl) porphyrin chloride (metal porphyrin catalyst): The porphyrin (0.063 mmol) obtained in (1) and ferric chloride (2.51 mmol) were dissolved in 5 mL of N,N-dimethylformamide (DMF), reacted at 120° C. for 2 h, and then the reaction solution was cooled to room temperature. The unreacted ferric 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. The DCM phase was collected and spin-dried to obtain iron (III)-tetrakis (4-methylphenyl) porphyrin chloride, which has the same structure as the metal porphyrin catalyst in Example 1.

[0042] Preparation of 3-nitropyrazole:

[0043] In a 50 mL single-mouth bottle, 3-aminopyrazole (0.25 mmol, 20 mg) was added and dissolved in 20 mL of acetonitrile, and then iron (III)-tetrakis (4-methylphenyl) porphyrin chloride (2.5 × 10 -5 mmol, 1.9 mg), tert-butyl hydroperoxide (0.75 mmol, 103 μL), 1-methylimidazole ligand (0.1 mmol, 8.3 μL), react at room temperature for 0.5 h, add methanol to dilute the product to a concentration of 1000 ppm, and then use liquid chromatography for quantitative analysis. The conversion rate of 3-aminopyrazole is 99.0%, and the yield of 3-nitropyrazole is 34.8%.

[0044] Example 3

[0045] Preparation of Metalloporphyrin Catalysts:

[0046] (1) Preparation of porphine: 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. The solution gradually turned brown-black and the temperature was controlled to be 131°C. The reaction was continued for 0.5 h. After cooling and standing for a period of time, a purple solid precipitated. The solid was directly filtered and washed with anhydrous ethanol until it turned light purple. The solid was air-dried to obtain porphine.

[0047] (2) Preparation of iron (III)-tetrakis (4-methylphenyl) porphyrin chloride (metal porphyrin catalyst): The porphyrin (0.063 mmol) obtained in (1) and ferric chloride (2.51 mmol) were dissolved in 5 mL of N,N-dimethylformamide (DMF), reacted at 120° C. for 2 h, and then the reaction solution was cooled to room temperature. The unreacted ferric 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. The DCM phase was collected and spin-dried to obtain iron (III)-tetrakis (4-methylphenyl) porphyrin chloride, which has the same structure as the metal porphyrin catalyst in Example 1.

[0048] Preparation of 3-nitropyrazole:

[0049] In a 50 mL single-mouth bottle, 3-aminopyrazole (0.25 mmol, 20 mg) was added and dissolved in 20 mL of dichloromethane, and then iron (III)-tetrakis (4-methylphenyl) porphyrin chloride (2.5 × 10 -5 mmol, 1.9 mg), tert-butyl hydroperoxide (0.75 mmol, 103 μL), 1-methylimidazole ligand (0.1 mmol, 8.3 μL), after reacting at room temperature for 0.5 h, methanol was added to dilute the product to a concentration of 1000 ppm and then quantified by liquid chromatography. The conversion rate of 3-aminopyrazole was 99.6%, and the yield of 3-nitropyrazole was 44.8%.

[0050] Example 4

[0051] Preparation of Metalloporphyrin Catalysts:

[0052] (1) Preparation of porphine: 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. The solution gradually turned brown-black and the temperature was controlled to be 131°C. The reaction was continued for 0.5 h. After cooling and standing for a period of time, a purple solid precipitated. The solid was directly filtered and washed with anhydrous ethanol until it turned light purple. The solid was air-dried to obtain porphine.

[0053] (2) Preparation of iron (III)-tetrakis (4-methylphenyl) porphyrin chloride (metal porphyrin catalyst): The porphyrin (0.063 mmol) obtained in (1) and ferric chloride (2.51 mmol) were dissolved in 5 mL of N,N-dimethylformamide (DMF), reacted at 120° C. for 2 h, and then the reaction solution was cooled to room temperature. The unreacted ferric 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. The DCM phase was collected and spin-dried to obtain iron (III)-tetrakis (4-methylphenyl) porphyrin chloride, which has the same structure as the metal porphyrin catalyst in Example 1.

[0054] Preparation of 3-nitropyrazole:

[0055] In a 50 mL single-mouth bottle, 3-aminopyrazole (0.25 mmol, 20 mg) was dissolved in 20 mL of dichloromethane, and then iron (III)-tetrakis (4-methylphenyl) porphyrin chloride (6.25 × 10 -6 mmol, 0.47 mg), tert-butyl hydroperoxide (0.75 mmol, 103 μL), 1-methylimidazole ligand (0.1 mmol, 8.3 μL), react at room temperature for 0.5 h, add methanol to dilute the product to a concentration of 1000 ppm, and then use liquid chromatography for quantitative analysis. The conversion rate of 3-aminopyrazole is 96.6%, and the yield of 3-nitropyrazole is 40.3%.

[0056] Example 5

[0057] Preparation of Metalloporphyrin Catalysts:

[0058] (1) Preparation of porphine: 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. The solution gradually turned brown-black and the temperature was controlled to be 131°C. The reaction was continued for 0.5 h. After cooling and standing for a period of time, a purple solid precipitated. The solid was directly filtered and washed with anhydrous ethanol until it turned light purple. The solid was air-dried to obtain porphine.

[0059] (2) Preparation of iron (III)-tetrakis (4-methylphenyl) porphyrin chloride (metal porphyrin catalyst): The porphyrin (0.063 mmol) obtained in (1) and ferric chloride (2.51 mmol) were dissolved in 5 mL of N,N-dimethylformamide (DMF), reacted at 120° C. for 2 h, and then the reaction solution was cooled to room temperature. The unreacted ferric 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. The DCM phase was collected and spin-dried to obtain iron (III)-tetrakis (4-methylphenyl) porphyrin chloride, which has the same structure as the metal porphyrin catalyst in Example 1.

[0060] Preparation of 3-nitropyrazole:

[0061] In a 50 mL single-mouth bottle, 3-aminopyrazole (0.25 mmol, 20 mg) was added and dissolved in 20 mL of dichloromethane, and then iron (III)-tetrakis (4-methylphenyl) porphyrin chloride (1.25 × 10 -4 mmol, 9.5 mg), tert-butyl hydroperoxide (0.75 mmol, 103 μL), 1-methylimidazole ligand (0.1 mmol, 8.3 μL), react at room temperature for 0.5 h, add methanol to dilute the product to a concentration of 1000 ppm, and then use liquid chromatography for quantitative analysis. The conversion rate of 3-aminopyrazole is 98.9%, and the yield of 3-nitropyrazole is 45.5%.

[0062] Example 6

[0063] Preparation of Metalloporphyrin Catalysts:

[0064] (1) Preparation of porphine: 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. The solution gradually turned brown-black and the temperature was controlled to be 131°C. The reaction was continued for 0.5 h. After cooling and standing for a period of time, a purple solid precipitated. The solid was directly filtered and washed with anhydrous ethanol until it turned light purple. The solid was air-dried to obtain porphine.

[0065] (2) Preparation of iron (III)-tetrakis (4-methylphenyl) porphyrin chloride (metal porphyrin catalyst): The porphyrin (0.063 mmol) obtained in (1) and ferric chloride (2.51 mmol) were dissolved in 5 mL of N,N-dimethylformamide (DMF), reacted at 120° C. for 2 h, and then the reaction solution was cooled to room temperature. The unreacted ferric 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. The DCM phase was collected and spin-dried to obtain iron (III)-tetrakis (4-methylphenyl) porphyrin chloride, which has the same structure as the metal porphyrin catalyst in Example 1.

[0066] Preparation of 3-nitropyrazole:

[0067] In a 50 mL single-mouth bottle, 3-aminopyrazole (0.25 mmol, 20 mg) was added and dissolved in 20 mL of dichloromethane, and then iron (III)-tetrakis (4-methylphenyl) porphyrin chloride (2.5 × 10 -5 mmol, 1.9 mg), tert-butyl hydroperoxide (0.75 mmol, 103 μL), 1-methylimidazole ligand (0.1 mmol, 8.3 μL), react at room temperature for 24 hours, add methanol to dilute the product to a concentration of 1000 ppm, and then use liquid chromatography for quantitative analysis. The conversion rate of 3-aminopyrazole is 99.1%, and the yield of 3-nitropyrazole is 43.3%.

[0068] Example 7

[0069] Preparation of Metalloporphyrin Catalysts:

[0070] (1) Preparation of porphine: 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. The solution gradually turned brown-black and the temperature was controlled to be 131°C. The reaction was continued for 0.5 h. After cooling and standing for a period of time, a purple solid precipitated. The solid was directly filtered and washed with anhydrous ethanol until it turned light purple. The solid was air-dried to obtain porphine.

[0071] (2) Preparation of iron (III)-tetrakis (4-methylphenyl) porphyrin chloride (metal porphyrin catalyst): The porphyrin (0.063 mmol) obtained in (1) and ferric chloride (2.51 mmol) were dissolved in 5 mL of N,N-dimethylformamide (DMF), reacted at 120° C. for 2 h, and then the reaction solution was cooled to room temperature. The unreacted ferric 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. The DCM phase was collected and spin-dried to obtain iron (III)-tetrakis (4-methylphenyl) porphyrin chloride, which has the same structure as the metal porphyrin catalyst in Example 1.

[0072] Preparation of 3-nitropyrazole:

[0073] In a 50 mL single-mouth bottle, 3-aminopyrazole (0.25 mmol, 20 mg) was added and dissolved in 20 mL of dichloromethane, and then iron (III)-tetrakis (4-methylphenyl) porphyrin chloride (2.5 × 10 -5 mmol, 1.9 mg), tert-butyl hydroperoxide (0.75 mmol, 103 μL), imidazole ligand (0.1 mmol, 6.8 mg), react at room temperature for 0.5 h, add methanol to dilute the product to a concentration of 1000 ppm, and then use liquid chromatography for quantitative analysis. The conversion rate of 3-aminopyrazole is 99.9%, and the yield of 3-nitropyrazole is 46.8%.

[0074] Example 8

[0075] Preparation of Metalloporphyrin Catalysts:

[0076] (1) Preparation of porphine: 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. The solution gradually turned brown-black and the temperature was controlled to be 131°C. The reaction was continued for 0.5 h. After cooling and standing for a period of time, a purple solid precipitated. The solid was directly filtered and washed with anhydrous ethanol until it turned light purple. The solid was air-dried to obtain porphine.

[0077] (2) Preparation of iron (III)-tetrakis (4-methylphenyl) porphyrin chloride (metal porphyrin catalyst): The porphyrin (0.063 mmol) obtained in (1) and ferric chloride (2.51 mmol) were dissolved in 5 mL of N,N-dimethylformamide (DMF), reacted at 120° C. for 2 h, and then the reaction solution was cooled to room temperature. The unreacted ferric 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. The DCM phase was collected and spin-dried to obtain iron (III)-tetrakis (4-methylphenyl) porphyrin chloride, which has the same structure as the metal porphyrin catalyst in Example 1.

[0078] Preparation of 3-nitropyrazole:

[0079] In a 50 mL single-mouth bottle, 3-aminopyrazole (0.25 mmol, 20 mg) was added and dissolved in 20 mL of dichloromethane, and then iron (III)-tetrakis (4-methylphenyl) porphyrin chloride (2.5 × 10 -5 mmol, 1.9 mg), tert-butyl hydroperoxide (0.75 mmol, 103 μL), phenol ligand (0.1 mmol, 9.4 mg), react at room temperature for 0.5 h, add methanol to dilute the product to a concentration of 1000 ppm, and then use liquid chromatography for quantitative analysis. The conversion rate of 3-aminopyrazole is 92.4%, and the yield of 3-nitropyrazole is 21.4%.

[0080] Example 9

[0081] Preparation of Metalloporphyrin Catalysts:

[0082] (1) Preparation of porphine: p-Bromo-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. The solution gradually turned brown-black and the temperature was controlled to be 131°C. The reaction was continued for 0.5 h. After cooling and standing for a period of time, a purple solid precipitated. The solid was directly filtered and washed with anhydrous ethanol until it turned light purple. The solid was air-dried to obtain porphine.

[0083] (2) Preparation of iron (III)-tetrakis (4-bromophenyl) porphyrin chloride (metal porphyrin catalyst): The porphyrin (0.063 mmol) obtained in (1) and ferric chloride (2.51 mmol) were dissolved in 5 mL of N,N-dimethylformamide (DMF), reacted at 120°C for 2 h, and then the reaction solution was cooled to room temperature. The unreacted ferric 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. The DCM phase was collected and spin-dried to obtain iron (III)-tetrakis (4-bromophenyl) porphyrin chloride, whose structure is as follows:

[0084]

[0085] Among them, M is Fe and R is bromine.

[0086] Preparation of 3-nitropyrazole:

[0087] In a 50 mL single-mouth bottle, 3-aminopyrazole (0.25 mmol, 20 mg) was added and dissolved in 20 mL of dichloromethane, and then iron (III)-tetrakis (4-bromophenyl) porphyrin chloride (2.5 × 10 -5 mmol, 1.9 mg), tert-butyl hydroperoxide (0.75 mmol, 103 μL), 1-methylimidazole ligand (0.1 mmol, 8.3 μL), react at room temperature for 0.5 h, add methanol to dilute the product obtained after the reaction to a concentration of 1000 ppm, and then use liquid chromatography for quantitative analysis. The detection shows that the conversion rate of 3-aminopyrazole is 98.8%, and the yield of 3-nitropyrazole is 45.5%.

[0088] Example 10

[0089] Preparation of Metalloporphyrin Catalysts:

[0090] (1) Preparation of porphine: p-Trifluoromethyl-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 then added dropwise to the reaction system. The addition was completed over 2 min, and the solution gradually turned brown-black. The temperature was controlled to 131°C and the reaction was continued for 0.5 h. After cooling and standing for a period of time, a purple solid precipitated. The solid was directly filtered and washed with anhydrous ethanol until it turned light purple. The solid was air-dried to obtain porphine.

[0091] (2) Preparation of iron (III)-tetrakis (4-trifluoromethylphenyl) porphyrin chloride (metal porphyrin catalyst): The porphyrin (0.063 mmol) obtained in (1) and ferric chloride (2.51 mmol) were dissolved in 5 mL of N,N-dimethylformamide (DMF), reacted at 120°C for 2 h, and then the reaction solution was cooled to room temperature. The unreacted ferric chloride was removed by filtration, and the DMF was dried by spin drying. The solution was extracted with 10 mL of a solution of dichloromethane (DCM) and H2O in a volume ratio of 1:1, and the DCM phase was collected and dried by spin drying to obtain iron (III)-tetrakis (4-trifluoromethylphenyl) porphyrin chloride, the structure of which is as follows:

[0092]

[0093] Wherein, M is Fe and R is trifluoromethyl.

[0094] Preparation of 3-nitropyrazole:

[0095] In a 50 mL single-mouth bottle, 3-aminopyrazole (0.25 mmol, 20 mg) was added and dissolved in 20 mL of dichloromethane, and then iron (III)-tetrakis (4-trifluoromethylphenyl) porphyrin chloride (2.5 × 10 -5 mmol, 1.9 mg), tert-butyl hydroperoxide (0.75 mmol, 103 μL), 1-methylimidazole ligand (0.1 mmol, 8.3 μL), react at room temperature for 0.5 h, add methanol to dilute the product to a concentration of 1000 ppm, and then use liquid chromatography for quantitative analysis. The conversion rate of 3-aminopyrazole is 99.31%, and the yield of 3-nitropyrazole is 50.0%.

[0096] Comparative Example 1

[0097] 3-Aminopyrazole (0.25mmol, 20mg) was added to a 50mL single-mouth bottle and dissolved in 20mL of dichloromethane. Then m-chloroperbenzoic acid (0.75mmol, 0.152g) was added. After reacting at room temperature for 0.5h, methanol was added to dilute the sample to a concentration of 1000ppm and then liquid phase quantification was performed. The conversion rate of 3-aminopyrazole was 94.6% and the yield of 3-nitropyrazole was 21.1%.

[0098] The above description is only a preferred specific implementation manner of the present invention, but the protection scope of the present invention is not limited thereto. Any technician familiar with the technical field can make equivalent replacements or changes according to the technical scheme and inventive concept of the present invention within the technical scope disclosed by the present invention, which should be covered by the protection scope of the present invention.

Claims

1. A method for synthesizing 3-nitropyrazole by metalloporphyrin catalysis, characterized in that: The method comprises the steps of dissolving 3-aminopyrazole in a solvent to form a 3-aminopyrazole solution, then adding a metal porphyrin catalyst, an oxidant and a ligand, reacting at room temperature for a certain period of time, performing extraction, reduced pressure distillation and chromatographic separation steps to obtain 3-aminopyrazole.

2. The method according to claim 1, characterized in that The structural formula of the metal porphyrin catalyst is: wherein M is one of Fe, Mn, Co, Mg, Ni, Cu, and Zn; R is one of carboxyl, alkyl, hydroxyl, alkoxy, nitro and halogen.

3. The method according to claim 1, characterized in that The solvent is one of water, dichloromethane, 1,2-dichloromethane, chloroform, dimethyl sulfoxide, N,N-dimethylformamide, tetrahydrofuran, 1,4-dioxane, acetonitrile, acetone and carbonate buffer solution.

4. The method according to claim 1, characterized in that: The concentration of 3-aminopyrazole solution is (0.1-10) g / L.

5. The method according to claim 1, characterized in that: The oxidant is one of hydrogen peroxide and tert-butyl hydroperoxide.

6. The method according to claim 1, characterized in that The ligand is one of imidazole, 1-methylimidazole, phenol, pyridine, thiophene and 2-mercaptobenzoic acid.

7. The method according to claim 1, characterized in that: The amount of metal porphyrin catalyst used was (2.5×10 -5 )~(5×10 -4 ) molar equivalent.

8. The method according to claim 1, characterized in that: The amount of the oxidant used is 2 to 4 molar equivalents of 3-aminopyrazole.

9. The method according to claim 1, characterized in that The amount of the ligand used is 0.2 to 0.6 molar equivalent of 3-aminopyrazole.

10. The method according to claim 1, characterized in that: The reaction time is 0.3 to 24 hours.

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