A new method for the synthesis of 3,6-dinitropyrazolo[4,3-c]pyrazoles
By using nitrosation, reduction, acetylation, and cyclization reactions with 3,5-dimethylpyrazole as the starting material, the safety and operational complexity issues of the MPP synthesis process were solved, enabling the efficient synthesis and large-scale production of MPP.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- BEIJING INST OF TECH
- Filing Date
- 2026-01-29
- Publication Date
- 2026-06-05
AI Technical Summary
The existing synthesis process for 3-methylpyrazole[4,3-c]pyrazole (MPP) is characterized by high reactivity, high operational difficulty, high safety risks, and complex post-processing, which hinders its large-scale production and industrial application.
Using 3,5-dimethylpyrazole as the starting material, the acetylated isomer of MPP is synthesized through nitrosation, reduction, acetylation, cyclization and hydrolysis reactions, avoiding the accumulation of hazardous intermediates, and adopting an in-situ diazonium salt generation method, thus simplifying the operation process.
It achieves high safety, excellent yield, convenient post-processing, and is easy to scale up production, which is in line with the green and safe development trend in the field of energetic materials.
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Figure CN122145469A_ABST
Abstract
Description
Technical Field
[0001] This application relates to the field of materials technology, and in particular to a novel method for synthesizing 3,6-dinitropyrazole[4,3-c]pyrazole. Background Technology
[0002] 3,6-Dinitropyrazole[4,3-c]pyrazole (DNPP), as a typical fused nitrogen heterocyclic energetic compound, possesses excellent comprehensive properties, such as high specific impulse, high positive oxygen balance, high density, high nitrogen content, high thermal decomposition temperature, excellent detonation performance, low sensitivity, and high heat of formation. Based on these superior properties, DNPP and its series of high-performance derivatives and ionic salts have been widely used in energetic materials such as propellants, initiators, and multi-component mixed explosives, demonstrating significant industrial application value.
[0003] 3-Methylpyrazole[4,3-c]pyrazole (MPP) is an indispensable key precursor in the synthesis of DNPP, and the quality of its synthesis process directly affects the large-scale production, production cost, and safety level of DNPP and its derivatives. In related technologies, most MPP synthesis methods rely on diazotization reactions, and require the separation and extraction of the diazonium salt generated during the reaction.
[0004] However, the existing MPP synthesis processes described above have significant technical defects and safety hazards: on the one hand, the diazotization reaction itself has high reactivity, and the controllability of the reaction process requires stringent control; on the other hand, the separation, extraction, temporary storage, and transfer of diazonium salts place extremely high demands on the sealing performance, corrosion resistance, and precise control of process parameters of the production equipment, making operation difficult and posing significant safety risks, resulting in a low inherent safety level of the entire synthesis process. These problems have become the core bottleneck restricting the large-scale production of MPP and hindering the green and industrial application of DNPP and its derivatives.
[0005] Therefore, developing an MPP synthesis process that is green, environmentally friendly, safe, and has simple post-processing steps is of great practical significance and industrial value for breaking through existing technological bottlenecks and promoting the large-scale production and practical industrial application of DNPP and its derivatives. It also conforms to the development trend of greening and safety in the field of energetic materials. Summary of the Invention
[0006] To address the aforementioned shortcomings in existing technologies, this application aims to provide a novel method for synthesizing 3,6-dinitropyrazole[4,3-c]pyrazole. The synthetic method provided in this application uses 3,5-dimethylpyrazole (compound 1) as the starting material, and sequentially undergoes nitrosation, reduction, acetylation, cyclization, and hydrolysis reactions to efficiently synthesize two acetylated isomers of MPP (compounds 5 and 6). This process does not involve the accumulation of hazardous intermediates and has advantages such as simple operation, high safety, excellent yield, and convenient post-processing. It is easy to scale up for production. This has significant practical and industrial value for overcoming existing technological bottlenecks and promoting the large-scale production and practical industrial application of DNPP (compound 7) and its derivatives, and also aligns with the green and safe development trend in the field of energetic materials.
[0007] To achieve the above-mentioned objectives, this application provides a novel method for synthesizing 3,6-dinitropyrazole[4,3-c]pyrazole, comprising the following steps: S1, Compound 1 and the first nitrosating agent undergo a nitrosation reaction in the first solvent to obtain Compound 2. Then, the nitroso group of Compound 2 is reduced by a reducing agent to obtain Compound 3. The reaction route is as follows: ; S2 and compound 3 undergo an acetylation reaction with an acetylation reagent in a second solvent to obtain compound 4. Then, a first base and a second nitrosating reagent are added to carry out a nitrosation reaction to obtain compound 5 and compound 6. The reaction route is as follows: ; S3, compound 5 and compound 6 are reacted in a third solvent to give compound 7, wherein the third solvent contains a second base or acid solution.
[0008] The reaction route is as follows: .
[0009] The beneficial effects of this application include at least the following: using 3,5-dimethylpyrazole (compound 1) as the starting material, through sequential nitrosation, reduction, acetylation, cyclization, and hydrolysis reactions, two acetylated isomers of MPP (compound 5 and compound 6) are efficiently synthesized. This process does not involve the accumulation of hazardous intermediates and has the advantages of simple operation, high safety, excellent yield, and convenient post-processing. It is easy to scale up production. This is of great practical significance and industrial value for breaking through existing technical bottlenecks and promoting the large-scale production and practical industrial application of DNPP (compound 7) and its derivatives. It also conforms to the green and safe development trend in the field of energetic materials. Attached Figure Description
[0010] To more clearly illustrate the technical solutions in the embodiments of this application, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.
[0011] Figure 1 This is the proton NMR spectrum of compound 3 obtained in Example 1 of this application; Figure 2 This is the carbon NMR spectrum of compound 3 obtained in Example 1 of this application; Figure 3 This is the mass spectrum of compound 3 obtained in Example 1 of this application; Figure 4 This is the proton NMR spectrum of compound 5 obtained in Example 1 of this application; Figure 5 This is the carbon NMR spectrum of compound 5 obtained in Example 1 of this application; Figure 6 This is the mass spectrum of compound 5 obtained in Example 1 of this application; Figure 7 This is the proton NMR spectrum of compound 6 obtained in Example 1 of this application; Figure 8 This is the carbon NMR spectrum of compound 6 obtained in Example 1 of this application; Figure 9 This is the proton NMR spectrum of compound 7 obtained in Example 1 of this application; Figure 10 This is the carbon NMR spectrum of compound 7 obtained in Example 1 of this application; Figure 11 This is the mass spectrum of compound 7 obtained in Example 1 of this application. Detailed Implementation
[0012] To make the technical problems, technical solutions, and beneficial effects to be solved by this application clearer, the following detailed description is provided in conjunction with embodiments. It should be understood that the specific embodiments described herein are only for explaining this application, but the implementation of this application is not limited thereto.
[0013] Unless otherwise defined, the technical terms used in the following embodiments have the same meanings as commonly understood by those skilled in the art to which this application pertains. Unless otherwise specified, the experimental reagents used in the following embodiments are conventional biochemical reagents; the amounts of experimental reagents used are, unless otherwise specified, the amounts used in conventional experimental operations; and the experimental methods used are, unless otherwise specified, conventional methods.
[0014] Currently, the mainstream synthesis process of DNPP is as follows: (1) Synthesis of 4-amino-3,5-dimethylpyrazole (ADMP); (2) 4-amino-3,5-dimethylpyrazole (ADMP) is synthesized into 3-methylpyrazole[4,3-c]pyrazole (MPP) through diazotization reaction, diazo product extraction and separation, and cyclization reaction; (3) 3-methylpyrazole[4,3-c]pyrazole is nitrated, oxidized, and decarboxylated to obtain DNPP.
[0015] In step (1), the synthesis route of ADMP mainly includes reaction route A and reaction route B; wherein, in reaction route A, pentanedione is used as raw material, and an oxime group is introduced at the 3 position of pentanedione through oxime reaction, and then 4-nitroso-3,5-dimethylpyrazole is generated through cyclization reaction with hydrazine hydrate. Finally, the nitroso group is reduced by hydrazine hydrate to generate an amino group, thereby generating ADMP; Reaction route A is as follows: Reaction route B uses pentanedione as a raw material, which is first cyclized with hydrazine hydrate to generate 3,5-dimethylpyrazole. Then, under the action of nitric acid and sulfuric acid, a nitro group is introduced at the 4-position of the pyrazole. Finally, reduced iron powder is used to reduce the nitro group to an amino group. Reaction route B is as follows: .
[0016] For reaction route A, optimization focuses on optimizing the optimal conditions for the oxime reaction and proposing a one-pot reaction method (such as a three-step one-pot reaction involving oxime, cyclization, and reduction). For reaction route B, optimization focuses on optimizing the post-treatment of the nitration reaction, such as adjusting the pH of the reaction solution after nitration, or the effect of different solvents on the yield of the subsequent cyclization reaction of the diazo product. However, in the synthesis route of ADMP, the conditions for introducing a nitro group onto the pyrazole ring using a nitric-sulfuric acid mixture are quite demanding, the reproducibility of the two-step / one-pot method is low, and it is prone to generating byproducts.
[0017] In step (2), there are significant technical defects and safety hazards: on the one hand, the diazotization reaction itself has high reactivity, and the controllability of the reaction process is strictly required; on the other hand, the separation, extraction, temporary storage, and transfer of diazonium salts place extremely high demands on the sealing performance, corrosion resistance, and precise control of process parameters of the production equipment, making the operation difficult and posing significant safety risks, resulting in a low inherent safety level of the entire synthesis process. The above problems have become the core bottleneck restricting the large-scale production of MPP and hindering the green and industrial application of DNPP and its derivatives.
[0018] In view of this, this application provides a novel method for synthesizing 3,6-dinitropyrazole[4,3-c]pyrazole. This method has significant advantages over existing technologies, specifically as follows: Firstly, addressing the issue that existing synthetic routes for 4-amino-3,5-dimethylpyrazole (ADMP) require strong acids and stringent reaction conditions, this application uses compound 1 as a raw material, reacting it with a first nitrosating reagent in a first solvent to generate compound 2 containing nitroso groups. Then, a reducing agent is used to reduce the nitroso groups in compound 2 to obtain compound 3. This route does not require strong acids, and nitroso groups are more easily reduced to amino groups than nitro groups. The reaction conditions are mild, environmentally friendly, and the operation process is simple. On the other hand, in view of the problems of existing synthetic routes for 3-methylpyrazole[4,3-c]pyrazole (MPP, a key precursor of DNPP) that rely on diazonium salt separation and extraction, pose safety hazards, and have complex post-processing, this application adopts a new route for synthesizing MPP by first acetylation of 4-amino-3,5-dimethylpyrazole, then nitrosation, and then cyclization reaction. Its reaction mechanism is the in-situ generation of diazonium salt, which can completely avoid the accumulation of dangerous diazonium intermediates and separation and extraction operations. This not only greatly improves the safety of the reaction and the product yield, but also simplifies the post-processing and makes it easy to realize industrial scale-up production.
[0019] This application provides a novel method for synthesizing 3,6-dinitropyrazole[4,3-c]pyrazole, comprising the following steps: S1, Compound 1 and the first nitrosating agent undergo a nitrosation reaction in the first solvent to obtain Compound 2. Then, the nitroso group of Compound 2 is reduced by a reducing agent to obtain Compound 3. The reaction route is as follows: ; S2 and compound 3 undergo an acetylation reaction with an acetylation reagent in a second solvent to obtain compound 4. Then, a first base and a second nitrosating reagent are added to carry out a nitrosation reaction to obtain compound 5 and compound 6. The reaction route is as follows: ; S3, compound 5 and compound 6 are reacted in a third solvent to give compound 7, wherein the third solvent contains a second base or acid solution.
[0020] The reaction route is as follows: .
[0021] In some embodiments, in step S1, the molar ratio of compound 1 to the first nitrosating agent is 1:1.2 to 2. Specifically, the molar ratio can be 1:1.2, 1:1.5, 1:1.8 or 1:2, etc.
[0022] In some embodiments, in step S1, the first solvent is selected from acetonitrile, N,N-dimethylformamide, tetrahydrofuran, ethyl acetate, tert-butanol, and methanol.
[0023] In some embodiments, in step S1, the reaction temperature of the nitrosation reaction is 60 ℃ to 80 ℃. Specifically, the reaction temperature of the nitrosation reaction can be 60 ℃, 65 ℃, 70 ℃, 75 ℃ or 80 ℃, etc.
[0024] In some embodiments, in step S1, the first nitrosating agent is selected from tert-butyl nitrite and isoamyl nitrite.
[0025] In some embodiments, in step S1, the reducing agent is selected from zinc powder and Pd / C.
[0026] In some embodiments, in step S2, the molar ratio of compound 3, acetylation reagent, first base, and second nitrosating reagent is 1:3~6:0.2~1:1.2~2.
[0027] In some embodiments, in step S2, the second nitrosating agent is selected from tert-butyl nitrite and isoamyl nitrite.
[0028] In some embodiments, in step S2, the acetylation reagent is selected from acetic anhydride and acetic acid.
[0029] In some embodiments, in step S2, the second solvent is selected from ethyl acetate, isopropyl acetate, toluene, xylene, benzene, and tetrahydrofuran.
[0030] In some embodiments, in step S2, the first base is selected from potassium acetate, triethylamine, 1,8-diazabicyclo[5.4.0]undec-7-ene, and 2,6-dimethylpyridine.
[0031] In some embodiments, in step S2, the reaction temperature of the nitrosation reaction is 25 ℃ to 82 ℃, for example, the reaction temperature of the nitrosation reaction is 25 ℃, 30 ℃, 35 ℃, 40 ℃, 50 ℃, 60 ℃, 70 ℃, 82 ℃, etc.
[0032] In some embodiments, in step S3, the second base is selected from sodium hydroxide and potassium hydroxide.
[0033] In some embodiments, in step S3, the acid solution is selected from acetic acid solution, hydrochloric acid solution, and sulfuric acid solution.
[0034] In some embodiments, the reaction temperature in step S3 is 40 ℃ to 70 ℃, for example, it can be 40 ℃, 50 ℃, 60 ℃ or 70 ℃.
[0035] This application has undergone multiple experiments, and some of the test results are presented here for reference to further describe the invention in detail. The following is a detailed description in conjunction with specific embodiments.
[0036] Example 1 first step: ; Synthesis of Compound 2 (4-nitroso-3,5-dimethylpyrazole): 0.96 g (10 mmol) of 3,5-dimethylpyrazole (Compound 1) was added to 20 mL of the first solvent (acetonitrile) and stirred until dissolved. Then, 1.15 g (90%, 10 mmol) of the first nitrosating agent (tert-butyl nitrite) was added dropwise. After the addition was complete, the mixture was heated to 40 °C and reacted for 5 hours. After the reaction was completed, the mixture was concentrated under vacuum and purified by column chromatography (elution: petroleum ether: ethyl acetate = 10:1) to give 1.02 g of blue solid 4-nitroso-3,5-dimethylpyrazole (Compound 2) in 81.6% yield.
[0037] Synthesis of Compound 3 (4-amino-3,5-dimethylpyrazole): 0.48 g (5 mmol) of 4-nitroso-3,5-dimethylpyrazole was added to 20 mL of acetonitrile and stirred until dissolved. The mixture was heated to 40 °C, and 0.859 g (7.5 mmol) of 90% tert-butyl nitrite was added dropwise. After the addition was complete, the mixture was heated to 65 °C and reacted for 5 hours. After the reaction was completed, the solution was cooled to room temperature, and 20 mL of 6M hydrochloric acid aqueous solution and 4.9 g (75 mmol) of zinc powder were added with stirring. The mixture was heated to 50 °C and reacted for 4 hours. After the reaction was completed, excess zinc powder was removed by filtration, and 20 mL of water was added to adjust the pH of the solution to 7-8. The solution was concentrated under reduced pressure, cooled, and allowed to stand. A white solid precipitated out. The solid was filtered, washed with water, and dried to obtain 0.41 g of white solid 4-amino-3,5-dimethylpyrazole (Compound 3), with a yield of 74.8%.
[0038] Step Two: ; Synthesis of compounds 4, 5 and 6: 1.11 g (10 mmol) of 4-amino-3,5-dimethylpyrazole (compound 3) was added to 50 mL of ethyl acetate, and 3.06 g (30 mmol) of acetic anhydride was added dropwise. The mixture was stirred at room temperature for 1 hour. After the reaction was complete, compound 4 was obtained. Then, 10 mmol of the first base (potassium acetate) and 1.30 g (90%, 10) were added. The second nitrosating agent (isoamyl nitrite) was heated to 40°C and reacted for 22 hours. After the reaction was completed, a solid precipitated upon cooling. The solid was filtered, washed with ethyl acetate and water to obtain solid product A. The filtrate was concentrated by rotary evaporation, cooled, filtered, and washed with water to obtain solid product B. Solid products A and B were combined, purified by recrystallization, and dried to obtain a grayish-white solid mixture, namely a mixture of 1,1'-(3-methylpyrazolo[4,3-c]pyrazol-1,5-diyl)bis(ethane-1-one) (compound 5) and 1,1'-(6-methylpyrazolo[4,3-c]pyrazol-1,5-diyl)bis(ethane-1-one) (compound 6), totaling 1.62 g, with a yield of 78.6%. This mixture could be separated by recrystallization or column chromatography to obtain compounds 5 and 6.
[0039] Step 3: ; Synthesis of Compound 7 (3-methylpyrazolo[4,3-c]pyrazole): A mixture (1.62 g, 7.86 mmol) of 1,1'-(3-methylpyrazolo[4,3-c]pyrazole-1,5-diyl)bis(ethane-1-one) (Compound 5) and 1,1'-(6-methylpyrazolo[4,3-c]pyrazole-1,5-diyl)bis(ethane-1-one) (Compound 6) was added to 10 mL of methanol. 0.22 g (3.93 mmol) of a second base (potassium hydroxide) was added under stirring. The mixture was heated to 60 °C and reacted for 1.5 h. After the reaction was complete, 20 mL of water was added, and the pH of the solution was adjusted to 7-8 using hydrochloric acid aqueous solution. The solution was concentrated by rotary evaporation, cooled, filtered, washed with water, and dried to give 0.88 g of yellow solid 3-methylpyrazolo[4,3-c]pyrazole (Compound 7), with a yield of 91.7%.
[0040] The obtained yellow solids (compound 3), compound 5, compound 6 and compound 7 were identified as follows: The proton NMR spectrum of the yellow solid (compound 3) is shown below. Figure 1 As shown, 1 H NMR (600MHz, Methanol, d4) δ: 4.92 (s, 2H), 2.14 (s, 6H). The carbon NMR spectrum of the yellow solid (compound 3) is shown below. Figure 2 As shown,13 C NMR (151MHz, Methanol-d4) δ: 123.12, 9.57. The mass spectrum of the yellow solid (compound 3) is as follows: Figure 3 As shown.
[0041] The obtained compounds 5 and 6 were identified as follows: The proton NMR spectrum of compound 5 is shown below. Figure 4 As shown, 1 H NMR (400 MHz, Chloroform-d) δ:7.87 (s, 1H), 2.68 (s, 3H), 2.64 (s, 3H), 2.61 (s, 3H). The carbon NMR spectrum of compound 5 is shown below. Figure 5 As shown, 13 C NMR (101 MHz, CDCl3) δ: 169.37, 168.64, 138.84, 138.51, 137.74, 128.18, 21.51, 21.03. The mass spectrum of compound 5 is as follows: Figure 6 As shown.
[0042] The proton NMR spectrum of compound 6 is shown below. Figure 7 As shown, 1 H NMR (400 MHz, Chloroform-d) δ: 8.41 (s, 1H), 2.79 (s, 3H), 2.60 (s, 3H), 2.56 (s, 3H). The carbon NMR spectrum of compound 6 is shown below. Figure 8 As shown, 13 C NMR (101 MHz, CDCl3) δ: 171.20, 167.61, 152.98, 144.03, 130.44, 111.39, 21.98, 20.94. The proton NMR spectrum of compound 7 is shown below. Figure 9 As shown, 1 H NMR (600 MHz, DMSO-d6) δ: 12.30 (s, 1H), 12.00 (s, 1H), 7.36 (s, 1H), 2.33 (s, 3H). The carbon NMR spectrum of compound 7 is shown below. Figure 10 As shown, 13C NMR (151 MHz, DMSO) δ: 139.17, 137.32, 125.89, 118.02, 12.57. The mass spectrum of compound 7 is as follows: Figure 11 As shown.
[0043] Example 2 first step: Synthesis of compound 2 (4-nitroso-3,5-dimethylpyrazole): same as in Example 1.
[0044] Synthesis of compound 3 (4-amino-3,5-dimethylpyrazole): 1.25 g (10 mmol) of 4-nitroso-3,5-dimethylpyrazole was added to 25 mL of ethanol and stirred until dissolved. 0.213 g (1 mol%) of 5% Pd / C was added, and the mixture was reacted with hydrogen gas at 60 °C for 4 h. After the reaction was complete, the mixture was filtered, concentrated by rotary evaporation, cooled, filtered again, and recrystallized to obtain 1.02 g of white solid 4-amino-3,5-dimethylpyrazole (compound 3), with a yield of 92%.
[0045] Step 2: Same as in Example 1.
[0046] Step 3: Same as in Example 1.
[0047] Example 3 Step 1: Synthesis of Compound 2 (4-nitroso-3,5-dimethylpyrazole): 0.96 g (10 mmol) of 3,5-dimethylpyrazole (Compound 1) was added to 20 ml of the first solvent (ethyl acetate) and stirred until dissolved. Then, 2.29 g (90%, 20 mmol) of the first nitrosating agent (tert-butyl nitrite) was added dropwise. After the addition was complete, the mixture was heated to 80 °C and reacted for 3 hours. After the reaction was completed, the mixture was concentrated under vacuum and purified by column chromatography (elution: petroleum ether: ethyl acetate = 10:1) to give 0.98 g of blue solid 4-nitroso-3,5-dimethylpyrazole (Compound 2) in a yield of 76.6%.
[0048] Synthesis of compound 3 (4-amino-3,5-dimethylpyrazole): same as in Example 1.
[0049] Step 2: Same as in Example 1.
[0050] Step 3: Same as in Example 1.
[0051] Example 4 Step 1: Synthesis of Compound 2 (4-nitroso-3,5-dimethylpyrazole): 0.96 g (10 mmol) of 3,5-dimethylpyrazole (Compound 1) was added to 20 ml of the first solvent (tetrahydrofuran) and stirred until dissolved. Then, 2.29 g (90%, 20 mmol) of the first nitrosating agent (amyl nitrite) was added dropwise. After the addition was complete, the mixture was heated to 80 °C and reacted for 3 hours. After the reaction was completed, the mixture was concentrated under vacuum and purified by column chromatography (elution: petroleum ether: ethyl acetate = 10:1) to obtain 0.96 g of blue solid 4-nitroso-3,5-dimethylpyrazole (Compound 2) in 75% yield.
[0052] Synthesis of compound 3 (4-amino-3,5-dimethylpyrazole): same as in Example 1.
[0053] Step 2: Same as in Example 1.
[0054] Step 3: Same as in Example 1.
[0055] Example 5 Step 1: Same as in Example 1.
[0056] Step 2: Synthesis of compounds 4, 5, and 6: 1.11 g (10 mmol) of 4-amino-3,5-dimethylpyrazole (compound 3) was added to 50 ml of toluene, and 6.12 g (60 mmol) of acetic anhydride was added dropwise. The mixture was stirred at room temperature for 1 hour. After the reaction was complete, compound 4 was obtained. Then, 10 mmol of the first base (1,8-diazabicyclo[5.4.0]undec-7-ene) and 2.60 g (90%, 20) were added. The second nitrosating agent (isoamyl nitrite) was heated to 80°C and reacted for 22 hours. After the reaction was completed, a solid precipitated upon cooling. The solid was filtered, washed with ethyl acetate and water to obtain solid product A. The filtrate was concentrated by rotary evaporation, cooled, filtered, and washed with water to obtain solid product B. Solid products A and B were combined, purified by recrystallization, and dried to obtain a grayish-white solid mixture, namely a mixture of 1,1'-(3-methylpyrazolo[4,3-c]pyrazol-1,5-diyl)bis(ethane-1-one) (compound 5) and 1,1'-(6-methylpyrazolo[4,3-c]pyrazol-1,5-diyl)bis(ethane-1-one) (compound 6), totaling 1.58 g, with a yield of 71.8%.
[0057] Step 3: Same as in Example 1.
[0058] Example 6 Step 1: Same as in Example 1.
[0059] Step 2: Synthesis of compounds 4, 5, and 6: 1.11 g (10 mmol) of 4-amino-3,5-dimethylpyrazole (compound 3) was added to 50 mL of tert-butanol, followed by the dropwise addition of 6.12 g (60 mmol) of acetic anhydride. The mixture was stirred at room temperature for 1 hour. After the reaction was complete, compound 4 was obtained. Then, 10 mmol of the first base (2,6-dimethylpyridine) and 2.60 g (90%, 20) were added. The second nitrosating agent (tert-butyl nitrite) was heated to 70°C and reacted for 22 hours. After the reaction was completed, a solid precipitated upon cooling. The solid was filtered, washed with ethyl acetate and water to obtain solid product A. The filtrate was concentrated by rotary evaporation, cooled, filtered, and washed with water to obtain solid product B. Solid products A and B were combined, purified by recrystallization, and dried to obtain a grayish-white solid mixture, namely a mixture of 1,1'-(3-methylpyrazolo[4,3-c]pyrazol-1,5-diyl)bis(ethane-1-one) (compound 5) and 1,1'-(6-methylpyrazolo[4,3-c]pyrazol-1,5-diyl)bis(ethane-1-one) (compound 6), totaling 1.55 g, with a yield of 70.5%.
[0060] Step 3: Same as in Example 1.
[0061] Comparative Example 1 Except for replacing the first nitrosating agent in the synthesis step of compound 2 (4-nitroso-3,5-dimethylpyrazole) in the first step with sodium nitrite, and replacing the second nitrosating agent in the synthesis steps of compounds 5 and 6 in the second step with sodium nitrite, the other steps and process conditions are the same as in Example 1.
[0062] The yield of compound 2 obtained in Comparative Example 1 was only 23.8%, and the total yield of the mixture of compounds 5 and 6 was only 31.2%. Therefore, when sodium nitrite was used as the first nitrosation reagent in the first nitrosation reaction, the yield of the target product compound 2 was significantly lower than that when tert-butyl nitrite or isoamyl nitrite was used as the first nitrosation reagent (81.6%); and when sodium nitrite was used as the second nitrosation reagent in the second nitrosation reaction, the total yield of the target product (the mixture of compounds 5 and 6) was significantly lower than that when tert-butyl nitrite or isoamyl nitrite was used as the second nitrosation reagent (78.6%).
[0063] In summary, the novel method for synthesizing 3,6-dinitropyrazole[4,3-c]pyrazole provided in this application has significant advantages over existing technologies, specifically as follows: On the one hand, addressing the problem that existing synthetic routes for 4-amino-3,5-dimethylpyrazole (ADMP) require strong acids and harsh reaction conditions, this application uses 3,5-dimethylpyrazole as the starting material and tert-butyl nitrite or isoamyl nitrite as the first nitrosating agent to synthesize 4-nitroso-3,5-dimethylpyrazole via nitrosation, followed by a reduction reaction to obtain 4-amino-3,5-dimethylpyrazole. This route does not require the use of strong acids, and the nitrosyl group is more easily reduced to an amino group than the nitro group. The reaction conditions are mild, environmentally friendly, and the operation process is simple. On the other hand, addressing the issues of existing synthetic routes for 3-methylpyrazole[4,3-c]-pyrazole (MPP, a key precursor of DNPP) relying on diazonium salt separation and extraction, posing safety hazards, and involving complex post-processing, this application adopts a novel route to synthesize the acetylated product of 3-methylpyrazole[4,3-c]-pyrazole (MPP) via acetylation, nitrosation, and cyclization of 4-amino-3,5-dimethylpyrazole. The reaction mechanism involves in-situ generation of diazonium salts, which completely avoids the accumulation and separation / extraction of hazardous diazonium intermediates. This not only significantly improves reaction safety and product yield but also simplifies post-processing and facilitates industrial-scale production.
[0064] The above embodiments are only used to illustrate the technical solutions of this application, and are not intended to limit them. Although this application has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of this application, and should all be included within the protection scope of this application.
Claims
1. A novel method for synthesizing 3,6-dinitropyrazole[4,3-c]pyrazole, characterized in that, Includes the following steps: S1, Compound 1 and the first nitrosating agent undergo a nitrosation reaction in the first solvent to obtain Compound 2. Then, the nitroso group of Compound 2 is reduced by a reducing agent to obtain Compound 3. The reaction route is as follows: ； S2 and compound 3 undergo an acetylation reaction with an acetylation reagent in a second solvent to give compound 4. Then, a first base and a second nitrosating reagent are added to carry out a nitrosation reaction to give compounds 5 and 6. The reaction route is as follows: ； S3, compound 5 and compound 6 are reacted in a third solvent to give compound 7, wherein the third solvent contains a second base or acid solution. The reaction route is as follows: 。 2. The novel method for synthesizing 3,6-dinitropyrazole[4,3-c]pyrazole according to claim 1, characterized in that, In step S1, the molar ratio of compound 1 to the first nitrosating agent is 1:1.2~2.
3. The novel method for synthesizing 3,6-dinitropyrazole[4,3-c]pyrazole according to claim 1, characterized in that, In step S1, the first solvent is selected from acetonitrile, N,N-dimethylformamide, tetrahydrofuran, ethyl acetate, tert-butanol, and methanol.
4. The novel method for synthesizing 3,6-dinitropyrazole[4,3-c]pyrazole according to claim 1, characterized in that, In step S1, the reaction temperature of the nitrosation reaction is 60 ℃~80 ℃.
5. The novel method for synthesizing 3,6-dinitropyrazole[4,3-c]pyrazole according to claim 1, characterized in that, In step S1, the first nitrosating agent is selected from tert-butyl nitrite and isoamyl nitrite; The reducing agent is selected from zinc powder and Pd / C.
6. The novel method for synthesizing 3,6-dinitropyrazole[4,3-c]pyrazole according to claim 1, characterized in that, In step S2, the molar ratio of compound 3, acetylation reagent, first base, and second nitrosation reagent is 1:3~6:0.2~1:1.2~2.
7. The novel method for synthesizing 3,6-dinitropyrazole[4,3-c]pyrazole according to claim 1, characterized in that, In step S2, the second nitrosating agent is selected from tert-butyl nitrite and isoamyl nitrite; The acetylation reagent is selected from acetic anhydride and acetic acid; The second solvent is selected from ethyl acetate, isopropyl acetate, toluene, xylene, benzene, and tetrahydrofuran; The first base is selected from potassium acetate, triethylamine, 1,8-diazabicyclo[5.4.0]undec-7-ene, and 2,6-dimethylpyridine.
8. The novel method for synthesizing 3,6-dinitropyrazole[4,3-c]pyrazole according to claim 1, characterized in that, In step S2, the reaction temperature of the nitrosation reaction is 25 ℃ to 82 ℃.
9. The novel method for synthesizing 3,6-dinitropyrazole[4,3-c]pyrazole according to claim 1, characterized in that, In step S3, the second alkali is selected from sodium hydroxide and potassium hydroxide; The acid solution is selected from acetic acid solution, hydrochloric acid solution, and sulfuric acid solution.
10. The novel method for synthesizing 3,6-dinitropyrazole[4,3-c]pyrazole according to claim 1, characterized in that, In step S3, the reaction temperature is 40 ℃~70 ℃.