Method for continuously and efficiently synthesizing 2, 6-diamino piperazine-1-oxide

Abstract

The invention provides a method for continuously and efficiently synthesizing 2, 6-diamino piperazine-1-oxide, which comprises the following steps: S1, preparing an N-nitroso iminodiacetonitrile solution at room temperature, and stirring and dissolving for 5 minutes; s2, sequentially adding hydroxylamine salt and alkali into a solvent, stirring at room temperature for 10-15 minutes for pre-dissolving, adding a proper amount of metal salt catalyst into the obtained solution, and continuously stirring for 5-10 minutes; s3, exhausting the continuous tubular reactor by using a hydroxylamine solution until the continuous tubular reactor is full of the solution; s4, feeding the N-nitrosoiminodiacetonitrile solution and the hydroxylamine solution into a continuous tubular reactor through a mixer according to a certain proportion by adopting a delivery pump, and optimizing the flow velocity and temperature of the reaction solution and the pressure in the continuous tubular reactor; and S5, enabling the reaction liquid to flow out from an outlet of the continuous tubular reactor, performing suction filtration, washing a filter cake with an alcoholic solution, and drying. The method can obviously improve the reaction rate, reduce the generation of impurities and improve the production efficiency.

Description

Technical Field

[0001] This invention relates to the field of energetic materials technology, specifically to a method for the continuous and efficient synthesis of 2,6-diaminopiperazine-1-oxide. Background Technology

[0002] 2,6-Diamino-3,5-dinitropyrazine-1-oxide (LLM-105) is a novel high-energy, insensitive energetic material. Its synthesis was reported by Lawrence Livermore National Laboratory in 1995. It possesses high energy, low sensitivity, and good thermal stability, making it promising for applications in military and aerospace fields. However, the batch-process preparation of 2,6-diaminopiperazine-1-oxide (DAPO), a precursor to LLM-105, suffers from long reaction times and unstable product quality, often requiring additional purification steps to remove impurities, resulting in high costs. Therefore, there is an urgent need to optimize the production process of 2,6-diaminopiperazine-1-oxide to achieve efficient preparation, improve product purity, and reduce production costs. Summary of the Invention

[0003] To address the problems existing in the prior art, this invention provides a method for the continuous and efficient synthesis of 2,6-diaminopiperazine-1-oxide. To achieve the above objective, this invention is implemented through the following technical solution: This application discloses a method for the continuous and efficient synthesis of 2,6-diaminopiperazine-1-oxide, the structural formula of which is shown below:

[0004] The method includes the following steps: S1. At room temperature, prepare an N-nitrosoimino diacetonitrile solution. After stirring and dissolving for 5 minutes, transfer the N-nitrosoimino diacetonitrile solution to storage bottle A. S2. Add hydroxylamine salt and base to the solvent in sequence, stir at room temperature for 10-15 min for pre-dissolution, then add an appropriate amount of metal salt catalyst to the resulting solution, continue stirring for 5-10 min, and then transfer the hydroxylamine solution to storage bottle B. S3. Use the hydroxylamine solution in storage bottle B to purge the continuous tubular reactor until the continuous tubular reactor is filled with solution. S4. Using a transfer pump, the N-nitrosoimino diacetonitrile solution in storage bottle A and the hydroxylamine solution in S3 are respectively introduced into a continuous tubular reactor through a mixer at a certain ratio. The flow rate, temperature and pressure of the reaction solution in the continuous tubular reactor are adjusted to carry out the reaction to obtain the reaction solution. The reaction solutions obtained from S5 and S4 flow out through the outlet of a continuous tubular reactor. After collecting the reaction solution, it is filtered through container C with a vacuum filtration function. The filter cake is washed with alcohol solution and dried to obtain 2,6-diaminopiperazine-1-oxide.

[0005] Preferably, in step S1, the organic solvent is one or more of methanol, ethanol, isopropanol, ethylene glycol, a methanol-water mixture with a volume ratio of 5:1 to 10:1, and an ethanol-water mixture with a volume ratio of 5:1 to 10:1, and the concentration of the N-nitrosoiminodiacetonitrile solution is 0.1 mol / L to 3 mol / L.

[0006] Preferably, in step S2, the hydroxylamine salt is one or both of hydroxylamine hydrochloride and hydroxylamine sulfate; the base is one or more of triethylamine, sodium hydroxide, sodium methoxide, and sodium carbonate.

[0007] Preferably, in step S2, the solvent is one or more of methanol, ethanol, ethylene glycol, and isopropanol.

[0008] Preferably, in step S2, the metal salt catalyst is one or more of cuprous chloride, cuprous bromide, cuprous iodide, cuprous oxide, ferrous chloride, copper chloride, copper bromide, copper iodide, copper oxide, and ferric chloride.

[0009] Preferably, in step S2, the concentration of the obtained hydroxylamine solution is 0.1 mol / L to 5 mol / L.

[0010] Preferably, in step S4, the volume ratio of N-nitrosoiminodiacetonitrile solution to hydroxylamine solution is 1:1 to 1:15, and the molar ratio of N-nitrosoiminodiacetonitrile to hydroxylamine is 1:1 to 1:3.

[0011] Preferably, in step S4, the material of the continuous tubular reactor is one of silicon carbide, 316L, PTFE, and Hastelloy, and the reactor heat exchange structure has one side as a reaction channel and the upper and lower sides as heat exchange channels.

[0012] Preferably, in step S4, the reaction temperature is 10℃~45℃, the pressure is 0.1~5MPa, and the reaction residence time is 0.1min~5min.

[0013] Preferably, in step S4, the liquid holding capacity of the continuous tubular reactor is 1 mL to 1000 mL, and the reactor flux is 0.1 mL / min to 1000 mL / min.

[0014] The beneficial effects of this invention are as follows: This invention provides a continuous and efficient method for synthesizing 2,6-diaminopiperazine-1-oxide. Using N-nitrosoiminodiacetonitrile and hydroxylamine hydrochloride or hydroxylamine sulfate as starting materials, and under preferred catalyst conditions, a continuous tubular reactor is used to obtain 2,6-diaminopiperazine-1-oxide with good purity and high yield under mild process conditions. Compared with batch reactor processes, this method significantly improves the mass and heat transfer efficiency of the reaction system, can significantly increase the reaction rate, reduce impurity formation, effectively avoid the problem of poor product quality consistency, and can achieve continuous preparation of high-purity 2,6-diaminopiperazine-1-oxide.

[0015] The present invention provides a method for the continuous and efficient synthesis of 2,6-diaminopiperazine-1-oxide, which enables the continuous and efficient preparation of 2,6-diaminopiperazine-1-oxide without the need for additional purification steps and eliminates the risk of material overflow during the nitration process due to impurities. Attached Figure Description

[0016] Figure 1 This is a schematic diagram of the process flow for a continuous and efficient synthesis of 2,6-diaminopiperazine-1-oxide in an embodiment of the present invention. Detailed Implementation

[0017] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention. Example 1: This embodiment discloses a method for the continuous and efficient synthesis of 2,6-diaminopiperazine-1-oxide, comprising the following steps: S1. At room temperature, prepare a 0.5 mol / L N-nitrosoiminodiacetonitrile methanol solution, stir and dissolve for 5 min, and transfer the N-nitrosoiminodiacetonitrile solution to storage bottle A; S2. Add 0.5 mol hydroxylamine hydrochloride and 0.7 mol triethylamine to methanol solution in sequence to prepare 0.5 mol / L hydroxylamine methanol solution. Stir at room temperature for 10-15 min for pre-dissolution. Then add 0.005 mol cuprous iodide to hydroxylamine solution and continue stirring for 5-10 min. Then transfer hydroxylamine solution to storage bottle B. S3. Use a transfer pump to purge the hydroxylamine methanol solution from the continuous tubular reactor until the reactor is full of solution. S4. Using a transfer pump, N-nitrosoiminodiacetonitrile solution and hydroxylamine solution are fed into a continuous tubular reactor via a mixer at rates of 10 mL / min and 12 mL / min, respectively. The temperature of the continuous tubular reactor is adjusted to 25℃, the pressure to atmospheric pressure, and the residence time to 5 min to obtain the reaction solution. S5. The reaction solution flowed out of the outlet of the continuous tubular reactor and was collected in container C, which is equipped with a vacuum filtration function. After filtration, the filter cake was washed with methanol and dried to obtain 2,6-diaminopiperazine-1-oxide, with a yield of 69.4%. Samples were taken and characterized by 1H NMR and mass spectrometry: 1H NMR (500 MHz, DMSO-d6) δ: 6.71 (s, 4H, NH2), 7.31 (s, 2H, CH); ESI-MS, m / z: 127.058 [M+H]+. Example 2: This embodiment discloses a method for the continuous and efficient synthesis of 2,6-diaminopiperazine-1-oxide, comprising the following steps: S1. At room temperature, prepare a 0.5 mol / L N-nitrosoiminodiacetonitrile methanol solution, stir and dissolve for 5 min, and transfer the N-nitrosoiminodiacetonitrile solution to storage bottle A; S2. Add 0.5 mol hydroxylamine hydrochloride and 0.7 mol triethylamine to methanol solution in sequence to prepare 0.5 mol / L hydroxylamine methanol solution. Stir at room temperature for 10-15 min for pre-dissolution. Then add 0.01 mol cuprous iodide to hydroxylamine solution and continue stirring for 5-10 min. Then transfer hydroxylamine solution to storage bottle B. S3. Use a transfer pump to purge the hydroxylamine methanol solution from the continuous tubular reactor until the reactor is full of solution. S4. Using a transfer pump, N-nitrosoiminodiacetonitrile solution and hydroxylamine solution are fed into a continuous tubular reactor via a mixer at rates of 10 mL / min and 15 mL / min, respectively. The temperature of the continuous tubular reactor is adjusted to 35℃, the pressure to atmospheric pressure, and the residence time to 4.5 min to obtain the reaction solution. S5. The reaction liquid flows out of the outlet of the continuous tubular reactor and is collected in container C with a vacuum filtration function. After filtration, the filter cake is washed with methanol and dried to obtain 2,6-diaminopiperazine-1-oxide with a yield of 71.5%. Example 3: This embodiment discloses a method for the continuous and efficient synthesis of 2,6-diaminopiperazine-1-oxide, comprising the following steps: S1. At room temperature, prepare a 1 mol / L N-nitrosoiminodiacetonitrile methanol solution, stir and dissolve for 5 min, and transfer the N-nitrosoiminodiacetonitrile solution to storage bottle A. S2. Add 1 mol of hydroxylamine hydrochloride and 2 mol of triethylamine to the methanol solution in sequence to prepare a 1 mol / L hydroxylamine methanol solution. Stir at room temperature for 10-15 min for pre-dissolution. Then add 0.01 mol of cuprous oxide to the hydroxylamine solution and continue stirring for 5-10 min. Then transfer the hydroxylamine solution to the storage bottle B. S3. Use a transfer pump to purge the hydroxylamine methanol solution from the continuous tubular reactor until the reactor is full of solution. S4. Using a transfer pump, N-nitrosoiminodiacetonitrile solution and hydroxylamine solution are fed into a continuous tubular reactor via a mixer at rates of 10 mL / min and 12 mL / min, respectively. The temperature of the continuous tubular reactor is adjusted to 45℃, the pressure to 0.5 MPa, and the residence time to 3 min to obtain the reaction solution. S5. The reaction liquid flows out of the outlet of the continuous tubular reactor and is collected in container C with a vacuum filtration function. After filtration, the filter cake is washed with methanol and dried to obtain 2,6-diaminopiperazine-1-oxide with a yield of 73.2%. Example 4: This embodiment discloses a method for the continuous and efficient synthesis of 2,6-diaminopiperazine-1-oxide, comprising the following steps: S1. At room temperature, prepare a 1 mol / L N-nitrosoiminodiacetonitrile methanol solution, stir and dissolve for 5 min, and transfer the N-nitrosoiminodiacetonitrile solution to storage bottle A. S2. Add 1 mol of hydroxylamine hydrochloride and 2 mol of sodium hydroxide to methanol solution in sequence to prepare a 1 mol / L hydroxylamine methanol solution. Stir at room temperature for 10-15 min for pre-dissolution. Then add 0.01 mol of copper chloride to the hydroxylamine solution and continue stirring for 5-10 min. Then transfer the hydroxylamine solution to storage bottle B. S3. Use a transfer pump to purge the hydroxylamine methanol solution from the continuous tubular reactor until the reactor is full of solution. S4. Using a transfer pump, N-nitrosoiminodiacetonitrile solution and hydroxylamine solution are fed into a continuous tubular reactor via a mixer at rates of 10 mL / min and 13 mL / min, respectively. The temperature of the continuous tubular reactor is adjusted to 35℃, the pressure to 0.3 MPa, and the residence time to 2 min to obtain the reaction solution. S5. The reaction liquid flows out of the outlet of the continuous tubular reactor and is collected in container C with a vacuum filtration function. After filtration, the filter cake is washed with methanol and dried to obtain 2,6-diaminopiperazine-1-oxide with a yield of 69.7%. Example 5: This embodiment discloses a method for the continuous and efficient synthesis of 2,6-diaminopiperazine-1-oxide, comprising the following steps: S1. At room temperature, prepare a 1 mol / L N-nitrosoiminodiacetonitrile ethanol solution, stir and dissolve for 5 min, and transfer the N-nitrosoiminodiacetonitrile solution to storage bottle A. S2. Add 1 mol of hydroxylamine hydrochloride and 2 mol of triethylamine to the ethanol solution in sequence to prepare a hydroxylamine ethanol solution with a concentration of 1 mol / L. Stir at room temperature for 10-15 min for pre-dissolution. Then add 0.01 mol of cuprous oxide to the hydroxylamine solution and continue stirring for 5-10 min. Then transfer the hydroxylamine solution to the storage bottle B. S3. Use a transfer pump to purge the hydroxylamine ethanol solution from the continuous tubular reactor until the reactor is full of solution. S4. Using a transfer pump, N-nitrosoiminodiacetonitrile solution and hydroxylamine solution are fed into a continuous tubular reactor via a mixer at rates of 5 mL / min and 10 mL / min, respectively. The temperature of the continuous tubular reactor is adjusted to 25℃, the pressure to 0.3 MPa, and the residence time to 2.5 min to obtain the reaction solution. S5. The reaction solution flows out of the outlet of the continuous tubular reactor and is collected in container C, which is equipped with a vacuum filtration function. After filtration, the filter cake is washed with ethanol and dried to obtain 2,6-diaminopiperazine-1-oxide with a yield of 72.6%. In summary, this invention provides a continuous and efficient method for synthesizing 2,6-diaminopiperazine-1-oxide. Using N-nitrosoiminodiacetonitrile and hydroxylamine hydrochloride or hydroxylamine sulfate as starting materials, and under preferred catalyst conditions, the method yields high-purity and high-yield 2,6-diaminopiperazine-1-oxide in a continuous tubular reactor under mild process conditions. Compared with batch reactor processes, this method significantly improves the mass and heat transfer efficiency of the reaction system, substantially increases the reaction rate, reduces impurity formation, effectively avoids the problem of inconsistent product quality, and enables the continuous preparation of high-purity 2,6-diaminopiperazine-1-oxide. The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the present invention 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 the present invention.

Claims

1. A method for the continuous and efficient synthesis of 2,6-diaminopiperazine-1-oxide, characterized in that, Includes the following steps: S1. At room temperature, prepare an N-nitrosoimino diacetonitrile solution. After stirring and dissolving for 5 minutes, transfer the N-nitrosoimino diacetonitrile solution to storage bottle A. S2. Add hydroxylamine salt and base to the solvent in sequence, stir at room temperature for 10-15 min for pre-dissolution, then add an appropriate amount of metal salt catalyst to the resulting solution, continue stirring for 5-10 min, and then transfer the hydroxylamine solution to storage bottle B. S3. Use the hydroxylamine solution in storage bottle B to purge the continuous tubular reactor until the continuous tubular reactor is filled with solution. S4. Using a transfer pump, the N-nitrosoimino diacetonitrile solution in storage bottle A and the hydroxylamine solution in S3 are respectively introduced into a continuous tubular reactor through a mixer at a certain ratio. The flow rate, temperature and pressure of the reaction solution in the continuous tubular reactor are adjusted to carry out the reaction to obtain the reaction solution. The reaction solutions obtained from S5 and S4 flow out through the outlet of a continuous tubular reactor. After collecting the reaction solution, it is filtered through container C with a vacuum filtration function. The filter cake is washed with alcohol solution and dried to obtain 2,6-diaminopiperazine-1-oxide.

2. The method for continuous and efficient synthesis of 2,6-diaminopiperazine-1-oxide according to claim 1, characterized in that, In step S1, the organic solvent is one or more of methanol, ethanol, isopropanol, ethylene glycol, a methanol-water mixture with a volume ratio of 5:1 to 10:1, and an ethanol-water mixture with a volume ratio of 5:1 to 10:1, and the concentration of the N-nitrosoiminodiacetonitrile solution is 0.1 mol / L to 3 mol / L.

3. The method for continuous and efficient synthesis of 2,6-diaminopiperazine-1-oxide according to claim 2, characterized in that, In step S2, the hydroxylamine salt is one or both of hydroxylamine hydrochloride and hydroxylamine sulfate; the base is one or more of triethylamine, sodium hydroxide, sodium methoxide, and sodium carbonate.

4. The method for continuous and efficient synthesis of 2,6-diaminopiperazine-1-oxide according to claim 3, characterized in that, In step S2, the solvent is one or more of methanol, ethanol, ethylene glycol, and isopropanol.

5. The method for continuous and efficient synthesis of 2,6-diaminopiperazine-1-oxide according to claim 4, characterized in that, In step S2, the metal salt catalyst is one or more of cuprous chloride, cuprous bromide, cuprous iodide, cuprous oxide, ferrous chloride, copper chloride, copper bromide, copper iodide, copper oxide, and ferric chloride.

6. The method for continuous and efficient synthesis of 2,6-diaminopiperazine-1-oxide according to claim 5, characterized in that, In step S2, the concentration of the obtained hydroxylamine solution is 0.1 mol / L to 5 mol / L.

7. The method for continuous and efficient synthesis of 2,6-diaminopiperazine-1-oxide according to claim 6, characterized in that, In step S4, the volume ratio of N-nitrosoiminodiacetonitrile solution to hydroxylamine solution is 1:1 to 1:15, and the molar ratio of N-nitrosoiminodiacetonitrile to hydroxylamine is 1:1 to 1:

3.

8. The method for continuous and efficient synthesis of 2,6-diaminopiperazine-1-oxide according to claim 7, characterized in that, In step S4, the material of the continuous tubular reactor is one of silicon carbide, 316L, PTFE, or Hastelloy. The reactor heat exchange structure has one side as a reaction channel and the upper and lower sides as heat exchange channels.

9. The method for continuous and efficient synthesis of 2,6-diaminopiperazine-1-oxide according to claim 8, characterized in that, In step S4, the reaction temperature is 10℃~45℃, the pressure is 0.1~5MPa, and the reaction residence time is 0.1min~5min.

10. The method for continuous and efficient synthesis of 2,6-diaminopiperazine-1-oxide according to claim 9, characterized in that, In step S4, the liquid holdup of the continuous tubular reactor is 1 mL to 1000 mL, and the reactor flux is 0.1 mL / min to 1000 mL / min.

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