Method for safely and efficiently preparing [1, 4, 5] oxadiazepine

Abstract

The invention discloses a method for safely and efficiently preparing [1, 4, 5] oxadiazepine. The method comprises the following steps: by taking N, N '-diacetyl [1, 4, 5] oxadiazepine as a substrate and an acetate solution as an accelerant, carrying out hydrolysis reaction in an alkali solution system at a certain reaction temperature, and carrying out post-treatment to obtain a target product. The preparation method of [1, 4, 5] oxadiazepine provided by the invention has the characteristics of simple operation steps, short reaction time and high yield, effectively reduces the amount of three wastes generated in experiments, and is simple to operate, safe and environment-friendly.

Description

Technical Field

[0001] The invention relates to the field of organic synthesis, and in particular to a method for safely and efficiently preparing [1,4,5]oxydiazepine. Background Art

[0002] [1,4,5] Oxydiazepine is an essential raw material for the synthesis of a new phenylpyrazoline herbicide, pinoxaden. The mechanism of action of pinoxaden is an acetyl-CoA carboxylase (ACC) inhibitor. It blocks fatty acid synthesis, stops cell growth and division, destroys the lipid structure of the cell membrane, and causes weed death. It has systemic conductivity and is mainly used to control annual grass weeds in barley fields. The results of indoor activity tests and field efficacy tests show that it has a good control effect on annual grass weeds in barley fields such as wild oats, foxtail grass, and barnyard grass. Its preparation and synthesis methods have been reported both at home and abroad, mainly in the following two types:

[0003] Synthesis method 1:

[0004]

[0005] Synthesis method 2:

[0006]

[0007] For traditional synthesis methods, the BOC protected hydrazine contained in method one is usually selected, and the highly toxic hydrobromic acid is finally used to remove the BOC protecting group. However, the anhydride containing BOC is expensive, has poor atom economy, and is difficult to produce in large quantities. In addition, the hydrobromic acid introduced by the reaction causes heavy pollution. The conversion rate of N,N'-diacetyl[1,4,5]oxydiazepine in method two is low, resulting in a large waste of raw materials, and the product [1,4,5]oxydiazepine is unstable and prone to decomposition. Therefore, it is urgent to develop a method for preparing [1,4,5]oxydiazepine that is simple to operate, safe and efficient, and has less waste. Summary of the invention

[0008] In view of the above problems, the present invention proposes a method for preparing [1,4,5]oxydiazepine safely and efficiently, which can achieve hydrolysis at a relatively low temperature, has a high conversion rate, and the product liquid is not easy to decompose.

[0009] The method provided by the present invention comprises the steps of:

[0010] A method for preparing [1,4,5]oxydiazepine safely and efficiently comprises the steps of using N,N'-diacetyl[1,4,5]oxydiazepine as a substrate and an acetate solution as a promoter, hydrolyzing the N,N'-diacetyl[1,4,5]oxydiazepine in an alkaline solution system at a certain reaction temperature, and obtaining a target product through post-treatment.

[0011]

[0012] Furthermore, the molar ratio of N,N'-diacetyl[1,4,5]oxydiazepine to acetate is 1:2.0-3.5.

[0013] Furthermore, the molar ratio of N,N'-diacetyl[1,4,5]oxydiazepine to the base is 1:2.0-4.0.

[0014] Furthermore, the alkali is potassium hydroxide, sodium hydroxide, potassium carbonate, or sodium carbonate.

[0015] Furthermore, the acetate is potassium acetate or sodium acetate.

[0016] Furthermore, the reaction temperature is 80-100° C., and the insulation time is 1-6 h.

[0017] Furthermore, the post-treatment refers to reduced pressure filtration, washing, desolventizing after extraction of the mother liquor, and reduced pressure distillation.

[0018] Furthermore, the extractant is dichloromethane, chlorobenzene, or ethyl acetate.

[0019] Furthermore, the desolvation temperature is 25-80°C.

[0020] Furthermore, the reduced pressure distillation temperature is 90-110°C.

[0021] Compared with the existing synthesis method, the present invention has the following significant advantages: (1) the present invention has a fast reaction speed, low heat release, and easy control of the synthesis process; (2) during the synthesis process of the present invention, the unstable intermediate exists in the reaction system for a short time and can be quickly converted into [1,4,5]oxydiazepine, which is significantly safer than the synthesis method 1 in the background technology. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 This is the DSC chart of the product [1,4,5]oxydiazepine in Example 1.

[0023] Figure 2 This is the hydrogen nuclear magnetic resonance spectrum of the product [1,4,5]oxydiazepine in Example 1. DETAILED DESCRIPTION

[0024] In order to explain the technical content, objectives and effects of the present invention in detail, the following is a detailed description with reference to embodiments and drawings.

[0025] Embodiment 1:

[0026] Prepare a solution by mixing 32g of potassium acetate with 10g of water. Prepare a solution by mixing 22g of potassium hydroxide with 14g of water and heat it to 70°C. Add 20g of N,N'-diacetyl[1,4,5]oxydiazepine to the three-necked flask containing the potassium acetate solution, heat it to 90°C and stir until dissolved. Slowly add the potassium hydroxide solution to the three-necked flask. Maintain the reaction temperature at 95°C for 5 hours. After the reaction is completed, filter under reduced pressure, rinse with dichloromethane, extract the mother liquor, and combine the upper organic phases. Remove dichloromethane at 60°C under reduced pressure. Distill under reduced pressure at 100°C to obtain 9.3g of the product with a yield of 84.5%. Its DSC and nuclear magnetic resonance hydrogen spectra are shown as follows: Figure 1 and Figure 2 .

[0027] Embodiment 2:

[0028] Other conditions were the same as those in Example 1. Experiments using different alkaline substances and their acetates were performed. The experimental results are shown in Table 1.

[0029] Table 1 Experiments to test different bases and corresponding cation acetates

[0030]

[0031] From the above results, it can be seen that potassium hydroxide and potassium acetate are preferred (Example 1).

[0032] Embodiment 3:

[0033] The other conditions were the same as those in Example 1. The order of adding acetate and alkali was reversed to test the order of adding alkali and acetate. The experimental results are shown in Table 2.

[0034] Table 2 Experiments with different alkali and acetate addition orders

[0035]

[0036] From the above results, it can be seen that the order of adding base and acetate has almost no effect on the yield.

[0037] Embodiment 4:

[0038] The other conditions were the same as those in Example 1. Experiments were conducted with different molar ratios of substrate to base, i.e., N,N'-diacetyl[1,4,5]oxydiazepine / base. The experimental results are shown in Table 3.

[0039] Table 3 Experiments with different N,N'-diacetyl[1,4,5]oxydiazepine / base molar ratios

[0040]

[0041] From the above results, it can be seen that the molar ratio of N,N'-diacetyl[1,4,5]oxydiazepine / acetate is preferably 1:3.5 (Example 1).

[0042] Embodiment 5:

[0043] Other conditions were the same as those in Example 1. Experiments were conducted with different molar ratios of substrate to acetate, i.e., N,N'-diacetyl[1,4,5]oxydiazepine / acetate. The experimental results are shown in Table 4.

[0044] Table 4 Experiments with different N,N'-diacetyl[1,4,5]oxydiazepine / acetate molar ratios

[0045]

[0046] From the above results, it can be seen that the molar ratio of N,N'-diacetyl[1,4,5]oxydiazepine / acetate is preferably 1:3.0 (Example 1).

[0047] Embodiment 6:

[0048] The other conditions were the same as those in Example 1. The experiments with different reaction temperatures were tested. The experimental results are shown in Table 5.

[0049] Table 5 Experiments with different reaction temperatures

[0050]

[0051] From the above results, it can be seen that the reaction temperature is preferably 95°C (Example 1).

Claims

1. A method for safely and efficiently preparing [1,4,5]oxydiazepine, characterized in that: include: The method comprises the steps of using N,N'-diacetyl[1,4,5]oxydiazepine as a substrate and an acetate solution as a promoter, causing a hydrolysis reaction in an alkaline solution system at a certain reaction temperature, and obtaining a target product through post-treatment.

2. The method according to claim 1, characterized in that The molar ratio of N,N'-diacetyl[1,4,5]oxydiazepine to acetate is 1:2.0-3.

5.

3. The method according to claim 1, characterized in that The molar ratio of N,N'-diacetyl[1,4,5]oxydiazepine to the base is 1:2.0-4.

0.

4. The method according to claim 1, characterized in that The alkali is potassium hydroxide, sodium hydroxide, potassium carbonate, sodium carbonate.

5. The method according to claim 1, characterized in that The acetate is potassium acetate or sodium acetate.

6. The method according to claim 1, characterized in that The reaction temperature is 80-100°C and the insulation time is 1-6h.

7. The method according to claim 1, characterized in that Post-treatment refers to reduced pressure filtration, cleaning, desolventizing after extraction of the mother liquor, and reduced pressure distillation.

8. The method according to claim 7, characterized in that The extractants are dichloromethane, chlorobenzene and ethyl acetate.

9. The method according to claim 7, characterized in that The desolvation temperature is 25-80°C.

10. The method according to claim 7, characterized in that The reduced pressure distillation temperature is 90-110°C.

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