A kind of N,N-diacetyl-[1,4,5]oxadiazepine and its preparation method

Abstract

The present invention relates to the technical field of herbicides, and provides an N,N-diacetyl-[1,4,5]oxadiazepane and a preparation method thereof. The method is obtained by reacting N,N-diacetylhydrazine with 2,2-dichlorodiethyl ether in the presence of a base, and specifically includes: further mixing a mixture composed of the N,N-diacetylhydrazine, the 2,2-dichlorodiethyl ether and a solvent with the base so that the mass concentration of the N,N-diacetylhydrazine in the reaction system is below 5% for reaction. The method of the present invention can promote more intramolecular reactions of reaction intermediates rather than intermolecular reactions, improve the selectivity of the reaction, and improve the yield of N,N-diacetyl-[1,4,5]oxadiazepane.

Description

Technical Field

[0001] The present invention relates to the technical field of herbicides, and particularly relates to an N,N-diacetyl-[1,4,5]oxadiazepane and a preparation method thereof. Background Art

[0002] Pinoxaden is mainly used for post-emergence control of annual gramineous weeds in wheat and barley fields, such as Alopecurus aequalis, Alopecurus japonicus, Avena fatua, Lolium perenne, Setaria viridis, Sclerochloa kengyii, Bolboschoenus maritimus and Polypogon fugax, etc. The key intermediate for preparing pinoxaden is N,N-diacetyl-[1,4,5]oxadiazepane, and the structural formula of N,N-diacetyl-[1,4,5]oxadiazepane is as follows:

[0003]

[0004] Currently, the main synthesis method of N,N-diacetyl-[1,4,5]oxadiazepane is the method mentioned in Patent CN1279032C. Specifically, potassium hydroxide powder is first added to a mixture of N,N-diacetylhydrazine and a solvent and dissolved in a reaction kettle. Then, 2,2-dichlorodiethyl ether is slowly added dropwise under heating, and the reaction is kept warm for a period of time. Then, the temperature is lowered and filtered, the mother liquor is desolvated, crystallized, etc. Finally, the product is obtained. However, the method has the defect that the product yield of N,N-diacetyl-[1,4,5]oxadiazepane is low.

[0005] In view of this, the present invention is proposed. Summary of the Invention

[0006] The method mentioned in CN1279032C is to mix N,N-diacetylhydrazine and potassium hydroxide and then slowly add dropwise 2,2-dichlorodiethyl ether. During the reaction process, N,N-diacetylhydrazine first reacts with 2,2-dichlorodiethyl ether to form an intermediate, and this intermediate then undergoes intramolecular cyclization to form N,N-diacetyl-[1,4,5]oxadiazepane. The specific reaction process is as follows:

[0007]

[0008] The present invention further analyzes the obtained reaction product and finds that the reaction product contains the following impurities:

[0009]

[0010] It can be seen from the above impurity structures that during the reaction process, while the intermediate formed by the reaction of N,N-diacetylhydrazine with 2,2-dichlorodiethyl ether undergoes intramolecular cyclization to form N,N-diacetyl-[1,4,5]oxadiazepane, intermolecular reactions will also occur to form impurities, thereby resulting in a reduction in the yield.

[0011] The present invention provides an N,N-diacetyl-[1,4,5]oxadiazepane and a preparation method thereof, aiming to solve the defect of low yield in the preparation of N,N-diacetyl-[1,4,5]oxadiazepane in the prior art.

[0012] Specifically, it is obtained by reacting N,N-diacetylhydrazine with 2,2-dichlorodiethyl ether in the presence of a base, including: further mixing a mixture composed of the N,N-diacetylhydrazine, the 2,2-dichlorodiethyl ether and a solvent with a base so that the mass concentration of the N,N-diacetylhydrazine in the reaction system is below 5% for reaction.

[0013] The 2,2-dichlorodiethyl ether in the present invention is also called 2,2-dichloroethyl ether.

[0014] By first mixing N,N-diacetylhydrazine and 2,2-dichlorodiethyl ether in a solvent and then mixing with a base, and at the same time controlling the mass concentration of N,N-diacetylhydrazine during the reaction to be below 5%, the present invention can effectively avoid the intermolecular reaction of intermediates, thereby improving the product yield.

[0015] Preferably, according to the preparation method of the N,N-diacetyl-[1,4,5]oxadiazepane as described above provided by the present invention, the base is a compound of an alkali metal and / or an alkaline earth metal, and the compound of the alkaline earth metal is a hydroxide of an alkaline earth metal, a carbonate of an alkaline earth metal, an alcoholate of an alkaline earth metal;

[0016] Preferably, the base is one or more of potassium hydroxide, sodium hydroxide, potassium carbonate and potassium ethoxide. Taking potassium hydroxide as an example, when the base is potassium hydroxide, the involved reaction formula is as follows:

[0017]

[0018] Preferably, according to the preparation method of the N,N-diacetyl-[1,4,5]oxadiazepane as described above provided by the present invention, the solvent is one or more of DMSO ((CH3)2SO), sulfolane ((CH2)4SO2), NMP ((CH2)3CONCH3) and DMA (CH3CON(CH3)2);

[0019] Preferably, the solvent is one or more of DMSO, sulfolane and DMA. It is found in the experiment that when the solvent is DMSO, it is more conducive to the dispersion of the substrate and has the best solubility for potassium hydroxide, thereby improving the yield. Therefore, further preferably, the solvent is DMSO.

[0020] Preferably, according to the preparation method of the N,N-diacetyl-[1,4,5]oxadiazepane as described above provided by the present invention, it includes:

[0021] Mix N,N-diacetylhydrazine, 2,2-dichlorodiethyl ether and a solvent so that the mass concentration of N,N-diacetylhydrazine is >5%, and raise the temperature to a reaction system temperature of 80°C or higher, preferably 110°C or higher, and more preferably 110 - 150°C;

[0022] Maintain the temperature of the reaction system above 110°C, and add the mixture containing the base and the solvent to the reaction system so that the mass concentration of N,N-diacetylhydrazine is below 5% and react for 0.05 - 0.2 h to obtain a first product containing N,N-diacetyl-[1,4,5]oxadiazepane.

[0023] Pre-dissolve the base in a solvent to obtain the above mixture, and then add the mixture to the reaction system. In addition to promoting the dispersion of the base in the system, it can also reduce the generation of impurities, thereby improving selectivity. Generally speaking, the mass concentration of the base in the mixture added to the reaction system is within 30%, and when reacting, the mass ratio of the base to N,N-diacetylhydrazine ≥2.156 is sufficient, preferably 2 - 3. In order to further avoid the intermolecular reaction of intermediates, reduce the generation of impurities, and improve the product yield, the mass concentration of the base in the mixture is preferably 5 - 15%.

[0024] Meanwhile, adding the base to the reaction system under high temperature conditions can accelerate the reaction process, but if the temperature is too high, the yield will also decrease.

[0025] Preferably, according to the preparation method of N,N-diacetyl-[1,4,5]oxadiazepane provided by the present invention as described above, the preparation method is carried out by a continuous process, and in the continuous process, when adding the mixture containing the base and the solvent to the reaction system so that the mass concentration of N,N-diacetylhydrazine is below 5% and reacting for 0.05 - 0.2 h, discharge the material.

[0026] It has been found in practice that the method mentioned in CN1279032C will cause a large heat release during the reaction and a high reaction risk level, which is very unfavorable for industrial production. While in the method of the present invention when using a continuous process, the mixture of N,N-diacetylhydrazine, 2,2-dichlorodiethyl ether and DMSO, and the mixture containing the base can be simultaneously fed into a tubular reactor for continuous reaction. By continuously adding the base, it is more conducive to reducing the reaction concentration of intermediates in the continuous reaction device. At the reaction temperature of the present invention, it promotes more intramolecular reactions, thereby improving selectivity. At the same time, this method has the advantages of fast heat exchange, large throughput, high production efficiency, inherent safety, and low reaction risk level.

[0027] In addition, it was found in the experiment that in a continuous reaction, if the reaction time of the material is prolonged, the impurity content will increase, which is not conducive to the improvement of the yield.

[0028] Preferably, according to the preparation method of N,N-diacetyl-[1,4,5]oxadiazepane provided by the present invention as described above, during the reaction, the mass ratio of the N,N-diacetylhydrazine to 2,2-dichlorodiethyl ether is 1:1.85 - 2.5.

[0029] In the method of the present invention, controlling the raw materials in the reaction system within the above ranges is more conducive to the forward progress of the reaction and avoids the generation of impurities.

[0030] Preferably, according to the preparation method of N,N-diacetyl-[1,4,5]oxadiazepane provided by the present invention as described above, it includes:

[0031] Filter the product to remove potassium chloride solid;

[0032] Perform desolvation on the filtrate after filtration to recover the solvent and 2,2-dichlorodiethyl ether therein;

[0033] Add the substrate after desolvation to an alcohol solution for crystallization, filtration, and drying to obtain a second product containing the N,N-diacetyl-[1,4,5]oxadiazepane. The purity of N,N-diacetyl-[1,4,5]oxadiazepane in the second product is ≥91%, and the main impurity is potassium chloride.

[0034] Preferably, according to the preparation method of N,N-diacetyl-[1,4,5]oxadiazepane provided by the present invention as described above, the alcohol solution is an aqueous solution containing at least one of methanol, ethanol, propanol, isopropanol, methoxyisopropanol, and ethoxyethanol; preferably, the volume concentration of alcohol in the alcohol solution is more than 95%.

[0035] The present invention also provides a product prepared by the preparation method of N,N-diacetyl-[1,4,5]oxadiazepane as described above.

[0036] A kind of N,N-diacetyl-[1,4,5]oxadiazepane and its preparation method provided by the present invention, by mixing N,N-diacetylhydrazine, 2,2-dichlorodiethyl ether and a solvent and heating, and then adding a base to the reaction system to make the mass concentration of the N,N-diacetylhydrazine below 5% for reaction. This method can promote more intramolecular reactions of the reaction intermediate rather than intermolecular reactions, improve the selectivity of the reaction, and improve the yield of N,N-diacetyl-[1,4,5]oxadiazepane. Detailed implementation mode

[0037] To make the objectives, technical solutions and advantages of the present invention clearer, the technical solutions in the present invention will be clearly and completely described below. Apparently, the described embodiments are some, but not all, of the embodiments of the present invention. All other embodiments obtained by those of ordinary skill in the art based on the embodiments in the present invention without creative efforts shall fall within the protection scope of the present invention.

[0038] For those not specifying specific techniques or conditions in the embodiments, follow the techniques or conditions described in the literature in this field or according to the product specifications. For reagents or instruments without indicating the manufacturer, they are all conventional products that can be obtained through regular channels. Among them, the content of potassium hydroxide in the potassium hydroxide powder is 91%, and the remaining part is impurities that do not affect the reaction.

[0039] Normal temperature in the present invention refers to 20 ± 15 °C.

[0040] Example 1

[0041] A preparation method of N,N-diacetyl-[1,4,5]oxadiazepane is as follows:

[0042] (1) Raw material preparation:

[0043] Mixture A: Composed of N,N-diacetylhydrazine, 2,2-dichlorodiethyl ether and DMSO. Among them, the mass ratio of N,N-diacetylhydrazine to 2,2-dichlorodiethyl ether is 50:92.5, and the mass concentration of N,N-diacetylhydrazine is 6.73%.

[0044] Mixture B: Composed of potassium hydroxide powder and DMSO. Among them, the mass concentration of potassium hydroxide is 12.63%.

[0045] (2) Preheat mixture A to 120 °C, pump mixture A into a continuous reaction device with pump I. At this time, the temperature in the reaction system is 120 °C. Preheat mixture B to 120 °C and pump it into the reaction system with pump II. Maintain the temperature of this reaction system at 120 °C, and control the pumping amounts of mixture A and mixture B so that the mass concentration of N,N-diacetylhydrazine in the reaction system is 4.1%. After reacting for 0.1 h, discharge the material and collect the product.

[0046] (3) Filter the product obtained in step (2) to remove the potassium chloride solid therein, and collect the filtrate.

[0047] (4) Decant the filtrate obtained in step (3) to recover DMSO and 2,2-dichlorodiethyl ether therein, and collect the substrate; DMSO and 2,2-dichlorodiethyl ether can be reused in step (1) after dehydration.

[0048] (5) The substrate obtained in step (4) is added to a 95% ethanol solution for crystallization at -15°C, then filtered, and the filter cake is dried to obtain the product. The purity of N,N-diacetyl-[1,4,5]oxadiazepane in this product is 95.2% (the main impurity component is potassium chloride), and the yield of N,N-diacetyl-[1,4,5]oxadiazepane reaches 90.3%.

[0049] Example 2

[0050] A preparation method of N,N-diacetyl-[1,4,5]oxadiazepane, the steps of which are basically the same as those in Example 1, except that: DMSO in step (1) is replaced with sulfolane in equal mass.

[0051] Example 3

[0052] A preparation method of N,N-diacetyl-[1,4,5]oxadiazepane, the steps of which are basically the same as those in Example 1, except that: DMSO in step (1) is replaced with NMP in equal mass.

[0053] Example 4

[0054] A preparation method of N,N-diacetyl-[1,4,5]oxadiazepane, the steps of which are basically the same as those in Example 1, except that: DMSO in step (1) is replaced with DMA in equal mass.

[0055] Example 5

[0056] A preparation method of N,N-diacetyl-[1,4,5]oxadiazepane, the steps of which are basically the same as those in Example 1, except that: potassium hydroxide in step (1) is replaced with sodium hydroxide in equal mass.

[0057] Example 6

[0058] A preparation method of N,N-diacetyl-[1,4,5]oxadiazepane, the steps of which are basically the same as those in Example 1, except that: potassium hydroxide in step (1) is replaced with potassium carbonate in equal mass.

[0059] Example 7

[0060] A preparation method of N,N-diacetyl-[1,4,5]oxadiazepane, the steps of which are basically the same as those in Example 1, except that: potassium hydroxide in step (1) is replaced with potassium ethoxide in equal mass.

[0061] Example 8

[0062] A preparation method of N,N-diacetyl-[1,4,5]oxadiazepane, the steps of which are basically the same as those in Example 1, except that: the temperature of each material in step (2) is always maintained at 150 °C.

[0063] Example 9

[0064] A preparation method of N,N-diacetyl-[1,4,5]oxadiazepane, the steps of which are basically the same as those in Example 1, except that: the mass concentration of potassium hydroxide powder in the mixture B in step (1) is reduced to 5%.

[0065] Example 10

[0066] A preparation method of N,N-diacetyl-[1,4,5]oxadiazepane, the steps of which are basically the same as those in Example 1, except that: the temperature of each material in step (2) is always maintained at 110 °C.

[0067] Example 11

[0068] A preparation method of N,N-diacetyl-[1,4,5]oxadiazepane, the steps of which are basically the same as those in Example 1, except that: the mass concentration of N,N-diacetylhydrazine in the mixture A in step (1) is increased to 10%.

[0069] Comparative Example 1

[0070] A preparation method of N,N-diacetyl-[1,4,5]oxadiazepane, the steps of which are basically the same as those in Example 11, except that: in step (2), the pumping amounts of the mixture A and the mixture B are controlled to increase the mass concentration of N,N-diacetylhydrazine in the reaction system to 7%.

[0071] Comparative Example 2

[0072] A preparation method of N,N-diacetyl-[1,4,5]oxadiazepane is as follows:

[0073] (1) Potassium hydroxide powder is added to the mixed solution C of N,N-diacetylhydrazine and DMSO to obtain a mixed solution D;

[0074] (2) 2,2-Dichlorodiethyl ether is added to the mixed solution D at a temperature of 120 °C to obtain a mixed solution E, and the temperature of the mixed solution E is maintained at 120 °C for reaction for 0.1 h and then discharged to collect the product; among them, in the mixed solution E, the contents of N,N-diacetylhydrazine, 2,2-dichlorodiethyl ether and alkali are the same as those in the reaction system of step (2) of Example 1.

[0075] The obtained product was processed according to steps (3) to (5) in Example 1.

[0076] Comparative Example 3

[0077] A method for preparing N,N-diacetyl-[1,4,5]oxadiazepane, the steps are as follows:

[0078] (1) Potassium hydroxide powder was added to the mixed solution F of 2,2-dichlorodiethyl ether and DMSO to obtain a mixed solution G;

[0079] (2) N,N-diacetylhydrazine was added to the mixed solution G at a temperature of 120 °C to obtain a mixed solution H. The temperature of the mixed solution H was maintained at 120 °C for reaction for 0.1 h and then discharged, and the product was collected; among them, in the mixed solution H, the contents of N,N-diacetylhydrazine, 2,2-dichlorodiethyl ether and base were the same as those in the reaction system of step (2) of Example 1.

[0080] The obtained product was processed according to steps (3) to (5) in Example 1.

[0081] Comparative Example 4

[0082] A method for preparing N,N-diacetyl-[1,4,5]oxadiazepane, the steps are as follows:

[0083] (1) The DMSO solution of N,N-diacetylhydrazine and the DMSO solution of 2,2-dichlorodiethyl ether were simultaneously pumped into the DMSO solution of potassium hydroxide, and the temperature of each solution was 120 °C, so that in the reaction system, the contents of N,N-diacetylhydrazine, 2,2-dichlorodiethyl ether and base were the same as those in the reaction system of step (2) of Example 1. The temperature of the reaction system was maintained at 120 °C for reaction for 0.25 h and then discharged, and the product was collected.

[0084] The obtained product was processed according to steps (3) to (5) in Example 1.

[0085] The purities of the corresponding products and the yields of N,N-diacetyl-[1,4,5]oxadiazepane of the methods of Examples 2 to 11 and Comparative Examples 1 to 4 are shown in the following table:

[0086] Purity (%) Yield (%) Example 2 94.1 61 Example 3 92.9 52 Example 4 92.3 66 Example 5 94.2 83 Example 6 93.7 77 Example 7 94.8 55 Example 8 93 84.5 Example 9 95.3 89 Example 10 92 83.3 Example 11 95.7 90.1 Comparative Example 1 92.2 70.3 Comparative Example 2 93.7 68.3 Comparative Example 3 90.2 71.1 Comparative Example 4 89.4 62.2

[0087] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand that they can still modify the technical solutions described in the foregoing embodiments, or perform equivalent replacements for some of the technical features; and these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the various embodiments of the present invention.

Claims

1. A method for preparing N,N-diacetyl-[1,4,5]oxadiazepane, which is obtained by reacting N,N-diacetylhydrazine with 2,2-dichlorodiethyl ether in the presence of a base, characterized in that, Comprising: Mix the N,N-diacetylhydrazine, 2,2-dichlorodiethyl ether and a solvent, and heat up to a reaction system temperature of T °C, where T °C is above 80 °C; Maintain the temperature of the reaction system above T °C, add a mixed solution comprising the base and the solvent to the reaction system to make the mass concentration of the N,N-diacetylhydrazine below 5%, react for 0.05 - 0.2 h and then discharge to obtain a first product containing the N,N-diacetyl-[1,4,5]oxadiazepane; The preparation method is carried out by a continuous process; The base is one or more of potassium hydroxide and sodium hydroxide; The solvent is DMSO; The structural formula of the N,N-diacetyl-[1,4,5]oxadiazepane is as follows: 。 2. The preparation method of N,N-diacetyl-[1,4,5]oxadiazepine according to claim 1, characterized in that, T °C is above 110 °C.

3. The preparation method of N,N-diacetyl-[1,4,5]oxadiazepine according to claim 2, characterized in that, T °C is 110 - 150 °C.

4. The preparation method of N,N-diacetyl-[1,4,5]oxadiazepine according to claim 1, characterized in that, During the reaction, the mass ratio of the N,N-diacetylhydrazine to the 2,2-dichlorodiethyl ether is 1:1.85 - 2.

5.

5. The preparation method of N,N-diacetyl-[1,4,5]oxadiazepine according to claim 1, characterized in that, The mass concentration of the base in the mixed solution added to the reaction system is within 30%.

6. The preparation method of N,N-diacetyl-[1,4,5]oxadiazepine according to claim 5, characterized in that, The mass concentration of the base in the mixed solution added to the reaction system is 5 - 15%.

7. The preparation method of N,N-diacetyl-[1,4,5]oxadiazepine according to any one of claims 1 to 6, characterized in that, Comprising: Filter the first product to remove potassium chloride solid; Carry out desolvation on the filtrate after filtration to recover the solvent and 2,2-dichlorodiethyl ether therein; Add the substrate after desolvation to an alcohol solution for crystallization, filtration, and drying to obtain a second product containing the N,N-diacetyl-[1,4,5]oxadiazepane, and the purity of the N,N-diacetyl-[1,4,5]oxadiazepane in the second product is ≥91%.

8. The preparation method of N,N-diacetyl-[1,4,5]oxadiazepine according to claim 7, characterized in that, The alcohol solution is an aqueous solution containing at least one of methanol, ethanol, propanol, isopropanol, methoxyisopropanol, and ethoxyethanol.

9. The preparation method of N,N-diacetyl-[1,4,5]oxadiazepine according to claim 8, characterized in that, The volume concentration of the alcohol in the alcohol solution is above 95%.

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