An enoxamacetam amine salt, a preparation method and application thereof

Abstract

The application discloses an enoxamate amine salt, a preparation method and application thereof, the enoxamate amine salt is enoxamate tert-butylamine salt, and a chemical structural formula is as follows: The application discloses enoxamate tert-butylamine salt, and the enoxamate tert-butylamine salt is characterized by various means. The enoxamate tert-butylamine salt prepared in the application has good stability, simultaneously maintains the herbicidal activity of enoxamate, and the stability and the herbicidal activity of the enoxamate tert-butylamine salt prepared in the application are superior to other amine salts of enoxamate reported in the literature. The enoxamate tert-butylamine salt prepared in the application has a low degradation rate in the process of high-temperature heat storage, is easier to store for a long time than enoxamate, and a commercial product thereof can be kept more stable in a shelf life. The enoxamate tert-butylamine salt prepared in the application has a high melting point, is a solid at normal temperature, and can be processed into more various dosage forms as a herbicide, so that the dosage forms of the enoxamate tert-butylamine salt can be expanded from the current emulsifiable concentrate (EC) to new dosage forms such as water dispersible granules (WG) and wettable powders (WP), and the commercial prospect is good.

Description

Technical Field

[0001] The present application relates to the field of agricultural herbicides, and in particular to a clethodim salt, a preparation method and application thereof. Background Art

[0002] Clethodim, whose Chinese chemical name is 2-{1-[(3-chloro-2-allyl)oxy]iminopropyl}-5-[2-(ethylthio)propyl]-3-hydroxy-2-cyclohexene-1-one, is a cyclohexanedione herbicide with excellent herbicidal activity. Currently, the commercially available industrialized clethodim product is a liquid with an ingredient content of 86-93%. The clethodim structure contains multiple non-adjacent carbon-carbon double bonds and oxime functional groups, which make it unstable, susceptible to external conditions, prone to configurational inversion, and sensitive to ultraviolet light, heat, strong acids, and strong bases. Therefore, it is prone to decomposition during long-term transportation and storage, resulting in a reduced clethodim content in the product and a weakened herbicidal efficacy. Once clethodim decomposes, the content of the active ingredient decreases, which has a serious impact on the subsequent dosage form processing and efficacy. Therefore, it is very important to reduce the decomposition rate of clethodim technical and formulations during storage, improve stability, and increase the content of the active ingredient. At the same time, the clethodim preparations currently available on the market are all emulsifiable concentrates (EC), such as 240EC and 360EC formulations, and there are no solid formulations such as water-dispersible granules (WG) or wettable powders (WP), which also limits the application scenarios and commercial uses of clethodim.

[0003] Different clethodim salts may have different stabilities, different physical and chemical properties, and may also have different herbicidal activities and different efficacy. Different clethodim salts may have different efficacy and effects, and the dosage form and performance of economically important preparations may be different.

[0004] Therefore, there is a need to develop new clethodim derivatives that exhibit one or more improved properties, such as improved storage stability, improved herbicidal activity, and efficacy. Summary of the Invention

[0005] In order to solve the problems of poor stability of clethodim and rapid weakening of herbicidal efficacy, a clethodim amine salt, a preparation method and application thereof are provided.

[0006] The first invention objective of this application is achieved through the following technical solutions:

[0007] A clethodim-amine salt, which is clethodim-t-butylamine salt, has the following chemical structure:

[0008]

[0009] Optionally, the alkylamino salt of clethodim can be characterized by one or more of the following, including but not limited to high performance liquid chromatography (HPLC), nuclear magnetic resonance (HNMR), differential scanning calorimetry (DSC) curve showing an endothermic melting peak at 104℃ and a melting range of 93-107℃.

[0010] By adopting the technical solutions described above, the present application confirms the structure of the alkylamino salt of clethodim, including but not limited to nuclear magnetic resonance (HNMR) and differential scanning calorimetry (DSC), as shown in the accompanying Figure 1 HNMR spectrum of the alkylamino salt of clethodim of the present application, as shown in the accompanying Figure 2 HNMR spectrum of the alkylamino salt of clethodim of the present application, as shown in the accompanying

[0011] The alkylamino salt of clethodim prepared by the present application has good stability, which is better than that of clethodim and other alkylamino salts of clethodim, and also maintains the herbicidal activity of clethodim; the degradation rate of the alkylamino salt of clethodim during high-temperature heat storage is lower than that of clethodim and other alkylamino salts of clethodim reported in the literature, and it is easier to store for a long time than clethodim.

[0012] The above second invention purpose of the present application is achieved by the following technical solutions:

[0013] A preparation method of the alkylamino salt of clethodim,

[0014] S1: dissolving clethodim in a solvent to obtain a mixture A;

[0015] S2: adding tert-butylamine in the mixture A for reaction, and after the reaction is completed, the alkylamino salt of clethodim is precipitated from the reaction system;

[0016] S3: separating the precipitate to obtain the alkylamino salt of clethodim.

[0017] By adopting the technical solutions described above, the method for preparing the alkylamino salt of clethodim is simple, the process is mature and stable, and the yield is high and the production cost is low. Compared with the current commercial clethodim technical material, the content of the alkylamino salt of clethodim product can be significantly improved.

[0018] Optionally, the reaction temperature in S2 is -5℃ to 45℃.

[0019] By adopting the technical solutions described above, the reaction conditions of the preparation method of the present application are mild, and the process is mature and safe.

[0020] Optionally, the molar ratio of clethodim to tert-butylamine in S2 is (1:1.2) to (1:1).

[0021] By adopting the technical solutions described above, the yield and content of the alkylamino salt of clethodim product are high.

[0022] Optionally: the alkene ketone amine salt obtained by S3 is further washed and purified.

[0023] By adopting the technical scheme, the content of the alkene ketone tert-butylamine salt product is high.

[0024] The above third application purpose of the present application is realized by the following technical scheme:

[0025] The application of the above alkene ketone amine salt on herbicides.

[0026] By adopting the technical scheme, the stability and herbicidal efficacy of the alkene ketone tert-butylamine salt are good, which is expected to be prepared into a commercialized preparation with economic value, and has superior storage stability and good efficacy.

[0027] In summary, the present application has at least the following beneficial effects:

[0028] 1. The present application discloses alkene ketone tert-butylamine salt and characterizes it by various means; the long-term storage stability of the alkene ketone tert-butylamine salt of the present application is improved, which is not only superior to alkene ketone, but also superior to other alkene ketone amine salts, and has excellent herbicidal activity while improving stability; and the stability and herbicidal activity of the alkene ketone tert-butylamine salt prepared by the present application are superior to other alkene ketone amine salts reported in the literature;

[0029] 2. The preparation method of the present application has mild reaction conditions, mature process, good stability, high yield and low production cost; compared with the current commercial alkene ketone technical material, the content of the alkene ketone amine salt product can be significantly improved;

[0030] 3. The alkene ketone tert-butylamine salt of the present application is conducive to the preparation of a commercialized preparation with economic value, and has superior storage stability and good efficacy; the alkene ketone tert-butylamine salt of the present application has a lower degradation rate than alkene ketone and other alkene ketone amine salts reported in the literature during high-temperature heat storage, and is more easily stored for a long time than alkene ketone, which is conducive to the shelf life stability of commercialized products, and at the same time, is conducive to changing the current single commercialization of alkene ketone dosage forms, such as expanding to new dosage forms of alkene ketone solid preparations, such as water dispersible granules (WG) or wettable powders (WP), etc., which has good commercialization prospects. BRIEF DESCRIPTION OF DRAWINGS

[0031] The various features and aspects of the embodiments of the present application disclosed herein can be more clearly understood by referring to the attached drawings, which are intended to illustrate and explain and not to limit the scope of the present application, and wherein:

[0032] Figure 1 . is the nuclear magnetic hydrogen spectrum (HNMR) diagram of alkene ketone tert-butylamine salt.

[0033] Figure 2is a differential scanning calorimetry (DSC) graph of the alkoxycarbonyl amine salt of clethodim. DETAILED DESCRIPTION

[0034] Example 1

[0035] An alkoxycarbonyl amine salt of clethodim, which is a tert-butyl amine salt of clethodim, has the following chemical structure:

[0036]

[0037] The preparation method of the tert-butyl amine salt of clethodim is as follows:

[0038] S1: 40.2 g of clethodim technical material (89.5 wt%, 0.10 mol) and 25 g of solvent A were stirred and mixed uniformly at a temperature of 16°C, the temperature was raised to a mixing temperature of 18°C, and 7.39 g of tert-butyl amine liquid (99 wt%, 0.1 mol) was added at a constant rate for 5 min, and after the addition was completed, the mixture was stirred at 18°C for 1.0 h, and then 120.0 g of solvent B was added to obtain a mixture A;

[0039] S2: The reaction was continued to be stirred at 15°C for 5.0 h to obtain a reaction material;

[0040] S3: The reaction material was filtered to obtain a solid;

[0041] S4: The solid was washed with 5 times the mass of solvent B, and after washing, it was vacuum dried at 20°C to obtain the product tert-butyl amine salt of clethodim.

[0042] The solvent A is toluene, and the solvent B is cyclohexane.

[0043] Examples 2-7

[0044] An alkoxycarbonyl amine salt of clethodim, which is a tert-butyl amine salt of clethodim, has the following chemical structure:

[0045] Table 1. Preparation method parameter table of examples 1-7

[0046]

[0047]

[0048] The products obtained in examples 1-7 were detected by high performance liquid chromatography (HPLC) and the yield was calculated, and the results are shown in Table 2.

[0049] Table 2. Purity and yield table of products of examples 1-7

[0050]

[0051] Combining Table 1 and Table 2, it can be seen that when clethodim is reacted with tert-butylamine to obtain the target product of the present application, in order to ensure the effective utilization of clethodim, the yield is improved by appropriately increasing the amount of tert-butylamine. Comparative Examples 1 to 4 show that too much excess tert-butylamine has a negative impact on both the yield and the product content. Taking into account both the production cost of the product and the final product quantity index, the molar ratio of clethodim to tert-butylamine in the present application is preferably controlled to be (1:1) to (1:1.2).

[0052] In combination with Example 2 and Examples 5 to 6, it can be seen that the preparation method of the present application can stably control the reaction within -5 to 45°C when obtaining the tert-butylamine salt of the present application, and appropriately adjust the reaction time to obtain a high-purity target product with high yield. At a lower temperature, the reaction time is longer, and the product purity is higher. The preparation method has low production cost, mature and simple preparation method, good stability, and high yield.

[0053] From Example 2 and Example 7, it can be seen that the liquid phase environment used in the reaction of the tert-butylamine salt of clethodim in the present application can be one of the chlorinated alkane and benzene solvents.

[0054] The sample obtained from Example 2 with the highest product purity was selected as a test sample for testing, and the melting point was 92-94° C.; a stability test was performed.

[0055] Comparative Example 1

[0056] A clethodim salt, which differs from Example 2 in that the amine used in S2 is sec-butylamine, the molar ratio of clethodim to sec-butylamine is 1:1.1, and the obtained clethodim salt is specifically shown in Table 3.

[0057] Comparative Example 2

[0058] A clethodim salt, which differs from Example 2 in that the amine used in S2 is isobutylamine, and the molar ratio of clethodim to isobutylamine is 1:1.1. The obtained clethodim salt is specifically shown in Table 3.

[0059] Comparative Examples 3 to 7

[0060] A clethodim-amine salt, which differs from Example 2 in that the amine used in S2 is different, and the molar ratio of clethodim to the amine is 1:1.1. The obtained clethodim-amine salt is specifically shown in Table 3.

[0061] The contents and melting points of the clethodim salts obtained in Comparative Examples 1 to 7 were tested, and the yields were calculated. The results are recorded in Table 3.

[0062] The melting point of the product is determined by taking 12 samples of the same analyte and testing them. The distribution range of the melting point results is recorded if the maximum deviation is within 5°C. If the maximum deviation is greater than 5°C, the analyte is re-prepared and samples are re-tested.

[0063] Table 3. Information table, product content and yield of amines used in Comparative Examples 1 to 7

[0064]

[0065] *The melting point fluctuation range of the clethodim salt obtained in Comparative Example 7 exceeded 10°C during the melting point test, and multiple resampling and measurement failed to obtain a test result within the fluctuation range of 5°C. Analysis showed that this was because the clethodim salt was too low, and the decomposition of clethodim or other by-products during the heating process triggered the decomposition of the clethodim salt.

[0066] The stability of the samples of Example 2 and Comparative Examples 1 to 7 was tested by an accelerated storage test.

[0067] According to CIPAC MT46.4 Accelerated Storage Procedure, an international method for the physical and chemical determination of pesticide technicals and formulations, the shelf life of pesticide technicals and formulations under standard storage conditions is at least two years. Accelerated storage testing can be used to determine the shelf life of pesticide technicals and formulations under standard storage conditions. Accelerated storage testing can be performed using the following six storage temperature and storage period combinations specified in CIPAC MT 46.4 Accelerated Storage Procedure. The results of the residual active ingredient test in the samples can be used as predictive values ​​for two years of storage:

[0068] (1) 54 ± 2°C for 14 days;

[0069] (2) 50 ± 2°C for 4 weeks;

[0070] (3) 45 ± 2°C for 6 weeks;

[0071] (4) 40 ± 2°C for 8 weeks;

[0072] (5) 35 ± 2°C for 12 weeks;

[0073] (6) 30 ± 2°C for 18 weeks;

[0074] That is, continuous storage at 54±2℃ for 14 days is equivalent to continuous storage at 50±2℃ for 4 weeks, and so on.

[0075] Among the combinations of storage temperature and storage period, storage temperature has a significant impact on the accelerated storage test of pesticide technicals and formulations, determining their accelerated storage test cycle and reflecting the upper limit of the extreme storage conditions that pesticide technicals and formulations can tolerate.

[0076] This application uses "54±2°C for 14 days" as the test parameter. This refers to the CIPAC method, an international method for the physicochemical determination of pesticide technicals and formulations. The rate of change curves for samples at different parameters differ, making conversion impossible. For example, the behavior of a sample at 54±2°C for 7 days is not the same as that of a sample at 35±2°C for 6 weeks.

[0077] The specific detection method is: seal the sample with an ampoule and store it in a constant temperature box at 54±2°C for 14 days. Then, use high-performance liquid chromatography analysis to analyze and detect the purity changes of the active ingredients before and after hot storage, and use a commercially purchased sethoxydim sample (mass content of 89.50%) as a control example.

[0078] The test results are shown in Table 4.

[0079] Table 4. Stability test results of Example 2 and Comparative Examples 1 to 7

[0080]

[0081]

[0082] The sample content is the content of the corresponding active ingredient (clethodim salt or clethodim) in the sample after heat storage; the decomposition rate calculation formula is: decomposition rate (%) = (initial content - hot storage sample content) / initial content × 100%.

[0083] During the research process of this application, it was found that some samples in Comparative Examples 1 to 7 decomposed rapidly when stored at 54±2°C. In order to better and comprehensively compare Example 2 with Comparative Examples 1 to 7, this application conducted additional independent storage tests at 54±2°C for 3 days and 7 days on the same samples in addition to the 14 days at 54±2°C required by CIPAC MT 46.4 Accelerated Storage procedure, to better indicate the decomposition during storage and reflect the stability performance of each sample.

[0084] As shown in Table 4, after 14 days of accelerated storage at 54±1°C, the samples of Comparative Examples 1 to 7 and the control example all showed significant decomposition, while the decomposition in Example 2 was gradual and the final decomposition rate after 14 days was much lower than that of Examples 1 to 7. Therefore, the stability of the clethodim of the present application is superior to that of clethodim and other clethodim salts, and it is reasonable to infer that the prepared technical or preparation is not easily decomposed during long-term storage.

[0085] In addition, samples were obtained from Example 2 (tert-butylamine salt of clethodim), Comparative Example 1 (tertiary and secondary amine salt of clethodim), and Comparative Example 2 (tertiary isoamine salt of clethodim) for herbicidal test.

[0086] The herbicidal test was performed according to the method of NY / T 1155.4-2006 in the Pesticide Indoor Biological Test Guideline, Part 4: Herbicide, Method of Active Determination Test, Foliar Spray Method, and the test targets were Echinochloa crus-galli, Digitaria sanguinalis, and Eupatorium odoratum. An oxadiazon sample (content 89.50%) purchased on the market was used as a control, and the test results were the fresh weight control effects of the weeds after 21 days at different dosages.

[0087] The herbicidal test results are shown in Table 5.

[0088] Table 5. Herbicidal test results of Example 2 and Comparative Examples 1-2

[0089]

[0090] *Note: The table shows the fresh weight control effects of the drugs on different weeds after 21 days at two dosages.

[0091] The test results were analyzed as follows: when the dosage was 6.25 g a.i. / hm 2 , the herbicidal activities of the different drugs on Echinochloa crus-galli from low to high were: Comparative Example 2 < Comparative Example 1 < Example 2 < Control; on Digitaria sanguinalis from low to high were: Comparative Example 2 < Comparative Example 1 < Example 2 < Control; and on Eupatorium odoratum from low to high were: Comparative Example 2 < Comparative Example 1 < Example 2 < Control; when the dosage was 12.5 g a.i. / hm 2 , the herbicidal activities of the different drugs on Echinochloa crus-galli from low to high were: Comparative Example 2 < Comparative Example 1 < Control < Example 2; on Digitaria sanguinalis from low to high were: Comparative Example 1 < Comparative Example 2 < Example 2 < Control; and on Eupatorium odoratum from low to high were: Comparative Example 2 < Comparative Example 1 < Control < Example 2.

[0092] According to the results in Table 5, the fresh weight control effect of Example 2 was similar to that of the control, the herbicidal activity was good, and there was no obvious attenuation. Even at a dosage of 12.5 g a.i. / hm 2 , the herbicidal activity on Echinochloa crus-galli and Eupatorium odoratum was slightly better than that of the control.

[0093] Comparative Examples 1-2 showed a significant decrease in herbicidal activity at different dosages compared with the control.

[0094] From the above data, it can be seen that the physicochemical properties of different alkylamides of propisochlor are different, resulting in significant differences in stability and herbicidal activity. Even the alkylamides of propisochlor formed by isomers (tert-butylamine, sec-butylamine, isobutylamine) and propisochlor (propisochlor tert-butylamine salt, propisochlor sec-butylamine salt, propisochlor isobutylamine salt) have significant differences in storage stability and herbicidal activity. In addition, the process difficulty, product performance, and economic cost of different alkylamides of propisochlor processed into various dosage forms may be different. The propisochlor tert-butylamine salt disclosed in the present application has very excellent comprehensive performance, and has broad commercial prospects.

[0095] In addition, the sample of Example 2 was subjected to nuclear magnetic hydrogen spectrum and differential scanning calorimetry detection to further determine the structure of the sample of Example 2. The detection chart is shown in FIGS. 2A and 2B. Figure 1 and FIGS. 2A and 2B. Figure 2 .

[0096] The specific embodiments are merely an explanation of the present application, and are not a limitation of the present application. Those skilled in the art can make modifications to the embodiments without creative contribution after reading the present specification, as long as the modifications are within the scope of the present application.

Claims

1. A clethodim salt, characterized in that The clethodim amine salt is clethodim tert-butylamine salt, and its chemical structure is as follows:

2. A clethodim salt according to claim 1, characterized in that: A differential scanning calorimetry (DSC) curve exhibited an endothermic melting peak at 104°C and a melting range of 93-107°C.

3. The method for preparing a clethodim salt according to claim 1, wherein: S1: dissolving clethodim in a solvent to obtain a mixture A; S2: adding tert-butylamine to the mixture A to carry out a reaction, and after the reaction is completed, precipitating the clethodim salt from the reaction system; S3: Separate the precipitate to obtain clethodim salt.

4. The method for preparing a clethodim salt according to claim 3, wherein: The reaction temperature in S2 is -5°C to 45°C.

5. The method for preparing a clethodim salt according to claim 3, wherein: The molar ratio of clethodim to tert-butylamine in S2 is (1:1) to (1:1.2).

6. The method for preparing a clethodim salt according to claim 3, wherein: The clethodim salt obtained in S3 is further purified by washing.

7. Use of the clethodim salt according to claim 1 in herbicides.

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