Clethodim amine salt as well as preparation method and application thereof

Abstract

The invention discloses clethodim amine salt as well as a preparation method and application thereof, the clethodim amine salt is clethodim tert-butylamine salt, and the chemical structural formula of the clethodim amine salt is as follows: # imgabs0. The invention discloses the clethodim tert-butylamine salt, and the clethodim tert-butylamine salt is characterized by various means. The prepared clethodim tert-butylamine salt is good in stability, meanwhile, the herbicidal activity of the prepared clethodim tert-butylamine salt is not weaker than that of clethodim, and the stability and the herbicidal activity of the prepared clethodim tert-butylamine salt are both superior to those of other clethodim amine salts reported in documents. The prepared clethodim tert-butylamine salt is low in degradation rate in the high-temperature heat storage process and can be stored for a long time more easily compared with clethodim, and commercial products of the clethodim tert-butylamine salt can be kept more stable in the shelf life. The clethodim tert-butylamine salt prepared by the invention is high in melting point, is solid at normal temperature, can be processed into richer dosage forms as a herbicide, can be expanded to water dispersible granules (WG), wettable powder (WP) and other new dosage forms from the current dosage forms mainly comprising clethodim emulsifiable concentrate (EC), and is good in commercial prospect.

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. It is a cyclohexanedione herbicide with excellent herbicidal activity. The currently commercially available industrial products of Clethodim are liquids with an ingredient content of 86-93%. Clethodim's structural formula contains multiple non-adjacent carbon-carbon double bonds, oxime and other functional groups, which determine its poor stability, the influence of external conditions, easy configuration flipping, and sensitivity to ultraviolet rays, heat, strong acids, strong bases, etc. Therefore, it is easy to decompose during long-term transportation and storage, resulting in a decrease in the content of Clethodim in the product and a weakening of the herbicidal efficacy. Once clethodim decomposes, the content of active ingredients decreases, which will have 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 preparations during storage, improve stability, and increase the content of active ingredients. At the same time, the clethodim preparations currently available on the market are all emulsifiable concentrates (EC), such as 240EC and 360EC dosage forms, and there are no solid dosage forms, such as water dispersible granules (WG) or wettable powders (WP), which also limits the application scenarios and commercial uses of clethodim.

[0003] Different salts of clethodim will have different stabilities, different physical and chemical properties, and may also have different herbicidal activities and different efficacy; different salts of clethodim will 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 the present application is achieved through the following technical solutions: A clethodim amine salt, which is clethodim tert-butylamine salt, and its chemical structure is as follows:

[0007] Optionally: The clethodim salt can be characterized by one or more of the following methods, including but not limited to high performance liquid chromatography (HPLC), nuclear magnetic resonance (HNMR), and a differential scanning calorimetry (DSC) curve having an endothermic melting peak at 104°C and a melting range of 93-107°C.

[0008] By adopting the above technical solution, the present application has confirmed the structure of clethodim tert-butylamine salt, including but not limited to nuclear magnetic resonance (HNMR), differential scanning calorimetry (DSC), etc., as shown in the attached Figure 1 As shown, the clethodim tert-butylamine salt of the present application is characterized by a nuclear magnetic hydrogen spectrum (HNMR), as shown in the attached Figure 2 As shown, the clethodim tert-butylamine salt of the present application is characterized by a differential scanning calorimetry (DSC) spectrum.

[0009] The tert-butylamine salt of clethodim prepared in the present application has good stability, and its stability is better than that of clethodim and other clethodim amine salts, while maintaining herbicidal activity that is not weaker than that of clethodim; the degradation rate of the tert-butylamine salt of clethodim during high-temperature heat storage is lower than that of clethodim and other clethodim amine salts reported in the literature, and it is easier to store for a long time than clethodim.

[0010] The above second invention objective of the present application is achieved through the following technical solutions: A method for preparing a clethodim salt, 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 precipitated clethodim salt.

[0011] By adopting the above technical scheme, the method for preparing clethodim salt is simple, the process is mature, the stability is good, the yield is high, and the production cost is low. Compared with the currently commercialized clethodim original drug, the content of the clethodim salt product can be significantly improved.

[0012] Optional: The reaction temperature in S2 is -5°C to 45°C.

[0013] By adopting the above technical solution, the reaction conditions of the preparation method of the present application are mild, and the process is mature and safe.

[0014] Optionally, the molar ratio of clethodim to tert-butylamine in S2 is (1:1.2) to (1:1).

[0015] By adopting the above technical scheme, the yield and content of the tert-butylamine salt of clethodim are high.

[0016] Optionally: the clethodim salt obtained in S3 is further purified by washing.

[0017] By adopting the above technical solution, the content of the tert-butylamine salt product of clethodim is high.

[0018] The third invention objective of the present application is achieved through the following technical solutions: The application of the above-mentioned clethodim salt in herbicides.

[0019] By adopting the above technical scheme, the stability and herbicidal efficacy of clethodim tert-butylamine salt are good, and it is expected to be prepared into a commercial preparation with economic value, and it has excellent storage stability and good efficacy.

[0020] In summary, this application has at least the following beneficial effects: 1. The present application discloses a clethodim tert-butylamine salt, and characterizes it by various means; the long-term storage stability of the clethodim tert-butylamine salt of the present application is improved, which is not only better than clethodim, but also better than other clethodim amine salts, and has excellent herbicidal activity while improving stability; and the stability and herbicidal activity of the clethodim tert-butylamine salt prepared in the present application are better than other clethodim amine salts reported in the literature; 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 currently commercialized clethodim original drug, the content of the clethodim amine salt product can be significantly improved; 3. The tert-butylamine salt of clethodim of the present application is conducive to the preparation of commercial preparations with economic value, and has excellent storage stability and good efficacy; the degradation rate of the tert-butylamine salt of clethodim during high-temperature heat storage is lower than that of clethodim and other clethodim amine salts reported in the literature, and it is easier to store for a long time than clethodim, which is conducive to the shelf life stability of commercial products. At the same time, it is conducive to changing the singleness of the current commercial dosage form of clethodim and expanding it to new dosage forms such as solid preparations of clethodim, such as water dispersible granules (WG) or wettable powders (WP), and has good commercial prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] The various features and aspects of the embodiments of the present application disclosed herein may be more clearly understood by reference to the accompanying drawings, which are intended to illustrate and explain rather than limit the scope of the present application, and in which: Figure 1 . is the hydrogen nuclear magnetic spectrum (HNMR) of tert-butylamine salt of clethodim.

[0022] Figure 2 . is a differential scanning calorimetry (DSC) diagram of tert-butylamine salt of clethodim. DETAILED DESCRIPTION

[0023] Example 1 A clethodim amine salt, which is clethodim tert-butylamine salt, and its chemical structure is as follows:

[0024] The preparation method of the clethodim tert-butylamine salt is as follows: S1: At a temperature of 16°C, 40.2g of clethodim technical (89.5wt%, 0.10mol) and 25g of solvent A were stirred and mixed uniformly, the temperature was raised to a mixing temperature of 18°C, 7.39g of tert-butylamine liquid (99wt%, 0.1mol) was uniformly added dropwise for 5min, and after the addition was completed, the mixture was stirred at 18°C ​​for 1.0h, and then 120.0g of solvent B was added to obtain a mixture A; S2: Continue stirring the reaction at 15°C for 5.0 h to obtain a reaction mass; S3: filtering the reaction material to obtain a solid; S4: The solid is washed with solvent B in an amount 5 times the mass ratio, and then dried in vacuo at 20° C. to obtain the product clethodim tert-butylamine salt.

[0025] Solvent A is toluene and solvent B is cyclohexane.

[0026] Embodiments 2 to 7 A clethodim tert-butylamine salt, which is different from Example 1 in that the process parameters of the preparation method are different, and the specific differences are shown in Table 1.

[0027] Table 1. Preparation method parameter table of Examples 1 to 7 The products obtained in Examples 1 to 7 were subjected to high performance liquid chromatography (HPLC) detection and yield calculation. The results are shown in Table 2.

[0028] Table 2. Product purity and yield of Examples 1 to 7 Combining Table 1 and Table 2, it can be seen that when clethodim reacts 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 the product production cost and the final product quantity index, so the molar ratio of clethodim to tert-butylamine in the present application is preferably controlled to be (1:1) to (1:1.2).

[0029] 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 clethodim of the present application, and appropriately adjust the reaction time, so that the target product of high purity can be obtained 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.

[0030] It can be seen from Example 2 and Example 7 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.

[0031] 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.

[0032] Comparative Example 1 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.

[0033] Comparative Example 2 A clethodim salt, which differs from Example 2 in that the amine used in S2 is isobutylamine, the molar ratio of clethodim to isobutylamine is 1:1.1, and the obtained clethodim salt is specifically shown in Table 3.

[0034] Comparative Examples 3 to 7 A clethodim salt, which differs from Example 2 in that the amine used in S2 is different, the molar ratio of clethodim to the amine is 1:1.1, and the obtained clethodim salt is specifically shown in Table 3.

[0035] The content and melting point of the clethodim salts obtained in Comparative Examples 1 to 7 were tested, and the yield was calculated. The results are recorded in Table 3.

[0036] The melting point of the product is determined by taking 12 samples of the same test object for testing. The test results are recorded within the distribution range of the melting point results when the maximum deviation is within 5°C. If the maximum deviation is greater than 5°C, the test object is re-prepared and samples are re-tested.

[0037] Table 3. Information table, product content, and yield table of amines used in Comparative Examples 1 to 7 *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 clethodim or other by-products decomposed during the heating process, triggering the decomposition of the clethodim salt.

[0038] The stability of the samples of Example 2 and Comparative Examples 1 to 7 was tested by an accelerated storage test.

[0039] According to the 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 operation is at least 2 years. The shelf life of pesticide technicals and formulations under standard operation can be tested through accelerated storage. According to the CIPAC MT 46.4 Accelerated Storage procedure, the following 6 groups of storage temperature and storage period combinations are carried out for accelerated storage test, and the test results of residual active ingredients in the samples can be regarded as the predictive value of 2-year storage: (1) 54 ± 2°C for 14 days; (2) 50 ± 2°C for 4 weeks; (3) 45 ± 2°C for 6 weeks; (4) 40 ± 2°C for 8 weeks; (5) 35 ± 2°C for 12 weeks; (6) 30 ± 2°C for 18 weeks; That is, continuous storage at 54±2℃ for 14 days is equivalent to continuous storage at 50±2℃ for 4 weeks, and so on.

[0040] Among the combinations of storage temperature and storage period, storage temperature has a great influence on the accelerated storage test of pesticide technical and formulations, determines the accelerated storage test cycle and reflects the upper limit of extreme storage conditions that pesticide technical and formulations can tolerate.

[0041] This application uses "54±2℃, for 14 days" as the test parameter. The provisions of the test experiment in the international method for the physical and chemical determination of pesticide technical and formulations - CIPAC method are quoted here. The change rate curves of samples under different parameters are different and it is not feasible to convert them. For example, the situation of samples at 54±2℃ for 7 days is not the same as that of samples at 35℃±2℃ for 6 weeks.

[0042] The specific detection method is: seal the sample with an ampoule bottle, store it in a constant temperature box at 54±2°C for 14 days, and 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.

[0043] The test results are shown in Table 4.

[0044] Table 4. Stability test results of Example 2 and Comparative Examples 1 to 7 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%.

[0045] During the research process of the present application, it was found that when stored at 54±2°C, some samples in Comparative Examples 1 to 7 decomposed faster. In order to better and comprehensively compare Example 2 with Comparative Examples 1 to 7, the present application independently conducted additional tests of storage at 54±2°C for 3 days and 7 days with the same samples in addition to the 14 days at 54±2°C required by CIPAC MT 46.4 Accelerated Storage procedure, so as to better remind the decomposition during the storage process and reflect the stability performance of each sample.

[0046] Combined with Table 4, it can be seen that 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 gentle and the final decomposition rate after 14 days was much lower than that in Examples 1 to 7. Therefore, the stability of clethodim of the present application is better than that of clethodim and other clethodim salts, and it is reasonable to infer that the prepared original drug or preparation is not easy to decompose during long-term storage.

[0047] In addition, samples were obtained from Example 2 (tert-butylamine salt of clethodim), Comparative Example 1 (tert-secondary amine salt of clethodim) and Comparative Example 2 (tert-isoamine salt of clethodim) for herbicidal test.

[0048] Herbicidal test: It was conducted according to the Herbicide Part 4: Activity Determination Test Stem and Leaf Spray Method (NY / T 1155.4-2006) in the Guidelines for Indoor Bioassay Tests of Pesticides. The test targets were barnyard grass, cloverleaf grass, and goosegrass. A commercially available sample of clethodim (content 89.50%) was used as a control. The test results were the fresh weight control effects on weeds at different dosages for 21 days.

[0049] The herbicidal test results are shown in Table 5.

[0050] Table 5. Herbicidal test results of Example 2 and Comparative Examples 1-2* *Note: The table shows the 21-day fresh weight control test results of the drugs at two dosages against different weeds.

[0051] Test result analysis: When the dosage is 6.25g ai / hm 221 days after application, the herbicidal activities of different agents on barnyard grass from low to high were: Comparative Example 2 < Comparative Example 1 < Example 2 < Control Example; the herbicidal activities on sedge grass from low to high were: Comparative Example 2 < Comparative Example 1 < Example 2 < Control Example; the herbicidal activities on goosegrass from low to high were: Comparative Example 2 < Comparative Example 1 < Example 2 < Control Example; when the dosage was 12.5 g ai / hm 2 At 21 days after the application, the herbicidal activities of different agents on barnyard grass from low to high were: Comparative Example 2 < Comparative Example 1 < Control Example < Example 2; the herbicidal activities on stick-head grass from low to high were: Comparative Example 1 < Comparative Example 2 < Example 2 < Control Example; the herbicidal activities on goosegrass from low to high were: Comparative Example 2 < Comparative Example 1 < Control Example < Example 2.

[0052] From the results in Table 5, it can be seen that the fresh weight control effect of Example 2 is similar to that of the control example, and the herbicidal activity is good without obvious attenuation, even at a dosage of 12.5 g ai / hm 2 The herbicidal activity against barnyard grass and goosegrass was slightly better than that of the control.

[0053] Compared with the control example, the herbicidal activity of Comparative Examples 1 and 2 at different dosages decreased significantly.

[0054] From the above data, it can be seen that the physicochemical properties of different clethodim salts are different, resulting in a significant gap in their stability and herbicidal activity. Even the clethodim salts (clethodim tert-butylamine salt, clethodim sec-butylamine salt, clethodim isobutylamine salt) formed by isomers of amines (tert-butylamine, sec-butylamine, isobutylamine) and clethodim will have significant differences in storage stability and herbicidal activity. In addition, the process difficulty, product performance and economic cost of processing different clethodim salts into various dosage forms may be different. The clethodim tert-butylamine salt disclosed in this application is a compound with excellent comprehensive performance and broad commercial prospects.

[0055] In addition, the sample of Example 2 was tested by nuclear magnetic resonance hydrogen spectrum and differential scanning calorimetry to further determine the structure of the sample of Example 2. The test diagram is shown in the attached Figure 1 and attached Figure 2 .

[0056] This specific embodiment is merely an explanation of the present application and is not a limitation of the present application. After reading this specification, those skilled in the art may make modifications to the present embodiment without any creative contribution as needed. However, as long as the modifications are within the scope of protection required by the present application, they shall be protected by the patent law.

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: It can be characterized by one or more of the following methods, including but not limited to high performance liquid chromatography (HPLC), nuclear magnetic resonance (HNMR), and a differential scanning calorimetry (DSC) curve having 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, characterized in that: 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 precipitated clethodim salt.

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

5. The method for preparing a clethodim salt according to claim 3, characterized in that: 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, characterized in that: 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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