Azole selenourea carboxylate as well as preparation method and application thereof

Abstract

The invention discloses azole selenourea carboxylate as well as a preparation method and application thereof. The structural formula of the azole selenourea carboxylate is shown as a formula (I), wherein in the formula (I), R is C1-C12 alkyl or difluoromethyl; m is Na, K or a quaternary ammonium cation; x is N or C; and n is 0-11. Compared with the prior art, after carboxylate is introduced to a zoleselenourea framework, the obtained compound has very excellent internal uptake and conductivity, high-dose safety, water solubility and light and heat stability, and the stress resistance and oxidation resistance of plants can be remarkably improved. # imgabs0 #

Description

Technical Field

[0001] The present invention belongs to the fields of organic chemistry and agricultural technology, and specifically relates to a selenazole urea carboxylate, a preparation method thereof, and an application thereof. Background Art

[0002] Existing studies have shown that N-difluoromethyl triazole selenourea compounds exhibit excellent biological activities against pests, plant pathogens, weeds, and harmful plants in the fields of agriculture, forestry, and other fields, and also possess functions such as insecticidal, bactericidal, and herbicidal effects (Chinese Patent Application CN 115650926A); N-difluoromethyl selenazole urea-based organic selenium reagents can effectively promote plant growth and improve the nutritional value of agricultural products (Chinese Patent Application CN 115650926A). However, in the specific application process, it has been found that N-difluoromethyl selenazole urea compounds have disadvantages such as instability, easy selenium removal, and poor water solubility, making it difficult to prepare application preparations, with a relatively high cost and being unfavorable for large-scale field applications. Therefore, there is a need to develop organic selenium reagents with excellent water solubility, photothermal stability, biocompatibility, and systemic conduction performance. Summary of the Invention

[0003] To solve the drawbacks and deficiencies of the existing technology, the primary object of the present invention is to provide a selenazole urea carboxylate with high biocompatibility, stability, and water solubility. The inventors have found through a large number of experiments that when a carboxylate is introduced into the selenazole urea skeleton, it has very excellent systemic conduction performance, high-dose safety, water solubility, and photothermal stability, and can significantly improve the stress resistance and antioxidant capacity of plants.

[0004] Another object of the present invention is to provide a preparation method for the above-mentioned selenazole urea carboxylate.

[0005] Still another object of the present invention is to provide an application of the above-mentioned selenazole urea carboxylate.

[0006] The objects of the present invention are achieved through the following technical solutions:

[0007] A selenazole urea carboxylate, whose structural formula is shown as formula (I):

[0008]

[0009] In general formula (I):

[0010] R is C 1 -C 12 alkyl or difluoromethyl;

[0011] M is Na, K or a quaternary ammonium cation;

[0012] X is N or C;

[0013] n is 0 to 11.

[0014] Preferably, the quaternary ammonium cation may be a tetraalkylammonium ion, an imidazole ammonium ion, a pyridine ammonium ion, a betaine ammonium ion or a choline ammonium ion.

[0015] The specific compounds listed below for the compounds of general formula (I) of the present invention are taken as examples, but the present invention is not limited to these compounds:

[0016]

[0017]

[0018]

[0019] The reaction pathway of the compounds of general formula (I) of the present invention is shown as follows:

[0020]

[0021] Among them, R, M, X, n are as defined above; the preparation method of the compounds of general formula (I) of the present invention includes the following steps:

[0022] S1: Compound A reacts with an alkyl bromide under the action of a base by heating in an organic solvent to obtain compound B;

[0023] S2: Compound B reacts with an alkyl bromocarboxylate and selenium powder under the action of a base by heating in an organic solvent to obtain compound C;

[0024] S3: Compound C is heated and reacted in an organic solvent in the presence of a base to obtain the compound of formula (I).

[0025] In step S1: The base is preferably at least one of sodium bicarbonate, potassium bicarbonate, potassium carbonate, and sodium carbonate; the organic solvent may be at least one of acetonitrile and tetrahydrofuran; the temperature of the heating reaction is 40-120 °C, preferably 80 °C.

[0026] In step S2: The base is selected from at least one of cesium carbonate, potassium carbonate, lithium carbonate, sodium carbonate, potassium bicarbonate, sodium bicarbonate, potassium tert-butoxide, sodium tert-butoxide, and lithium tert-butoxide, preferably at least one of sodium carbonate, potassium bicarbonate, and sodium bicarbonate;

[0027] The organic solvent is selected from at least one of acetonitrile, dimethyl sulfoxide, tetrahydrofuran, N,N-dimethylformamide, and N,N-dimethylacetamide, preferably acetonitrile;

[0028] The temperature of the heating reaction is 40-140 °C, preferably 100 °C.

[0029] In step S3: the base is selected from at least one of sodium hydroxide and potassium hydroxide; the organic solvent is selected from at least one of methanol, ethanol, and water; the temperature of the heating reaction is 30 - 80 °C, preferably 60 °C.

[0030] The compound of general formula (I) of the present invention can be used for enhancing plant stress resistance.

[0031] Preferably, the enhancement of plant stress resistance includes but is not limited to stress resistance effects such as salt stress tolerance, alkali stress tolerance, oxidative stress tolerance, drought stress tolerance, metal stress tolerance, etc.

[0032] Preferably, the plant is a food crop, vegetable, fruit, and aquatic floating herb.

[0033] More preferably, the food crops include but are not limited to wheat, rice, corn, potato, soybean, broad bean, pea, mung bean, etc.; the vegetables include but are not limited to flowering Chinese cabbage, Chinese cabbage, cabbage, mustard, celery, tomato, cowpea, chili pepper, cucumber, radish, balsam pear, etc.; the fruits include but are not limited to Sanhua plum, orange, grapefruit, apple, grape, strawberry, mango, etc.; the aquatic floating herbs include but are not limited to Pistia stratiotes, duckweed, water lily, lotus, calamus, etc.

[0034] Preferably, the use concentration of the selenazole urea carboxylate in enhancing the stress resistance of crops is any concentration between 0.1 mg / L and 20 mg / L.

[0035] The present invention also provides a stress resistance regulating composition, which contains an active ingredient and an agriculturally acceptable carrier, and the weight percentage content of the active ingredient in the composition is 0.01 - 99.99%; the active ingredient refers to the compound of general formula (I), which can be a single compound or a mixture of several compounds of the present invention.

[0036] Preparation method of the composition as defined above: Mix the compound of general formula (I) with the carrier.

[0037] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0038] (1) The selenazole urea carboxylate of general formula (I) of the present invention has good water solubility and stable physical and chemical properties. An aqueous solution containing a high concentration of selenazole urea carboxylate will not deteriorate after being continuously heated at 50 °C and placed under light conditions for two weeks.

[0039] (2) The preparation method of the selenazole urea carboxylate of general formula (I) of the present invention is simple, the raw materials are easy to obtain, and the cost is low. It can increase the plant stress resistance ability, antioxidant ability, etc.

[0040] (3) The general formula (I) selenourea carboxylate of the present invention can be applied to plants by irrigation or spraying within the range of 0.1 mg / L to 100 mg / L, and has strong applicability. Detailed implementation manners

[0041] The present invention will be further described in detail below in conjunction with embodiments, but the implementation manners of the present invention are not limited thereto. The raw materials involved in the present invention can be directly purchased from the market. For process parameters not specifically noted, conventional techniques can be referred to.

[0042] Example 1: Preparation of Compound I-1

[0043] Step 1: Add selenium powder (0.4 mmol) and sodium bicarbonate (0.4 mmol) to a reaction tube, dissolve them with acetonitrile (2 mL), then add 1-methyl-1,2,4-triazole (0.2 mmol) and ethyl bromoacetate (0.2 mmol). After sealing the reaction tube, place it in an oil bath at 100 °C and stir for 8 h. After monitoring the reaction by TLC until it ends, wait for the reaction mixture to cool to room temperature, extract with ethyl acetate solution, combine the organic phases, and dry over anhydrous Na 2 SO 4 After drying, evaporate the solvent under reduced pressure. The residue is purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain an intermediate, a yellow oil, with a yield of 75%.

[0044] Step 2: Add the intermediate prepared in the first step (0.2 mmol) and potassium hydroxide (0.2 mmol) to a reaction tube, dissolve them with methanol (2 mL). After sealing the reaction tube, place it in an oil bath at 60 °C and stir for 6 h. After monitoring the reaction by TLC until it ends, wait for the reaction mixture to cool to room temperature, extract with methanol solution, combine the organic phases, and dry over anhydrous Na 2 SO 4 After drying, evaporate the solvent under reduced pressure to obtain a white solid product with a yield of 90%.

[0045] Example 2: Preparation of Compound I-9

[0046] Step 1: Add imidazole (0.4 mmol) and cesium carbonate (0.8 mmol) to a reaction tube, dissolve them with acetonitrile (2 mL), then add ethyl bromoacetate (0.8 mmol). After sealing the reaction tube, place it in an oil bath at 70 °C and stir for 6 h. After monitoring the reaction by TLC until it ends, wait for the reaction mixture to cool to room temperature, extract with ethyl acetate solution, combine the organic phases, and dry over anhydrous Na 2 SO 4 After drying, evaporate the solvent under reduced pressure, and separate by column chromatography to obtain an intermediate, a yellow oil, with a yield of 74%.

[0047] Step 2: Add the intermediate obtained in Step 1 (0.4 mmol), potassium carbonate (0.8 mmol), and selenium powder (0.8 mmol) into the reaction tube. Add acetonitrile (2.0 mL) to the mixture, then add ethyl bromodifluoroacetate (1.0 mmol). Seal the reaction tube and immerse it in an oil bath preheated to 100 °C. Stir the reaction for 24 hours and cool it to room temperature. Then dilute the crude reaction mixture with ethyl acetate and filter it through a short column of diatomaceous earth. Concentrate the filtrate under vacuum, and purify the obtained residue by column chromatography to obtain the intermediate, a pale yellow solid, with a yield of 83%.

[0048] Step 3: Add the intermediate obtained in Step 2 (0.2 mmol) and sodium hydroxide (0.2 mmol) into the reaction tube, dissolve them with methanol (2 mL). Seal the reaction tube and place it in an oil bath at 60 °C and stir the reaction for 6 h. After monitoring the reaction by TLC until it is completed, wait for the reaction mixture to cool to room temperature, extract it with methanol solution, and combine the organic phases. After drying over anhydrous Na 2 SO 4 After drying, evaporate the solvent under reduced pressure to obtain a white solid product with a yield of 80.0%.

[0049] Example 3: Preparation of Compound I-2

[0050] Step 1: Add selenium powder (0.4 mmol) and sodium carbonate (0.4 mmol) into the reaction tube, dissolve them with acetonitrile (2 mL). Subsequently, add 1-ethyl-1,2,4-triazole (0.2 mmol) and ethyl bromoacetate (0.2 mmol). Seal the reaction tube and place it in an oil bath at 100 °C and stir the reaction for 12 h. After monitoring the reaction by TLC until it is completed, wait for the reaction mixture to cool to room temperature, extract it with ethyl acetate solution, and combine the organic phases. After drying over anhydrous Na 2 SO 4 After drying, evaporate the solvent under reduced pressure. Purify the residue by column chromatography (eluting with a mixed solvent of petroleum ether and ethyl acetate) to obtain the intermediate, a brown oil, with a yield of 70%.

[0051] Step 2: Add the intermediate in Step 1 (0.2 mmol) and potassium hydroxide (0.2 mmol) into the reaction tube, dissolve them with methanol (2 mL). Seal the reaction tube and place it in an oil bath at 60 °C and stir the reaction for 6 h. After monitoring the reaction by TLC until it is completed, wait for the reaction mixture to cool to room temperature, extract it with methanol solution, and combine the organic phases. After drying over anhydrous Na 2 SO 4 After drying, evaporate the solvent under reduced pressure to obtain a pale green solid powder with a yield of 92%.

[0052] Example 4: Preparation of Compound I-6

[0053]

[0054] Step 1: Add selenium powder (0.4 mmol) and sodium bicarbonate (0.4 mmol) into a reaction tube, dissolve them with acetonitrile (2 mL), then add 1-ethylimidazole (0.2 mmol) and ethyl bromoacetate (0.2 mmol). After sealing the reaction tube, place it in an oil bath at 100 °C and stir for reaction for 10 h. After monitoring the reaction by TLC until it is completed, wait for the reaction mixture to cool to room temperature, extract it with ethyl acetate solution, combine the organic phases, and dry over anhydrous Na 2 SO 4 After drying, remove the solvent under reduced pressure. The residue is purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain an intermediate, a pale yellow oil, with a yield of 70%.

[0055] Step 2: Add the intermediate obtained in Step 1 (0.2 mmol) and potassium hydroxide (0.2 mmol) into a reaction tube, dissolve them with methanol (2 mL). After sealing the reaction tube, place it in an oil bath at 60 °C and stir for reaction for 6 h. After monitoring the reaction by TLC until it is completed, wait for the reaction mixture to cool to room temperature, extract it with methanol solution, combine the organic phases, and dry over anhydrous Na 2 SO 4 After drying, remove the solvent under reduced pressure to obtain a white solid product with a yield of 93%.

[0056] Example 5: Preparation of Compound I-12

[0057] Step 1: Add selenium powder (0.4 mmol) and sodium bicarbonate (0.4 mmol) into a reaction tube, dissolve them with acetonitrile (2 mL), then add 1-methyl-1,2,4-triazole (0.2 mmol) and ethyl 3-bromopropionate (0.2 mmol). After sealing the reaction tube, place it in an oil bath at 100 °C and stir for reaction for 12 h. After monitoring the reaction by TLC until it is completed, wait for the reaction mixture to cool to room temperature, extract it with ethyl acetate solution, combine the organic phases, and dry over anhydrous Na 2 SO 4 After drying, remove the solvent under reduced pressure. The residue is purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain an intermediate, a pale yellow oil, with a yield of 74%.

[0058] Step 2: Add the intermediate obtained in Step 1 (0.2 mmol) and sodium hydroxide (0.2 mmol) into a reaction tube, dissolve them with methanol (2 mL). After sealing the reaction tube, place it in an oil bath at 60 °C and stir for reaction for 6 h. After monitoring the reaction by TLC until it is completed, wait for the reaction mixture to cool to room temperature, extract it with methanol solution, combine the organic phases, and dry over anhydrous Na 2 SO 4 After drying, remove the solvent under reduced pressure to obtain a white solid product with a yield of 90%.

[0059] Example 6: Preparation of Compound I-17

[0060]

[0061] Step 1: Add selenium powder (0.4 mmol) and sodium bicarbonate (0.4 mmol) into a reaction tube, dissolve them with acetonitrile (2 mL), then add 1-methyl-1,2,4-triazole (0.2 mmol) and ethyl 4-bromobutyrate (0.2 mmol). After sealing the reaction tube, place it in an oil bath at 100 °C and stir for reaction for 12 h. After monitoring the end of the reaction by TLC, wait for the reaction mixture to cool to room temperature, extract it with ethyl acetate solution, and combine the organic phases. After drying over anhydrous Na 2 SO 4 After drying, evaporate the solvent under reduced pressure. The residue is purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain the intermediate, a pale yellow oil, with a yield of 70%.

[0062] Step 2: Add the intermediate prepared in Step 1 (0.2 mmol) and potassium hydroxide (0.2 mmol) into a reaction tube, dissolve them with methanol (2 mL). After sealing the reaction tube, place it in an oil bath at 60 °C and stir for reaction for 6 h. After monitoring the end of the reaction by TLC, wait for the reaction mixture to cool to room temperature, extract it with methanol solution, and combine the organic phases. After drying over anhydrous Na 2 SO 4 After drying, evaporate the solvent under reduced pressure to obtain a white solid product, with a yield of 90%.

[0063] Example 7: Preparation of Compound I-24

[0064] Step 1: Add selenium powder (0.4 mmol) and sodium bicarbonate (0.4 mmol) into a reaction tube, dissolve them with acetonitrile (2 mL), then add 1-methyl-1,2,4-triazole (0.2 mmol) and ethyl 5-bromovalerate (0.2 mmol). After sealing the reaction tube, place it in an oil bath at 100 °C and stir for reaction for 12 h. After monitoring the end of the reaction by TLC, wait for the reaction mixture to cool to room temperature, extract it with ethyl acetate solution, and combine the organic phases. After drying over anhydrous Na 2 SO 4 After drying, evaporate the solvent under reduced pressure. The residue is purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain the intermediate, a pale yellow oil, with a yield of 71%.

[0065] Step 2: Add the intermediate prepared in Step 1 (0.2 mmol) and sodium hydroxide (0.2 mmol) into a reaction tube, dissolve them with methanol (2 mL). After sealing the reaction tube, place it in an oil bath at 60 °C and stir for reaction for 6 h. After monitoring the end of the reaction by TLC, wait for the reaction mixture to cool to room temperature, extract it with methanol solution, and combine the organic phases. After drying over anhydrous Na 2 SO 4After drying, the solvent was removed by distillation under reduced pressure to obtain a white solid product with a yield of 88%.

[0066] Example 8: Preparation of Compound I-29

[0067]

[0068] Step 1: Selenium powder (0.4 mmol) and sodium bicarbonate (0.4 mmol) were added to a reaction tube, dissolved in acetonitrile (2 mL), and then 1-methyl-1,2,4-triazole (0.2 mmol) and ethyl 6-bromohexanoate (0.2 mmol) were added. After sealing the reaction tube, it was placed in an oil bath at 100 °C and stirred for 12 h. After monitoring the reaction by TLC until it was completed, the reaction mixture was cooled to room temperature and extracted with ethyl acetate solution. The combined organic phases were dried over anhydrous Na 2 SO 4 After drying, the solvent was removed by distillation under reduced pressure, and the residue was purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain an intermediate as a pale yellow oil with a yield of 76%.

[0069] Step 2: The intermediate prepared in Step 1 (0.2 mmol) and sodium hydroxide (0.2 mmol) were added to a reaction tube, dissolved in methanol (2 mL). After sealing the reaction tube, it was placed in an oil bath at 60 °C and stirred for 6 h. After monitoring the reaction by TLC until it was completed, the reaction mixture was cooled to room temperature and extracted with methanol solution. The combined organic phases were dried over anhydrous Na 2 SO 4 After drying, the solvent was removed by distillation under reduced pressure to obtain a white solid product with a yield of 91%.

[0070] Example 9: Preparation of Compound I-34

[0071] Step 1: Selenium powder (0.4 mmol) and sodium bicarbonate (0.4 mmol) were added to a reaction tube, dissolved in acetonitrile (2 mL), and then 1-methyl-1,2,4-triazole (0.2 mmol) and ethyl 7-bromoheptanoate (0.2 mmol) were added. After sealing the reaction tube, it was placed in an oil bath at 100 °C and stirred for 12 h. After monitoring the reaction by TLC until it was completed, the reaction mixture was cooled to room temperature and extracted with ethyl acetate solution. The combined organic phases were dried over anhydrous Na2SO 4 After drying, the solvent was removed by distillation under reduced pressure, and the residue was purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain an intermediate as a pale yellow oil with a yield of 73%.

[0072] Step 2: Add the intermediate prepared in Step 1 (0.2 mmol) and sodium hydroxide (0.2 mmol) into the reaction tube, dissolve them with methanol (2 mL). Seal the reaction tube and place it in an oil bath at 60 °C and stir for 6 h. After monitoring the reaction by TLC until it is completed, wait for the reaction mixture to cool to room temperature, extract it with methanol solution, and combine the organic phases. After drying over anhydrous Na 2 SO 4 After drying, evaporate the solvent under reduced pressure to obtain a white solid product with a yield of 88%.

[0073] Example 10: Preparation of Compound I-39

[0074] Add selenium powder (0.4 mmol), sodium bicarbonate (0.4 mmol) into the reaction tube, dissolve them with acetonitrile (2 mL). Then add 1-methyl-1,2,4-triazole (0.2 mmol) and ethyl 9-bromononanoate (0.2 mmol). Seal the reaction tube and place it in an oil bath at 100 °C and stir for 12 h. After monitoring the reaction by TLC until it is completed, wait for the reaction mixture to cool to room temperature, extract it with ethyl acetate solution, and combine the organic phases. After drying over anhydrous Na 2 SO 4 After drying, evaporate the solvent under reduced pressure. The residue is purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain an intermediate as a white oil with a yield of 68%.

[0075] Step 2: Add the intermediate prepared in Step 1 (0.2 mmol) and potassium hydroxide (0.2 mmol) into the reaction tube, dissolve them with methanol (2 mL). Seal the reaction tube and place it in an oil bath at 60 °C and stir for 6 h. After monitoring the reaction by TLC until it is completed, wait for the reaction mixture to cool to room temperature, extract it with methanol solution, and combine the organic phases. After drying over anhydrous Na 2 SO 4 After drying, evaporate the solvent under reduced pressure to obtain a white solid product with a yield of 83%.

[0076] Example 11: Preparation of Compound I-43

[0077] Step 1: Add selenium powder (0.4 mmol), sodium bicarbonate (0.4 mmol) into the reaction tube, dissolve them with acetonitrile (2 mL). Then add 1-methyl-1,2,4-triazole (0.2 mmol) and ethyl 10-bromodecanoate (0.2 mmol). Seal the reaction tube and place it in an oil bath at 100 °C and stir for 12 h. After monitoring the reaction by TLC until it is completed, wait for the reaction mixture to cool to room temperature, extract it with ethyl acetate solution, and combine the organic phases. After drying over anhydrous Na2SO 4 After drying, evaporate the solvent under reduced pressure. The residue is purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain an intermediate as a white oil with a yield of 67%.

[0078] Step 2: Add the intermediate prepared in Step 1 (0.2 mmol) and sodium hydroxide (0.2 mmol) into the reaction tube, dissolve them with methanol (2 mL), seal the reaction tube and place it in an oil bath at 60 °C and stir for reaction for 6 h. After monitoring the end of the reaction by TLC, wait for the reaction mixture to cool to room temperature, extract with methanol solution, combine the organic phases and dry over anhydrous Na 2 SO 4 After drying, evaporate the solvent under reduced pressure to obtain a white solid product with a yield of 78%.

[0079] Example 12: Preparation of Compound I-46

[0080] Step 1: Add selenium powder (0.4 mmol) and sodium bicarbonate (0.4 mmol) into the reaction tube, dissolve them with acetonitrile (2 mL), then add 1-methyl-1,2,4-triazole (0.2 mmol) and ethyl 12-bromododecanoate (0.2 mmol), seal the reaction tube and place it in an oil bath at 100 °C and stir for reaction for 12 h. After monitoring the end of the reaction by TLC, wait for the reaction mixture to cool to room temperature, extract with ethyl acetate solution, combine the organic phases and dry over anhydrous Na 2 SO 4 After drying, evaporate the solvent under reduced pressure, and purify the residue by column chromatography (eluting with a mixed solvent of petroleum ether and ethyl acetate) to obtain the intermediate as a white oily substance with a yield of 64%.

[0081] Step 2: Add the intermediate prepared in Step 1 (0.2 mmol) and sodium hydroxide (0.2 mmol) into the reaction tube, dissolve them with methanol (2 mL), seal the reaction tube and place it in an oil bath at 60 °C and stir for reaction for 6 h. After monitoring the end of the reaction by TLC, wait for the reaction mixture to cool to room temperature, extract with methanol solution, combine the organic phases and dry over anhydrous Na 2 SO 4 After drying, evaporate the solvent under reduced pressure to obtain a white solid product with a yield of 72.5%.

[0082] Example 13: Preparation of Compound I-47

[0083] Add the acid corresponding to selenourea carboxylate I-3 (2 mmol) to a 50 mL round-bottom flask, add MeOH (5 mL) and stir to obtain a homogeneous solution, add didodecyldimethylammonium chloride (2 mmol, 0.836 g), and continue to stir at room temperature for 2 h. Then concentrate the reaction mixture under vacuum in a 35 °C water bath and dry under vacuum to obtain Compound I-47.

[0084] Example 14: Preparation of Compound I-48

[0085] Add the acid corresponding to selenourea carboxylate I-3 (2 mmol) to a 50 mL round-bottom flask, add MeOH (5 mL), stir to obtain a homogeneous solution, add chloroethyltrimethylammonium chloride (2 mmol, 0.316 g), and continue stirring at room temperature for 2 hours. Then, in a 35 °C water bath, concentrate the reaction mixture under vacuum conditions and dry it under vacuum to obtain compound I-48.

[0086] NMR data of some compounds. The NMR of the sodium salt and potassium salt is basically the same (for the rest of the compounds, unless otherwise specified): 1 HNMR, 500 MHz; 13 CNMR, 125 MHz, internal standard TMS, solvent: CD 3 OD) are as follows: Compounds I-1 and I-3: 1 H NMR (500 MHz, CD 3 OD): δ H 9.89 (s, 1H), 6.27 (s, 2H), 5.39 (s, 3H). 13 C NMR (125 MHz, CD 3 OD): δ C 171.33, 159.99, 142.62, 50.09, 48.11, 47.94, 47.77, 47.60, 47.43, 47.26, 47.09, 37.04. MS(ESI): m / z [M] － calcd for C 5 H 6 N 3 O 2 Se: 219.9, found: 219.9.

[0087] Compounds I-2 and I-4: 1 H NMR (500 MHz, CD 3 OD): δ H 8.34 (s, 1H), 4.72 (s, 2H), 4.30 (q, J = 7.2 Hz, 2H), 1.39 (t, J = 7.2 Hz, 3H). 13 C NMR (125 MHz, CD 3 OD): δ C 142.85, 49.91, 47.89 (dd, J = 42.9, 21.5 Hz), 47.46, 47.29, 47.12, 45.54, 12.23. MS(ESI): m / z [M] － calcd forC 6 H 8 N 3 O 2Se: 233.9, found: 233.9.

[0088] Compounds I-5 and I-7: 1 H NMR (500 MHz, CD 3 OD): δ H 7.17–7.14 (m, 2H), 4.71 (s, 2H), 3.65 (s, 3H). 13 C NMR (125 MHz, CD 3 OD): δ C 172.70, 154.06, 120.47, 119.85, 52.57, 35.94. MS (ESI): m / z [M] － calcd for C 6 H 7 N 2 O 2 Se: 218.9, found: 218.9.

[0089] Compounds I-6 and I-8: 1 H NMR (500 MHz, CD 3 OD): δ H 7.19 (d, J = 2.3 Hz, 1H), 7.17 (d, J = 2.3 Hz, 1H), 4.77 (s, 2H), 4.18 (q, J = 7.3 Hz, 2H), 1.38 (t, J = 7.3 Hz, 3H). 13 C NMR (125 MHz, CD 3 OD): δ C 174.11, 122.07, 119.53, 53.68, 45.62, 14.79. MS (ESI): m / z [M] － calcd for C 7 H 9 N 2 O 2 Se: 232.9, found: 232.9.

[0090] Compound I-9: 1 H NMR (500 MHz, CD 3 OD): δ H 7.82 (t, J = 59.6 Hz, 1H), 7.43 (d, J = 2.6 Hz, 1H), 7.29 (d, J = 2.6 Hz, 1H), 4.75 (s, 2H). MS (ESI): m / z [M] － calcd for C 6 H 5 F 2N 2 O 2 Se: 254.9, found: 254.9.

[0091] Compounds I-11 and I-12: 1 H NMR (500 MHz, CD 3 OD): δ H 8.37 (s, 1H), 4.31 (t, J = 6.5 Hz, 2H), 3.82 (s, 3H), 2.68 (t, J = 6.5 Hz, 2H). MS (ESI): m / z [M] － calcd for C 6 H 8 N 3 O 2 Se: 233.9, found: 233.9.

[0092] Compounds I-13 and I-14: 1 H NMR (500 MHz, CD 3 OD): δ H 7.26 (d, J = 2.3 Hz, 1H), 7.15 (d, J = 2.3 Hz, 1H), 4.35 (t, J = 6.9 Hz, 2H), 3.64 (s, 3H), 2.63 (t, J = 7.0 Hz, 2H). 13 C NMR (125 MHz, CD 3 OD): δ C 178.68, 154.58, 121.31, 121.00, 48.16, 38.04, 37.10. MS (ESI): m / z [M] － calcd for C 7 H 9 N 2 O 2 Se: 232.9, found: 232.9.

[0093] Compounds I-15 and I-16: 1 H NMR (500 MHz, CD 3 OD): δ H 7.28 (d, J = 2.3 Hz, 1H), 7.18 (d, J = 2.3 Hz, 1H), 4.37 (t, J = 6.9 Hz, 2H), 4.16 (q, J = 7.2 Hz, 2H), 2.64 (t, J = 6.9 Hz, 2H), 1.35 (t, J = 7.2 Hz, 3H). 13 C NMR (125 MHz, CD 3 OD): δ C178.62,121.35,119.79,47.99,45.46,38.14,14.83. MS(ESI): m / z [M] － calcd for C 8 H 11 N 2 O 2 Se: 247.0, found: 247.0.

[0094] Compounds I-19 and I-20: 1 H NMR(500 MHz, CD 3 OD): δ H 6.91 (d, J = 2.3 Hz, 1H), 6.84 (d, J = 2.2 Hz, 1H), 3.84–3.77 (m, 2H), 3.31 (s, 3H), 1.86 (t, J = 7.4 Hz, 2H), 1.71 (dt, J = 14.8, 7.4 Hz, 2H). 13 C NMR(125 MHz, CD 3 OD): δ C 181.14, 154.80, 121.58, 120.78, 50.44, 37.18, 35.60, 27.16. MS(ESI): m / z [M] － calcd for C 8 H 11 N 2 O 2 Se: 247.0, found: 247.0.

[0095] Compounds I-21 and I-22: 1 H NMR(500 MHz, CD 3 OD): δ H 7.26 (d, J = 2.3 Hz, 1H), 7.21 (d, J = 2.3 Hz, 1H), 4.15 (q, J = 7.0 Hz, 4H), 2.20 (dd, J = 9.2, 5.7 Hz, 2H), 2.05 (p, J = 7.5 Hz, 2H), 1.34 (t, J = 7.2 Hz, 3H). MS(ESI): m / z [M] － calcd for C 9 H 13 N 2 O 2 Se: 261.0, found: 261.0.

[0096] Compounds I-23 and I-24: 1 H NMR(500 MHz, CD 3OD): δ H 8.46 (s, 1H), 4.13 (t, J = 7.4 Hz, 2H), 3.84 (s, 3H), 2.22 (q, J = 7.8 Hz, 3H), 1.93–1.82 (m, 3H), 1.65 (q, J = 7.7 Hz, 4H). MS(ESI): m / z [M] － calcd for C 8 H 12 N 3 O 2 Se: 262.0, found: 262.0.

[0097] Compounds I-29 and I-32: 1 H NMR (500 MHz, CD 3 OD): δ H 7.94 (s, 1H), 3.90 (t, J = 5.7 Hz, 3H), 3.52 (s, 3H), 2.37 (t, J = 8.1 Hz, 3H), 1.71–1.65 (m, 2H), 1.59 (dd, J = 8.1, 7.5 Hz, 2H), 1.43–1.36 (m, 2H). 13 C NMR (125 MHz, CD 3 OD): δ C 180.02, 173.94, 141.47, 49.10, 39.49, 34.36, 27.44, 26.50, 23.45. MS(ESI): m / z [M] － calcd for C 9 H 14 N 3 O 2 Se: 276.0, found: 276.0.

[0098] Compound I-30: 1 H NMR (500 MHz, CD 3 OD): δ H 7.96 (s, 1H), 4.04–3.84 (m, 5H), 2.37 (d, J = 16.2 Hz, 1H), 1.71–1.65 (m, 2H), 1.59 (td, J = 7.9, 0.9 Hz, 2H), 1.43–1.36 (m, 2H), 1.28 (t, J = 7.0 Hz, 3H). 13 C NMR (125 MHz, CD 3 OD): δ C174.96, 173.94, 140.55, 49.10, 47.23, 34.36, 27.44, 26.50, 23.45, 13.38. MS(ESI): m / z [M] － calcd for C 10 H 16 N 3 O 2 Se: 290.0, found: 290.0.

[0099] Compounds I-33 and I-34: 1 H NMR(500 MHz, CD 3 OD): δ H 8.43 (s, 1H), 4.12–4.08 (m, 2H), 3.83 (s, 3H), 2.17 (s, 2H), 1.83 (t, J = 7.1 Hz, 2H), 1.61 (d, J = 7.4 Hz, 2H), 1.41–1.36 (m, 4H). MS(ESI): m / z [M] － calcd for C 10 H 16 N 3 O 2 Se: 290.0, found: 290.0. Compounds I-36 and I-37: 1 H NMR(500 MHz, CD 3 OD): δ H 8.43 (s, 1H), 4.13–4.08 (m, 2H), 3.85 (s, 3H), 2.18 (d, J = 7.5 Hz, 2H), 1.65–1.60 (m, 2H), 1.43–1.33 (m, 8H). MS(ESI): m / z [M] － calcd for C 11 H 18 N 3 O 2 Se: 304.0, found: 304.0.

[0100] Compounds I-39 and I-40: 1 H NMR(500 MHz, CD 3 OD): δ H 8.42 (s, 1H), 4.10–4.07 (m, 2H), 3.83 (s, 3H), 2.17–2.14 (m, 2H), 1.90 (s, 1H), 1.84–1.79 (m, 2H), 1.61–1.57 (m, 2H), 1.37–1.28 (m, 12H). MS(ESI): m / z [M]－ Calculated for C 12 H 20 N 3 O 2 Se: 318.0, found: 318.0.

[0101] Compounds I-42 and I-43: 1 H NMR (500 MHz, CD 3 OD): δ H 8.41 (s, 1H), 4.09 (dd, J = 8.2, 6.7 Hz, 2H), 3.83 (s, 3H), 3.61 (q, J = 7.1 Hz, 2H), 2.17–2.12 (m, 3H), 1.82 (t, J = 7.2 Hz, 2H), 1.60 (t, J = 7.4 Hz, 3H), 1.34 (d, J = 10.9 Hz, 13H), 1.18 (t, J = 7.0 Hz, 3H). MS (ESI): m / z [M] － Calculated for C 13 H 22 N 3 O 2 Se: 332.1, found: 332.1.

[0102] Compounds I-44 and I-45: 1 H NMR (500 MHz, CD 3 OD): δ H 8.41 (s, 1H), 4.10–4.07 (m, 2H), 3.83 (s, 3H), 2.15 (dd, J = 8.4, 6.9 Hz, 2H), 1.84–1.79 (m, 2H), 1.59 (t, J = 7.4 Hz, 2H), 1.36–1.30 (m, 14H). MS (ESI): m / z [M] － Calculated for C 14 H 24 N 3 O 2 Se: 346.1, found: 346.1.

[0103] Compound I-46: 1 H NMR (500 MHz, CD 3 OD): δ H8.41(s,1H),4.08(t,J=7.5Hz,2H),3.83(s,3H),3.42(s,1H),2.15(t,J=7.6Hz,4H),1.81(t,J=7.2Hz,2H),1.59(t,J=7.4Hz,4H),1.36–1.28(m,28H).MS(ESI):m / z[M] － calcd for C 15 H 26 N 3 O 2 Se:360.1,found:360.1.

[0104] Compound I-47: 1 H NMR(500MHz,CD 3 OD):δ H 8.33(s,1H),4.70(s,2H),3.83(s,3H),3.05(s,6H),1.78–1.71(m,4H),1.44–1.26(m,30H),0.91–0.87(m,6H).MS(ESI):m / z[M] － calcd for C 27 H 52 N 4 O 2 Se:544.3,found:544.3.

[0105] Compound I-48: 1 H NMR(500MHz,CD3OD):δ H 8.36(s,1H),4.72(s,2H),4.09–4.04(m,2H),3.86(s,3H),3.81(t,J=6.6Hz,2H),3.25(s,9H).MS(ESI):m / z[M] － calcd forC 10 H 19 ClN 4 O 2 Se:342.0,found:342.0.

[0106] Example 15: Drought resistance of selenazoleurea carboxylate to tomato seedlings

[0107] Mature seeds of tomatoes were purchased from Shouguang City, China. Tomato seeds were surface-sterilized with 10% sodium hypochlorite for 10 min and washed 3 times with distilled water. During the initiation of tomato seeds, 1 mg·mL -1The tomato seeds were soaked in a solution of selenazole carboxylate at a certain concentration for 24 h in the dark at 20 °C. Subsequently, the treated seeds were dried to their original weight. Twenty seeds were placed on filter paper (moistened with distilled water or 10% PEG-6000 solution) and put into a petri dish with a diameter of 12 cm. The seeds were grown in an artificial climate chamber with a light cycle of 16 / 8 h (day / night), a relative humidity of 60%, and a temperature of 25 / 16 °C (day / night). The treatment conditions were as follows: control (CK), seeds soaked in water and then germinated in distilled water; PEG (germinated in 10% PEG-6000 solution); soaked in 1.0 mg·L -1 of selenazole carboxylate and then germinated in 10% PEG-6000 solution.

[0108] The germination rate (%) was calculated as the number of germinated seeds divided by the total number of seeds after germination.

[0109] Table 1: The drought resistance effect of compound I-30 on tomato seeds in PEG

[0110]

[0111] Example 16: The salt stress resistance effect of compounds I-29 and I-30 on rice

[0112] Using rice variety Huahang 38 as the experimental material. The rice seeds were disinfected with 0.5% sodium hypochlorite for 10 min, and the disinfectant attached to the surface of the seeds was removed with distilled water. Then the seeds were distributed into 96-well hydroponic plastic pots (Zhongtai Experimental Equipment Factory, Nantong, Jiangsu, China), and 1.5 L of nutrient solution was added (Kimura B solution: 0.18 mM (NH 4 ) 2 SO 4 , 0.27 mM MgSO 4 ·7H 2 O, 0.09 mM KNO 3 , 0.18 mM Ca(NO 3 ) 2 ·4H 2 O, 0.09 mM KH 2 PO 4 , 20 μM NaEDTA-Fe·3H 2 O, 6.7 μM MnCl 2 ·4H 2 O, 9.4 μM H 3 BO 3 , 0.015 μM (NH 4 )6Mo 7 O 24 ·4H 2 O, 0.15 μM ZnSO 4 ·7H2 O, 0.16 μM CuSO 4 ·5H 2 O), and the pH was adjusted to 5.5 ± 0.05 with sulfuric acid. Rice seeds were grown at 28 °C during the day under a photosynthetic photon flux of 150 μmol m -2 s -1 for 14 h and at 25 °C at night for 10 h.

[0113] A total of four treatment groups were set up: CK, NaCl (150 mM), NaCl (150 mM) + I-30 (0.5 mg / L), and NaCl (150 mM) + I-29 (0.5 mg / L). Each treatment was replicated three times, and each replicate had 64 seedlings.

[0114] Table 2: Effects of Compounds I-30 and I-29 on Salt Stress Resistance of Rice

[0115]

[0116] Example 17: Salt Stress Resistance of Selenazole Ureido Carboxylate to Rice Seeds

[0117] Using rice variety Huahang 31 as the experimental material. The seeds were sterilized with 0.1% saturated sodium hypochlorite solution for 30 min and then rinsed with distilled water to remove the disinfectant adhering to the seed surface for standby. The rice seeds were soaked at room temperature according to the designed dose. After 24 h, the seeds were rinsed 5 times with distilled water, blotted dry with filter paper, and placed in a germination dish containing an NaCl aqueous solution (10 mL, 5000 mg / L) and selenazole ureido carboxylate (1.5 mg / L). The germination method on paper was used, and the prepared culture utensils were transferred to an artificial climate chamber. The rice seeds were grown at 28 °C, 80% humidity, and in the dark for 5 days. Each treatment was replicated four times, and each replicate had 60 seeds. The experimental results are shown in Table 3.

[0118] Table 3: Effects of Selenazole Ureido Carboxylate on Salt Stress Resistance of Rice Seeds

[0119] Compound Germination rate (%) Root length (cm) Shoot length (cm) Seed vigor index (%) CK 90±3 4.77±0.88 2.46±0.17 460.67±17.43 I-3 98±4 5.50±0.96 2.85±0.29 540.25±9.92 I-5 97±3 5.45±0.72 2.76±0.31 529.15±8.76 I-10 98±2 5.27±0.83 2.78±0.45 547.23±9.65 I-14 100±0 5.53±1.0 2.66±0.27 565.0±11.11 I-18 96±3 5.15±0.64 2.16±0.42 519.15±7.16 I-19 96±3 5.75±0.94 3.03±0.39 524.5±42.76 I-22 99±3 5.06±0.89 2.85±0.25 503.94±22.67 I-23 100±0 5.43±0.75 2.91±0.37 543.33±36.43 I-29 100±0 5.67±0.58 3.02±0.18 548.36±35.27 I-33 98±2 5.14±0.75 2.95±0.15 513.57±21.49 I-37 98±2 5.09±0.81 2.97±0.23 517.26±23.83 I-45 99±3 5.03±0.79 2.86±0.25 507.85±22.67 I-47 100±0 5.27±0.85 3.01±0.23 538.27±33.72 I-48 100±0 5.35±0.58 2.97±0.25 541.16±35.34

[0120] Note: In the above table, the stress concentration of NaCl in CK and all treatment groups is 5000 mg / L;

[0121] Germination rate = number of normal seedlings / total number of tested seeds × 100%

[0122] Seed vigor index:

[0123] Where: VI = vigor index; X 1 = number of germinated seeds in the treatment; X 0= Number of treated seeds; S = Average root length (or fresh root weight) or shoot length (or fresh shoot weight) per germinated seedling, in centimeters (cm) or grams (g)

[0124] Example 18: Regulatory effect of selenourea carboxylate on Sanhua plums

[0125] Select 10 Sanhua plums and test Compounds I-1 to I-8 respectively at a spraying concentration of 10 mg / L. Conduct three spraying tests. The spraying time is uniformly selected after 5 pm. If it is washed by rain within 4 hours after spraying, it needs to be re-sprayed the next day. For the first spraying (during the flowering period), directly mix with water and spray in fog until the leaves are completely atomized; the same operation is carried out for the second spraying (during the fruit-setting period). The same operation is carried out for the third spraying (during the young fruit swelling period). After the plums turn red, pick the plums, slice them, and then conduct vacuum freeze-drying. Use inductively coupled plasma mass spectrometry (ICP-MS) to quantify selenium elements. The selenium content is between 10 μg / kg and 30 μg / kg, and the selenium-enriching effect is significant. The sweetness of the plums increases by 10-20%, the fruit powder becomes thicker, the number of cracked and dropped fruits significantly decreases, and the sooty mold significantly decreases.

[0126] Example 19: Stability of selenourea carboxylate in aqueous solution

[0127] (1) Indoor stability test

[0128] Dissolve 100 mg of selenourea carboxylates I-1 to I-10 in 30 mL of water in a 100 mL beaker, place it indoors and expose it to air and sunlight. Observe and sample every week, and use mass spectrometry and liquid phase detection. After placing for one month, selenourea carboxylates I-1 to I-10 did not deteriorate.

[0129] The reference substance (2-benzyl, 4-difluoromethyltriazoleselenourea, 10 mg, CAS: 2611400-60-1, preparation method see ACS Agric. Sci. Technol. 2023, 3, 1044-1054) was dissolved in 50 μL of DMSO and diluted with 10 mL of water in a test tube. Place it indoors and expose it to air and sunlight. Observe and sample every other day, and use mass spectrometry and liquid phase detection. Deterioration occurred on the second day with selenium loss.

[0130] (2) Outdoor stability test

[0131] Dissolve 100 mg of selenourea carboxylates I-3 and I-7 in 30 mL of water in a 100 mL beaker, place it outdoors and expose it to air and sunlight. Observe and sample every 1 day, and use mass spectrometry and liquid phase for detection. After placing for one week, selenourea carboxylate did not deteriorate.

[0132] The reference substance (2-benzyl, 4-difluoromethyltriazoleselenourea, 10 mg) was dissolved in 50 μL of DMSO, diluted with 10 mL of water in a test tube, placed outdoors and exposed to air and sunlight. Observation and sampling were carried out every 1 day, and detection was performed using mass spectrometry and liquid chromatography. Degradation occurred on the first day, and the phenomenon of selenium loss was observed.

[0133] Example 20: Biocompatibility of Triazoleselenourea Carboxylate

[0134] Taking triazoleselenourea carboxylate I-3 as a representative, it was compared with Pistia stratiotes treated with sodium selenite and without drugs respectively to explore the tolerance of Pistia stratiotes to organic selenium reagents and inorganic selenium reagents at different concentrations.

[0135] Experimental procedure: The concentration gradients were set as: 15 mg / L, 10 mg / L, 5 mg / L, 2.5 mg / L, 1 mg / L, and three parallels were set for each treatment group. After dissolving the drug in clear water, it was added to 1 L of Hoagland nutrient solution according to the dose. After cultivating Pistia stratiotes for seven days, the roots of Pistia stratiotes were soaked and rinsed with clear water 4-5 times. After ensuring that there was no drug residue on the roots, they were placed in Hoagland nutrient solution prepared with clear water and cultivated for three days. Finally, the growth status and root loss of Pistia stratiotes were observed.

[0136] Table 4 Biocompatibility of Triazoleselenourea Carboxylate I-3

[0137]

[0138] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications made without departing from the spirit and principle of the present invention shall be equivalent replacement methods and are all included in the protection scope of the present invention.

Claims

1. A azole selenourea carboxylate, characterized in that Its structural formula is shown in formula (I): In the general formula (I): R is C1-C 12 Alkyl or difluoromethyl; M is Na, K or a quaternary ammonium cation; X is N or C; n is 0 to 11.

2. A azole selenourea carboxylate according to claim 1, characterized in that: The quaternary ammonium cation is a tetraalkylammonium ion, an imidazole ammonium ion, a pyridinium ammonium ion, a betaine ammonium ion or a choline ammonium ion.

3. A azole selenourea carboxylate according to claim 1, characterized in that: It is selected from the compounds of the following structural formula:

4. The method for preparing a azole selenourea carboxylate according to any one of claims 1 to 3, characterized in that: The reaction pathway is shown below: In the formula, R is C1-C 12 Alkyl or difluoromethyl; M is Na, K or a quaternary ammonium cation; X is N or C; n is 0 to 11; The specific steps include: S1: Compound A reacts with bromoalkane in an organic solvent under the action of a base to obtain compound B; S2: Compound B reacts with bromocarboxylate and selenium powder in an organic solvent under the action of a base to obtain compound C; S3: Compound C is subjected to a heating reaction in an organic solvent in the presence of a base to obtain a compound of formula (I).

5. The preparation method according to claim 4, characterized in that: In step S1, the base is at least one of sodium bicarbonate, potassium bicarbonate, potassium carbonate and sodium carbonate; the organic solvent is at least one of acetonitrile and tetrahydrofuran; and the temperature of the heating reaction is 40-120°C.

6. The preparation method according to claim 4, characterized in that: In step S2: the base is selected from at least one of cesium carbonate, potassium carbonate, lithium carbonate, sodium carbonate, potassium bicarbonate, sodium bicarbonate, potassium tert-butoxide, sodium tert-butoxide, and lithium tert-butoxide; The organic solvent is selected from at least one of acetonitrile, dimethyl sulfoxide, tetrahydrofuran, N,N-dimethylformamide and N,N-dimethylacetamide; The temperature of the heating reaction is 40-140°C.

7. The preparation method according to claim 4, characterized in that: In step S3: the base is selected from at least one of sodium hydroxide and potassium hydroxide; the organic solvent is selected from at least one of methanol, ethanol and water; the temperature of the heating reaction is 30-80°C.

8. The use of a azole selenourea carboxylate according to any one of claims 1 to 3, characterized in that: It is used to enhance the stress resistance of plants.

9. The use according to claim 8, characterized in that The stress resistance includes resistance to salt stress, resistance to alkali stress, resistance to oxidative stress, resistance to drought stress or resistance to metal stress.

10. The use according to claim 8, characterized in that The plants are food crops, vegetables, fruits or aquatic floating herbs.

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