Indole-3-acetamide derivative as well as preparation method and application thereof

Abstract

The invention provides an indole-3-acetamide derivative and a preparation method and application thereof.According to the indole-3-acetamide derivative with the structure shown in the formula (7), a natural product indole ring serves as a core framework, a series of indole-3-acetamide compounds are obtained, and it is shown through experimental results that the indole-3-acetamide derivative has the advantages that the indole-3-acetamide derivative can be used for preparing the indole-3-acetamide derivative with the structure shown in the formula (7); the compound provided by the invention has good herbicidal activity, and has good application prospects in the fields of agriculture, horticulture and forestry.

Description

Technical Field

[0001] The technical scheme of the present invention relates to indole-3-acetamide compounds, and specifically to an indole-3-acetamide derivative and a preparation method and application thereof. Background Art

[0002] The creation of new pesticides is one of the important means of reducing the amount of pesticides used and increasing their efficiency in my country. It is also an important guarantee for the implementation of my country's policy of replacing highly toxic pesticides. It is of great value to the prevention and control of agricultural pests and weeds and to ensure high yields and harvests in China (J.Agric.FoodChem.2023,71,276–287.). For example, Central China Normal University and Xinda Agrochemical Company jointly developed the herbicide quinclorac, which effectively solved the technical problem of controlling malignant weeds in sorghum fields (J.Agric.FoodChem.2010,58,2696–2702.); the new herbicide varieties such as bispyribac and fenpyradone developed by Qingyuan Agro-Crown Company have had an important impact on agricultural production in China and the world. +

[0003] Target-based pesticide molecular design is one of the important ways to create new pesticides. From the 1950s to the 1990s, about 20 existing commercial herbicide targets were discovered, and many herbicide varieties were developed based on these targets. For example, protoporphyrinogen oxidase inhibitor herbicides, acetyl-CoA carboxylase inhibitor herbicides, etc. However, the excessive abuse of existing target herbicides has caused serious weed resistance problems and created a vicious cycle. Therefore, the sustainable development of agriculture urgently requires the development of new, efficient, environmentally friendly and novel herbicides (J. Agric. Food Chem. 2020, 68 (18): 5059–5067.).

[0004] Natural products have unique structures, rich biological activities and novel mechanisms of action, and are an important source for the creation of new green pesticides. Therefore, introducing natural product active skeletons based on natural product skeletons or in pesticide lead molecules has become an important method for the creation of new environmentally friendly pesticides (J. Agric. Food Chem. 2023, 71, 267–275). Transketolase is an important enzyme in plant carbon metabolism and Calvin cycle. Its activity changes significantly affect the growth rate of plants, changes in phenylalanine and aromatic amino acid metabolites, and transketolase has been proven to be a new potential target for herbicides. Molecular design of herbicidal active compounds can be carried out with transketolase as the target (J. Agric. Food Chem. 2022, 70, 12819-12829.).

[0005] Therefore, it is of great significance to study and explore new herbicides containing natural skeletons. Summary of the invention

[0006] The technical problem to be solved by the present invention is to provide a new type of indole-3-acetamide derivatives and a preparation method and application thereof. The indole-3-acetamide derivatives provided by the present invention have good herbicidal activity and are of great significance in the application in the fields of agriculture, horticulture and forestry.

[0007] The present invention provides an indole-3-acetamide derivative, a preparation method and application thereof. The indole-3-acetamide derivative provided by the present invention has a structure shown in formula (7), and uses a natural product indole ring as a core skeleton to obtain a series of indole-3-acetamide compounds. Experimental results show that the compounds provided by the present invention have good herbicidal activity and have good application prospects in the fields of agriculture, horticulture and forestry.

[0008] The present invention provides an indole-3-acetamide derivative having a structure shown in formula (7):

[0009]

[0010] Among them, R 1 is selected from 4-fluorophenyl, 2,4-dichlorophenyl, 6-chloropyridin-3-yl or cyclopropyl;

[0011] R 2 Selected from 4-trifluorophenyl, pyridin-3-methylene, 1-methyl-1H-pyrazol-5-yl, furan-2-methylene, thiophene-2-methylene or cyclopropyl.

[0012] Preferably, the formula (7) has the following structure:

[0013]

[0014] The present invention also provides a method for synthesizing an indole-3-acetamide derivative, comprising:

[0015] 1) mixing indole-3-acetic acid methyl ester of formula (1) with a halide of formula (2) to obtain a compound of formula (3);

[0016]

[0017] Among them, R 1 Selected from: 4-fluorophenyl, 2,4-dichlorophenyl, 6-chloropyridin-3-yl or cyclopropyl;

[0018] 2) converting the compound of formula (3) into a compound of formula (4);

[0019]

[0020] 3) reacting the compound of formula (4) with oxalyl chloride to obtain a compound of formula (5);

[0021]

[0022] 4) mixing the compound of formula (6) and the compound of formula (5) to obtain a compound of formula (7), which is an indole-3-acetamide derivative.

[0023] R 2 NH2 formula (6),

[0024] Among them, R 2 Selected from: 4-trifluorophenyl, pyridin-3-methylene, 1-methyl-1H-pyrazol-5-yl, furan-2-methylene, thiophene-2-methylene or cyclopropyl.

[0025] Specifically, the reaction equation is as follows:

[0026]

[0027] Among them, R 1 Selected from: 4-fluorophenyl, 2,4-dichlorophenyl, 6-chloropyridin-3-yl or cyclopropyl; R 2 Selected from: 4-trifluorophenyl, pyridin-3-methylene, 1-methyl-1H-pyrazol-5-yl, furan-2-methylene, thiophene-2-methylene or cyclopropyl;

[0028] The specific method for the synthesis of the indole-3-acetamide derivative 7 of the present invention and the determination of the biological activity is divided into the following steps: A. Preparation method of compound 3:

[0029] In a 100 mL single-necked flask, 10.57 mmol of indole-3-acetic acid methyl ester was added, and then a certain volume of N,N-dimethylformamide was added to dissolve it. Under magnetic stirring, 15.86 mmol of a halide and 12.68 mmol of potassium hydroxide were added in sequence. The halide was selected from: 4-fluorobenzyl chloride, 2,4-dichlorobenzyl chloride, 2-chloro-5-chloromethylpyridine, chloromethylcyclopropane. The reaction progress was monitored by TLC. After the reaction was completed, 50 mL of ethyl acetate was added to the reaction bottle to dissolve, and the mixture was washed with saturated brine, extracted and layered, and the organic layer solution was dried with anhydrous sodium sulfate. The mixture was filtered under reduced pressure, and the solvent was removed by rotary evaporation. The crude product was purified by column chromatography to obtain an indole carboxylic acid ester derivative 3. The eluent was petroleum ether: ethyl acetate 5:1-15:1, and the yield was 67-85%. The amount of compound 3 prepared and the volume of the reaction container were enlarged or reduced in corresponding proportions.

[0030] B. Preparation method of compound 4:

[0031] In a 100 mL round-bottom flask, 1.00 mmol of indolecarboxylic acid ester derivative 3 was added, and then a certain volume of CH3CH2OH solvent was added to dissolve it, and 5.00 mmol of 10% potassium hydroxide solution was slowly dropped in. At room temperature, the reaction was continuously stirred and the reaction progress was monitored by TLC. After the reaction was completed, the solvent was removed by vacuum rotary evaporation, 10 mL of distilled water was added to dissolve the residue, and the pH of the solution was adjusted to 5 with concentrated HCl. The solution was transferred to a separatory funnel, 50 mL of ethyl acetate was added to dissolve it, and 40 mL×3 of saturated NaCl solution was used for washing, and the organic layer was extracted by oscillation. The organic layer was dried with anhydrous Na2SO4, filtered, and vacuum rotary evaporation was performed without further purification to obtain an indolecarboxylic acid derivative 4 with a yield of 95-97%. The amount of compound 4 prepared and the volume of the reaction container were enlarged or reduced in proportion.

[0032] C. Preparation method of compound 5:

[0033] In a 100 mL round-bottom flask, 1.00 mmol of indolecarboxylic acid derivative 4 was added, and a certain amount of dry dichloromethane was used to dissolve it. Under magnetic stirring, 3.00 mmol of anhydrous dichloromethane solution of oxalyl chloride was added dropwise to the above solution under ice bath conditions. The reaction progress was monitored by TLC. After the reaction was completed, the solvent was removed by vacuum rotary evaporation without further purification to obtain the acyl chloride intermediate 5 with a yield of 100%. The amount of compound 5 prepared and the volume of the reaction container were enlarged or reduced in the corresponding proportion;

[0034] D. Preparation method of compound 7:

[0035] In a 100 mL single-necked flask, 1.2 mmol of an amino compound, dichloromethane and 1.2 mmol of triethylamine were added in sequence. The amino compound was selected from: p-trifluoromethylaniline, 3-aminomethylpyridine, 1-methyl-5-aminopyrazole, 2-thiophene-methylamine, 2-furan-methylamine, cyclopropylamine, and magnetic stirring was performed. Then, under ice bath conditions, a dichloromethane solution containing 1.0 mmol of the acyl chloride intermediate 5 was added dropwise to the above solution. The reaction progress was monitored by TLC. After the reaction was completed, 50 mL of dichloromethane solvent was added, and the mixture was washed with saturated NaCl solution and extracted. The organic layer was dried over anhydrous Na2SO4, filtered, and evaporated under reduced pressure. The crude product was purified by column chromatography to obtain the target compound 7. The eluent was petroleum ether:ethyl acetate 15:1-5:1, with a yield of 54-90%. The amount of compound 7 prepared and the volume of the reaction container were increased or decreased in corresponding proportions.

[0036] E. Determination of the herbicidal activity of the indole-3-acetamide derivative 7 of the present invention:

[0037] The herbicidal activity of the indole-3-acetamide derivative 7 of the present invention is tested by the small cup method and the stem and leaf spray method, and the specific steps are as follows: 20 mg of the sample is dissolved in 1 ml of N,N-dimethylformamide to prepare a 20 g / L mother solution, and then the mother solution is diluted to 100 mg / L of the agent using an aqueous solution containing 0.1% Tween 80 emulsifier. Small cup method: 10 weed seeds with uniform germination are selected with tweezers and evenly distributed on a filter paper in a 50 ml small beaker. Each treatment is repeated 3 times, and 1 ml of the reagent solution is sucked with a pipette and slowly dripped onto the filter paper. All treatments are placed in an artificial climate chamber for moisturizing culture, with a temperature of 25±0.5°C, a humidity of 60±5%, a light intensity, and a light cycle of 16:8 for day and night. After 7 days, the root length and stem length of the weeds are measured, and the root inhibition rate and stem inhibition rate of the compound on the weeds are calculated. Stem and leaf spray method: The concentration used is 150 grams of effective content / hectare. In the stem and leaf treatment method, when dicotyledonous weeds grow to the two-leaf stage and monocotyledonous weeds grow to the 3-5-leaf stage, use a walking spray tower to evenly spray the test agent on the weed leaves, and use a solution without adding reagents as a blank control. Each treatment is repeated 3 times, and the treated weeds are cultured in an artificial climate room. After 14 days, the degree of inhibition of the sample on weed growth is investigated by visual inspection. The test plants are species of most typical weeds that actually occur in the fields in my country's agricultural production. Their names are as follows: Digitaria sanguinalis L., Amaranthus retroflexus L.

[0038]

[0039] The beneficial effects of the present invention are: the indole-3-acetamide derivative 7 is derivatized and synthesized, and the herbicidal activity of the indole-3-acetamide derivative 7 is screened.

[0040] The present invention further specifically illustrates the synthesis, biological activity and application of indole-3-acetamide derivative 7 through specific preparation and biological activity determination examples. The examples are only used to specifically illustrate the present invention but not to limit the present invention. In particular, the biological activity is only an example and not to limit the present patent. The specific implementation method is as follows:

[0041] Example 1: Preparation of Compound 3:

[0042] In a 100 mL single-necked flask, 10.57 mmol of indole-3-acetic acid methyl ester was added, and then a certain volume of N,N-dimethylformamide was added to dissolve it. Under magnetic stirring, 15.86 mmol of halide and 12.68 mmol of potassium hydroxide were added in sequence. The halide was selected from: 4-fluorobenzyl chloride, 2,4-dichlorobenzyl chloride, 2-chloro-5-chloromethylpyridine, chloromethylcyclopropane, and the reaction progress was monitored by TLC. After the reaction was completed, 50 mL of ethyl acetate was added to the reaction bottle to dissolve, and the mixture was washed with saturated brine, extracted and layered, and the organic layer solution was dried with anhydrous sodium sulfate, filtered under reduced pressure, and the solvent was removed by rotary evaporation. The crude product was purified by column chromatography to obtain indole carboxylic acid ester derivative 3, and the eluent was petroleum ether: ethyl acetate 5:1-15:1, with a yield of 67-85%. When R 1 =4-fluorophenyl, the NMR data are as follows: 1 HNMR (CD3Cl, 400MHz) δ7.65 (d, J = 7.8Hz, 1H), 7.25 (d, J = 7.1Hz, 1H), 7.21 (t, J = 7.3Hz, 1H), 7.16 (t, J = 7.0Hz, 1H), 7.12-7.09m, 3H), 6.99 (t, J = 8.6Hz, 2H), 5.25 (s, 2H), 3.81 (s, 2H), 3.72 (s, 3H). The amount of compound 3 prepared and the volume of the reaction container are enlarged or reduced in the corresponding proportion;

[0043] Example 2: Preparation of Compound 4:

[0044] In a 100 mL round-bottom flask, 1.00 mmol of indolecarboxylic acid ester derivative 3 was added, and then a certain volume of CH3CH2OH solvent was added to dissolve it, and 5.00 mmol of 10% potassium hydroxide solution was slowly dropped in. At room temperature, the reaction was continuously stirred and the reaction progress was monitored by TLC. After the reaction was completed, the solvent was removed by rotary evaporation under reduced pressure, and 10 mL of distilled water was added to dissolve the residue. The pH of the solution was adjusted to 5 with concentrated HCl, and the solution was transferred to a separatory funnel, and 50 mL of ethyl acetate was added to dissolve it, and then it was washed with 40 mL×3 saturated NaCl solution, and extracted by oscillation. The organic layer was dried with anhydrous Na2SO4, filtered, and rotary evaporation under reduced pressure was performed without further purification to obtain indolecarboxylic acid derivative 4 with a yield of 95-97%. When R 1 =4-fluorophenyl, the NMR data are as follows: 1HNMR (DMSO-d6, 400MHz) δ7.63 (d, J = 7.8Hz, 1H), 7.25 (d, J = 10.9Hz, 1H), 7.20 (t, J = 7.4Hz, 1H), 7.15 (t, J = 7.1Hz, 1H), 7.12–7.03 (m, 3H), 6.98 (t, J = 8.6Hz, 2H), 5.25 (s, 2H), 3.81 (s, 2H). The amount of compound 4 prepared and the volume of the reaction vessel were enlarged or reduced in the corresponding proportion;

[0045] Example 3: Preparation of Compound 5:

[0046] In a 100 mL round-bottom flask, 1.00 mmol of indolecarboxylic acid derivative 4 was added and dissolved in a certain amount of dry dichloromethane. Under magnetic stirring, 3.00 mmol of anhydrous dichloromethane solution of oxalyl chloride was added dropwise to the above solution under ice bath conditions. The reaction progress was monitored by TLC. After the reaction was completed, the solvent was removed by vacuum rotary evaporation without further purification to obtain the acyl chloride intermediate 5 with a yield of 100%. When R 1 =4-fluorophenyl, the NMR data are as follows: 1 H NMR (400MHz, CDCl3) δ7.63 (d, J = 7.8 Hz, 1H), 7.25 (d, J = 10.9 Hz, 1H), 7.20 (t, J = 7.4 Hz, 1H), 7.15 (t, J = 7.1 Hz, 1H), 7.12–7.03 (m, 3H), 6.98 (t, J = 8.6 Hz, 2H), 5.25 (s, 2H), 3.81 (s, 2H). The amount of compound 5 prepared and the volume of the reaction vessel were enlarged or reduced in the corresponding proportion;

[0047] Example 4: Preparation of Compound 7:

[0048] In a 100 mL single-necked flask, 1.2 mmol of an amino compound, dichloromethane and 1.2 mmol of triethylamine were added in sequence. The amino compound was selected from: p-trifluoromethylaniline, 3-aminomethylpyridine, 1-methyl-5-aminopyrazole, 2-thiophene-methylamine, 2-furan-methylamine, cyclopropylamine, and magnetic stirring was performed. Then, under ice bath conditions, a dichloromethane solution containing 1.0 mmol of the acyl chloride intermediate 5 was added dropwise to the above solution. The reaction progress was monitored by TLC. After the reaction was completed, 50 mL of dichloromethane solvent was added, and the mixture was washed with saturated NaCl solution and extracted. The organic layer was dried over anhydrous Na2SO4, filtered, and evaporated under reduced pressure. The crude product was purified by column chromatography to obtain the target compound 7. The eluent was petroleum ether:ethyl acetate 15:1-5:1. The yield was 54-90%. When R 1 =4-fluorophenyl, R 2=4-trifluorophenyl, the NMR data are as follows: 1 H NMR (400MHz, CDCl3) δ7.66–7.55 (m, 2H), 7.48 (dd, J = 20.2, 8.6 Hz, 4H), 7.35 (d, J = 8.3 Hz, 1H), 7.28 (d, J = 7.6 Hz, 1H), 7.19 (t, J = 7.4 Hz, 1H), 7.13 (d, J = 9.4 Hz, 3H), 7.01 (t, J = 8.6 Hz, 2H), 5.31 (s, 2H), 3.90 (s, 2H). The amount of compound 7 prepared and the volume of the reaction vessel were enlarged or reduced in proportion. The physicochemical parameters and structural parameters of compound 7 are shown in Table 1;

[0049] Example 5: Results of determination of herbicidal activity of indole-3-acetamide derivative 7 of the present invention:

[0050] The common weeds tested in the present invention are as follows: Digitaria sanguinalis L. (Ds) and Amaranthus retroflexus L. (Ar). These weeds are very representative and can represent most of the weeds occurring in the field during agricultural production. The herbicidal activity test adopts the small cup method and the stem and leaf treatment method.

[0051] The results of the cup method are shown in Table 2. At 100 μg / ml, except for compounds 7c, 7d, 7e, 7l, 7u and 7x, most of the indole-3-acetamide derivatives 7 synthesized by the present invention have root and stem inhibition rates of more than 70% on Digitaria and Amaranthus retroflexus, showing good herbicidal activity. Among them, the inhibition rates of compounds 7g, 7h, 7p, 7r and 7t on Digitaria and Amaranthus retroflexus are 80-85%, which is equivalent to the positive control. In addition, at a concentration of 100 mg / L, the inhibition rates of compounds 7m, 7n and 7q on Digitaria and Amaranthus retroflexus reach more than 85%, which is better than the positive control. More importantly, at the same concentration, compounds 7m and 7q show the best herbicidal effect on Digitaria and Amaranthus retroflexus, with an inhibition rate of more than 95%.

[0052] Most of the indole-3-acetamide derivatives of the present invention have good herbicidal effects at a dosage of 150 g effective content / hectare by foliar spraying. The results are shown in Table 2. Except for compounds 7c, 7e, and 7f, which have an inhibitory effect on crabgrass of less than 50%, and compounds 7d, 7f, and 71, which have an inhibitory effect on Amaranthus retroflexus of less than 50%, most of the compounds have a herbicidal effect on crabgrass and Amaranthus retroflexus of greater than 50%. Among them, the inhibitory rates of compounds 7h, 7n, 7p, 7q, and 7r on crabgrass and Amaranthus retroflexus are 70-89%, which are comparable to the positive control. More significantly, compound 7m has a better herbicidal effect on crabgrass and Amaranthus retroflexus (inhibition rate of more than 90%). Since the ClogP value of compound 7m (5.307) is higher than that of compound 7q (3.638), compound 7m has a higher lipophilicity than 7q, which may promote its absorption and transport in plants. Therefore, in the stem and leaf spray method, 7m has a better herbicidal effect than 7q. In addition, 7m exhibits a higher transketolase inhibitory activity, which shows that compound 7m is a promising candidate compound for a highly efficient herbicide targeting transketolase.

[0053] Example 6: Use of the indole-3-acetamide derivative 7 of the present invention in combination with an agriculturally acceptable adjuvant and any one or more of the following commercial herbicides in the preparation of a compound herbicide:

[0054] The commercial herbicide is selected from nicosulfuron, bensulfuron-methyl, monosulfuron, sulfamethoxam, penoxsulam, alachlor, acetochlor, butachlor, isopropyl metolachlor, fluramide, mesotrione, mesotrione, benzachlor, pendimethalin, atrazine, promethazine, cyanazine, ametryn, metribuzin, nitropropene, oxyfluorfen, trifluorfen, lactofen, fluazifop-butyl, pyraclostrobin, isopropylpyraclostrobin, imazapic, imazapic, imazapic, imazapic, imazaquin, methyl imazapic, pyrimidine sulfamethoxam, pyrimidine sulfamethoxam, pyrimidine sulfamethoxam, cyclamate, betaine, betaine, avena cava, diamine, barnyardgra, dicamba, dicamba, pyraclostrobin, pyrimidine sulfamethoxam, oxazolidinone, oxazolidinone, pyrimidine sulfamethoxam ... Azofenac, quizalofop-p-butyl, thiamethoxam, fluroxypyr, fluthiopyra, fluazifop-butyl, fluazifop-butyl, fluazifop-butyl, paraquat, glyphosate, sedge barnyardgrass, flufenac, fluazifop-butyl, fluthiophanate-butyl, flufenac-butyl, fluazifop-butyl, pyraclostrobin, pyraclostrobin, pyraclostrobin, pyraclostrobin, isoxathiocarb, isoxathiocarb, bromoxynil, etc.; the total mass percentage of the indole-3-acetamide derivative 7 of the present invention in the obtained composite herbicide is 1%-90%, and the ratio of the indole-3-acetamide derivative 7 of the present invention to the commercial herbicide is 1%:99% to 99%:1% by mass; the formulation suitable for the composite herbicide is selected from any one of the following formulations: wettable powder, microcapsule suspension, dispersible liquid Preparations, dispersible solid preparations, seed treatment emulsions, water emulsions, large granules, microemulsions, oil suspensions, water-soluble granules, soluble concentrates, water-dispersible granules, poisonous valleys, aerosols, slow-release blocks, capsule granules, dry seed powders, emulsifiable concentrates, electrostatic sprays, water-in-oil emulsions, oil-in-water emulsions, smoke cans, fine granules, smoke candles, smoke tubes, smoke sticks, seed treatment suspensions, smoke tablets, smoke pills, gassing agents, drifting powders, ointments, hot fog agents, solid / liquid mixed preparations, liquid / liquid mixed preparations, cold fog agents, solid / solid mixed preparations, lacquers, seed treatment liquids, microgranules, oil-dispersible powders, concentrated glues, pouring agents, smears, suspension emulsions, film-forming oils, soluble powders, water-soluble powders for seed treatment agent, ultra-low volume suspension, tracking powder, ultra-low volume liquid, steam release agent, wet seed dressing water dispersible powder; the plants suitable for the compound herbicide are selected from rice, wheat, barley, oats, corn, sorghum, sweet potato, potato, cassava, soybean, snow pea, broad bean, pea, mung bean, red bean, cotton, sericulture, peanut, rape, sesame, sunflower, beet, sugarcane, coffee, cocoa, ginseng, fritillaria, rubber, coconut, oil palm, sisal, tobacco, tomato, pepper, radish, cucumber, cabbage, celery, mustard, beet, rape, onion, garlic, watermelon, melon, cantaloupe, papaya, apple, citrus, peach, tea, wild vegetables, bamboo shoots, hops, pepper, banana, papaya, orchid, bonsai;The compound herbicide is suitable for controlling weeds selected from: Gramineae weeds: Digitaria, Setaria, Goosegrass, Echinochloa, Leptochloa, Chlorophytum, Wild Oats, Teff, Golden Setaria, Long-awned Coptis, Alopecuroides, etc.; Broadleaf weeds: Amaranthus retroflexus, Purslane, Chenopodium album, Artemisia selengensis, Amaranthus, Xanthium sibiricum, Ambrosia, Amaranthus, Abutilon, Kochia, Solanum nigrum, Willowleaf Prickly, Chickweed, Elsholtzia, Waterthorn Needle, Rumex, Cupressus, Field Bindweed, Cuscuta, etc.; Cyperaceae weeds: Fernleaf Felt, Cyperus heterosexualus, Cyperus watergrass, Salsola, Onion, etc.;

[0055] Table 1 Chemical structure and physicochemical parameters of indole-3-acetamide derivative 7 of the present invention

[0056]

[0057]

[0058] Table 2 Herbicidal activity of indole-3-acetamide derivative 7 of the present invention against Digitaria tangutica and Amaranthus retroflexus (cup method: inhibition rate / %) at 100 μg / ml

[0059]

[0060] Table 3 Herbicidal activity of indole-3-acetamide derivative 7 of the present invention by foliar spraying (inhibition rate / % at 150 g effective content / hectare)

[0061]

[0062] Rating scale for percentage inhibition compared with blank control: ++++≥90%; +++70–89%; ++50–69%; +30–49%; –<30%.

Claims

1. An indole-3-acetamide derivative having the structure shown in formula (7): in, R 1 is selected from 4-fluorophenyl, 2,4-dichlorophenyl, 6-chloropyridin-3-yl or cyclopropyl; R 2 Selected from 4-trifluorophenyl, pyridin-3-methylene, 1-methyl-1H-pyrazol-5-yl, furan-2-methylene, thiophene-2-methylene or cyclopropyl.

2. The indole-3-acetamide derivative according to claim 1, characterized in that The formula (7) has the following structure:

3. A method for synthesizing an indole-3-acetamide derivative, comprising: 1) mixing indole-3-acetic acid methyl ester of formula (1) with a halide of formula (2) to obtain a compound of formula (3); Among them, R 1 Selected from: 4-fluorophenyl, 2,4-dichlorophenyl, 6-chloropyridin-3-yl or cyclopropyl; 2) converting the compound of formula (3) into a compound of formula (4); 3) reacting the compound of formula (4) with oxalyl chloride to obtain a compound of formula (5); 4) mixing the compound of formula (6) and the compound of formula (5) to obtain a compound of formula (7), which is an indole-3-acetamide derivative. R 2 NH2 formula (6), Among them, R 2 Selected from: 4-trifluorophenyl, pyridin-3-methylene, 1-methyl-1H-pyrazol-5-yl, furan-2-methylene, thiophene-2-methylene or cyclopropyl.

4. The synthesis method according to claim 3, characterized in that The step 2) specifically comprises dissolving the compound of formula (3) in ethanol, then slowly adding 10% potassium hydroxide solution, reacting at room temperature, and monitoring the reaction progress by TLC. After the reaction is completed, the solvent is removed by rotary evaporation under reduced pressure, and 10 mL of distilled water is added to dissolve the residue. The pH of the solution is adjusted to 5 with concentrated HCl, and then extracted with ethyl acetate to obtain the compound of formula (4).

5. The synthesis method according to claim 3, characterized in that The step 3) is specifically to dissolve the indolecarboxylic acid derivative having the structure of formula (4) in dichloromethane, and then dropwise add 3.00 mmol of an anhydrous dichloromethane solution of oxalyl chloride into the above solution under ice bath conditions to react and obtain a compound having the structure of formula (5).

6. The synthesis method according to claim 3, characterized in that The step 4) is specifically to mix the amino compound of formula (6), dichloromethane and 1.2 mmol triethylamine, and dropwise add the dichloromethane solution containing the compound of formula (5) into the above solution under ice bath condition, and mix and react to obtain the compound of formula (7).

7. The synthesis method according to claim 3, characterized in that The compound of formula (6) is p-trifluoromethylaniline, 3-aminomethylpyridine, 1-methyl-5-aminopyrazole, 2-thiophene-methylamine, 2-furan-methylamine or cyclopropylamine.

8. The synthesis method according to claim 3, characterized in that The halogenated compound having the structure of formula (2) is 4-fluorobenzyl chloride, 2,4-dichlorobenzyl chloride, 2-chloro-5-chloromethylpyridine or chloromethylcyclopropane.

9. Use of the indole-3-acetamide derivative according to any one of claims 1 to 2 or the indole-3-acetamide derivative prepared by the preparation method according to any one of claims 3 to 8 in the preparation of herbicides.

10. A herbicide composition comprising: The indole-3-acetamide derivative according to any one of claims 1 to 2 or the preparation method according to any one of claims 3 to 8 is used to prepare the indole-3-acetamide derivative.

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