Novel methylpyrazole propionamide derivative as well as preparation method and application thereof

Abstract

The invention discloses a novel methylpyrazole propionamide derivative as well as a preparation method and application thereof. According to the invention, 3-hydroxypyrazole is used as an active matrix skeleton and is combined with a pharmacodynamic group propionamide with herbicidal activity to develop a novel hydroxypyrazole herbicide, and a series of novel 3-oxypropionamide-1-methylpyrazole-carboxylic ester derivatives are designed and synthesized. The invention also provides biological activity of the compounds for controlling agricultural, horticultural and forestry weeds, a determination method of the compounds, and application of the compounds in the fields of agriculture, horticultural and forestry.

Description

Technical Field

[0001] The technical scheme of the present invention relates to methylpyrazole propionamide compounds, specifically to 3-oxypropionamide-1-methylpyrazole-carboxylate derivatives. Background Art

[0002] Weeds compete with crops for survival resources, resulting in economic losses in agricultural production. Therefore, integrated weed control strategies play an important role in agricultural production, including Al laser mechanical control, chemical control, and biological control. Among them, chemical control is still the most commonly used and effective measure. However, with the continued use of synthetic herbicides with the same or similar modes of action (MoAs), the frequency of resistant weeds has increased. Therefore, the discovery of herbicides with new MoAs is an important R&D activity to meet the market demand for herbicides.

[0003] Key proteases in plants have become important targets for herbicide research and development, such as plant transketolase (TKL; EC 2.2.1.1), which has gradually become a potential target for herbicide development in the past decade. It plays an important role in the pentose phosphate pathway and the Calvin cycle, and slight fluctuations in TKL activity affect plant photosynthesis and phenylalanine metabolism. Therefore, the development of herbicides targeting this target is constantly advancing. For example, it has been reported that the herbicidal natural product (+)-cornexistin can target corn transketolase, and the crystal structure of its complex has been resolved (Steinborn, C., Chem. Eur. J. 2023, 29, No. e202300199), which further accelerates the pace of discovery of TKL inhibitors targeting plants.

[0004] Heterocyclic compounds are widely used in the structure of medicines and pesticides. About three-quarters of medicines and pesticides on the market contain at least one heterocycle. Among them, hydroxypyrazole, as a typical nitrogen-containing heterocycle, has a wide range of biological activities, including anti-infective and antibacterial agents (Bhavanarushi, S., Med. Chem. Res. 2014, 23, 158-167), antimalarial drugs (Pippione, AC, Eur. J. Med. Chem. 2019, 163, 266-280), antiviral (Shi, HB, ACS Infect. 2020, 6, 302-312), and potential herbicidal activity, and has shown potential to inhibit TKL activity. Therefore, it can be used as a lead structure for herbicidal activity targeting TKL for optimization research.

[0005] In order to discover a transketolase inhibitory active skeleton with herbicidal activity, the present invention uses 3-hydroxypyrazole as the active parent skeleton and combines it with the herbicidal pharmacological group propionamide to develop a new hydroxypyrazole herbicide. A series of new 3-oxypropionamide-1-methylpyrazole-carboxylate derivatives were designed and synthesized, and their biological activities were systematically screened and evaluated, in order to provide more candidate compounds with high activity and low resistance risk for the creation and research of new target herbicides. Summary of the invention

[0006] The technical problem to be solved by the present invention is to provide a method for synthesizing a new type of 3-oxypropionamide-methylpyrazole-carboxylate derivatives, and a method for determining their biological activity in controlling agricultural, horticultural and forestry weeds, and to provide applications of these compounds in the agricultural, horticultural and forestry fields.

[0007] The technical solution adopted by the present invention to solve the technical problem is: the chemical structure of the 3-oxypropionamide-1-methylpyrazole-carboxylate compound with herbicidal activity in the agricultural field, the horticultural field, and the forestry field is shown in Formula V:

[0008] V:

[0009] Wherein, R is selected from: isopropyl, propargyl, butyl, pentyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-methoxyphenyl, 4-isopropylphenyl, 4-tert-butylphenyl, 4-trifluoromethylphenyl, 2,4-difluorophenyl, 2,4-dichlorophenyl, 3,4-difluorophenyl, 3,4-methylenedioxyphenyl, 2,3,4-trifluorophenyl, 2,3,4,5-tetrafluorophenyl, 2-thienyl, 2-pyridylethyl, 5-fluoropyridin-2-yl, 2,6-dichloropyridin-3-yl, N-morpholinyl, 4-methoxy-6-methylpyrimidin-2-yl, 5-chloro-2-phenoxyphenyl, 4-(4-chlorophenoxy)phenyl, 4-(4-methoxyphenoxy)phenyl.

[0010] The synthesis method of the 3-oxypropionamide-methylpyrazole-carboxylate derivative V of the present invention is as follows:

[0011]

[0012] a.CH2C12, Et3N, rt.b. CH3NHNH2·H2SO4, Toluene / AcOH, NaOAc, reflux. c. Acetone, K2CO3, reflux.

[0013] Wherein, R is selected from: isopropyl, propargyl, butyl, pentyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-methoxyphenyl, 4-isopropylphenyl, 4-tert-butylphenyl, 4-trifluoromethylphenyl, 2,4-difluorophenyl, 2,4-dichlorophenyl, 3,4-difluorophenyl, 3,4-methylenedioxyphenyl, 2,3,4-trifluorophenyl, 2,3,4,5-tetrafluorophenyl, 2-thienyl, 2-pyridylethyl, 5-fluoropyridin-2-yl, 2,6-dichloropyridin-3-yl, N-morpholinyl, 4-methoxy-6-methylpyrimidin-2-yl, 5-chloro-2-phenoxyphenyl, 4-(4-chlorophenoxy)phenyl, 4-(4-methoxyphenoxy)phenyl.

[0014] The specific method for the synthesis of the 3-oxypropionamide-methylpyrazole-carboxylate derivative V of the present invention and the determination of the biological activity is divided into the following steps:

[0015] A. Preparation of Compound II:

[0016] 3.21 mmol of R-substituted amine was added to a 50 ml single-mouth round-bottom flask, 10 ml of dichloromethane was added to dissolve, 3.21 mmol of triethylamine was slowly added dropwise, and the reaction was carried out at room temperature for 5 minutes, and then 2.92 mmol of compound I was slowly added dropwise, and the reaction was carried out at room temperature for 3 hours, and the reaction progress was monitored by TLC. After the reaction was completed, the mixed solution was washed 3 times with saturated brine, the aqueous phase was separated, the organic layer was retained, the aqueous layer was stripped twice, the organic layers were combined, and the compound II was purified by 100-200 mesh silica gel column chromatography, the eluent was petroleum ether: ethyl acetate, the volume ratio was 8:1, and the yield was 40-78%; the amount of compound II prepared and the volume of the reaction container were enlarged or reduced in the corresponding proportion.

[0017] B. Preparation of Compound IV:

[0018] In a 200 ml single-necked round-bottom flask, 16.70 mmol of compound III and 20.88 mmol of methylhydrazine sulfate were added, 12 ml of toluene and 12 ml of glacial acetic acid were added to dissolve, and then 41.75 mmol of sodium acetate was added, and the mixture was stirred at 100° C. for 2.5 hours. After the reaction was complete, the solvent was removed under reduced pressure, and the residue was purified by 100-200 mesh silica gel column chromatography to obtain compound IV, the eluent was dichloromethane:ethyl acetate, the volume ratio was 10:1, and the yield was 45%; the amount of compound IV prepared and the volume of the reaction container were enlarged or reduced in corresponding proportions.

[0019] C. Preparation of Compound V:

[0020] 1.92 mmol of compound IV was added to a 50 ml single-mouth round-bottom flask, 12 ml of acetone was added to dissolve, 2.30 mmol of potassium carbonate was slowly added, and then 2.12 mmol of compound II was added, and the mixture was stirred at 60°C for 2.5 hours. After the reaction was completed, the mixed solution was washed 3 times with saturated brine, the aqueous phase was separated, the organic layer was retained, the aqueous layer was back-extracted twice, the organic layers were combined, and the compound V was purified by 100-200 mesh silica gel column chromatography, the eluent was petroleum ether: ethyl acetate, the volume ratio was 8:1, and the yield was 33-73%; the amount of compound V prepared and the volume of the reaction container were increased or decreased in the corresponding proportion.

[0021] D. Determination of herbicidal activity of the methylpyrazole propionamide derivative V of the present invention:

[0022] a. Small cup method herbicidal activity test:

[0023] Take 20 mg of compound V and dissolve it in 1 ml of N, N-dimethylformamide to prepare a mother solution with a concentration of 20,000 mg / L, and then dilute it to 200 mg / L with distilled water containing 0.1% Tween 80 emulsifier. The final content of DMF in the test solution is less than 1%. Germinate the seeds of the test weeds two days in advance, then pick the seeds with the same germination effect with tweezers and place them evenly in a 50 ml beaker, 9 seeds per cup, and repeat each treatment 3 times. Finally, add 1 ml of the agent with a concentration of 200 mg / L evenly to the beaker, and cultivate it for one week under the conditions of temperature of 25°C, humidity of 75%, and light day and night ratio of 16:8. Measure the root length and stem length of the weeds, and calculate the root length inhibition rate and stem length inhibition rate by comparing with the blank control weeds. The test weeds are species of most typical weeds actually occurring in the field during agricultural production, and their codes and names are as follows: DS: Digitaria sanguinalis, its Latin name is: AR: Amaranthus retroflexus, its Latin name is: Amaranthus retroflexus.

[0024]

[0025] b. Leaf spray herbicidal activity test:

[0026] Take 20 mg of compound V and dissolve it in 1 ml of N, N-dimethylformamide to prepare a mother solution with a concentration of 20,000 mg / L, and then dilute it to 150 g / hectare with distilled water containing 0.1% Tween 80 emulsifier. The final content of N, N-dimethylformamide in the test solution is less than 1%. Mix the nutrient soil and vermiculite in a volume ratio of 1:1, put the prepared mixed soil into the flower pot, and use the bottom of the pot to make the soil completely wet. Use tweezers to take 9 seeds of the spare test plants and place them evenly in the flower pot in turn, and cover the soil to the pot mouth. Cultivate in a greenhouse at 25°C, add water in time to keep it moist, and when the test plants grow to the two-leaf and one-heart stage, use a walking spray tower (3WP-2000) to spray the medicine uniformly, and repeat each treatment 3 times. Cultivate the treated weeds in the greenhouse, add water in time during the period to ensure that the soil is moist, and after 14 days, evaluate the herbicidal activity by visual inspection. The test weeds are species of most typical weeds actually occurring in the field in agricultural production. Their codes and names are as follows: DS: crabgrass, its Latin name is Digitaria sanguinalis, AR: Amaranthus retroflexus, its Latin name is Amaranthus retroflexus, SV: Setaria viridis, its Latin name is Setaria viridis, EC: Echinochloa crusgalli, its Latin name is Echinochloa crusgalli, PO: Purslane, its Latin name is Portulaca oleracea, LP: Perennial ryegrass, its Latin name is Lolium perenne, SJ: Sage, its Latin name is Salvia japonica, TR: Clover, its Latin name is Trifolium repens, CE: Chicory, its Latin name is Cichorium endivia.

[0027] c. Soil sealing method herbicidal activity test:

[0028] Take 20 mg of compound V and dissolve it in 1 ml of N,N-dimethylformamide to prepare a mother solution with a concentration of 20,000 mg / L, and then dilute it to 150 g / hectare with distilled water containing 0.1% Tween 80 emulsifier. The final content of DMF in the test solution is less than 1%. Mix the nutrient soil and vermiculite in a volume ratio of 1:1, put the prepared mixed soil into the flower pot, and use the bottom of the pot to make the soil completely wet. Use tweezers to take 9 seeds of the spare test plants and place them evenly in the flower pot in turn, and cover the soil to the pot mouth. Cultivate in a greenhouse at 25°C, add water in time to keep it moist, and after 3 days of planting, use a walking spray tower (3WP-2000) to spray the medicine uniformly, and repeat each treatment 3 times. Cultivate the treated weeds in the greenhouse, add water in time during the period to ensure that the soil is moist, and after 14 days, use visual inspection to evaluate the herbicidal activity. The test weeds are species of most typical weeds actually occurring in the field during agricultural production, and their codes and names are as follows: DS: Digitaria sanguinalis, its Latin name is: AR: Amaranthus retroflexus, its Latin name is: Amaranthus retroflexus.

[0029] E. SvTKL inhibitory activity of the methylpyrazole propionamide derivative V of the present invention:

[0030] The transketolase protein (SvTKL) of Setaria viridis was expressed and purified by prokaryotic expression. The specific test method of the methylpyrazole propionamide derivative V of the present invention on the enzyme activity of SvTKL is as follows: First, a 1.5 mg / ml SvTKL concentration was treated with a gradient concentration compound (v:v=99:1) at 30°C, and after 10 minutes, a magnesium chloride aqueous solution (1.80×10 4 mg / L, 20 μL), TPP coenzyme (1.10×10 4 mg / L, 20 μL) and phenol red (99.2 mg / L, 20 μL), and then incubated at 37°C for 5 minutes. After the incubation, the mixture (160 μL) was transferred to a 96-well plate. Then, 1.80×10 5 mg / L d-glyceraldehyde (20 μL) and 5.40×10 4 mg / L β-hydroxyacetic acid lithium salt hydrate (20 μL), mixed for 60 seconds, and then the corresponding enzyme activity inhibition rate was calculated according to the absorbance measured at 650 nm. SPSS19.0 software was used to calculate IC 50 value.

[0031] F. Crop safety of the methylpyrazole propionamide derivative V of the present invention:

[0032] Take 20 mg of compound V and dissolve it in 1 ml of N, N-dimethylformamide to prepare a mother solution with a concentration of 20,000 mg / L, and then dilute it to 150 g / hectare with distilled water containing 0.1% Tween 80 emulsifier. The final content of DMF in the test solution is less than 1%. Mix the nutrient soil and vermiculite in a volume ratio of 1:1, put the prepared mixed soil into the flower pot, and use the bottom of the pot to make the soil completely wet. Plant the crops and place them in a greenhouse at 25°C for cultivation. Supplement water in time to keep them moist. After 14 days of planting, spray them uniformly through a walking spray tower (3WP-2000), and repeat each treatment 3 times. The treated crops are placed in a greenhouse for cultivation, and water is supplemented in time during the period to ensure that the soil is moist. After 14 days, observe the visual damage and growth rate of each crop to evaluate the safety of the crops. The test crops are four conventional crops in agricultural production, including wheat, corn, cotton and soybeans.

[0033] The beneficial effects of the present invention are: the methylpyrazole propionamide derivative V is optimized first, the herbicidal activity of the methylpyrazole propionamide derivative V is screened, the SvTKL inhibitory activity is tested, and the crop safety is evaluated.

[0034] The present invention further specifically illustrates the synthesis, biological activity and application of methylpyrazole propionamide derivative V 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 but not to limit the present patent. The specific implementation methods are as follows:

[0035] Example 1: Preparation of Compound II:

[0036] 3.21 mmol of R-substituted amine was added to a 50 ml single-mouth round-bottom flask, 10 ml of dichloromethane was added to dissolve, 3.21 mmol of triethylamine was slowly added dropwise, and the reaction was carried out at room temperature for 5 minutes, and then 2.92 mmol of compound I was slowly added dropwise, and the reaction was carried out at room temperature for 3 hours, and the reaction process was monitored by TLC. After the reaction was completed, the mixed solution was washed with saturated brine for 3 times, the aqueous phase was separated, the organic layer was retained, the aqueous layer was stripped twice, the organic layers were combined, and the compound II was purified by 100-200 mesh silica gel column chromatography, the eluent was petroleum ether: ethyl acetate, the volume ratio was 8:1, and the yield was 40-78%; the amount of compound II prepared and the volume of the reaction container were enlarged or reduced in the corresponding proportion.

[0037] Example 2: Preparation of Compound IV:

[0038] In a 200 ml single-necked round-bottom flask, 16.70 mmol of compound III and 20.88 mmol of methylhydrazine sulfate were added, 12 ml of toluene and 12 ml of glacial acetic acid were added to dissolve, and then 41.75 mmol of sodium acetate was added, and the mixture was stirred at 100° C. for 2.5 hours. After the reaction was completed, the solvent was removed under reduced pressure, and the residue was purified by 100-200 mesh silica gel column chromatography to obtain compound IV, the eluent was dichloromethane:ethyl acetate, the volume ratio was 10:1, and the yield was 45%; the amount of compound IV prepared and the volume of the reaction container were enlarged or reduced in the corresponding proportion.

[0039] Example 3: Preparation of Compound V:

[0040] 1.92 mmol of compound IV was added to a 50 ml single-mouth round-bottom flask, 12 ml of acetone was added to dissolve, 2.30 mmol of potassium carbonate was slowly added, and then 2.12 mmol of compound II was added, and the mixture was stirred at 60°C for 2.5 hours. After the reaction was completed, the mixed solution was washed 3 times with saturated brine, the aqueous phase was separated, the organic layer was retained, the aqueous layer was back-extracted twice, the organic layers were combined, and the compound V was purified by 100-200 mesh silica gel column chromatography, the eluent was petroleum ether: ethyl acetate, the volume ratio was 8:1, and the yield was 33-72%; the amount of compound V prepared and the volume of the reaction container were increased or decreased in the corresponding proportion.

[0041] Example 4: Preparation of Compound D15:

[0042]

[0043] 1.92 mmol of compound IV was added to a 50 ml single-mouth round-bottom flask, 12 ml of acetone was added to dissolve, 2.30 mmol of potassium carbonate was slowly added, and then 2.12 mmol of compound II was added, and stirred at 60°C for 2.5 hours. After the reaction was completed, the mixed solution was washed 3 times with saturated brine, the aqueous phase was separated, the organic layer was retained, the aqueous layer was back-extracted twice, the organic layers were combined, and the compound V was purified by 100-200 mesh silica gel column chromatography. The eluent was petroleum ether: ethyl acetate, the volume ratio was 8:1, and the yield was 51%; the physicochemical parameters and structural parameters of compound V are shown in Table 1.

[0044] Example 5: Results of determination of herbicidal activity of the methylpyrazole propionamide derivative V of the present invention:

[0045] The codes and names of the common weeds tested in the present invention are as follows: DS: Digitaria sanguinalis, AR: Amaranthus retroflexus, SV: Setaria viridis, EC: Echinochloa crusgalli, PO: Portulaca oleracea, LP: Lolium perenne, SJ: Salvia japonica, TR: Trifolium repens, CE: Cichorium endivia, these weeds are very representative and can represent most of the weeds occurring in the field during agricultural production. The test methods include the small cup method, the stem and leaf spray method and the soil sealing method.

[0046] The herbicidal activity test results of the small cup method are shown in Table 2, which shows that at 200 mg / L, all the methylpyrazole propionamide compounds synthesized by the present invention have different degrees of herbicidal activity. For the root length of crabgrass, the inhibition rates of compounds D7, D8, D15, D16, D19, and D20 are above 60%, which are better than the control agents nicosulfuron, mesotrione, and metamifop, among which compound D15 has the best inhibition effect, which is higher than the control agent by more than 40%; for the stem length of crabgrass, the inhibition rates of compounds D9, D10, D15, D22, D24, and D25 are above 50%, among which compound D15 has the best inhibition effect, which is higher than the control agents nicosulfuron, mesotrione, and metamifop by more than 20%. For the root length of Amaranthus retroflexus, the inhibition rates of compounds D3, D5, D7, D8, D15, D20, and D22 were above 65%, which were better than the control agents nicosulfuron and mesotrione, among which compound D15 had the best effect, which was more than 30% higher than the control agent; for the stem length of Amaranthus retroflexus, the inhibition rates of compounds D5, D7, D11, D14, D15, D16, D20, D22, and D23 were above 70%, which were better than the control agents nicosulfuron and mesotrione, among which compound D15 had the best effect, which was more than 40% higher than the control agent; in summary, in the small cup method test, compounds D15, D20, D22, and D25 had good growth inhibitory activity on Digitaria retroflexus, and compounds D5, D7, D15, D20, and D22 had good growth inhibitory activity on Amaranthus retroflexus.

[0047] The test results of herbicidal activity by soil sealing method are shown in Table 3, which shows that at 150 g / hectare, all the methylpyrazole propionamide compounds synthesized by the present invention have different degrees of herbicidal activity. For Amaranthus retroflexus, compounds D11, D12, D13, D15, D16, D18, D19, D20, and D22 have good inhibitory effects, with an inhibition rate of more than 70%; for Crabgrass, compounds D2, D5, D7, D8, D11, D12, D13, D15, D16, D17, D18, D19, D20, D22, D23, and D25 have good inhibitory effects, with an inhibition rate of more than 70%, among which compound D15 has the best inhibitory effect, which is better than the control agent mesotrione. In summary, in the soil sealing method test, the inhibition rates of compounds D11, D12, D13, D15, D16, D18, D19, D20, and D22 on Digitaria and Amaranthus retroflexus were all above 70%, indicating that they had good herbicidal activity.

[0048] The herbicidal activity test results of the stem and leaf spray method are shown in Table 3. Table 3 shows that at 150 grams per hectare, all the methylpyrazole propionamide compounds synthesized by the present invention have different degrees of herbicidal activity. For Amaranthus retroflexus, compounds D7, D8, D9, D11, D12, D13, D14, D15, D16, D18, D19, D20, D23, D24, and D27 have good inhibitory effects, with an inhibition rate of more than 70%, which is better than the control agent oxadiazine, among which D20 has the best inhibitory effect, reaching more than 90%; for Crabgrass, compounds D20 and D22 have good inhibitory effects, with an inhibition rate of more than 70%. In summary, in the stem and leaf spray method test, the inhibition rates of compounds D20 and D22 on Crabgrass and Amaranthus retroflexus are all above 70%, and have good herbicidal activity.

[0049] The broad-spectrum test results of the methylpyrazole propionamide derivative V of the present invention are shown in Table 4. Table 4 shows that at 150 g / hectare, all compounds have different degrees of herbicidal activity against Setaria, barnyard grass, purslane, perennial ryegrass, sage, clover, and chicory. For Setaria, the inhibition rates of compounds D15 and D20 are above 70%, which are comparable to the control agents mesotrione, oxadiazine, and pretilachlor, and are better than the control agent nicosulfuron; for barnyard grass, compound D15 and D20 have an inhibition rate of more than 70%, which is comparable to the control agents mesotrione, oxadiazine, and pretilachlor, and is ... The inhibition rates of compounds D15 and D20 were above 70%, close to those of the control agents mesotrione and pretilachlor, and better than those of the control agent nicosulfuron; for purslane, the inhibition rates of compounds D15 and D20 were above 50%, better than those of the control agents oxadiazole and pretilachlor; for perennial ryegrass, the inhibition rates of compounds D15 and D20 were above 30%; for sage, the inhibition rate of compound D15 was above 50%, better than those of the control agents oxadiazole and pretilachlor; for clover, the inhibition rates of compounds D15 and D20 were above 50%, better than those of the control agents nicosulfuron and oxadiazole; for chicory, the inhibition rates of compounds D15 and D20 were above 50%, better than those of the control agents oxadiazole and pretilachlor.

[0050] Example 6: SvTKL inhibitory activity of the methylpyrazole propionamide derivative V of the present invention:

[0051] The results of the SvTKL inhibitory activity of the methylpyrazole propionamide derivative V of the present invention are shown in Table 5. Table 5 shows that the IC values ​​of compounds D15 and D20 are 50 The values ​​were 0.384 mg / L and 0.655 mg / L, respectively, which were close to the control drug p-hydroxyphenylpyruvic acid 0.167 mg / L. The results showed that the pyrazole propionamide derivative V of the present invention is an inhibitor of transketolase and is worthy of further study.

[0052] Example 7: Crop safety of the methylpyrazole propionamide derivative V of the present invention:

[0053] The crop safety results of the methylpyrazole propionamide derivative V of the present invention are shown in Table 6, which shows that D15 and D20 exhibit lower damage to wheat, corn and cotton at a dosage of 150 g / hectare, showing better crop safety than the herbicides nicosulfuron, mesotrione and metamifop. This shows that compounds D15 and D20 are promising herbicide candidates for wheat, corn, soybean and cotton fields.

[0054] Example 8: Use of the methylpyrazole propionamide derivative V 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:

[0055] The commercial herbicide is selected from nicosulfuron, bensulfuron-methyl, monosulfuron, sulfamethoxam, penoxsulam, alachlor, acetochlor, butachlor, isopropyl metolachlor, 2-methyl-4-chloro, fluralin, 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, pyrimidine sulfamethoxam, pyrimidine sulfamethoxam, betamethoxam, betamethoxam, avena cava, diamine, cypermethrin, cypermethrin, pyrimidine sulfamethoxam ... Chlorfenapyr, oxazolidinone, quizalofop-p-butyl, thiazolinone, fluroxypyr, fluthiopyr, fluridone, thiamethoxam, flufenacet, paraquat, glyphosate, sedge barnyardgrass, flufenac, fluazifop-butyl, fluthiophanate-butyl, flufenacet-butyl, pyrazoline, pyraclostrobin, pyraclostrobin, benzothiazolin, isoxathiocarb, isoxathiocarb, bromoxynil, etc.; the total mass percentage of the methylpyrazole propionamide derivative V in the obtained compound herbicide is 1%-90%, and the ratio of the methylpyrazole propionamide derivative V to the commercial herbicide is 1%:99% to 99%:1% by mass; the formulation suitable for the compound herbicide is selected from any one of the following formulations: wettable powder, microcapsule suspension, dispersible liquid solid 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, sustained-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, gasifiers, drifting powders, ointments, hot mists, solid / liquid mixed preparations, liquid / liquid mixed preparations, cold mists, 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 seed treatments Powder, 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, adzuki 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, Ambrosia, Amaranthus, Abutilon, Kochia, Solanum nigrum, Willowleaf Prickly, Chickweed, Waterthorn Needle, Rumex, Cupressus, Field Bindweed, Cuscuta, etc.; Cyperaceae weeds: Cyperus rotundus, Cyperus heterosexualus, Cyperus watergrass, Salsola, Onion, etc.;

[0056]

[0057]

[0058]

[0059]

[0060] Table 2 Herbicidal activity of the methylpyrazole propionamide derivative V of the present invention by the small cup method

[0061]

[0062] Table 3 Herbicidal activity of the methylpyrazole propionamide derivative V of the present invention

[0063]

[0064] Note: Inhibition percentage levels compared to blank control: ++++>90%; +++70%-89%; ++50%-69%; +30%-49%; -<30% or no inhibition.

[0065] Table 4 Broad spectrum test of methylpyrazole propionamide derivative V of the present invention

[0066]

[0067] Note: Inhibition percentage levels compared to blank control: ++++>90%; +++70%-89%; ++50%-69%; +30%-49%; -<30% or no inhibition.

[0068] Table 5 Inhibitory effect of the methylpyrazole propionamide derivative V of the present invention on SvTKL

[0069]

[0070] Table 6 Crop safety of the methylpyrazole propionamide derivative V of the present invention

[0071]

Claims

1. A class of 3-oxypropionamide-1-methylpyrazole-carboxylate derivatives, characterized in that It has a general chemical structure as shown in Formula V: Wherein, R is selected from: isopropyl, propargyl, butyl, pentyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-methoxyphenyl, 4-isopropylphenyl, 4-tert-butylphenyl, 4-trifluoromethylphenyl, 2,4-difluorophenyl, 2,4-dichlorophenyl, 3,4-difluorophenyl, 3,4-methylenedioxyphenyl, 2,3,4-trifluorophenyl, 2,3,4,5-tetrafluorophenyl, 2-thienyl, 2-pyridylethyl, 5-fluoropyridin-2-yl, 2,6-dichloropyridin-3-yl, N-morpholinyl, 4-methoxy-6-methylpyrimidin-2-yl, 5-chloro-2-phenoxyphenyl, 4-(4-chlorophenoxy)phenyl, 4-(4-methoxyphenoxy)phenyl.

2. The method for synthesizing the 3-oxypropionamide-1-methylpyrazole-carboxylate derivative V according to claim 1, wherein the specific synthetic route is as follows: a.CH2Cl2,Et3N,rt.b.CH3NH2·H2SO4,Toluene / AcOH,NaOAc,reflux.c.Acetone,K2CO3,reflux. in, R is selected from the group consisting of isopropyl, propargyl, butyl, pentyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-methoxyphenyl, 4-isopropylphenyl, 4-tert-butylphenyl, 4-trifluoromethylphenyl, 2,4-difluorophenyl, 2,4-dichlorophenyl, 3,4-difluorophenyl, 3,4-methylenedioxyphenyl, 2,3,4-trifluorophenyl, 2,3,4,5-tetrafluorophenyl, 2-thienyl, 2-pyridylethyl, 5-fluoropyridin-2-yl, 2,6-dichloropyridin-3-yl, N-morpholinyl, 4-methoxy-6-methylpyrimidin-2-yl, 5-chloro-2-phenoxyphenyl, 4-(4-chlorophenoxy)phenyl, 4-(4-methoxyphenoxy)phenyl. The specific method for synthesizing the 3-oxypropionamide-1-methylpyrazole-carboxylate derivatives according to claim 1 is divided into the following steps: A. Preparation of Compound II: 3.21 mmol of R-substituted amine was added to a 50 ml single-mouth round-bottom flask, 10 ml of dichloromethane was added to dissolve, 3.21 mmol of triethylamine was slowly added dropwise, and the reaction was carried out at room temperature for 5 minutes, and then 2.92 mmol of compound I was slowly added dropwise, and the reaction was carried out at room temperature for 3 hours. The reaction progress was monitored by TLC. After the reaction was completed, the mixed solution was washed 3 times with saturated brine, the aqueous phase was separated, the organic layer was retained, the aqueous layer was stripped twice, the organic layers were combined, and the compound II was purified by 100-200 mesh silica gel column chromatography, the eluent was petroleum ether: ethyl acetate, the volume ratio was 8:1, and the yield was 40-78%; The amount of compound II prepared and the volume of the reaction vessel can be enlarged or reduced in corresponding proportions. B. Preparation of Compound IV: In a 200 ml single-necked round-bottom flask, 16.70 mmol of compound III and 20.88 mmol of methylhydrazine sulfate were added, 12 ml of toluene and 12 ml of glacial acetic acid were added to dissolve, and then 41.75 mmol of sodium acetate was added, and stirred at 100° C. for 2.5 hours. After the reaction was complete, the solvent was removed under reduced pressure, and the residue was purified by 100-200 mesh silica gel column chromatography to obtain compound IV, the eluent was dichloromethane:ethyl acetate, the volume ratio was 10:1, and the yield was 45%; the amount of compound IV prepared and the volume of the reaction container were enlarged or reduced in the corresponding proportion. C. Preparation of Compound V: 1.92 mmol of compound IV was added to a 50 ml single-mouth round-bottom flask, 12 ml of acetone was added to dissolve, 2.30 mmol of potassium carbonate was slowly added, and then 2.12 mmol of compound II was added, and the mixture was stirred at 60°C for 2.5 hours. After the reaction was completed, the mixed solution was washed 3 times with saturated brine, the aqueous phase was separated, the organic layer was retained, the aqueous layer was back-extracted twice, the organic layers were combined, and the compound V was purified by 100-200 mesh silica gel column chromatography, the eluent was petroleum ether: ethyl acetate, the volume ratio was 8:1, and the yield was 33-73%; the amount of compound V prepared and the volume of the reaction container were expanded or reduced in the corresponding proportion.

3. Use of the 3-oxypropionamide-1-methylpyrazole-carboxylate derivative V according to claim 1 and an agriculturally acceptable adjuvant in the preparation of a herbicide.

4. The 3-oxypropionamide-1-methylpyrazole-carboxylate derivative V of claim 1 is used in combination with any one or more of the following commercial herbicides to prepare a compound herbicide composition for controlling agricultural, forestry and gardening weeds: The commercial herbicide is selected from nicosulfuron, bensulfuron-methyl, monosulfuron, sulfamethoxam, penoxsulam, alachlor, acetochlor, butachlor, isopropyl metolachlor, 2-methyl-4-chloro, fluralin, mesotrione, mesotrione, benzachlor, pendimethalin, atrazine, promethazine, cyanazine, ametryn, metribuzin, nitropropene, oxyfluorfen, trifluorfen, lactofen, fluazifop-butyl, pyraclostrobin, isopropylpyraclostrobin, imazapic, imazapic, imazapic, imazapic, imazaquin, methazapic, methyl imazapic, pyrimidine sulfamethoxam, pyrimidine sulfamethoxam, pyrimidine sulfamethoxam, pyrimidine sulfamethoxam, pyrimidine sulfamethoxam, betamethoxam, betamethoxam, avena cava, diamine, cypermethrin, cypermethrin, pyrimidine sulfamethoxam ... Diclofenac, quizalofop-p-butyl, thiamethoxam, fluroxypyr, fluthiopyr, fluridone, thiamethoxam, flufenacet, paraquat, glyphosate, sedge barnyardgrass, flufenac, fluazifop-butyl, fluthiophanate-butyl, flufenacet-butyl, pyrazoline, pyraclostrobin, pyraclostrobin, pyraclostrobin, isoxathiocarb, isoxathiocarb, bromoxynil, etc.; the total mass percentage of the 3-oxypropionamide-1-methylpyrazole-carboxylate derivative V in the obtained compound herbicide is 1%-90%, and the ratio of the 3-oxypropionamide-1-methylpyrazole-carboxylate derivative V to the commercial herbicide is 1%:99% to 99%:1% by mass; the formulation suitable for the compound herbicide is selected from any one of the following formulations: wettable powder , microcapsule suspension, dispersible liquid preparation, dispersible solid preparation, seed treatment emulsion, water emulsion, large granules, microemulsion, oil suspension, water-soluble granules, soluble concentrate, water-dispersible granules, poisonous valley, aerosol, sustained-release block, capsule granules, dry seed powder, emulsifiable concentrate, electrostatic spray, oil-in-water emulsion, water-in-oil emulsion, smoke can, fine granules, smoke candle, smoke tube, smoke stick, seed treatment suspension, smoke tablet, smoke pill, gasifier, drifting powder, ointment, hot fog agent, solid / liquid mixed agent, liquid / liquid mixed agent, cold fog agent, solid / solid mixed agent, lacquer, seed treatment liquid, microgranules, oil-dispersible powder, concentrated glue, pouring agent, smear, suspension emulsion, film-forming oil, soluble powder, seed The invention relates to water-soluble powder for seed treatment, ultra-low volume suspension, tracking powder, ultra-low volume liquid, steam release agent, and water-dispersible powder for wet seed dressing; 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, adzuki bean, cotton, sericulture, peanut, rape, sesame, sunflower, beet, sugar cane, coffee, cocoa, ginseng, fritillaria, rubber, coconut, oil palm, sisal, tobacco, tomato, pepper, radish, cucumber, cabbage, celery, mustard tuber, beet, rape, onion, garlic, watermelon, melon, cantaloupe, papaya, apple, citrus, peach, tea, wild vegetables, bamboo shoots, hops, pepper, banana, papaya, orchid, and 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, Waterthorn Needle, Rumex, Cupressus, Field Bindweed, Cuscuta, etc.; Cyperaceae weeds: Cyperus rotundus, Cyperus heterosexualus, Cyperus watergrass, Salsola, Onion, etc.;

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