A bisamide compound containing a substituted heterocycle, a preparation method thereof, and an application thereof

Abstract

The present invention discloses a disubstituted amide compound containing a substituted heterocycle, a preparation method thereof and an application thereof. The disubstituted amide compound containing a substituted heterocycle of the present invention has a structural formula as shown in Formula Ia, Formula Ib, Formula Ic or Formula Id below. The disubstituted amide compound containing a substituted heterocycle of the present invention can be prepared by protecting the amino group and carrying out a condensation reaction. The present invention has a novel structure, good insecticidal, acaricidal and bactericidal activities, and has a short process route, mild reaction conditions and simple preparation.

Description

Technical Field

[0001] The present invention relates to a bisamide compound containing a substituted heterocycle, a preparation method thereof and an application thereof, and belongs to the technical field of discovery and synthesis of agricultural chemical insecticides and fungicides. Background Art

[0002] With the growth of the population and the reduction of per capita arable land area, the global food supply is facing a severe test. Pesticides, as an important material, play an important role in social economy and human production. As people's understanding of pesticides becomes deeper and deeper, seeking novel-structured, low-toxic and environmentally friendly pesticide active compounds has become the direction of new pesticide creation. In recent years, some compounds containing an amide structure have developed into important pesticide active molecules due to their novel structures, special action mechanisms, high activities, and high safety for mammals. For example, chlorantraniliprole discovered by DuPont Company in the United States and fluxapyroxad discovered by BASF Company in Germany. Therefore, the design and synthesis of active molecules containing an amide structure have become a hot topic in current pesticide research and development. Heterocyclic compounds have received extensive attention in the research and development of pesticides due to the particularity of their structures and the diversity of their biological activities, especially nitrogen-containing heterocyclic compounds. Pyrazole and pyridine structures are both nitrogen-containing heterocyclic compounds with a wide range of biological activities, and they have been included in the structures of active molecules in various fields such as medicine, pesticides, veterinary drugs, and cosmetics. Therefore, it is of great significance to seek to connect different substituents at different positions on the pyrazole and pyridine rings to synthesize compounds with different biological activities of pyrazole and pyridine structures. Summary of the Invention

[0003] The purpose of the present invention is to provide a bisamide compound containing a substituted heterocycle, a preparation method thereof and an application thereof. The present invention has a novel structure, good insecticidal, acaricidal and fungicidal activities, and has a short process route, mild reaction conditions and simple preparation.

[0004] The present invention provides a bisamide compound containing a substituted heterocycle, and its structural formula is shown as formula Ia, formula Ib, Ic or formula Id as follows:

[0005]

[0006] In formula Ia, formula Ib, Ic and formula Id, R1 is an alkyl group with 1 to 6 carbon atoms;

[0007] R2 is H, F or methoxy;

[0008] R3 is H, halogen, cyano, trifluoromethyl, difluoromethyl, an alkyl group with 1 to 6 carbon atoms or a substituted alkyl group with 1 to 6 carbon atoms;

[0009] Both R4 and R5 are H, C1-C6 alkyl or substituted C1-C6 alkyl, and R4 and R5 are the same or different groups;

[0010] R6 is H, halogen, cyano, trifluoromethyl, difluoromethyl, C1-C6 alkyl, substituted C1-C6 alkyl, alkoxy or ester group;

[0011] Y is alkoxy, H, halogen, cyano, trifluoromethyl, difluoromethyl, C1-C6 alkyl or substituted C1-C6 alkyl.

[0012] In the present invention, the substituted C1-C6 alkyl refers to the common knowledge in the art, that is, the C1-C6 alkyl is substituted by various common substituents.

[0013] In the above-mentioned bisamide compounds containing substituted heterocycles, the halogen is fluorine, chlorine, bromine or iodine;

[0014] The C1-C6 alkyl is a straight-chain or branched-chain C1-C6 alkyl;

[0015] The ester group is at least one of formate, oxalate, acetate and isopropyl acetate.

[0016] The present invention also provides a preparation method of the above-mentioned bisamide compounds containing substituted heterocycles, which comprises the following steps:

[0017] 1) In an organic solvent, the amino group in the compound shown by formula II is subjected to a protection reaction to obtain the compound shown by formula III;

[0018]

[0019] In formula II and formula III, R1 is C1-C6 alkyl;

[0020] 2) In an organic solvent, the compound shown by formula III and the compound shown by formula IV are mixed for an amino condensation reaction to obtain the compound shown by formula V;

[0021]

[0022] In formula IV and formula V, R1 is C1-C6 alkyl;

[0023] R2 is H, F or methoxy;

[0024] Y is alkoxy, H, halogen, cyano, trifluoromethyl, difluoromethyl, C1-C6 alkyl or substituted C1-C6 alkyl;

[0025] 3) In an organic solvent, the amino protecting group in the compound shown by formula V is removed to obtain the compound shown by formula VI;

[0026]

[0027] In formula VI, R1 is an alkyl group having 1 to 6 carbon atoms;

[0028] R2 is H, F or methoxy;

[0029] Y is an alkoxy group, H, a halogen, a cyano group, a trifluoromethyl group, a difluoromethyl group, an alkyl group having 1 to 6 carbon atoms or a substituted alkyl group having 1 to 6 carbon atoms;

[0030] 4) In an organic solvent, the compound represented by formula VI and the compound represented by formula VIIa, formula VIIb, formula VIIc or formula VIId are mixed for a condensation reaction to obtain the compound represented by formula Ia, formula Ib, Ic or formula Id;

[0031]

[0032] R3 is H, a halogen, a cyano group, a trifluoromethyl group, a difluoromethyl group, an alkyl group having 1 to 6 carbon atoms or a substituted alkyl group having 1 to 6 carbon atoms;

[0033] R4 and R5 are both H, an alkyl group having 1 to 6 carbon atoms or a substituted alkyl group having 1 to 6 carbon atoms, and R4 and R5 are the same or different groups;

[0034] R6 is H, a halogen, a cyano group, a trifluoromethyl group, a difluoromethyl group, an alkyl group having 1 to 6 carbon atoms, a substituted alkyl group having 1 to 6 carbon atoms, an alkoxy group or an ester group.

[0035] The reaction equation of the present invention is as follows:

[0036]

[0037] In the above preparation method, in step 1), an amino protecting agent is added to protect the amino group;

[0038] The amino protecting agent is selected from at least one of benzyl chloroformate, di-tert-butyl dicarbonate, fluorenylmethoxycarbonyl chloride, p-methoxybenzyl chloride and p-toluenesulfonyl chloride;

[0039] The molar ratio of the amino protecting agent to the compound represented by formula II can be 1 to 10:1, specifically 1:1 or 1 to 5:1;

[0040] The temperature of the protection reaction can be from -10°C to the boiling point of the organic solvent, specifically room temperature, and the time can be 0.5 to 48 hours, specifically 2 h, 0.5 to 2 hours, 2 to 48 hours, 2 to 12 hours or 1 to 30 hours.

[0041] In the above preparation method, in steps 1)-4), the organic solvent is the same or different solvents, and is selected from at least one of water, dichloromethane, chloroform, carbon tetrachloride, benzene, toluene, xylene, cyclohexane, n-hexane, ethyl acetate, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, and dimethyl sulfoxide.

[0042] In the method of the present invention, the post-treatment of obtaining the compound shown in formula III in step 1) is carried out by a conventional method in the art, specifically: after the reaction is completed, the solvent is removed by rotary evaporation, the pH is adjusted with a citric acid solution, extracted with ethyl acetate, the organic phase is collected and dried over anhydrous sodium sulfate, and the solvent is removed by rotary evaporation to obtain the product.

[0043] In the above preparation method, in step 2), the molar ratio of the compound shown in formula III to the compound shown in formula IV can be 1:1 to 10, specifically 1:1, 1-5:1 or 1-8:1;

[0044] A condensing agent is added in the amino condensation reaction;

[0045] The condensing agent is selected from at least one of dicyclohexylcarbodiimide (abbreviated as DCC in English), diisopropylcarbodiimide (abbreviated as DIC in English), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (abbreviated as EDCI in English), and 1-hydroxybenzotriazole (abbreviated as HoBT in English);

[0046] The molar ratio of the condensing agent to the compound shown in formula III can be 1-20:1, specifically 1:1.5, 1-1.5:1, 1.5-10:1 or 1-15:1;

[0047] The temperature of the amino condensation reaction can be from -10°C to the boiling point of the organic solvent, specifically room temperature, and the time can be 0.5-48 hours, specifically 12h, 0.5-12 hours, 12-48 hours or 5-30 hours.

[0048] In the method of the present invention, the post-treatment of obtaining the compound shown in formula V in step 2) is carried out by a conventional method in the art, specifically: after the reaction is completed, the reaction solution is washed successively with a saturated sodium bicarbonate solution and a saturated sodium chloride solution, the organic phase is collected, dried over anhydrous sodium sulfate, the solvent is removed by distillation under reduced pressure, and the residue is purified by column chromatography.

[0049] In the above preparation method, in step 3), an acid is added to remove the amino protecting group;

[0050] The acid is selected from at least one of trifluoroacetic acid, p-toluenesulfonic acid, hydrochloric acid, tert-butyldimethylsilyl trifluoromethanesulfonate, and zinc bromide;

[0051] The molar ratio of the acid to the compound represented by Formula V may be 1 to 20:1, specifically 6:1, 1 to 6:1, 6 to 20:1, or 5 to 10:1;

[0052] The temperature of the deprotection reaction may be from -10°C to the boiling point of the organic solvent, specifically room temperature, and the time may be 0.5 to 48 hours, specifically 12 h, 0.5 to 12 hours, 12 to 48 hours, or 5 to 30 hours.

[0053] In the method of the present invention, the post-treatment of the compound represented by Formula VI obtained in step 3) is carried out by a conventional method in the art, specifically: after the reaction is completed, the solvent is removed by distillation under reduced pressure, the residual liquid is adjusted to neutral pH with saturated sodium bicarbonate solution, the organic phase is collected and dried over anhydrous sodium sulfate, and the solvent is removed by distillation under reduced pressure to obtain the product.

[0054] In the above preparation method, in step 4), the molar ratio of the compound represented by Formula VI to the compound represented by Formula VIIa, Formula VIIb, Formula VIIc, or Formula VIId may be 1:1 to 10, specifically 1:1, 1 to 5:1, or 1 to 8:1;

[0055] A condensing agent is added in the condensation reaction;

[0056] The condensing agent is selected from at least one of dicyclohexylcarbodiimide (abbreviated as DCC in English), diisopropylcarbodiimide (abbreviated as DIC in English), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (abbreviated as EDCI in English), and 1-hydroxybenzotriazole (abbreviated as HoBT in English);

[0057] The molar ratio of the condensing agent to the compound represented by Formula VI may be 1 to 20:1, specifically 1:1.5, 1 to 1.5:1, 1.5 to 10:1, or 1 to 15:1;

[0058] The temperature of the condensation reaction may be from -10°C to the boiling point of the organic solvent, specifically room temperature, and the time may be 0.5 to 48 hours, specifically 12 h, 0.5 to 12 hours, 12 to 48 hours, or 5 to 30 hours.

[0059] In the method of the present invention, the post-treatment of the compound represented by Formula Ia, Formula Ib, Ic, or Formula Id obtained in step 4) is carried out by a conventional method in the art, specifically: after the reaction is completed, the reaction solution is washed successively with saturated sodium bicarbonate solution and saturated sodium chloride solution, the organic phase is collected and dried over anhydrous sodium sulfate, the solvent is removed by distillation under reduced pressure, and the residue is subjected to column chromatography.

[0060] In the method of the present invention, the room temperature is common knowledge in the art and refers to 10 to 30°C.

[0061] The diamide compounds containing substituted heterocycles represented by at least one of Formula Ia, Formula Ib, Formula Ic, and Formula Id of the present invention are used in the preparation of agrochemical insecticides.

[0062] The salts applicable in agriculture and / or their stereoisomers of Formula Ia, Formula Ib, Formula Ic, and Formula Id of the present invention are used in the preparation of agrochemical insecticides.

[0063] The present invention further provides an insecticide, which is composed of an active ingredient and an agriculturally acceptable adjuvant;

[0064] The active ingredient is the diamide compound containing substituted heterocycles represented by at least one of Formula Ia, Formula Ib, Formula Ic, and Formula Id and / or its salts applicable in agriculture, and / or its stereoisomers.

[0065] The present invention has the following advantages:

[0066] The compounds of the present invention have novel structures and remarkable insecticidal, acaricidal, and bactericidal activities; and the preparation route of the present invention is short, the reaction conditions are mild, the requirements for equipment are low, the post-treatment is convenient, and the preparation is simple. Detailed Embodiments

[0067] Unless otherwise specified, the experimental methods used in the following examples are all conventional methods.

[0068] Unless otherwise specified, the materials, reagents, etc. used in the following examples can all be obtained from commercial channels.

[0069] In the following examples, di-tert-butyl dicarbonate, 2-methyl-4-(heptafluoroisopropyl)aniline, pyrazole, dicyclohexylcarbodiimide, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, 1-hydroxybenzotriazole, etc. were all purchased from InnoChem Co., Ltd.; the remaining conventional reagents such as 1,4-dioxane and dichloromethane were all purchased from Beijing Chemical Reagent Company.

[0070] Example 1

[0071] Derivative N-(1-((2-methoxy-4-(perfluoropropan-2-yl)phenyl)amino)-1-oxopropan-2-yl)-1-methyl-1H-pyrazole-5-carboxamide:

[0072] Step A: Preparation of (tert-butoxycarbonyl)alanine.

[0073]

[0074] A 500 mL three-necked flask was charged with DL-alanine (17.8 g, 200 mmol), 100 mL of water, and 100 mL of 1,4-dioxane. While stirring at 0 °C, sodium hydroxide (16 g, 400 mmol) was slowly added. After the addition was complete, the mixture was stirred for 15 min. Then, di-tert-butyl dicarbonate (43.6 g, 200 mmol) was added dropwise. After the addition was complete, the mixture was stirred until the reaction ended. The reaction solution was concentrated by rotary evaporation to remove the solvent. The pH of the reaction solution was adjusted with a citric acid solution, and then it was extracted with ethyl acetate. The combined organic phases were dried over anhydrous sodium sulfate and then concentrated by rotary evaporation to obtain (tert-butoxycarbonyl)alanine (35.6 g, 190 mmol) with a yield of 95%.

[0075] 1 H NMR (500 MHz, Chloroform-d) δ 11.11 (s, 1H), 6.78 (s, 0.45H), 5.11 (s, 0.55H), 4.46–3.92 (m, 1H), 1.37 (d, J = 9.3 Hz, 12H).

[0076] Step B: Preparation of tert-butyl N-(1-((2-methoxy-4-heptafluoroisopropylphenyl)amino)-1-oxopropan-2-yl)carbamate.

[0077]

[0078] A 500 mL three-necked flask was charged with (tert-butoxycarbonyl)alanine (5.6 g, 30 mmol) and 250 mL of dry dichloromethane. At 0 °C, dicyclohexylcarbodiimide (9.13 g, 45 mmol) and 4-dimethylaminopyridine (0.72 g, 6 mmol) were added. Then, after stirring at 0 °C for 30 min, 2-methoxy-4-heptafluoroisopropylaniline (8.6 g, 30 mmol) was added. Then, the mixture was transferred to room temperature (25 °C) and reacted for 12 h. After the reaction was complete, the reaction solution was filtered. The filtrate was washed successively with a saturated sodium bicarbonate solution and a saturated sodium chloride solution. The collected organic phase was dried over anhydrous sodium sulfate, concentrated by rotary evaporation, and the residue was purified by column chromatography to obtain tert-butyl N-(1-((2-methoxy-4-heptafluoroisopropylphenyl)amino)-1-oxopropan-2-yl)carbamate (11.37 g, 24.6 mmol) with a yield of 82%.

[0079] 1 H NMR (500 MHz, Chloroform-d) δ 8.67 (s, 1H), 8.43 (d, J = 8.6 Hz, 1H), 7.11 (d, J = 8.6 Hz, 1H), 6.97 (s, 1H), 5.18 (s, 1H), 4.30 (s, 1H), 3.82 (s, 3H), 1.38 (d, J = 10.6 Hz, 12H).

[0080] Step C: Prepare 2-amino-N-(2-methoxy-4-heptafluoroisopropylphenyl)propanamide.

[0081]

[0082] In a 250 mL three-necked flask, dissolve tert-butyl (1-((2-methoxy-4-heptafluoroisopropylphenyl)amino)-1-oxopropan-2-yl)carbamate (6.93 g, 15 mmol) in 45 mL of dichloromethane and 45 mL of trifluoroacetic acid. Stir the reaction at room temperature (25 °C) for 2 h. After the reaction is completed, evaporate the solvent of the reaction solution by rotary evaporation. After dissolving with ethyl acetate, wash the filtrate successively with saturated sodium bicarbonate solution and saturated sodium chloride solution. The collected organic phase is dried over anhydrous sodium sulfate and evaporated to dryness by rotary evaporation to obtain 2-amino-N-(2-methoxy-4-heptafluoroisopropylphenyl)propanamide (5.21 g, 14.4 mmol), with a yield of 96%.

[0083] 1 H NMR (500 MHz, Chloroform-d) δ 10.01 (s, 1H), 8.54 (d, J = 8.6 Hz, 1H), 7.19 (d, J = 8.6 Hz, 1H), 7.05 (s, 1H), 3.93 (s, 3H), 3.66 (q, J = 7.0 Hz, 1H), 1.62 (s, 2H), 1.44 (d, J = 7.0 Hz, 3H).

[0084] Step D: Prepare N-(1-((2-methoxy-4-heptafluoroisopropylphenyl)amino)-1-oxopropan-2-yl)-1-methyl-1H-pyrazole-5-carboxamide.

[0085]

[0086] A 100 mL three-necked flask was charged with 1-methyl-1H-pyrazole-5-carboxylic acid (0.35 g, 2.76 mmol), which was dissolved in 50 mL of dichloromethane. Under stirring at 0 °C, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (0.53 g, 2.76 mmol), 1-hydroxybenzotriazole (0.357 g, 2.76 mmol), and N,N-diisopropylethylamine (0.36 g, 2.76 mmol) were successively added to the reaction flask. The mixture was stirred for 60 min, and then 2-amino-N-(2-methoxy-4-heptafluoroisopropylphenyl)propanamide (1 g, 2.76 mmol) was added to the reaction flask. After the addition was complete, the reaction was transferred to room temperature (25 °C) and continued for 12 h. After the reaction was completed, the pH of the reaction solution was adjusted with a citric acid solution, and then washed successively with a saturated sodium bicarbonate solution and a saturated sodium chloride solution. The collected organic phase was dried over anhydrous sodium sulfate, concentrated by rotary evaporation, and the residue was purified by column chromatography to obtain N-(1-((2-methoxy-4-heptafluoroisopropylphenyl)amino)-1-oxopropan-2-yl)-1-methyl-1H-pyrazole-5-carboxamide (0.73 g, 1.55 mmol), with a yield of 56%.

[0087] The structure confirmation of N-(1-((2-methoxy-4-heptafluoroisopropylphenyl)amino)-1-oxopropan-2-yl)-1-methyl-1H-pyrazole-5-carboxamide is as follows:

[0088] 1 H NMR (500 MHz, Chloroform-d) δ 8.53 (s, 1H), 8.47 (d, J = 8.6 Hz, 1H), 7.46 (d, J = 2.1 Hz, 1H), 7.21 (d, J = 8.7 Hz, 1H), 7.07 (s, 1H), 6.93 (d, J = 9.2 Hz, 1H), 6.65 (d, J = 2.1 Hz, 1H), 4.83 (m, 1H), 4.17 (s, 3H), 3.93 (s, 3H), 1.58 (d, J = 7.0 Hz, 3H).

[0089] Typical compounds represented by formula (I) of the present invention prepared using different raw materials according to the preparation method of the above examples are listed in Tables 1a, 1b, 1c, and 1d, but they in no way limit the scope of the present invention.

[0090] Table 1a Structures and melting points of heterocyclic-substituted bisamide compounds

[0091]

[0092] Table 1b Structures and melting points of heterocyclic-substituted bisamide compounds

[0093]

[0094] Table 1c Structures and melting points of heterocyclic-substituted bisamide compounds

[0095]

[0096] Table 1d Structures and melting points of heterocyclic-substituted bisamide compounds

[0097]

[0098]

[0099] The following Table 2 shows the NMR data of some of the compounds described in Table 1a, Table 1b, Table 1c and Table 1d.

[0100] Note: The compound numbers described in Table 2 correspond to those in Table 1. Where s is singlet, d is doublet, dd is doublet of doublets, dq is doublet of quartets, t is triplet, q is quartet, and m is multiplet.

[0101] Table 2 1 1H NMR data of heterocyclic-substituted bisamide compounds

[0102]

[0103]

[0104]

[0105]

[0106]

[0107] Example 2

[0108] Using the heterocyclic-substituted bisamide compounds provided in Example 1 of the present invention to test their biological activities against pests:

[0109] The following gives examples of biological activity assays using the compounds of the present invention. It should be noted that the present invention is not limited solely to the scope of the following examples.

[0110] The insecticidal activity evaluation test was carried out according to the following method:

[0111] Weigh a certain mass of the compound in Example 1 of the present invention (specifically, NO.1 in Table 1a), dissolve it in 1 mL of dimethyl sulfoxide (DMSO), add 100 mL of water and 0.1 g of the surfactant Triton X-100, mix to form a homogeneous aqueous phase, and dilute it with water to the required concentration for measurement when in use.

[0112] The test objects and test methods are as follows:

[0113] (1) Bioactivity evaluation against Plutella xylostella: The original flubendiamide was used as the positive control. The prepared test liquid was used to impregnate cabbage leaves (6 cm × 2 cm) with straight-tip ophthalmic forceps for 5 s, and the excess liquid was shaken off. They were placed on a petri dish (9 cm) with filter paper at the bottom in the order of sample labels, and air-dried naturally. 10 larvae of the 2nd - 3rd instar of Plutella xylostella were introduced into each treatment. The test treatment was placed in a standard treatment room, and the number of dead and alive insects was checked after 48 h. The insects were gently touched with a needle, and those that did not move were considered dead, and statistical analysis was carried out to calculate the mortality rate;

[0114] (2) Bioactivity evaluation against Aphis glycines: The original imidacloprid was used as the positive control. Soybean leaves with a large population density of insects were collected, and healthy 3rd instar nymphs (20) were carefully selected and left on the leaf surface. The soybean leaves with insects were immersed in the prepared test liquid for 5 s and then taken out, drained, and placed in a petri dish (6 cm) with moisturizing filter paper at the bottom, and placed in an artificial climate chamber at a temperature of 25 °C, a relative humidity of 78%, and a light time of 14 / 10 h for continued rearing. The death situation was recorded after 36 h, and statistical analysis was carried out to calculate the mortality rate.

[0115] (3) Bioactivity evaluation against Tetranychus cinnabarinus: The original fenpyroximate was used as the positive control. Cowpea leaves with 30 insects were immersed in the prepared test liquid for 5 s and then taken out, drained, and placed in a petri dish (6 cm) with moisturizing filter paper at the bottom, and placed in an artificial climate chamber at a temperature of 25 °C, a relative humidity of 50%, and a light time of 14 / 10 h for continued rearing. The death situation was recorded under a binocular microscope after 48 h, and statistical analysis was carried out to calculate the mortality rate.

[0116] Test statistics: The number of dead and alive insects in each treatment was counted, and the mortality rate was calculated.

[0117]

[0118] The mortality rate of the blank control group < 15%, and the test results are credible. The test results were corrected. The mortality rate of the blank control group < 5%, and the test results did not need to be corrected.

[0119] The results of the bioassay experiment showed that the compound of the present invention had good insecticidal activity.

[0120] As shown in Table 3, the compound of the present invention had good insecticidal activity against Lepidoptera pests (Plutella xylostella): at a concentration of 400 mg / L, the mortality rates of compounds 12, 27, and 32 against Plutella xylostella were 53%, 50%, and 60% respectively.

[0121] As shown in Table 4, the compounds of the present invention have significant insecticidal activity against homopteran pests (soybean aphids): at a concentration of 400 mg / L, the mortality rates of compounds 02, 07, and 17 against soybean aphids are 90%, 85%, and 88%, respectively; at a concentration of 200 mg / L, the mortality rates of compounds 02, 07, and 17 against soybean aphids are 73%, 63%, and 77%, respectively; at a concentration of 100 mg / L, the mortality rates of compounds 02 and 17 against soybean aphids are 55% and 58%, respectively.

[0122] As shown in Table 5, the compounds of the present invention have good insecticidal activity against mite pests (spider mites): at a concentration of 400 mg / L, the mortality rates of compounds 13, 20, and 42 against spider mites are 79%, 82%, and 53%, respectively; at a concentration of 200 mg / L, the mortality rates of compounds 13 and 20 against spider mites are 60% and 66%, respectively.

[0123] Note that the above mg / L refers to per milligram of active compound / liter.

[0124] The insecticidal activities (against diamondback moths) of some of the compounds numbered in Tables 1a - 1d in Example 1 of the present invention were compared with the control compound flubendiamide, and the results are listed in Table 3.

[0125] Table 3 Comparison of Insecticidal Activities

[0126]

[0127]

[0128] The insecticidal activities (against soybean aphids) of some of the compounds numbered in Tables 1a - 1d in Example 1 of the present invention were compared with the control compound imidacloprid, and the results are listed in Table 4.

[0129] Table 4 Comparison of Insecticidal Activities

[0130]

[0131] The insecticidal activities (against spider mites) of some of the compounds numbered in Tables 1a - 1d in Example 1 of the present invention were compared with the control compound fenpyroximate, and the results are listed in Table 5.

[0132] Table 5 Comparison of Insecticidal Activities

[0133]

[0134] Example 3

[0135] The diamide compounds containing substituted heterocycles provided in Example 1 of the present invention were used to test their biological activities against agricultural pathogens:

[0136] The following are examples of biological activity assays using the compounds of the present invention. It should be noted that the present invention is not limited to the following examples.

[0137] The insecticidal activity evaluation test was carried out according to the following method:

[0138] A certain amount of the compound described in Example 1 of the present invention (specifically, No. 1 in Table 1a) was weighed and dissolved in 5 mL of dimethyl sulfoxide (DMSO). When used, it can be diluted with culture medium to prepare the concentration required for determination.

[0139] The test objects and test methods are as follows:

[0140] (1) Test objects: Sclerotinia sclerotiorum, Valsamali, Fusarium graminearum, Rhizoctonia solani, Pythium aphanidermatum and Botrytis cinerea.

[0141] (2) Test method:

[0142] ① Preparation of PDA medium: Prepare potato dextrose agar (PDA) medium according to the ratio of 200 g potato, 1 L deionized water, 20 g agar strip, and 20 g glucose, and sterilize it in an autoclave for later use.

[0143] ② Preparation of test agents: Weigh 50 mg of the target compound and 50 mg of fluopicolide technical respectively, dissolve them in 5 mL of dimethyl sulfoxide, and prepare a solution with a concentration of 10,000 mg / L for use.

[0144] ③ Experimental method: Under sterile conditions, use a pipette to absorb the 10000 mg / L drug solution prepared above, add it to the prepared sterilized PDA medium, mix it thoroughly, and prepare a 50 mg / L drug-containing medium. Then pour it into a culture dish with a diameter of 9 cm, and repeat each drug 3 times. After the drug-containing medium in the dish cools and solidifies, prepare a drug-containing PDA plate. DMSO is the solvent control, and sterile water is the blank control. Prepare a 5 mm diameter bacterial cake along the edge of the colony on the prepared pathogen plate, inoculate it in the middle of the drug-containing and control PDA plates, and place it in a 25°C incubator to culture in the dark.

[0145] Test statistics: After the colonies in the control PDA plate have grown sufficiently, the diameters of each colony are measured by the cross method and the average value is taken. The inhibition rate calculation formula is as follows:

[0146]

[0147] The results of the bioassay experiments show that the compounds of the present invention have good bactericidal activity.

[0148] As shown in Table 6, the compounds of the present invention have good bactericidal activity against various fungal diseases: at a concentration of 50 mg / L, the inhibition rates of compounds 02, 18, 32, and 43 against Sclerotinia sclerotiorum of rapeseed are 65%, 70%, 65%, and 67% respectively; the inhibition rates of compounds 18, 22, and 32 against Gibberella zeae of wheat are 45%, 50%, and 58% respectively; the inhibition rates of compounds 02, 22, and 32 against Rhizoctonia solani of rice are 74%, 65%, and 61% respectively; the inhibition rates of compounds 02, 18, and 32 against Valsa mali of apple are 68%, 77%, and 71% respectively; the inhibition rates of compounds 02, 22, and 32 against Pythium aphanidermatum of fruits and vegetables are 34%, 29%, and 35% respectively; the inhibition rates of compounds 22, 32, and 59 against Botrytis cinerea of tomato are 37%, 37%, and 48% respectively.

[0149] Note: The above mg / L all refer to per milligram of active compound / liter.

[0150] The bactericidal activities of some of the compounds numbered in Tables 1a - 1d shown in Example 1 of the present invention were compared with the control compound fluxapyroxad, and the results are listed in Table 6.

[0151] Table 6 Comparison of bactericidal activities

[0152]

[0153]

Claims

1. A bisamide compound containing a substituted heterocycle, the structural formula of which is shown as formula Ia, formula Ib, Ic or formula Id below: In formula Ia, formula Ib, Ic and formula Id, R1 is an alkyl group with 1 - 6 carbon atoms; R2 is H, F or methoxy; R3 is H, halogen, cyano, trifluoromethyl, difluoromethyl or an alkyl group with 1 - 6 carbon atoms; Both R4 and R5 are H or an alkyl group with 1 - 6 carbon atoms, and R4 and R5 are the same or different groups; R6 is H, halogen, cyano, trifluoromethyl, difluoromethyl, an alkyl group with 1 - 6 carbon atoms, methoxy or an ester group; Y is methoxy, H, halogen, cyano, trifluoromethyl, difluoromethyl or an alkyl group with 1 - 6 carbon atoms; The ester group is at least one of formate, diformate, acetate and isopropionate.

2. The bisamide compound containing a substituted heterocycle according to claim 1, characterized in that The halogen is fluorine, chlorine, bromine or iodine; The C1-C6 alkyl group is a straight-chain or branched-chain C1-C6 alkyl group.

3. A preparation method of the bisamide compound containing a substituted heterocycle according to claim 1 or 2, comprising the following steps: 1) In an organic solvent, the amino group in the compound shown as formula II is subjected to a protection reaction to obtain the compound shown as formula III; In formula II and formula III, R1 is an alkyl group with 1 - 6 carbon atoms; 2) In an organic solvent, the compound shown as formula III and the compound shown as formula IV are mixed for an amino condensation reaction to obtain the compound shown as formula V; In formula IV and formula V, R1 is an alkyl group with 1 - 6 carbon atoms; R2 is H, F or methoxy; Y is methoxy, H, halogen, cyano, trifluoromethyl, difluoromethyl or an alkyl group with 1 - 6 carbon atoms; 3) In an organic solvent, the amino protecting group in the compound shown as formula V is removed to obtain the compound shown as formula VI; In formula VI, R1 is an alkyl group with 1 - 6 carbon atoms; R2 is H, F or methoxy; Y is methoxy, H, halogen, cyano, trifluoromethyl, difluoromethyl or an alkyl group with 1 - 6 carbon atoms; 4) In an organic solvent, the compound represented by Formula VI and the compound represented by Formula VIIa, Formula VIIb, Formula VIIc or Formula VIId are mixed for a condensation reaction to obtain the compound represented by Formula Ia, Formula Ib, Ic or Id; R3 is H, halogen, cyano, trifluoromethyl, difluoromethyl or C1-C6 alkyl; Both R4 and R5 are H or C1-C6 alkyl, and R4 and R5 are the same or different groups; R6 is H, halogen, cyano, trifluoromethyl, difluoromethyl, C1-C6 alkyl, methoxy or ester group; The ester group is at least one of formate, diformate, acetate and isopropionate.

4. The preparation method according to claim 3, wherein In step 1), an amino protecting agent is added to protect the amino group; The amino protecting agent is di-tert-butyl dicarbonate; The molar ratio of the amino protecting agent to the compound represented by formula II is 1-10:1; The temperature of the protection reaction is from -10°C to the boiling point of the organic solvent; In steps 1)-4), the organic solvent is the same or different solvents, and is selected from at least one of water, dichloromethane, chloroform, carbon tetrachloride, benzene, toluene, xylene, cyclohexane, n-hexane, ethyl acetate, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide and dimethyl sulfoxide.

5. The preparation method according to claim 3 or 4, wherein In step 2), the molar ratio of the compound represented by formula III to the compound represented by formula IV is 1:1-10; A condensing agent is added in the amino condensation reaction; The condensing agent is selected from at least one of dicyclohexylcarbodiimide, diisopropylcarbodiimide, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide and 1-hydroxybenzotriazole; The molar ratio of the condensing agent to the compound represented by formula III is 1-20:1; The temperature of the amino condensation reaction is from -10°C to the boiling point of the organic solvent, and the time is 0.5-48 hours.

6. The preparation method according to claim 3 or 4, wherein In step 3), an acid is added to remove the amino protecting group; The acid is selected from at least one of trifluoroacetic acid, p-toluenesulfonic acid, hydrochloric acid, tert-butyldimethylsilyl trifluoromethanesulfonate and zinc bromide; The molar ratio of the acid to the compound represented by formula V is 1-20:1; The temperature of the deprotection reaction is from -10°C to the boiling point of the organic solvent, and the time is 0.5-48 hours.

7. The preparation method according to claim 3 or 4, wherein In step 4), the molar ratio of the compound represented by formula VI to the compound represented by formula VIIa, formula VIIb, formula VIIc or formula VIId is 1:1-10; A condensing agent is added in the condensation reaction; The condensing agent is selected from at least one of dicyclohexylcarbodiimide, diisopropylcarbodiimide, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide and 1-hydroxybenzotriazole; The molar ratio of the condensing agent to the compound represented by formula VI is 1-20:1; The temperature of the condensation reaction is from -10°C to the boiling point of the organic solvent, and the time is 0.5-48 hours.

8. Use of the double amide compound containing a substituted heterocycle represented by at least one of Formula Ia, Formula Ib, Ic and Formula Id according to claim 1 or 2 in the preparation of an agrochemical insecticide.

9. Use of the agriculturally applicable salts of formula Ia, formula Ib, formula Ic and formula Id as claimed in claim 1 or 2 in the preparation of agrochemical insecticides.

10. An insecticide, which consists of an active ingredient and an agriculturally acceptable adjuvant; The active ingredient is at least one of the bisamide compounds containing a substituted heterocycle represented by formula Ia, formula Ib, formula Ic and formula Id as claimed in claim 1 or 2 and / or its agriculturally applicable salts.

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