A heterocyclic amide compound and its preparation method, and crop pesticide

Abstract

The present invention discloses a heterocyclic amide compound and a preparation method thereof, and a crop agent, wherein the heterocyclic amide compound simultaneously has a phenyl group, an alkyl substituent, a nitrogen-containing heterocyclic group, etc. The present invention prevents and controls crop diseases, insect pests and weeds by using an organic small molecule compound with excellent biological activity, thereby increasing food production and ensuring food security.

Description

Technical Field

[0001] The invention relates to the technical field of plant chemical control, and in particular to a heterocyclic amide compound and a preparation method thereof, and a crop pesticide. Background Art

[0002] Pesticides refer to chemical agents used in agriculture to prevent and control pests and diseases and regulate plant growth. They are widely used in agricultural, forestry and animal husbandry production, environmental and household hygiene pest control and epidemic prevention, and industrial product mildew and moth prevention. There are many varieties of pesticides. According to their uses, they can be mainly divided into insecticides, acaricides, rodenticides, nematicides, molluscicides, fungicides, herbicides, plant growth regulators, etc.; according to the source of raw materials, they can be divided into mineral pesticides (inorganic pesticides), biopesticides (natural organic matter, microorganisms, antibiotics, etc.) and chemical synthetic pesticides; according to chemical structure, there are mainly organochlorine, organophosphorus, organic nitrogen, organic sulfur, carbamate, pyrethroid, amide compounds, urea compounds, ether compounds, phenolic compounds, phenoxycarboxylic acids, amidines, triazoles, heterocyclics, benzoic acids, organometallic compounds, etc., all of which are organic synthetic pesticides; according to the processing dosage form, they can be divided into powders, wettable powders, emulsions, emulsifiable concentrates, creams, pastes, colloids, fumigants, smoke agents, aerosols, granules, microparticles and oils, etc.

[0003] Currently, due to the long-term use of pesticides, weeds, pests and pathogenic microorganisms have developed resistance, affecting the growth of crops and causing a decrease in food yield and quality. Summary of the invention

[0004] The main purpose of the present invention is to provide a heterocyclic amide compound and a preparation method thereof, as well as a crop pesticide, in order to provide an organic small molecule compound with excellent biological activity.

[0005] To achieve the above object, the present invention provides a heterocyclic amide compound, wherein the heterocyclic amide compound includes any one of the following structural formulas:

[0006]

[0007] Among them, R', R, R 1 and R 2 Each is independently selected from CH3, H, Cl, F or CF3. Optionally, the heterocyclic amide compound includes any one of the following structural formulas:

[0008]

[0009] Among them, R' and R 1 Each is independently selected from CH3, H, Cl, F or CF3.

[0010] Optionally, the heterocyclic amide compound includes any one of the following structural formulas:

[0011]

[0012] Among them, R' and R 1 Each is independently selected from CH3, H, Cl, F or CF3.

[0013] Optionally, the heterocyclic amide compound includes any one of the following structural formulas:

[0014]

[0015] wherein R' is selected from CH3, H, Cl, F or CF3.

[0016] Optionally, the heterocyclic amide compound includes any one of the following structural formulas:

[0017]

[0018] wherein R' is selected from CH3, H, Cl, F or CF3.

[0019] Optionally, the heterocyclic amide compound includes any one of the following structural formulas:

[0020]

[0021] Among them, R' and R 1 Each is independently selected from CH3, H, Cl, F or CF3.

[0022] The present invention also provides a method for preparing a heterocyclic amide compound, comprising the following steps:

[0023] S1, mixing a heterocyclic carboxylic acid compound with carbodiimide and hydroxybenzotriazole, and dissolving the mixture in dimethylformamide to obtain a mixed solution;

[0024] S2, mixing the mixed solution with amine to obtain a final reaction solution;

[0025] S3, adding water to the final reaction solution to quench the reaction, adding dichloromethane, extracting, combining the organic phases, and drying with anhydrous sodium sulfate to obtain a preliminarily dried mixture;

[0026] S4, distilling the preliminarily dried mixture under reduced pressure to remove dichloromethane to obtain a crude product;

[0027] S5. Separating and purifying the crude product to obtain heterocyclic amide compounds.

[0028] Optionally, in step S1, the heterocyclic carboxylic acid compound includes any one of pyridine-3-carboxylic acid and pyrazinecarboxylic acid.

[0029] The present invention also provides a crop pesticide, comprising the heterocyclic amide compound as described above.

[0030] Optionally, the crop pesticide includes at least one of a fungicide, a herbicide and an insecticide.

[0031] In the technical solution provided by the present invention, the heterocyclic amide compound is an organic small molecule with excellent biological activity and a novel structure. Through activity screening, it is found that it is an agricultural lead compound with potential for further development and application. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other related drawings can be obtained based on these drawings without paying creative work.

[0033] Figure 1 The present invention provides a schematic flow chart of an embodiment of a method for preparing heterocyclic amide compounds.

[0034] The realization of the purpose, functional features and advantages of the present invention will be further explained in conjunction with embodiments and with reference to the accompanying drawings. DETAILED DESCRIPTION

[0035] To make the purpose, technical scheme and advantages of the embodiment of the present invention clearer, the technical scheme in the embodiment of the present invention will be described clearly and completely below. If the specific conditions are not specified in the embodiment, it is carried out according to the normal conditions or the conditions recommended by the manufacturer. If the reagents or instruments used do not specify the manufacturer, they are all conventional products that can be purchased commercially. In addition, the meaning of "and / or" appearing in the full text includes three parallel schemes, taking "A and / or B" as an example, including scheme A, or scheme B, or schemes that A and B meet at the same time. In addition, the technical schemes between the various embodiments can be combined with each other, but must be based on the ability of ordinary technicians in the field to achieve. When the combination of technical solutions is contradictory or cannot be achieved, it should be considered that the combination of such technical solutions does not exist, and is not within the scope of protection required by the present invention. Based on the embodiments in the present invention, all other embodiments obtained by ordinary technicians in the field without making creative work belong to the scope of protection of the present invention.

[0036] Currently, due to the long-term use of pesticides, weeds, pests and pathogenic microorganisms have developed resistance, affecting the growth of crops and causing a decrease in food yield and quality.

[0037] In view of this, the present invention proposes a heterocyclic amide compound, including any one of the following structural formulas:

[0038]

[0039] Among them, R', R, R 1 and R 2 Each is independently selected from CH3, H, Cl, F or CF3.

[0040] The heterocyclic amide compounds provided by the present invention are small organic molecules with excellent biological activity and novel structures. Activity screening has found that the heterocyclic amide compounds are agricultural lead compounds with potential for further development and application.

[0041] Furthermore, the heterocyclic amide compound described in this embodiment includes any one of the following structural formulas:

[0042]

[0043]

[0044] Among them, R' and R 1 Each independently selected from CH3, H, Cl, F or CF3, in which case the R group and R 2 The groups are all CH3.

[0045] Furthermore, the heterocyclic amide compound described in this embodiment includes any one of the following structural formulas:

[0046]

[0047] Among them, R' and R 1 Each independently selected from CH3, H, Cl, F or CF3, in which case the R group and R 2 The groups are all Cl.

[0048] Furthermore, the heterocyclic amide compound described in this embodiment includes any one of the following structural formulas:

[0049]

[0050] Wherein, R' is selected from CH3, H, Cl, F or CF3, and the R group is F in this case.

[0051] Furthermore, the heterocyclic amide compound described in this embodiment includes any one of the following structural formulas:

[0052]

[0053] Wherein, R' is selected from CH3, H, Cl, F or CF3, and the R group is CF3.

[0054] Furthermore, the heterocyclic amide compound described in this embodiment includes any one of the following structural formulas:

[0055]

[0056]

[0057] Among them, R' and R 1 Each is independently selected from CH3, H, Cl, F or CF3, in which case the R group is H.

[0058] The present invention also provides a method for preparing a heterocyclic amide compound, and the synthetic route thereof is as follows:

[0059]

[0060] Figure 1 The schematic diagram of a process for preparing a heterocyclic amide compound provided by the present invention comprises the following steps:

[0061] S1, mixing a heterocyclic carboxylic acid compound with carbodiimide and hydroxybenzotriazole, and dissolving the mixture in dimethylformamide to obtain a mixed solution;

[0062] In this step, the heterocyclic carboxylic acid compound includes any one of pyridine-3-carboxylic acid and pyrazinecarboxylic acid, and the carbodiimide and hydroxybenzotriazole are condensing agents or dehydrating agents. The heterocyclic carboxylic acid compound and the catalyst are added and mixed in a certain ratio, and the molar ratio of the heterocyclic carboxylic acid compound, carbodiimide, and hydroxybenzotriazole is 1:(1-1.5):(1-1.5), preferably, the molar ratio is 1:1.2:1.2. Within this ratio range, the heterocyclic carboxylic acid compound can react completely.

[0063] S2, mixing the mixed solution with amine to obtain a final reaction solution;

[0064] The reaction in this step is carried out at room temperature and detected by TLC. The reaction time is 22 to 26 hours, preferably 24 hours.

[0065] S3, adding water to the final reaction solution to quench the reaction, adding dichloromethane, extracting, combining the organic phases, and drying with anhydrous sodium sulfate to obtain a preliminarily dried mixture;

[0066] After the above reaction is completed, water is added to quench the reaction, and then extracted three times with dichloromethane. The dichloromethane is then washed with saturated brine and finally dried over anhydrous sodium sulfate.

[0067] S4, distilling the preliminarily dried mixture under reduced pressure to remove dichloromethane to obtain a crude product;

[0068] In this step, a rotary evaporator is used to evaporate the solvent dichloromethane under reduced pressure. As the solvent decreases, the concentration of the solute increases continuously and precipitates after saturation, thereby obtaining a crude product.

[0069] S5. Separating and purifying the crude product to obtain heterocyclic amide compounds.

[0070] In order to further purify the crude product, the crude product was further purified by silica gel column chromatography, wherein the mobile phase was a mixed solvent of petroleum ether and ethyl acetate and the stationary phase was silica gel.

[0071] The present invention also provides a crop pesticide, comprising the heterocyclic amide compounds as described above, wherein the heterocyclic amide compounds are a class of synthetic organic small molecules with novel structures, have excellent biological activity, and are found to be agricultural lead compounds with potential for further development and application through activity screening.

[0072] Furthermore, the crop pesticide includes at least one of a bactericide, a herbicide and an insecticide. The heterocyclic amide compounds prepared by the present invention are found to be effective in sterilization, insecticide and weed control through biological activity tests.

[0073] The technical solution of the present invention is further described in detail below in conjunction with specific embodiments and drawings. It should be understood that the following embodiments are only used to explain the present invention and are not used to limit the present invention.

[0074] In order to distinguish heterocyclic amide compounds with different structures, they are sorted according to the numbers in Table 1 and Table 2 below.

[0075] Table 1 Target compound number (1)

[0076]

[0077]

[0078] Table 2 Target compound number (2)

[0079]

[0080] Example 1 Synthesis of heterocyclic amide compound (4a), the structural formula is:

[0081]

[0082] N-(5-benzyl-1,3,4-thiadiazol2-yl)-2-methylnicotinamide(4a)

[0083] The preparation process is:

[0084] (1) Nicotinic acid (1, 1.2 mmol), ECDI (1.2 mmol) and HOBt (1.2 mmol) were added to a 25 mL reaction bottle in sequence;

[0085] (2) Dissolve in 3 mL dry DMF, react at room temperature for 1 h, then add amine (2 or 3, 1.0 mmol), monitor the reaction by TLC, and the reaction is complete after 24 h;

[0086] (3) 30 mL of water was added to the reaction solution to quench the reaction, and the mixture was extracted with dichloromethane (3 × 30 mL). The organic phases were combined and dried over anhydrous sodium sulfate.

[0087] (4) The solvent was removed under reduced pressure, and the residue was separated and purified by column chromatography to obtain the target compound with a yield of 56%. Its molecular structure was identified as follows:

[0088] 1 H NMR (500MHz, DMSO-d6) δ12.97(s,1H),8.58(dd,J=4.8,1.4Hz,1H),7.96(dd,J=7. 7,1.3Hz,1H),7.41-7.33(m,5H),7.29(d,J=4.2Hz,1H),4.39(s,2H),2.54(s,3H).

[0089] 13 C NMR (126MHz, DMSO-d6) δ166.88,164.48,159.53,156.49,151.26,138.28,136.66,129.41,129.33,129.29,127.53,121.32,35.51,23.37.

[0090] This indicates that the structure of the obtained target compound is consistent with the structure shown in the above structural formula.

[0091] Example 2 Synthesis of heterocyclic amide compound (4b), the structural formula is:

[0092]

[0093] N-(5-(4-chlorobenzyl)-1,3,4-thiadiazol-2-yl)-2-methylnicotinamide(4b)

[0094] The preparation steps were the same as those in Example 1. The yield of the target compound was 72%. Its molecular structure was identified as follows:

[0095] 1 H NMR (500MHz, DMSO-d6) δ13.03(s,1H),8.59(d,J=2.8Hz,1H),7.97(d,J=7.0Hz,1H),7.40(dt,J=17.9,6.8Hz,5H),4.41(s,2H),2.55(s,3H).

[0096] 13 C NMR (126MHz, DMSO-d6) δ156.48,151.27,137.25,136.64,132.20,131.23,129.34,129.18,121.30,34.63,23.34.

[0097] This indicates that the structure of the obtained target compound is consistent with the structure shown in the above structural formula.

[0098] Example 3 Synthesis of heterocyclic amide compound (4c), the structural formula is:

[0099]

[0100] 2-chloro-N-(5-(4-chlorobenzyl)-1,3,4-thiadiazol-2-yl)nicotinamide(4c)

[0101] The preparation steps were the same as those in Example 1. The yield of the target compound was 62%. Its molecular structure was identified as follows:

[0102] 1 H NMR (500MHz, DMSO-d6) δ13.25 (s, 1H), 8.61-8.54 (m, 1H), 8.15 (d, J = 7.4Hz, 1H), 7.58 (dd, J = 7.4, 4.9Hz, 1H), 7.42 (q, J = 8.3Hz, 4H), 4.43 (s, 2H).

[0103] 13 C NMR (126MHz, DMSO-d6) δ164.28,151.89,147.05,139.36,137.19,132.25,131.25,131.02,129.21,123.52,34.65.

[0104] This indicates that the structure of the obtained target compound is consistent with the structure shown in the above structural formula.

[0105] Example 4 Synthesis of heterocyclic amide compound (4d), the structural formula is:

[0106]

[0107] N-(5-(4-chlorobenzyl)-1,3,4-thiadiazol-2-yl)-2-fluoronicotinamide(4d)

[0108] The preparation steps were the same as those in Example 1. The yield of the target compound was 63%. Its molecular structure was identified as follows:

[0109] 1 H NMR (500MHz, DMSO-d6) δ13.18(s,1H),8.47–8.42(m,1H),8.36–8.29(m,1H),7.56–7.50(m,1H),7.45–7.37(m,4H),4.42(s,2H).

[0110] 13 C NMR (126MHz, DMSO-d6) δ164.03,160.74,158.83,151.15,151.03,142.46,137.17,132.21,131.23,129.18,122.66,122.62,34.62.

[0111] This indicates that the structure of the obtained target compound is consistent with the structure shown in the above structural formula.

[0112] Example 5 Synthesis of heterocyclic amide compound (4e), the structural formula is:

[0113]

[0114] 2-methyl-N-(5-(2-methylbenzyl)-1,3,4-thiadiazol-2-yl)nicotinamide(4e)

[0115] The preparation steps were the same as those in Example 1. The yield of the target compound was 57%. Its molecular structure was identified as follows:

[0116] 1 H NMR(500MHz,DMSO-d6)δ13.01(s,1H),8.58(d,J=4.0Hz,1H),7.96(d,J=7.4Hz ,1H),7.41-7.28(m,2H),7.21(s,3H),4.38(s,2H),2.54(s,3H),2.30(s,3H).

[0117] 13 C NMR(126MHz,DMSO-d6)δ166.83,164.38,159.30,156.49,151.24,143.57,136.81,136.64 ,136.52,130.91,130.11,129.37,127.88,126.84,125.86,121.30,33.56,23.36,19.54.

[0118] This indicates that the structure of the obtained target compound is consistent with the structure shown in the above structural formula.

[0119] Example 6 Synthesis of heterocyclic amide compound (4f), the structural formula is:

[0120]

[0121] N-(5-(2-methylbenzyl)-1,3,4-thiadiazol-2-yl)-2-(trifluoromethyl)nicotinamide(4f)

[0122] The preparation steps were the same as those in Example 1. The yield of the target compound was 65%. Its molecular structure was identified as follows:

[0123] 1 H NMR(500MHz,DMSO-d6)δ13.28(s,1H),8.89(d,J=4.1Hz,1H),8.28(d,J=7.7Hz,1H) ,7.86(dd,J=7.6,4.8Hz,1H),7.33(s,1H),7.22(s,3H),4.39(s,2H),2.30(s,3H).

[0124] 13 C NMR (126MHz, DMSO-d6) δ151.36,138.33,136.82,136.54,130.93,130.13,129.75,127.94,127.57,126.87,122.74,114.14,33.55,19.52.

[0125] This indicates that the structure of the obtained target compound is consistent with the structure shown in the above structural formula.

[0126] Example 7 Synthesis of heterocyclic amide compounds (4 g), the structural formula is:

[0127]

[0128] 2-methyl-N-(5-(4-(trifluoromethyl)benzyl)-1,3,4-thiadiazol-2-yl)nicotinamide(4g)

[0129] The preparation steps were the same as those in Example 1. The yield of the target compound was 58%. Its molecular structure was identified as follows:

[0130] 1 H NMR(500MHz,DMSO-d6)δ13.06(s,1H),8.59(d,J=3.6Hz,1H),7.97(d,J=7.4Hz,1H),7.73(d, J=8.0Hz, 2H), 7.60 (d, J=7.9Hz, 2H), 7.35 (dd, J=7.5, 5.0Hz, 1H), 4.53 (s, 2H), 2.55 (s, 3H).

[0131] 13 C NMR(126MHz,DMSO-d6)δ163.26,156.49,151.29,148.73,143.00,136.66,130.28,130 .23,129.31,128.30,128.05,126.23,126.10,126.07,125.81,121.31,35.02,23.36.

[0132] This indicates that the structure of the obtained target compound is consistent with the structure shown in the above structural formula.

[0133] Example 8 Synthesis of heterocyclic amide compound (4h), the structural formula is:

[0134]

[0135] 2-chloro-N-(5-(4-(trifluoromethyl)benzyl)-1,3,4-thiadiazol-2-yl)nicotinamide(4h)

[0136] The preparation steps were the same as those in Example 1. The yield of the target compound was 68%. Its molecular structure was identified as follows:

[0137] 1 H NMR (500MHz, DMSO-d6) δ13.28(s,1H),8.57(dd,J=4.8,1.8Hz,1H),8.14(dd,J=7.6,1.8Hz,1H),7.73(d,J=8.1Hz,2H),7.64-7.53(m,3H),4.54(s,2H).

[0138] 13 C NMR(126MHz,DMSO-d6)δ164.24,163.65,159.18,151.92,147.06,142.95,139.38,130 .98,130.25,128.59,128.34,128.09,126.13,126.10,125.82,123.66,123.53,35.04.

[0139] This indicates that the structure of the obtained target compound is consistent with the structure shown in the above structural formula.

[0140] Example 9 Synthesis of heterocyclic amide compound (4i), the structural formula is:

[0141]

[0142] 2-fluoro-N-(5-(4-(trifluoromethyl)benzyl)-1,3,4-thiadiazol-2-yl)nicotinamide(4i)

[0143] The preparation steps were the same as those in Example 1. The yield of the target compound was 72%. Its molecular structure was identified as follows:

[0144] 1 H NMR (500MHz, DMSO-d6) δ13.22(s,1H),8.44(d,J=3.8Hz,1H),8.32(t,J=7.7Hz,1H),7.73(d,J=8.0Hz,2H),7.60(d,J=8.0Hz,2H),7.55–

[0145] 7.49(m,1H),4.54(s,2H).

[0146] 13 C NMR(126MHz,DMSO-d6)δ163.44,160.75,158.83,151.20,151.08,142.93,142.48,130.23,128 .31,128.06,126.10,126.07,126.04,125.81,123.65,122.67,122.63,117.33,35.00,31.16.

[0147] This indicates that the structure of the obtained target compound is consistent with the structure shown in the above structural formula.

[0148] Example 10 Synthesis of heterocyclic amide compound (4j), the structural formula is:

[0149]

[0150] N-(5-pheneethyl-1,3,4-thiadiazol-2-yl)nicotinamide(4j)

[0151] The preparation steps are the same as those in Example 1, except that the type of amine in step (2) is different. The yield of the target compound is 58%, and its molecular structure is identified as follows:

[0152] 1 H NMR (500MHz, DMSO-d6) δ13.14(s,1H),9.20(s,1H),8.80(d,J=4.0Hz,1H),8.41(d,J=8.0Hz,1H ),7.58(dd,J=7.8,4.9Hz,1H),7.36-7.15(m,5H),3.35(t,J=7.6Hz,2H),3.08(t,J=7.6Hz,2H).

[0153] 13 C NMR (126MHz, DMSO-d6) δ170.21,168.23,159.46,150.27,150.13,141.45,135.74,135.52,128.86,128.72,126.40,123.25,35.68,32.27.

[0154] This indicates that the structure of the obtained target compound is consistent with the structure shown in the above structural formula.

[0155] Example 11 Synthesis of heterocyclic amide compound (4k), the structural formula is:

[0156]

[0157] 2-methyl-N-(5-phenethyl-1,3,4-thiadiazol-2-yl)nicotinamide(4k)

[0158] The preparation steps were the same as those in Example 10. The yield of the target compound was 73%. Its molecular structure was identified as follows:

[0159] 1H NMR(500MHz,DMSO-d6)δ12.97(s,1H),8.59(dd,J=4.8,1.4Hz,1H),8.02-7.96(m,1H),7.36(dd,J=7.7,4.9Hz, 1H), 7.31 (dd, J=7.5, 5.7Hz, 4H), 7.24-7.19 (m, 1H), 3.36 (t, J=7.7Hz, 2H), 3.08 (t, J=7.7Hz, 2H), 2.57 (s, 3H).

[0160] 13 C NMR (126MHz, DMSO-d6) δ166.80,164.10,156.47,151.23,140.58,136.64,129.44,128.89,128.84,126.71,121.29,35.10,31.01,23.36.

[0161] This indicates that the structure of the obtained target compound is consistent with the structure shown in the above structural formula.

[0162] Example 12 Synthesis of heterocyclic amide compound (41), the structural formula is:

[0163]

[0164] N-(5-phenethyl-1,3,4-thiadiazol-2-yl)-2-(trifluoromethyl)nicotinamide(4l)

[0165] The preparation steps were the same as those in Example 10. The yield of the target compound was 67%. Its molecular structure was identified as follows:

[0166] 1 H NMR (500MHz, DMSO-d6) δ13.26(s,1H),8.90(d,J=4.3Hz,1H),8.31(d,J=7.6Hz,1H),7.87(dd,J=7. 8,4.8Hz,1H),7.36–7.27(m,4H),7.25–7.17(m,1H),3.37(t,J=7.7Hz,2H),3.08(t,J=7.7Hz,2H).

[0167] 13C NMR(126MHz,DMSO-d6)δ164.55,158.51,151.30,143.33,143.06,140.55,138.30,130.39 ,128.89,128.84,128.74,127.54,126.72,124.86,122.76,120.57,118.38,35.03,31.04.

[0168] This indicates that the structure of the obtained target compound is consistent with the structure shown in the above structural formula.

[0169] Example 13 Synthesis of heterocyclic amide compound (4m), the structural formula is:

[0170]

[0171] 2-chloro-N-(5-phenethyl-1,3,4-thiadiazol-2-yl)nicotinamide(4m)

[0172] The preparation steps were the same as those in Example 10. The yield of the target compound was 70%. Its molecular structure was identified as follows:

[0173] 1 H NMR (500MHz, DMSO-d6) δ13.17(s,1H),8.57(dd,J=4.7,1.7Hz,1H),8.16(dd,J=7.5,1.6Hz,1H),7.58(dd, J=7.5,4.9Hz,1H),7.36–7.27(m,4H),7.22(d,J=5.4Hz,1H),3.37(t,J=7.6Hz,2H),3.08(t,J=7.7Hz,2H).

[0174] 13 C NMR (126MHz, DMSO-d6) δ164.63,151.83,147.05,140.54,139.36,131.31,128.90,128.85,126.73,123.50,35.07,31.03.

[0175] This indicates that the structure of the obtained target compound is consistent with the structure shown in the above structural formula.

[0176] Example 14 Synthesis of heterocyclic amide compound (4n), the structural formula is:

[0177]

[0178] 2-fluoro-N-(5-phenethyl-1,3,4-thiadiazol-2-yl)nicotinamide(4n)

[0179] The preparation steps were the same as those in Example 10. The yield of the target compound was 70%. Its molecular structure was identified as follows:

[0180] 1 H NMR(500MHz,DMSO-d6)δ13.12(s,1H),8.45(s,1H),8.34(t,J=7.6Hz,1H),7.5 3(s,1H),7.29(s,4H),7.21(s,1H),3.40-3.34(m,2H),3.08(t,J=7.2Hz,2H).

[0181] 13 C NMR(126MHz,DMSO-d6)δ164.27,162.38,160.79,158.87,151.14,151.02,142 .49,140.54,128.94,128.86,126.74,122.66,122.62,117.47,35.08,31.08.

[0182] This indicates that the structure of the obtained target compound is consistent with the structure shown in the above structural formula.

[0183] Example 15 Synthesis of heterocyclic amide compound (4o), the structural formula is:

[0184]

[0185] 2-chloro-N-(5-(2,4-dichlorophenethyl)-1,3,4-thiadiazol-2-yl)nicotinamide(4o)

[0186] The preparation steps were the same as those in Example 10. The yield of the target compound was 59%. Its molecular structure was identified as follows:

[0187] 1 H NMR (500MHz, DMSO-d6) δ13.19(s,1H),8.57(dd,J=4.8,1.8Hz,1H),8.17(dd,J=7.6,1.8Hz,1H),7.61(d,J =2.0Hz, 1H), 7.58 (dd, J = 7.6, 4.9Hz, 1H), 7.47-7.36 (m, 2H), 3.35 (t, J = 7.6Hz, 2H), 3.18 (t, J = 7.6Hz, 2H).

[0188] 13 C NMR (126MHz, DMSO-d6) δ151.87,147.06,139.37,137.10,134.45,132.56,132.36,131.02,129.18,127.92,123.50,32.21,29.13.

[0189] This indicates that the structure of the obtained target compound is consistent with the structure shown in the above structural formula.

[0190] Example 16 Synthesis of heterocyclic amide compound (4p), the structural formula is:

[0191]

[0192] N-(5-(2,4-dichlorophenethyl)-1,3,4-thiadiazol-2-yl)-2-(trifluoromethyl)nicotinamide(4p)

[0193] The preparation steps were the same as those in Example 10. The yield of the target compound was 62%. Its molecular structure was identified as follows:

[0194] 1 H NMR(500MHz,DMSO-d6)δ13.32(s,1H),8.90(d,J=3.8Hz,1H),8.31(d,J=7.6Hz,1H),7.92–7.8 4(m,1H),7.62(s,1H),7.43(dd,J=31.6,8.1Hz,2H),3.39–3.33(m,2H),3.18(t,J=7.4Hz,2H).

[0195] 13 C NMR (126MHz, DMSO-d6) δ163.62,155.49,151.23,143.33,143.06,138.31,137.13,136.86 ,134.45,132.55,132.35,130.63,129.17,127.91,127.53,122.78,120.59,32.21,29.20.

[0196] This indicates that the structure of the obtained target compound is consistent with the structure shown in the above structural formula.

[0197] Example 17 Synthesis of heterocyclic amide compound (6a), the structural formula is:

[0198]

[0199] N-(5-(2-methylbenzyl)-1,3,4-thiadiazol-2-yl)pyrazine-2-ccarboxamide(6a)

[0200] The preparation steps are the same as those in Example 1, except that nicotinic acid in step (1) is replaced by pyrazinecarboxylic acid. The yield of the target compound is 55%, and its molecular structure is identified as follows:

[0201] 1 H NMR (500MHz, DMSO-d6) δ12.89(s,1H),9.27(s,1H),8.80(d,J=39.6Hz,2H),7.29(s,1H),7.19(s,3H),4.34(s,2H),2.29(s,3H).

[0202] 13 C NMR (126MHz, DMSO-d6) δ156.32,147.75,145.73,145.14,140.59,136.97,136.78,136.51,130.82,130.07,127.69,126.72,125.32,33.89,19.56.

[0203] This indicates that the structure of the obtained target compound is consistent with the structure shown in the above structural formula.

[0204] Example 18 Synthesis of heterocyclic amide compound (6b), the structural formula is:

[0205]

[0206] N-(5-(3-chlorobenzyl)-1,3,4-thiadiazol-2-yl)pyrazine-2-carboxamide(6b)

[0207] The preparation steps were the same as those in Example 17. The yield of the target compound was 52%. Its molecular structure was identified as follows:

[0208] 1 H NMR (500MHz, DMSO-d6) δ12.98(s,1H),9.28(s,1H),8.95(s,1H),8.84(s,1H),7.47(s,1H),7.43–7.27(m,3H),4.45(s,2H).

[0209] 13C NMR (126MHz, DMSO-d6) δ164.01,148.83,145.05,144.31,140.61,133.69,131.09,129.20,128.12,127.50,34.79.

[0210] This indicates that the structure of the obtained target compound is consistent with the structure shown in the above structural formula.

[0211] Example 19 Synthesis of heterocyclic amide compound (6c), the structural formula is:

[0212]

[0213] 3-methyl-N-(5-(2-methylbenzyl)-1,3,4-thiadiazol-2-yl)pyrazine-2-carboxamide(6c)

[0214] The preparation steps were the same as those in Example 17. The yield of the target compound was 61%. Its molecular structure was identified as follows:

[0215] 1 H NMR (500MHz, DMSO-d6) δ8.39 (d, J = 30.9 Hz, 2H), 7.25 (d, J = 3.9 Hz, 1H), 7.17 (s, 3H), 4.19 (s, 2H), 2.53 (s, 3H), 2.30 (s, 3H).

[0216] 13 C NMR(126MHz,DMSO-d6)δ170.64,169.57,159.89,153.92,151.31,142.81,14 1.13,137.84,136.66,130.64,130.06,127.25,126.53,34.67,22.52,19.65.

[0217] This indicates that the structure of the obtained target compound is consistent with the structure shown in the above structural formula.

[0218] Example 20 Synthesis of heterocyclic amide compound (6d), the structural formula is:

[0219]

[0220] N-(5-(4-fluorobenzyl)-1,3,4-thiadiazol-2-yl)-3-methylpyrazine-2-carboxamide(6d)

[0221] The preparation steps were the same as those in Example 17. The yield of the target compound was 77%. Its molecular structure was identified as follows:

[0222] 1 H NMR (500MHz, DMSO-d6) δ12.85 (s, 1H), 8.71 (d, J = 67.3Hz, 2H), 7.43 (s, 2H), 7.20 (s, 2H), 4.42 (s, 2H), 2.72 (s, 3H).

[0223] 13 C NMR (126MHz, DMSO-d6) δ164.73,162.73,160.79,154.11,147.04,143.68,141.60,134.41,131.36,131.30,116.10,115.93,34.57,22.68.

[0224] This indicates that the structure of the obtained target compound is consistent with the structure shown in the above structural formula.

[0225] Example 21 Synthesis of heterocyclic amide compound (6e), the structural formula is:

[0226]

[0227] 3-methyl-N-(5-(4-(trifluoromethyl)benzyl)-1,3,4-thiadiazol-2-yl)pyrazine-2-carboxamide(6e)

[0228] The preparation steps were the same as those in Example 17. The yield of the target compound was 68%. Its molecular structure was identified as follows:

[0229] 1 H NMR (500MHz, DMSO-d6) δ 12.89 (s, 1H), 8.71 (d, J = 67.0Hz, 2H), 7.67 (dd, J = 61.5, 7.3Hz, 4H), 4.54 (s, 2H), 2.72 (s, 3H).

[0230] 13 C NMR(126MHz,DMSO-d6)δ164.44,163.61,162.17,159.11,157.94,154.13,148.72,147.06 ,143.63,142.96,142.65,141.60,137.00,130.25,126.11,121.66,35.04,31.15,22.69.

[0231] This indicates that the structure of the obtained target compound is consistent with the structure shown in the above structural formula.

[0232] Example 22 Synthesis of heterocyclic amide compound (6f), the structural formula is:

[0233]

[0234] N-(5-(3,4-difluorobenzyl)-1,3,4-thiadiazol-2-yl)-3-methylpyrazine-2-carboxamide(6f)

[0235] The preparation steps were the same as those in Example 17. The yield of the target compound was 83%. Its molecular structure was identified as follows:

[0236] 1 H NMR (500MHz, DMSO-d6) δ12.86(s,1H),8.77(d,J=2.0Hz,1H),8.64(s,1H),7.54–7.36(m,2H),7.24(s,1H),4.43(s,2H),2.72(s,3H).

[0237] 13 C NMR (126MHz, DMSO-d6) δ164.42,163.93,159.06,154.13,150.80,150.08,148.84,148.74,148.13,148 .04,147.05,143.61,141.59,135.85,126.35,126.32,118.54,118.40,118.29,118.15,34.37,22.69.

[0238] This indicates that the structure of the obtained target compound is consistent with the structure shown in the above structural formula.

[0239] Example 23 Synthesis of heterocyclic amide compounds (6 g), the structural formula is:

[0240]

[0241] N-(5-(3-chlorobenzyl)-1,3,4-thiadiazol-2-yl)-3-methylpyrazine-2-carboxamide(6g)

[0242] The preparation steps were the same as those in Example 17. The yield of the target compound was 56%. Its molecular structure was identified as follows:

[0243] 1 H NMR (500MHz, DMSO-d6) δ12.86(s,1H),8.77(d,J=2.2Hz,1H),8.63(d,J=1.9Hz,1H),7.47(s,1H),7.46–7.27(m,3H),4.44(s,2H),2.72(s,3H).

[0244] 13 C NMR (126MHz, DMSO-d6) δ164.44,163.95,159.07,154.13,147.05,143.66,141.60,140.62,133.72,131.12,129.22,128.15,127.54,34.83,22.69.

[0245] This indicates that the structure of the obtained target compound is consistent with the structure shown in the above structural formula.

[0246] Example 24 Synthesis of heterocyclic amide compound (6h), the structural formula is:

[0247]

[0248] 3-chloro-N-(5-(2-methylbenzyl)-1,3,4-thiadiazol-2-yl)pyrazine-2-carboxamide(6h)

[0249] The preparation steps were the same as those in Example 17. The yield of the target compound was 66%. Its molecular structure was identified as follows:

[0250] 1 H NMR (500MHz, DMSO-d6) δ13.33(s,1H),8.78(d,J=26.5Hz,2H),7.33(s,1H),7.22(s,3H),4.40(s,2H),2.30(s,3H).

[0251] 13 C NMR (126MHz, DMSO-d6) δ165.20,152.89,147.00,145.75,143.22,136.85,136.49,130.94,130.14,129.03,127.95,126.87,33.57,19.53.

[0252] This indicates that the structure of the obtained target compound is consistent with the structure shown in the above structural formula.

[0253] Example 25 Synthesis of heterocyclic amide compound (6i), the structural formula is:

[0254]

[0255] 3-chloro-N-(5-(3-chlorobenzyl)-1,3,4-thiadiazol-2-yl)pyrazine-2-carboxamide(6i)

[0256] The preparation steps were the same as those in Example 17. The yield of the target compound was 60%. Its molecular structure was identified as follows:

[0257] 1 H NMR (500MHz, DMSO-d6) δ13.36 (s, 1H), 8.78 (dd, J = 26.8, 2.3Hz, 2H), 7.49 (s, 1H), 7.45–7.30 (m, 3H), 4.46 (s, 2H).

[0258] 13 C NMR (126MHz, DMSO-d6) δ147.01,145.75,143.22,140.46,133.70,131.13,129.24,128.16,127.56,34.83.

[0259] This indicates that the structure of the obtained target compound is consistent with the structure shown in the above structural formula.

[0260] Example 26 Synthesis of heterocyclic amide compound (6j), the structural formula is:

[0261]

[0262] 3-chloro-N-(5-(4-fluorobenzyl)-1,3,4-thiadiazol-2-yl)pyrazine-2-carboxamide(6j)

[0263] The preparation steps were the same as those in Example 17. The yield of the target compound was 79%. Its molecular structure was identified as follows:

[0264] 1 H NMR (500MHz, DMSO-d6) δ13.34(s,1H),8.78(dd,J=26.6,2.1Hz,2H),7.43(dd,J=8.1,5.7Hz,2H),7.20(t,J=8.8Hz,2H),4.43(s,2H).

[0265] 13C NMR (126MHz, DMSO-d6) δ165.12,162.74,160.81,146.99,146.27,145.75,143.23,134.29,131.39,131.32,116.11,115.94,34.58.

[0266] This indicates that the structure of the obtained target compound is consistent with the structure shown in the above structural formula.

[0267] Example 27 Synthesis of heterocyclic amide compound (6k), the structural formula is:

[0268]

[0269] 3-chloro-N-(5-(2,3-dichlorobenzyl)-1,3,4-thiadiazol-2-yl)pyrazine-2-carboxamide(6k)

[0270] The preparation steps were the same as those in Example 17. The yield of the target compound was 50%. Its molecular structure was identified as follows:

[0271] 1 H NMR (500MHz, DMSO-d6) δ 13.40 (s, 1H), 8.78 (dd, J = 27.0, 2.2Hz, 2H), 7.63 (d, J = 7.8Hz, 1H), 7.54 (d, J = 7.4Hz, 1H), 7.41 (t, J = 7.8Hz, 1H), 4.60 (s, 2H).

[0272] 13 C NMR (126MHz, DMSO-d6) δ162.96,147.03,146.14,145.79,143.22,138.23,132.61,131.83,130.76,130.25,129.06,34.50.

[0273] This indicates that the structure of the obtained target compound is consistent with the structure shown in the above structural formula.

[0274] Test methods and results

[0275] In the fungicidal activity test, the culture medium method was used to test the inhibitory mycelial growth of phytopthora capsici (Pc), Pythium ultimum (Pd), and Zymoseptoria tritici (Zt), with a test concentration of 20ppm. At the same time, the leaf disc method was used to test the activity of Uromyces viciae-fabae (Uv) at a concentration of 100ppm.

[0276] In the insecticidal activity test, the cotton spider (Tetranychus surticae) was sprayed with the drug at a concentration of 1000ppm for contact experiment; the aphid (Myzus persicae) was artificially fed at a concentration of 50ppm to test the insecticidal activity of the compound. The activity of the compound was observed 5-9 days after the application of the drug. The activity was evaluated using two levels, as shown in Tables 3 and 4. 99 means complete death, and 0 means no effect on the insects.

[0277] In the herbicidal activity test, the greenhouse pot method was used to conduct pre-emergence activity tests on Arabidopsis thaliana (At) and digitaria sanguinalis (Ds), with dosages of 10ppm, 32ppm and 32ppm respectively; the weeds were cultured in a greenhouse for 7 days after application and their survival conditions were observed. The inhibitory activity against weeds was expressed as a percentage, as shown in Tables 3 and 4, where 100 means complete inhibition and 0 means no inhibitory effect.

[0278] Table 3 Activity test table of heterocyclic amide compounds (1)

[0279]

[0280]

[0281]

[0282] Table 4 Activity test table of heterocyclic amide compounds (2)

[0283]

[0284]

[0285]

[0286]

[0287]

[0288] In summary, the heterocyclic amide compounds provided in the embodiments of the present invention are effective as agricultural lead compounds in terms of bactericidal, insecticidal and weed control, and specifically, heterocyclic amide compounds with different structures have different bactericidal, insecticidal and weed control effects.

[0289] The above are only preferred embodiments of the present invention, and do not limit the patent scope of the present invention. For those skilled in the art, the present invention may have various changes and modifications. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the patent protection scope of the present invention.

Claims

1. A heterocyclic amide compound, characterized in that: Any one of the following structural formulas:

2. A method for preparing a heterocyclic amide compound as claimed in claim 1, characterized in that: The following steps are involved: S1, mixing a heterocyclic carboxylic acid compound with carbodiimide and hydroxybenzotriazole, and dissolving the mixture in dimethylformamide to obtain a mixed solution; S2, mixing the mixed solution with amine to obtain a final reaction solution; S3, adding water to the final reaction solution to quench the reaction, adding dichloromethane, extracting, combining the organic phases, and drying with anhydrous sodium sulfate to obtain a preliminarily dried mixture; S4, distilling the preliminarily dried mixture under reduced pressure to remove dichloromethane to obtain a crude product; S5, separating and purifying the crude product to obtain a heterocyclic amide compound; The heterocyclic carboxylic acid compound is shown in Chemical Formula 1 or Chemical Formula 5; The amine is shown in Chemical Formula 2 or Chemical Formula 3; The substituent groups in the chemical formula structure as described above are as shown in the corresponding groups in the compound of claim 1; 3. A crop pesticide, characterized in that: Including the heterocyclic amide compound as claimed in claim 1.

4. The crop pesticide according to claim 3, characterized in that: The crop pesticide is selected from at least one of a fungicide, a herbicide and an insecticide.

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