A benzamide derivative containing a thiocyanatopyrazole structure, a preparation method thereof, and applications thereof

Abstract

The present invention discloses a benzamide derivative containing a thiocyanatopyrazole structure, a preparation method thereof and an application thereof. The structural formula of this benzamide derivative containing a thiocyanatopyrazole structure is as follows in general formula (I), #imgabs0# wherein, R1 is trifluoromethyl, difluoromethyl or methyl; R2 is hydrogen, methyl, methoxy, trifluoromethyl, trifluoromethoxy, fluorine, chlorine, bromine, cyano or a multi-substituted combination thereof substituted at different positions. The benzamide derivative containing a thiocyanatopyrazole structure prepared by the present invention has broad-spectrum antifungal and oomycete activities, and particularly shows significant inhibitory activities against Valsa mali and Phytophthora capsici, which provides a basis for the development of a novel fungicide with the benzamide derivative containing a thiocyanatopyrazole structure as an active ingredient.

Description

Technical Field

[0001] The present invention relates to the fields of chemical technology and medicinal chemistry, and particularly relates to a benzamide derivative containing a thiocyanopyrazole structure, a preparation method thereof, and an application thereof. Background Art

[0002] Pesticides are important production materials in the process of grain production and play a crucial role in ensuring high and stable yields of agricultural crops. According to statistics, plant pathogenic fungal infections cause a 20% reduction in global crop yields every year, and an additional 10% reduction after harvest. This not only brings huge economic losses to farmers but also seriously threatens global food production safety. The application of fungicides is currently the most effective measure to control plant pathogenic fungi and can recover a large amount of losses every year. Among many fungicides, SDHIs fungicides are widely used due to their high-efficiency and broad-spectrum antifungal activities. Their mechanism of action is as follows: by acting on protein complex II, they affect the respiratory chain electron transport system of pathogenic bacteria, hinder energy metabolism, inhibit the growth of pathogenic bacteria, and cause their death, thereby achieving the purpose of disease control.

[0003] The most significant feature of SDHIs fungicides in chemical structure is the presence of an amide group. The newly developed fungicides of this type are derived by substituting groups on the existing basis. From 1996 to 2023, 25 SDH inhibitors have been marketed, and the proportion containing a pyrazole ring is as high as 52.00% (13 / 25); due to their broad-spectrum and high-efficiency antifungal activities, this type of fungicide is used for the control of fungal diseases on many crops and has become an important type of fungicide variety in production. However, due to their excessive and unreasonable use, the drug resistance of fungi to this type of fungicide has become increasingly severe. The Fungicide Resistance Action Committee (FRAC) has classified SDHIs fungicides as medium- to high-risk fungicides for resistance in 2009. On the other hand, the bactericidal spectrum of SDHIs fungicides is already very broad, almost covering all fungal diseases, such as gray mold, powdery mildew, sheath blight, scab, and rust, etc. However, among the currently marketed varieties, there are no varieties with high control efficacy against oomycetes such as downy mildew of cucumber and Phytophthora blight of pepper, which is undoubtedly regrettable. Therefore, the development of new fungicides, the expansion of the control spectrum of fungicides, and the solution of the problem of fungal drug resistance play a very important role in the sustainable development of agriculture. Summary of the Invention

[0004] The technical problem to be solved by the present invention is: to overcome the deficiencies of the prior art and provide a benzamide derivative containing a thiocyanopyrazole structure, a preparation method thereof, and an application thereof. The present invention introduces a thiocyanogen group into the pyrazole benzamide lead structure and synthesizes a benzamide derivative containing a thiocyanopyrazole structure, which becomes a compound with high-efficiency and broad-spectrum activities for inhibiting plant pathogenic bacteria.

[0005] The technical solution adopted by the present invention to solve its technical problems is: a benzamide derivative containing a thiocyanatopyrazole structure, characterized in that its general structural formula (I) is as follows:

[0006]

[0007] Wherein, R1 is trifluoromethyl, difluoromethyl or methyl; R2 is hydrogen, methyl, methoxy, trifluoromethyl, trifluoromethoxy, fluorine, chlorine, bromine, cyano or a multi-substituted combination thereof substituted at different positions.

[0008] Further, the benzamide derivative containing a thiocyanatopyrazole structure preferably includes the following compounds:

[0009]

[0010]

[0011] A preparation method of a benzamide derivative containing a thiocyanatopyrazole structure as described above includes the following synthetic route:

[0012]

[0013] Further, the synthetic route specifically includes the following steps:

[0014] Step S1: Using 5-pyrazolamine (II) as a raw material, a certain proportion of ethanol / water as a solvent, adding an appropriate amount of ammonium thiocyanate and ammonium persulfate, stirring and reacting at room temperature to generate 4-thiocyanato-5-pyrazolamine (III), and the obtained product is purified by column chromatography or recrystallization to obtain a pure product;

[0015] Step S2: Using 4-thiocyanato-5-pyrazolamine (III) as a raw material, carrying out a condensation reaction with differently substituted benzoic acid or benzoyl chloride (IV) to obtain a benzamide derivative containing a thiocyanatopyrazole structure corresponding to the general formula (I), and the obtained product is separated by column chromatography to obtain a pure product.

[0016] An application of a benzamide derivative containing a thiocyanatopyrazole structure as described above, and its application in preventing and treating fungal / oomycete diseases such as Sclerotinia sclerotiorum of rape, Valsa canker of apple trees, sheath blight of rice, Fusarium head blight of wheat, gray mold of tomatoes, Phytophthora blight of peppers and Pythium aphanidermatum of fruits and melons.

[0017] In addition, this benzamide derivative containing a thiocyanatopyrazole structure can be used to prepare various pesticide preparations for preventing and treating plant diseases caused by plant pathogenic fungi and oomycetes.

[0018] The beneficial effects of the present invention are as follows: The present invention introduces a thiocyanato group into the pyrazole carboxamide lead structure, synthesizes a class of benzamide derivatives containing a thiocyanato pyrazole structure, and selects common plant fungi and oomycetes, such as Sclerotinia sclerotiorum, Valsa mali, Rhizoctonia solani, Gaeumannomyces graminis, Botrytis cinerea, Phytophthora capsici, etc. as the control objects for antibacterial activity determination. The results show that this class of compounds exhibits broad-spectrum antibacterial activity against plant fungi and oomycetes, especially excellent antibacterial activity against Valsa mali and Phytophthora capsici. Structure-activity relationship analysis shows that the substitution of the thiocyanato group on the pyrazole ring of the molecular skeleton is crucial for maintaining the high broad-spectrum antibacterial activity of this class of compounds. This class of compounds has original novelty in structure, is simple to synthesize, and is completely different from the structures of existing commercial fungicides, and is expected to be developed into a highly efficient and broad-spectrum new fungicide. Detailed implementation mode

[0019] Now, the present invention will be further described in detail with reference to the preferred embodiments, so that those skilled in the art can implement it according to the description in the specification.

[0020] Example 1

[0021] The preparation method of the thiocyanato-5-pyrazolamine compound III (R1 = trifluoromethyl), and the chemical formula of the thiocyanato-5-pyrazolamine compound III (R1 = trifluoromethyl) is as follows:

[0022]

[0023] In this example, the preparation method of the thiocyanato-5-pyrazolamine compound III (R1 = trifluoromethyl) is as follows: Under room temperature conditions, 5-pyrazolamine II (R1 = trifluoromethyl) (1.65 g, 10 mmol) and ammonium thiocyanate (3.04 g, 40 mmol) were dissolved in a mixed solution of 30 mL of ethanol and water (ethanol / water = 2:1), stirred for several minutes, and then ammonium persulfate (11.4 g, 50 mmol) was added in batches. The reaction was carried out at room temperature for about 24 hours, and TLC was used to monitor until the reaction of 5-pyrazolamine (II) was complete. After the reaction was completed, most of the ethanol was removed by rotary evaporation under vacuum, and then extracted with ethyl acetate (3 × 40 mL). The organic layers were combined, washed with saturated brine, and finally dried with anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to obtain a yellow crude product. Purification by silica gel column chromatography (petroleum ether / ethyl acetate = 5:1 → 3:1) gave the thiocyanato-5-pyrazolamine compound III (R1 = trifluoromethyl) (2.02 g, yield 91%). 1 H NMR (400 MHz, DMSO-d6) δ 6.71 (s, 2H, NH2), 3.63 (s, 3H, N-CH3); 1313C NMR (101 MHz, DMSO-d6) δ 152.2, 139.9 (q, J = 35.7 Hz), 120.7 (q, J = 269.5 Hz), 111.6, 72.7, 35.8.

[0024] Example 2

[0025] Preparation of Compound I-1. The chemical formula of Compound I-1 is as follows:

[0026]

[0027] The specific preparation method of Compound I-1 in this example is as follows: Dissolve the thiocyanato-5-pyrazolamine compound III (R1 = trifluoromethyl) (222.2 mg, 1 mmol) obtained in Example 1 and triethylamine (0.55 mL) in anhydrous dichloromethane (2 mL), and then slowly add benzoyl chloride dropwise under an ice bath. After reacting for 30 minutes under the ice bath, transfer it to room temperature and continue to react at room temperature for about 3 hours. Monitor by TLC until the reaction of thiocyanato-5-pyrazolamine (III) is complete. Extract with ethyl acetate (3 × 10 mL), combine the organic phases, wash with saturated brine, and finally dry with anhydrous magnesium sulfate, filter, and rotary evaporate the solvent under reduced pressure to obtain the crude product. Purify by silica gel column chromatography (petroleum ether / ethyl acetate = 3:1) to obtain a light yellow solid compound I-1 (254.5 mg, yield 78%), m.p. = 126.3–127.9 °C; 1 1H NMR (500 MHz, DMSO-d6) δ 11.01 (s, 1H, CONH-H), 8.05 (d, J = 7.2 Hz, 2H, Ph-H), 7.70 (t, J = 7.4 Hz, 1H, Ph-H), 7.61 (t, J = 7.6 Hz, 2H, Ph-H), 3.87 (s, 3H, NCH3); 13 13C NMR (126 MHz, DMSO-d6) δ 166.0, 142.3, 140.1 (q, J = 36.9 Hz), 132.9, 132.1, 128.7 (2C), 128.1 (2C), 120.3 (q, J = 269.8 Hz), 110.4, 93.5, 37.6.

[0028] Example 3

[0029] Preparation of Compound I-2. The chemical formula of Compound I-2 is as follows:

[0030]

[0031] The preparation method of compound I-2 in this example is as follows: Using the method described in Example 2, replace benzoyl chloride with o-fluorobenzoyl chloride, and the other steps are the same as those in Example 2. The obtained compound I-2 is a pale yellow solid (247.9 mg, yield 72%), m.p. = 139.1–141.5 °C; 1 H NMR (500 MHz, DMSO-d6) δ 11.03 (s, 1H, CONH-H), 7.84 (m, 1H, Ph-H), 7.69 (m, 1H, Ph-H), 7.42 (m, 2H, Ph-H), 3.88 (s, 3H, NCH3); 13 C NMR (126 MHz, DMSO-d6) δ 163.4, 159.4 (d, J = 251.3 Hz), 141.7, 140.2 (q, J = 37.0 Hz), 134.1 (d, J = 8.6 Hz), 130.5 (d, J = 2.2 Hz), 124.8 (d, J = 3.5 Hz), 121.8 (d, J = 13.6 Hz), 120.3 (q, J = 269.8 Hz), 116.5 (d, J = 21.5 Hz), 110.3, 93.5, 37.6.

[0032] Example 4

[0033] Preparation of compound I-3. The chemical formula of compound I-3 is as follows:

[0034]

[0035] The preparation method of compound I-3 in this example is as follows: Using the method described in Example 2, replace benzoyl chloride with m-fluorobenzoyl chloride, and the other steps are the same as those in Example 2. The obtained compound I-3 is a pale yellow solid (303.0 mg, yield 88%), m.p. = 122.7–124.8 °C; 1 H NMR (500 MHz, DMSO-d6) δ 11.11 (s, 1H, CONH-H), 7.89 (d, J = 7.7 Hz, 1H, Ph-H), 7.84 (d, J = 9.3 Hz, 1H, Ph-H), 7.68 (m, 1H, Ph-H), 7.56 (m, 1H, Ph-H), 3.88 (s, 3H, NCH3); 1313C NMR (126 MHz, DMSO-d6) δ 164.8 (d, J = 2.7 Hz), 162.0 (d, J = 245.2 Hz), 142.0, 140.1 (q, J = 36.9 Hz), 134.4 (d, J = 7.1 Hz), 131.0 (d, J = 8.0 Hz), 124.4 (d, J = 3.0 Hz), 120.3 (q, J = 269.8 Hz), 119.8 (d, J = 21.0 Hz), 115.0 (d, J = 23.3 Hz), 110.4, 93.6, 37.6.

[0036] Example 5

[0037] Preparation of Compound I-4. The chemical formula of Compound I-4 is as follows:

[0038]

[0039] The preparation method of Compound I-4 in this example is as follows: Using the method described in Example 2, replace benzoyl chloride with p-fluorobenzoyl chloride, and the other steps are the same as those in Example 2. The obtained Compound I-4 is a pale yellow solid (285.8 mg, yield 83%), m.p. = 168.8–170.5 °C; 1 1H NMR (500 MHz, DMSO-d6) δ 11.04 (s, 1H, CONH-H), 8.12 (m, 2H, Ph-H), 7.46 (m, 2H, Ph-H), 3.87 (s, 3H, NCH3); 13 13C NMR (126 MHz, DMSO-d6) δ 165.0, 164.9 (d, J = 251.1 Hz), 142.2, 140.1 (q, J = 37.1 Hz), 131.1, 131.0, 128.6 (d, J = 2.9 Hz), 120.4 (q, J = 270.0 Hz), 115.9, 115.7, 110.4, 93.6, 37.6.

[0040] Example 6

[0041] Preparation of Compound I-5. The chemical formula of Compound I-5 is as follows:

[0042]

[0043] The preparation method of Compound I-5 in this example is as follows: Using the method described in Example 2, replace benzoyl chloride with o-chlorobenzoyl chloride, and the other steps are the same as those in Example 2. The obtained Compound I-5 is a pale yellow solid (259.7 mg, yield 72%), m.p. = 145.6–146.9 °C. 11H NMR (500 MHz, DMSO-d6) δ 11.37 (s, 1H, CONH-H), 7.74 (d, J = 7.2 Hz, 1H, Ph-H), 7.65 (d, J = 7.9 Hz, 1H, Ph-H), 7.60 (m, 1H, Ph-H), 7.54 (t, J = 7.3 Hz, 1H, Ph-H), 3.91 (s, 3H, NCH3); 13 13C NMR (126 MHz, DMSO-d6) δ 165.7, 141.5, 140.3 (q, J = 37.1 Hz), 134.6, 132.1, 130.0, 129.9, 129.2, 127.4, 120.3 (q, J = 269.8 Hz), 110.4, 93.2, 37.8.

[0044] Example 7

[0045] Preparation of Compound I-6, the chemical formula of Compound I-6 is as follows:

[0046]

[0047] The preparation method of Compound I-6 in this example is as follows: Using the method described in Example 2, replace benzoyl chloride with m-chlorobenzoyl chloride, and the other steps are the same as those in Example 2. The obtained Compound I-6 is a pale yellow solid (299.4 mg, yield 83%), m.p. = 153.9–155.2 °C. 1 1H NMR (500 MHz, DMSO-d6) δ 11.15 (s, 1H, CONH-H), 8.08 (t, J = 1.9 Hz, 1H, Ph-H), 7.98 (d, J = 7.8 Hz, 1H, Ph-H), 7.78 (m, 1H, Ph-H), 7.65 (t, J = 7.9 Hz, 1H, Ph-H), 3.88 (s, 3H, NCH3); 13 13C NMR (126 MHz, DMSO-d6) δ 164.8, 142.0, 140.2 (q, J = 37.0 Hz), 134.1, 133.5, 132.7, 130.8, 127.9, 127.0, 120.3 (q, J = 270.0 Hz), 110.4, 93.6, 37.7.

[0048] Example 8

[0049] Preparation of Compound I-7, the chemical formula of Compound I-7 is as follows:

[0050]

[0051] The preparation method of compound I-7 in this example is as follows: Using the method described in Example 2, replace benzoyl chloride with p-chlorobenzoyl chloride, and the other steps are the same as those in Example 2. The obtained compound I-7 is a white solid (342.7 mg, yield 95%), m.p. = 141.5–143.4 °C; 1 H NMR(400 MHz, DMSO-d6) δ 11.12 (s, 1H, CONH-H), 8.06 (d, J = 8.6 Hz, 2H, Ph-H), 7.70 (d, J = 8.6 Hz, 2H, Ph-H), 3.87 (s, 3H, NCH3); 13 C NMR(101 MHz, DMSO-d6) δ 165.1, 142.1, 140.2 (q, J = 37.1 Hz), 137.9, 130.9, 130.1 (2C), 128.9 (2C), 120.4 (q, J = 269.9 Hz), 110.5, 93.6, 37.7.

[0052] Example 9

[0053] The preparation of compound I-8, and the chemical formula of compound I-8 is as follows:

[0054]

[0055] The preparation method of compound I-8 in this example is as follows: Using the method described in Example 2, replace benzoyl chloride with o-trifluoromethylbenzoyl chloride, and the other steps are the same as those in Example 2. The obtained compound I-8 is a light yellow solid (315.4 mg, yield 80%), m.p. = 172.1–174.0 °C; 1 H NMR(400 MHz, DMSO-d6) δ 11.50 (s, 1H, CONH-H), 7.92 (m, 3H, Ph-H), 7.81 (m, 1H, Ph-H), 3.90 (s, 3H, NCH3); 13 C NMR(101 MHz, DMSO-d6) δ 166.5, 141.4, 140.4 (q, J = 36.9 Hz), 133.8 (d, J = 2.4 Hz), 132.9, 131.2, 129.0, 126.7 (q, J = 4.6 Hz), 126.3 (q, J = 31.8 Hz), 125.0, 122.0 (q, J = 57.6 Hz), 110.5, 93.4, 37.7.

[0056] Example 10

[0057] The preparation of compound I-9, and the chemical formula of compound I-9 is as follows:

[0058]

[0059] In this example, the preparation method of compound I-9 is as follows: Using the method described in Example 2, replace benzoyl chloride with m-trifluoromethylbenzoyl chloride, and the other steps are the same as those in Example 2. The obtained compound I-9 is a pale yellow solid (374.6 mg, yield 95%), m.p. = 187.2–188.7 °C; 1 H NMR (400 MHz, DMSO-d6) δ 11.29 (s, 1H, CONH-H), 8.37 (s, 1H, Ph-H), 8.33 (d, J = 7.9 Hz, 1H, Ph-H), 8.08 (d, J = 7.8 Hz, 1H, Ph-H), 7.87 (t, J = 7.8 Hz, 1H, Ph-H), 3.89 (s, 3H, NCH3); 13 C NMR (101 MHz, DMSO-d6) δ 164.8, 141.9, 140.2 (q, J = 37.1 Hz), 133.1, 132.4, 130.2, 129.5 (q, J = 3.2 Hz), 129.5 (q, J = 32.3 Hz), 124.8 (q, J = 3.8 Hz), 122.1 (q, J = 81.0 Hz), 119.0, 110.5, 93.7, 37.7.

[0060] Example 11

[0061] Preparation of compound I-10. The chemical formula of compound I-10 is as follows:

[0062]

[0063] In this example, the preparation method of compound I-10 is as follows: Using the method described in Example 2, replace benzoyl chloride with p-trifluoromethylbenzoyl chloride, and the other steps are the same as those in Example 2. The obtained compound I-10 is a pale yellow solid (382.3 mg, yield 97%), m.p. = 164.1–166.2 °C; 1 H NMR (400 MHz, DMSO-d6) δ 11.29 (s, 1H, CONH-H), 8.24 (d, J = 8.1 Hz, 2H, Ph-H), 8.01 (d, J = 8.3 Hz, 2H, Ph-H), 3.89 (s, 3H, NCH3); 1313C NMR (101 MHz, DMSO-d6) δ 165.1, 141.9, 140.2 (q, J = 37.1 Hz), 135.9, 132.6 (q, J = 32.1 Hz), 129.2 (2C), 125.8 (q, J = 3.8 Hz), 125.2, 122.1 (q, J = 75.2 Hz), 119.0, 110.4, 93.7, 37.7; HRMS (ESI) m / z [M+Na] + : calcd for C 14 H8F6N4NaOS, 417.0215, found, 417.0222.

[0064] Example 12

[0065] Preparation of Compound I-11, the chemical formula of Compound I-11 is as follows:

[0066]

[0067] The preparation method of Compound I-11 in this example is as follows: Using the method described in Example 2, replace benzoyl chloride with o-methylbenzoyl chloride, and the other steps are the same as those in Example 2. The obtained Compound I-11 is a light yellow solid (306.3 mg, yield 90%), m.p. = 142.1–143.7 °C; 1 1H NMR (400 MHz, DMSO-d6) δ 11.05 (s, 1H, CONH-H), 7.68 (d, J = 7.2 Hz, 1H, Ph-H), 7.49 (m, 1H, Ph-H), 7.38 (t, J = 6.6 Hz, 2H, Ph-H), 3.90 (s, 3H, NCH3), 2.49 (s, 3H, Ph-CH3); 13 13C NMR (101 MHz, DMSO-d6) δ 168.4, 142.1, 140.2 (q, J = 37.1 Hz), 136.2, 134.3, 130.9, 130.8, 127.7, 125.8, 120.4 (q, J = 270.0 Hz), 110.4, 93.2, 37.7, 19.5.

[0068] Example 13

[0069] Preparation of Compound I-12, the chemical formula of Compound I-12 is as follows:

[0070]

[0071] The preparation method of compound I-12 in this example is as follows: Using the method described in Example 2, replace benzoyl chloride with m-methylbenzoyl chloride, and the other steps are the same as those in Example 2. The obtained compound I-12 is a white solid (313.1 mg, yield 92%), m.p. = 159.0–159.8 °C; 1 H NMR(400MHz,DMSO-d6)δ10.96(s,1H,CONH-H),7.84(m,2H,Ph-H),7.50(m,2H,Ph-H),3.86(s,3H,NCH3),2.43(s,3H,Ph-CH3); 13 C NMR(101MHz,DMSO-d6)δ166.1,142.4,140.1(q,J=37.1Hz),138.2,133.5,132.1,128.6,128.6,125.3,120.4(q,J=270.0Hz),110.4,93.5,37.6,20.9.

[0072] Example 14

[0073] The preparation of compound I-13, and the chemical formula of compound I-13 is as follows:

[0074]

[0075] The preparation method of compound I-13 in this example is as follows: Using the method described in Example 2, replace benzoyl chloride with p-methylbenzoyl chloride, and the other steps are the same as those in Example 2. The obtained compound I-13 is a light yellow solid (289.3 mg, yield 85%), m.p. = 131.1–132.8 °C; 1 H NMR(400MHz,DMSO-d6)δ10.91(s,1H,CONH-H),7.95(d,J=8.2Hz,2H,Ph-H),7.41(d,J=8.0Hz,2H,Ph-H),3.86(s,3H,NCH3),2.42(s,3H,Ph-CH3); 13 C NMR(101MHz,DMSO-d6)δ165.8,143.3,142.4,140.1(q,J=37.0Hz),129.3(2C),129.1,128.2(2C),120.4(q,J=269.7Hz),110.4,93.5,37.6,21.1.

[0076] Example 15

[0077] The preparation of compound I-14, and the chemical formula of compound I-14 is as follows:

[0078]

[0079] In this example, the preparation method of compound I-14 is as follows: Using the method described in Example 2, replace benzoyl chloride with o-methoxybenzoyl chloride, and the other steps are the same as those in Example 2. The obtained compound I-14 is a pale yellow solid (252.9 mg, yield 71%), m.p. = 120.5–121.3 °C; 1 H NMR (400 MHz, DMSO-d6) δ 10.55 (s, 1H, CONH-H), 7.85 (dd, J = 7.7, 1.8 Hz, 1H, Ph-H), 7.63 (m, 1H, Ph-H), 7.27 (d, J = 8.4 Hz, 1H, Ph-H), 7.13 (t, J = 7.5 Hz, 1H, Ph-H), 3.99 (s, 3H, Ph-OCH3), 3.86 (s, 3H, NCH3); 13 C NMR (101 MHz, DMSO-d6) δ 164.7, 157.5, 142.4, 139.9 (q, J = 37.0 Hz), 134.0, 130.8, 120.9, 120.8, 120.4 (q, J = 269.9 Hz), 112.4, 110.5, 93.5, 56.2, 37.6.

[0080] Example 16

[0081] Preparation of compound I-15. The chemical formula of compound I-15 is as follows:

[0082]

[0083] In this example, the preparation method of compound I-15 is as follows: Using the method described in Example 2, replace benzoyl chloride with m-methoxybenzoyl chloride, and the other steps are the same as those in Example 2. The obtained compound I-15 is a pale yellow solid (310.0 mg, yield 87%), m.p. = 132.5–133.7 °C; 1 H NMR (400 MHz, DMSO-d6) δ 11.00 (s, 1H, CONH-H), 7.63 (d, J = 7.9 Hz, 1H, Ph-H), 7.57 (dd, J = 2.7, 1.6 Hz, 1H, Ph-H), 7.53 (t, J = 7.9 Hz, 1H, Ph-H), 7.27 (m, 1H, Ph-H), 3.87 (s, 3H, Ph-OCH3), 3.86 (s, 3H, NCH3); 1313C NMR (101 MHz, DMSO-d6) δ 165.8, 159.4, 142.3, 140.1 (q, J = 37.1 Hz), 133.4, 130.0, 120.4 (q, J = 269.9 Hz), 120.4, 118.7, 113.4, 110.5, 93.6, 55.5, 37.6; HRMS (ESI) m / z [M+Na] + : calcd for C 14 H 11 F3N4NaO2S, 379.0447, found, 379.0443.

[0084] Example 17

[0085] Preparation of Compound I-16. The chemical formula of Compound I-16 is as follows:

[0086]

[0087] In this example, the preparation method of Compound I-16 is as follows: Using the method described in Example 2, replace benzoyl chloride with p-methoxybenzoyl chloride, and the other steps are the same as those in Example 2. The obtained Compound I-16 is a pale yellow solid (331.4 mg, yield 93%), m.p. = 133.8–134.5 °C; 1 1H NMR (400 MHz, DMSO-d6) δ 10.82 (s, 1H, CONH-H), 8.03 (d, J = 8.9 Hz, 2H, Ph-H), 7.14 (d, J = 8.9 Hz, 2H, Ph-H), 3.87 (s, 3H, NCH3), 3.85 (s, 3H, Ph-OCH3); 13 13C NMR (101 MHz, DMSO-d6) δ 165.3, 163.0, 142.6, 140.1 (q, J = 37.0 Hz), 130.3 (2C), 124.4, 120.4 (q, J = 269.8 Hz), 114.0 (2C), 110.5, 93.4, 55.6, 37.6.

[0088] Example 18

[0089] Preparation of Compound I-17. The chemical formula of Compound I-17 is as follows:

[0090]

[0091] The preparation method of compound I-17 in this example is as follows: Using the method described in Example 2, replace benzoyl chloride with o-bromobenzoyl chloride, and the other steps are the same as those in Example 2. The obtained compound I-17 is a pale yellow solid (368.7 mg, yield 91%), m.p. = 145.9–147.4 °C; 1 H NMR(400MHz,DMSO-d6)δ11.41(s,1H,CONH-H),7.80(d,J=7.8Hz,1H,Ph-H),7.71(dd,J=7.5,1.8Hz,1H,Ph-H),7.59(t,J=7.3Hz,1H,Ph-H),7.51(td,J=7.8,1.6Hz,1H,Ph-H),3.93(s,3H,NCH3); 13 C NMR(101MHz,DMSO-d6)δ166.5,141.4,140.3(q,J=37.0Hz),136.8,133.0,132.2,129.2,127.9,120.3(q,J=269.9Hz),118.8,110.5,93.2,37.9.

[0092] Example 19

[0093] Preparation of compound I-18. The chemical formula of compound I-18 is as follows:

[0094]

[0095] The preparation method of compound I-18 in this example is as follows: Using the method described in Example 2, replace benzoyl chloride with m-bromobenzoyl chloride, and the other steps are the same as those in Example 2. The obtained compound I-18 is a pale yellow solid (320.1 mg, yield 79%), m.p. = 172.8–174.9 °C; 1 H NMR(400MHz,DMSO-d6)δ11.15(s,1H,CONH-H),8.22(s,1H,Ph-H),8.02(d,J=7.9Hz,1H,Ph-H),7.91(d,J=8.1Hz,1H,Ph-H),7.58(t,J=7.9Hz,1H,Ph-H),3.88(s,3H,NCH3); 13 C NMR(101MHz,DMSO-d6)δ164.7,141.9,140.1(q,J=37.0Hz),135.6,134.3,131.0,130.7,127.3,121.9,120.3(q,J=269.9Hz),110.4,93.6,37.7.

[0096] Example 20

[0097] Preparation of Compound I-19. The chemical formula of Compound I-19 is as follows:

[0098]

[0099] The preparation method of Compound I-19 in this example is as follows: Using the method described in Example 2, replace benzoyl chloride with p-bromobenzoyl chloride, and the other steps are the same as those in Example 2. The obtained Compound I-19 is a light yellow solid (324.2 mg, yield 80%), m.p. = 174.3–176.5 °C; 1 H NMR (400 MHz, DMSO-d6) δ 11.10 (s, 1H, CONH-H), 7.98 (d, J = 8.5 Hz, 2H, Ph-H), 7.84 (d, J = 8.6 Hz, 2H, Ph-H), 3.87 (s, 3H, NCH3); 13 C NMR (101 MHz, DMSO-d6) δ 165.2, 142.0, 140.11 (q, J = 37.0 Hz), 131.8 (2C), 131.2, 130.2 (2C), 126.9, 120.33 (q, J = 269.9 Hz), 110.4, 93.6, 37.6; HRMS (ESI) m / z [M+Na] + : calcd for C 13 H8BrF3N4NaOS, 426.9446, found, 426.9451.

[0100] Example 21

[0101] Preparation of Compound I-20. The chemical formula of Compound I-20 is as follows:

[0102]

[0103] The preparation method of Compound I-20 in this example is as follows: Using the method described in Example 2, replace benzoyl chloride with m-cyanobenzoyl chloride, and the other steps are the same as those in Example 2. The obtained Compound I-20 is a light yellow solid (326.7 mg, yield 93%), m.p. = 163.6–164.8 °C; 1 H NMR (400 MHz, DMSO-d6) δ 11.25 (s, 1H, CONH-H), 8.48 (s, 1H, Ph-H), 8.31 (d, J = 8.0 Hz, 1H, Ph-H), 8.18 (d, J = 7.8 Hz, 1H, Ph-H), 7.84 (t, J = 7.9 Hz, 1H, Ph-H), 3.89 (s, 3H, NCH3);13 C NMR (101 MHz, DMSO-d6) δ 164.4, 141.8, 140.2 (q, J = 37.1 Hz), 136.2, 133.3, 132.9, 131.8, 130.2, 120.3 (q, J = 269.8 Hz), 118.0, 111.9, 110.4, 93.6, 37.7.

[0104] Example 22

[0105] Preparation of Compound I-21, the chemical formula of Compound I-21 is as follows:

[0106]

[0107] The preparation method of Compound I-21 in this example is as follows: Using the method described in Example 2, replace benzoyl chloride with p-cyanobenzoyl chloride, and the other steps are the same as those in Example 2. The obtained Compound I-21 is a light yellow solid (267.0 mg, yield 76%), m.p. = 186.5–188.5 °C; 1 H NMR (400 MHz, DMSO-d6) δ 11.30 (s, 1H, CONH-H), 8.19 (d, J = 8.3 Hz, 2H, Ph-H), 8.11 (d, J = 8.3 Hz, 2H, Ph-H), 3.89 (s, 3H, NCH3); 13 C NMR (101 MHz, DMSO-d6) δ 164.9, 141.8, 140.2 (q, J = 37.1 Hz), 136.1, 132.8 (2C), 129.0 (2C), 120.3 (q, J = 269.8 Hz), 118.1, 115.1, 110.4, 93.7, 37.7.

[0108] Example 23

[0109] Preparation of Compound I-22, the chemical formula of Compound I-22 is as follows:

[0110]

[0111] The preparation method of Compound I-22 in this example is as follows: Using the method described in Example 2, replace benzoyl chloride with o-trifluoromethoxybenzoyl chloride, and the other steps are the same as those in Example 2. The obtained Compound I-22 is a light yellow solid (393.9 mg, yield 96%), m.p. = 152.0–153.4 °C; 11H NMR (400 MHz, DMSO-d6) δ 11.35 (s, 1H, CONH-H), 7.87 (dd, J = 7.6, 1.4 Hz, 1H, Ph-H), 7.76 (td, J = 8.0, 1.6 Hz, 1H, Ph-H), 7.61 (m, 2H, Ph-H), 3.88 (s, 3H, NCH3); 13 13C NMR (101 MHz, DMSO-d6) δ 164.2, 145.0, 141.5, 140.3 (q, J = 34.1 Hz), 133.1, 130.1, 128.7, 127.9, 122.0, 121.5 (q, J = 37.1 Hz), 118.9 (q, J = 21.7 Hz), 110.3, 93.3, 37.6.

[0112] Example 24

[0113] Preparation of Compound I-23, the chemical formula of Compound I-23 is as follows:

[0114]

[0115] The preparation method of Compound I-23 in this example is as follows: Using the method described in Example 2, replace benzoyl chloride with 3-trifluoromethoxybenzoyl chloride, and the other steps are the same as those in Example 2. The obtained Compound I-23 is a pale yellow solid (377.5 mg, yield 92%), m.p. = 159.8–161.7 °C; 1 1H NMR (400 MHz, DMSO-d6) δ 11.20 (s, 1H, CONH-H), 8.09 (d, J = 7.5 Hz, 1H, Ph-H), 7.98 (s, 1H, Ph-H), 7.78 (t, J = 7.9 Hz, 1H, Ph-H), 7.73 (d, J = 8.4 Hz, 1H, Ph-H), 3.89 (s, 3H, NCH3); 13 13C NMR (101 MHz, DMSO-d6) δ 164.6, 148.4, 141.9, 140.2 (q, J = 37.0 Hz), 134.3, 131.1, 127.3, 125.4, 121.5 (q, J = 21.1 Hz), 120.7, 118.9 (q, J = 21.1 Hz), 110.5, 93.7, 37.7; HRMS (ESI) m / z [M+Na] + : calcd for C 14 H8F6N4NaO2S, 433.0164, found, 433.0166.

[0116] Example 25

[0117] Preparation of Compound I-24. The chemical formula of Compound I-24 is as follows:

[0118]

[0119] The specific preparation method of Compound I-24 in this example is as follows: Using the method described in Example 2, replace benzoyl chloride with p-trifluoromethoxybenzoyl chloride, and the other steps are the same as those in Example 2. The obtained Compound I-24 is a pale yellow solid (381.6 mg, yield 93%), m.p. = 153.6–154.7 °C; 1 H NMR (400 MHz, DMSO-d6) δ 11.15 (s, 1H, CONH-H), 8.18 (d, J = 8.7 Hz, 2H, Ph-H), 7.62 (d, J = 8.5 Hz, 2H, Ph-H), 3.88 (s, 3H, NCH3); 13 C NMR (101 MHz, DMSO-d6) δ 164.9, 151.4, 142.1, 140.2 (q, J = 37.1 Hz), 131.2, 130.7 (2C), 121.5 (q, J = 45.0 Hz), 121.0 (2C), 118.8 (q, J = 32.7 Hz), 110.5, 93.6, 37.7; HRMS (ESI) m / z [M+Na] + : calcd for C 14 H8F6N4NaO2S, 433.0164, found, 433.0171.

[0120] Example 26

[0121] Preparation of Compound I-25. The chemical formula of Compound I-25 is as follows:

[0122]

[0123] The specific preparation method of Compound I-25 in this example is as follows: Using the method described in Example 2, replace benzoyl chloride with 2,4-dichlorobenzoyl chloride, and the other steps are the same as those in Example 2. The obtained Compound I-25 is a pale yellow solid (355.7 mg, yield 90%), m.p. = 142.9–145.3 °C; 1 H NMR (400 MHz, DMSO-d6) δ 11.44 (s, 1H, CONH-H), 7.86 (d, J = 1.9 Hz, 1H, Ph-H), 7.78 (d, J = 8.3 Hz, 1H, Ph-H), 7.66 (dd, J = 8.3, 1.9 Hz, 1H, Ph-H), 3.91 (s, 3H, NCH3); 1313C NMR (101 MHz, DMSO-d6) δ 164.9, 141.3, 140.3 (q, J = 37.0 Hz), 136.0, 133.4, 131.4, 130.7, 129.6, 127.7, 120.3 (q, J = 269.8 Hz), 110.5, 93.3, 37.9.

[0124] Example 27

[0125] Preparation of Compound I-26, the chemical formula of Compound I-26 is as follows:

[0126]

[0127] The preparation method of Compound I-26 in this example is as follows: Using the method described in Example 2, replace benzoyl chloride with 3,4-dichlorobenzoyl chloride, and the other steps are the same as those in Example 2. The obtained Compound I-26 is a pale yellow solid (343.8 mg, yield 87%), m.p. = 160.3–161.8 °C; 1 1H NMR (400 MHz, DMSO-d6) δ 11.22 (s, 1H, CONH-H), 8.28 (d, J = 2.0 Hz, 1H, Ph-H), 7.99 (dd, J = 8.4, 2.1 Hz, 1H, Ph-H), 7.91 (d, J = 8.4 Hz, 1H, Ph-H), 3.88 (s, 3H, NCH3); 13 13C NMR (101 MHz, DMSO-d6) δ 164.0, 141.8, 140.2 (q, J = 37.0 Hz), 135.8, 132.5, 131.7, 131.2, 130.1, 128.5, 120.3 (q, J = 269.9 Hz), 110.4, 93.6, 37.7; HRMS (ESI) m / z [M+Na] + : calcd for C 13 H7Cl2F3N4NaOS, 416.9562, found, 416.9565.

[0128] Example 28

[0129] Preparation of Compound I-27, the chemical formula of Compound I-27 is as follows:

[0130]

[0131] The preparation method of compound I-27 in this example is as follows: Using the method described in Example 2, replace benzoyl chloride with 3,5-dichlorobenzoyl chloride, and the other steps are the same as those in Example 2. The obtained compound I-27 is a pale yellow solid (351.7 mg, yield 89%), m.p. = 174.5–175.8 °C; 1 H NMR (400 MHz, DMSO-d6) δ 11.26 (s, 1H, CONH-H), 8.04 (d, J = 1.8 Hz, 2H, Ph-H), 7.99 (q, J = 2.0 Hz, 1H, Ph-H), 3.88 (s, 3H, NCH3); 13 C NMR (101 MHz, DMSO-d6) δ 163.6, 141.6, 140.2 (q, J = 37.0 Hz), 135.4, 134.6 (2C), 132.2, 127.0 (2C), 120.3 (q, J = 269.9 Hz), 110.5, 93.6, 37.8; HRMS (ESI) m / z [M+Na] + : calcd for C 13 H7Cl2F3N4NaOS, 416.9562, found, 416.9557.

[0132] Example 29

[0133] The preparation of compound I-28, and the chemical formula of compound I-28 is as follows:

[0134]

[0135] The preparation method of compound I-28 in this example is as follows: Using the method described in Example 2, replace benzoyl chloride with 2-fluoro-4-chlorobenzoyl chloride, and the other steps are the same as those in Example 2. The obtained compound I-28 is a pale yellow solid (329.5 mg, yield 87%), m.p. = 156.0–156.7 °C; 1 H NMR (400 MHz, DMSO-d6) δ 11.39 (s, 1H, CONH-H), 7.84 (dd, J = 8.4, 6.2 Hz, 1H, Ph-H), 7.68 (dd, J = 9.0, 2.3 Hz, 1H, Ph-H), 7.45 (td, J = 8.5, 2.4 Hz, 1H, Ph-H), 3.91 (s, 3H, NCH3); 1313C NMR (101 MHz, DMSO-d6) δ 165.0, 162.9 (d, J = 251.4 Hz), 141.4, 140.3 (q, J = 37.0 Hz), 131.2 (d, J = 3.5 Hz), 131.3 (d, J = 9.6 Hz), 131.2 (d, J = 3.5 Hz), 120.3 (q, J = 270.0 Hz), 117.6 (d, J = 25.5 Hz), 114.8 (d, J = 21.6 Hz), 110.5, 93.3, 37.8.

[0136] Example 30

[0137] Preparation of Compound I-29, the chemical formula of Compound I-29 is as follows:

[0138]

[0139] The preparation method of Compound I-29 in this example is as follows: Using the method described in Example 2, replace benzoyl chloride with 3-fluoro-4-chloro-benzoyl chloride, and the other steps are the same as those in Example 2. The obtained Compound I-29 is a pale yellow solid (310.5 mg, yield 82%), m.p. = 154.8–155.9 °C; 1 1H NMR (400 MHz, DMSO-d6) δ 11.19 (s, 1H, CONH-H), 8.04 (dd, J = 10.0, 1.8 Hz, 1H, Ph-H), 7.89 (m, 2H, Ph-H), 3.88 (s, 3H, NCH3); 13 13C NMR (101 MHz, DMSO-d6) δ 164.0, 157.1 (d, J = 248.0 Hz), 141.8, 140.2 (q, J = 37.1 Hz), 132.9 (d, J = 6.4 Hz), 131.3, 125.5 (d, J = 3.6 Hz), 124.5, 120.3 (q, J = 269.8 Hz), 116.6 (d, J = 22.8 Hz), 110.5, 93.7, 37.7; HRMS (ESI) m / z [M+Na] + : calcd for C 13 17H7ClF4N4NaOS, 400.9857, found, 400.9858.

[0140] Example 31

[0141] Preparation of Compound I-30, the chemical formula of Compound I-30 is as follows:

[0142]

[0143] The preparation method of compound I-30 in this example is as follows: Using the method described in Example 2, replace benzoyl chloride with 2-trifluoromethyl-4-chloro-benzoyl chloride, and the other steps are the same as those in Example 2. The obtained compound I-30 is a light yellow solid (390.1 mg, yield 91%), m.p. = 169.2–172.6 °C; 1 H NMR (400 MHz, DMSO-d6) δ 11.55 (s, 1H, CONH-H), 8.06 (s, 1H, Ph-H), 8.03 (d, J = 8.4 Hz, 1H, Ph-H), 7.96 (d, J = 8.2 Hz, 1H, Ph-H), 3.89 (s, 3H, NCH3); 13 C NMR (101 MHz, DMSO-d6) δ 165.5, 141.2, 140.3 (q, J = 37.3 Hz), 135.9, 132.8, 132.5, 131.1, 128.2 (q, J = 34.3 Hz), 126.8 (q, J = 4.9 Hz), 122.7 (q, J = 274.4 Hz), 120.3 (q, J = 269.9 Hz), 110.5, 93.4, 37.7.

[0144] Example 32

[0145] Preparation of compound I-31. The chemical formula of compound I-31 is as follows:

[0146]

[0147] The preparation method of compound I-31 in this example is as follows: Using the method described in Example 2, replace benzoyl chloride with 3-trifluoromethyl-4-chloro-benzoyl chloride, and the other steps are the same as those in Example 2. The obtained compound I-31 is a light yellow solid (411.5 mg, yield 96%), m.p. = 160.2–162.5 °C; 1 H NMR (400 MHz, DMSO-d6) δ 11.34 (s, 1H, CONH-H), 8.46 (d, J = 2.1 Hz, 1H, Ph-H), 8.31 (dd, J = 8.4, 2.1 Hz, 1H, Ph-H), 8.01 (d, J = 8.4 Hz, 1H, Ph-H), 3.89 (s, 3H, NCH3); 1313C NMR(101MHz, DMSO-d6) δ 164.0, 141.7, 140.2 (q, J = 37.1 Hz), 135.3, 133.9, 132.4, 131.5, 127.6 (q, J = 5.3 Hz), 127.0 (q, J = 31.3 Hz), 120.33 (q, J = 269.9 Hz), 122.54 (q, J = 273.4 Hz), 110.5, 93.7, 37.8; HRMS(ESI) m / z [M+Na] + : calcd for C 14 H7ClF6N4NaOS, 450.9825, found, 450.9823.

[0148] Example 33

[0149] Preparation of Compound I-32, the chemical formula of Compound I-32 is as follows:

[0150]

[0151] The preparation method of Compound I-32 in this example is as follows: Using the method described in Example 2, replace benzoyl chloride with 2-fluoro-4-trifluoromethyl-benzoyl chloride, and the other steps are the same as those in Example 2. The obtained Compound I-32 is a light yellow solid (346.3 mg, yield 84%), m.p. = 132.6–133.9 °C; 1 1H NMR(400MHz, DMSO-d6) δ 11.34 (s, 1H, CONH-H), 8.04 (t, J = 7.4 Hz, 1H, Ph-H), 7.99 (d, J = 10.0 Hz, 1H, Ph-H), 7.82 (d, J = 8.0 Hz, 1H, Ph-H), 3.90 (s, 3H, NCH3); 13 13C NMR(101MHz, DMSO-d6) δ 162.4, 159.1 (d, J = 253.7 Hz), 141.3, 140.2 (q, J = 37.0 Hz), 133.5 (qd, J = 32.9, 7.7 Hz), 131.8 (d, J = 2.6 Hz), 126.1 (d, J = 13.8 Hz), 121.8 (q, J = 3.6 Hz), 120.3 (d, J = 269.9 Hz), 114.4 (d, J = 3.6 Hz), 114.2 (d, J = 3.7 Hz), 110.4, 93.6, 37.7.

[0152] Example 34

[0153] Preparation of Compound I-33, the chemical formula of Compound I-33 is as follows:

[0154]

[0155] In this example, the preparation method of compound I-33 is as follows: Using the method described in Example 2, replace benzoyl chloride with 3-fluoro-4-trifluoromethyl-benzoyl chloride, and the other steps are the same as those in Example 2. The obtained compound I-33 is a pale yellow solid (329.8 mg, yield 80%), m.p. = 172.1–173.5 °C; 1 H NMR (400 MHz, DMSO-d6) δ 11.36 (s, 1H, CONH-H), 8.09 (m, 3H, Ph-H), 3.90 (s, 3H, NCH3); 13 C NMR (101 MHz, DMSO-d6) δ 163.8, 158.7 (d, J = 252.8 Hz), 141.6, 140.2 (q, J = 37.0 Hz), 138.6 (d, J = 7.2 Hz), 128.3 (d, J = 4.7 Hz), 124.8 (d, J = 3.7 Hz), 122.2 (q, J = 272.0 Hz), 120.3 (q, J = 269.9 Hz), 120.1 (qd, J = 32.9, 11.6 Hz), 116.9 (d, J = 22.5 Hz), 110.4, 93.8, 37.8; HRMS (ESI) m / z [M+Na] + : calcd for C 14 H7F7N4NaOS, 435.0121, found, 435.0126.

[0156] Example 35

[0157] Preparation of compound I-34, the chemical formula of compound I-34 is as follows:

[0158]

[0159] In this example, the preparation method of compound I-34 is as follows: Using the method described in Example 2, replace benzoyl chloride with 2-chloro-4-trifluoromethyl-benzoyl chloride, and the other steps are the same as those in Example 2. The obtained compound I-34 is a pale yellow solid (390.1 mg, yield 91%), m.p. = 155.2–156.9 °C; 1 H NMR (400 MHz, DMSO-d6) δ 11.58 (s, 1H, CONH-H), 8.12 (s, 1H, Ph-H), 7.98 (m, 2H, Ph-H), 3.93 (s, 3H, NCH3); 1313C NMR (101 MHz, DMSO-d6) δ 164.7, 141.1, 140.3 (q, J = 37.1 Hz), 138.6, 132.1 (q, J = 32.8 Hz), 131.1, 130.3, 126.9 (d, J = 3.8 Hz), 125.7 (q, J = 273.1 Hz), 124.6 (d, J = 3.8 Hz), 120.3 (q, J = 270.2 Hz), 110.5, 93.4, 37.9.

[0160] Example 36

[0161] Preparation of Compound I-35, the chemical formula of Compound I-35 is as follows:

[0162]

[0163] The preparation method of Compound I-35 in this example is as follows: Using the method described in Example 2, replace benzoyl chloride with 2,4-bis(trifluoromethyl)benzoyl chloride, and the other steps are the same as those in Example 2. The obtained Compound I-35 is a pale yellow solid (379.1 mg, yield 82%), m.p. = 168.4–170.1 °C; 1 1H NMR (400 MHz, DMSO-d6) δ 11.68 (s, 1H, CONH-H), 8.35 (d, J = 8.1 Hz, 1H, Ph-H), 8.30 (s, 1H, Ph-H), 8.18 (d, J = 8.0 Hz, 1H, Ph-H), 3.91 (s, 3H, NCH3); 13 13C NMR (101 MHz, DMSO-d6) δ 165.3, 141.0, 140.4 (q, J = 37.0 Hz), 137.6, 131.3 (q, J = 33.2 Hz), 130.5, 130.1, 127.3 (q, J = 33.3 Hz), 123.8, 123.0 (q, J = 272.9 Hz), 122.8 (q, J = 274.1 Hz), 120.3 (q, J = 270.1 Hz), 110.5, 93.4, 37.8.

[0164] Example 37

[0165] Preparation of Compound I-36, the chemical formula of Compound I-36 is as follows:

[0166]

[0167] The preparation method of compound I-36 in this example is as follows: Using the method described in Example 2, replace benzoyl chloride with 3,5-bis(trifluoromethyl)benzoyl chloride, and the other steps are the same as those in Example 2. The obtained compound I-36 is a pale yellow solid (328.2 mg, yield 71%), m.p. = 182.1–183.3 °C; 1 H NMR (400 MHz, DMSO-d6) δ 11.51 (s, 1H, CONH-H), 8.65 (s, 2H, Ph-H), 8.50 (s, 1H, Ph-H), 3.91 (s, 3H, NCH3); 13 C NMR (101 MHz, DMSO-d6) δ 163.6, 141.6, 140.3 (q, J = 37.2 Hz), 134.6, 130.8 (q, J = 33.5 Hz) (2C), 129.1 (2C), 126.5, 123.1 (q, J = 272.9 Hz) (2C), 120.4 (q, J = 273.1 Hz), 110.6, 93.8, 37.9; HRMS (ESI) m / z [M+Na] + : calcd for C 15 H7F9N4NaOS, 485.0089, found, 485.0092.

[0168] Example 38

[0169] The preparation method of the thiocyanato-5-pyrazolamine compound III (R1 = difluoromethyl), and the chemical formula of the thiocyanato-5-pyrazolamine compound III (R1 = difluoromethyl) is as follows:

[0170]

[0171] The preparation method of the thiocyanato-5-pyrazolamine compound III (R1 = difluoromethyl) in this example is as follows: At room temperature, dissolve 5-pyrazolamine II (R1 = difluoromethyl) (1.47 g, 10 mmol) and ammonium thiocyanate (3.04 g, 40 mmol) in a mixed solution of 30 mL of ethanol and water (ethanol / water = 2:1), stir for several minutes, and then add ammonium persulfate (11.4 g, 50 mmol) in batches. React at room temperature for about 24 hours, and monitor by TLC until 5-pyrazolamine (II) reacts completely. After the reaction is completed, most of the ethanol is removed by rotary evaporation under vacuum, and then extracted with ethyl acetate (3 × 40 mL). The organic layers are combined, washed with saturated brine, and finally dried with anhydrous magnesium sulfate. After the solvent is dried under reduced pressure by rotary evaporation, a yellow crude product is obtained. Purification by silica gel column chromatography (petroleum ether / ethyl acetate = 5:1 → 3:1) gives the thiocyanato-5-pyrazolamine compound III (R1 = difluoromethyl) (1.76 g, yield 86%).1 1H NMR (400 MHz, DMSO-d6) δ 6.85 (t, J = 53.2 Hz, 1H, CHF2), 6.56 (s, 2H, NH2), 3.59 (s, 3H, N-CH3); 13 13C NMR (101 MHz, DMSO-d6) δ 151.9, 144.7 (t, J = 27.2 Hz), 111.9, 111.5 (t, J = 232.5 Hz), 71.6, 35.4.

[0172] Example 39

[0173] Preparation of Compound I-37, the chemical formula of Compound I-37 is as follows:

[0174]

[0175] The preparation method of Compound I-37 in this example is as follows: Dissolve the thiocyanato-5-pyrazolamine compound (R1 = difluoromethyl) (204.2 mg, 1 mmol) obtained in Example 38 and triethylamine (0.55 mL) in anhydrous dichloromethane (2 mL), and then slowly add o-chlorobenzoyl chloride dropwise under an ice bath. After reacting for 30 minutes under an ice bath, transfer it to room temperature and continue to react at room temperature for about 3 hours. Monitor by TLC until the thiocyanato-5-pyrazolamine (III) reacts completely. Extract with ethyl acetate (3 × 10 mL), combine the organic phases, wash with saturated brine, and finally dry with anhydrous magnesium sulfate, filter, and rotary evaporate the solvent under reduced pressure to obtain the crude product. Purify by silica gel column chromatography (petroleum ether / ethyl acetate = 3:1) to obtain the light yellow solid Compound I-37 (209.0 mg, yield 61%), m.p. = 141.6–144.0 °C; 1 1H NMR (400 MHz, DMSO-d6) δ 11.27 (s, 1H, CONH-H), 7.73 (d, J = 7.4 Hz, 1H, Ph-H), 7.65 (d, J = 7.8 Hz, 1H, Ph-H), 7.59 (m, 1H, Ph-H), 7.54 (t, J = 7.2 Hz, 1H, Ph-H), 7.14 (t, J = 53.0 Hz, 1H, CHF2), 3.86 (s, 3H, NCH3); 13 13C NMR (101 MHz, DMSO-d6) δ 165.8, 145.1 (t, J = 27.7 Hz), 140.9, 134.8, 132.1, 130.1, 130.0, 129.3, 127.5, 110.9 (t, J = 233.7 Hz), 110.9, 92.1, 37.4.

[0176] Example 40

[0177] Preparation of Compound I-38, and the chemical formula of Compound I-38 is as follows:

[0178]

[0179] The preparation method of Compound I-38 in this example is as follows: Using the method described in Example 39, replace o-chlorobenzoyl chloride with m-chlorobenzoyl chloride, and the other steps are the same as those in Example 39. The obtained Compound I-38 is a pale yellow solid (253.6 mg, yield 74%), m.p. = 150.7–151.6 °C; 1 H NMR(400MHz,DMSO-d6)δ11.05(s,1H,CONH-H),8.08(s,1H,Ph-H),7.98(d,J = 7.8Hz,1H,Ph-H),7.78(d,J = 8.1Hz,1H,Ph-H),7.65(t,J = 7.9Hz,1H,Ph-H),7.14(t,J = 53.0Hz,1H,CHF2),3.82(s,3H,NCH3); 13 C NMR(101MHz,DMSO-d6)δ164.8,145.0(t,J = 27.7Hz),141.3,134.3,133.6,132.7,130.9,127.9,127.0,111.0(t,J = 233.6Hz),110.8,92.5,37.3;HRMS(ESI)m / z[M+Na] + :calcd forC 13 H9ClF2N4NaOS,365.0046,found,365.0044.

[0180] Example 41

[0181] Preparation of Compound I-39, and the chemical formula of Compound I-39 is as follows:

[0182]

[0183] The preparation method of Compound I-39 in this example is as follows: Using the method described in Example 39, replace o-chlorobenzoyl chloride with p-chlorobenzoyl chloride, and the other steps are the same as those in Example 39. The obtained Compound I-39 is a pale yellow solid (267.3 mg, yield 78%), m.p. = 170.4–171.8 °C; 11H NMR (400 MHz, DMSO-d6) δ 11.00 (s, 1H, CONH-H), 8.05 (d, J = 8.3 Hz, 2H, Ph-H), 7.70 (d, J = 8.2 Hz, 2H, Ph-H), 7.14 (t, J = 53.0 Hz, 1H, CHF2), 3.81 (s, 3H, NCH3); 13 13C NMR (101 MHz, DMSO-d6) δ 165.0, 145.0 (t, J = 27.6 Hz), 141.4, 137.8, 131.0, 130.1 (2C), 128.9 (2C), 111.0 (t, J = 233.8 Hz), 110.8, 92.5, 37.3; HRMS (ESI) m / z [M+Na] + : calcd for C 13 H9ClF2N4NaOS, 365.0046, found, 365.0045.

[0184] Example 42

[0185] Preparation of Compound I-40, the chemical formula of Compound I-40 is as follows:

[0186]

[0187] The preparation method of Compound I-40 in this example is as follows: Using the method described in Example 39, replace o-chlorobenzoyl chloride with o-trifluoromethylbenzoyl chloride, and the other steps are the same as those in Example 39. The obtained Compound I-40 is a light yellow solid (312.3 mg, yield 83%), m.p. = 163.0–164.1 °C; 1 1H NMR (400 MHz, DMSO-d6) δ 11.37 (s, 1H, CONH-H), 7.94 (d, J = 7.9 Hz, 1H, Ph-H), 7.90 (d, J = 5.9 Hz, 2H, Ph-H), 7.81 (t, J = 6.7 Hz, 1H, Ph-H), 7.15 (t, J = 53.0 Hz, 1H, CHF2), 3.85 (s, 3H, NCH3); 13 13C NMR (101 MHz, DMSO-d6) δ 166.5, 145.2 (t, J = 27.6 Hz), 140.8, 133.9, 132.9, 131.2, 129.0, 126.7, 126.2 (q, J = 31.8 Hz), 123.6 (q, J = 273.8 Hz), 110.9 (t, J = 233.7 Hz), 110.8, 92.2, 37.3.

[0188] Example 43

[0189] Preparation of Compound I-41. The chemical formula of Compound I-41 is as follows:

[0190]

[0191] The specific preparation method of Compound I-41 in this example is as follows: Using the method described in Example 39, replace o-chlorobenzoyl chloride with m-trifluoromethylbenzoyl chloride, and the other steps are the same as those in Example 39. The obtained Compound I-41 is a light yellow solid (361.2 mg, yield 96%), m.p. = 185.4 - 186.1 °C; 1 H NMR (400 MHz, DMSO-d6) δ 11.18 (s, 1H, CONH-H), 8.37 (s, 1H, Ph-H), 8.33 (d, J = 7.9 Hz, 1H, Ph-H), 8.08 (d, J = 7.8 Hz, 1H, Ph-H), 7.87 (t, J = 7.8 Hz, 1H, Ph-H), 7.15 (t, J = 53.0 Hz, 1H, Ph-H), 3.84 (s, 3H, NCH3); 13 C NMR (101 MHz, DMSO-d6) δ 164.8, 145.0 (t, J = 27.7 Hz), 141.3, 133.3, 132.4, 130.2, 129.5 (q, J = 32.3 Hz), 129.4 (q, J = 3.0 Hz), 124.8 (q, J = 3.8 Hz), 123.9 (q, J = 272.4 Hz), 110.8, 111.0 (t, J = 233.7 Hz), 92.5, 37.3.

[0192] Example 44

[0193] Preparation of Compound I-42. The chemical formula of Compound I-42 is as follows:

[0194]

[0195] The specific preparation method of Compound I-42 in this example is as follows: Using the method described in Example 39, replace o-chlorobenzoyl chloride with p-trifluoromethylbenzoyl chloride, and the other steps are the same as those in Example 39. The obtained Compound I-42 is a light yellow solid (334.9 mg, yield 89%), m.p. = 184.0 - 185.1 °C; 1 H NMR (400 MHz, DMSO-d6) δ 11.18 (s, 1H, CONH-H), 8.23 (d, J = 8.1 Hz, 2H, Ph-H), 8.01 (d, J = 8.2 Hz, 2H, Ph-H), 7.15 (t, J = 53.0 Hz, 1H, CHF2), 3.83 (s, 3H, NCH3);13 C NMR(101MHz, DMSO-d6) δ 165.0, 145.0 (t, J=27.6Hz), 141.2, 136.1, 132.5 (q, J=32.0Hz), 129.1 (2C), 125.8 (2C), 123.8 (q, J=272.6Hz), 110.9 (t, J=233.7Hz), 110.7, 92.5, 37.3; HRMS(ESI) m / z [M+Na] + : calcd for C 14 H9F5N4NaOS, 399.0309, found, 399.0318.

[0196] Example 45

[0197] Preparation of Compound I-43, the chemical formula of Compound I-43 is as follows:

[0198]

[0199] In this example, the preparation method of Compound I-43 is as follows: Using the method described in Example 39, replace o-chlorobenzoyl chloride with o-trifluoromethoxybenzoyl chloride, and the other steps are the same as those in Example 39. The obtained Compound I-43 is a light yellow solid (251.1 mg, yield 64%), m.p. = 137.6–138.4 °C; 1 H NMR(400MHz, DMSO-d6) δ 11.24 (s, 1H, CONH-H), 7.86 (d, J=7.5Hz, 1H, Ph-H), 7.75 (t, J=7.8Hz, 1H, Ph-H), 7.61 (m, 2H, Ph-H), 7.15 (t, J=53.0Hz, 1H, CHF2), 3.83 (s, 3H, NCH3); 13 C NMR(101MHz, DMSO-d6) δ 164.2, 145.1 (t, J=27.7Hz), 145.0, 140.9, 133.1, 130.1, 128.9, 128.0, 122.1, 120.1 (q, J=257.5Hz), 110.9 (t, J=233.8Hz), 110.7, 92.2, 37.2.

[0200] Example 46

[0201] Preparation of Compound I-44, the chemical formula of Compound I-44 is as follows:

[0202]

[0203] The preparation method of compound I-44 in this example is as follows: Using the method described in Example 39, replace o-chlorobenzoyl chloride with m-trifluoromethoxybenzoyl chloride, and the other steps are the same as those in Example 39. The obtained compound I-44 is a light yellow solid (282.5 mg, yield 72%), m.p. = 150.6–151.6 °C; 1 H NMR (400 MHz, DMSO-d6) δ 11.10 (s, 1H, CONH-H), 8.09 (d, J = 7.4 Hz, 1H, Ph-H), 7.97 (s, 1H, Ph-H), 7.77 (t, J = 7.9 Hz, 1H, Ph-H), 7.73 (d, J = 8.3 Hz, 1H, Ph-H), 7.15 (t, J = 53.0 Hz, 1H, CHF2), 3.83 (s, 3H, NCH3); 13 C NMR (101 MHz, DMSO-d6) δ 164.6, 148.5, 145.0 (t, J = 27.6 Hz), 141.2, 134.5, 131.2, 127.3, 125.4, 120.1 (q, J = 257.3 Hz), 120.7, 110.9 (t, J = 233.7 Hz), 110.8, 92.6, 37.3; HRMS (ESI) m / z [M+Na] + : calcd for C 14 H9F5N4NaO2S, 415.0259, found, 415.0262.

[0204] Example 47

[0205] Preparation of compound I-45, the chemical formula of compound I-45 is as follows:

[0206]

[0207] The preparation method of compound I-45 in this example is as follows: Using the method described in Example 39, replace o-chlorobenzoyl chloride with p-trifluoromethoxybenzoyl chloride, and the other steps are the same as those in Example 39. The obtained compound I-45 is a light yellow solid (372.7 mg, yield 95%), m.p. = 135.8–136.9 °C; 1 H NMR (400 MHz, DMSO-d6) δ 11.05 (s, 1H, CONH-H), 8.17 (d, J = 8.5 Hz, 2H, Ph-H), 7.62 (d, J = 8.4 Hz, 2H, Ph-H), 7.14 (t, J = 53.0 Hz, 1H, CHF2), 3.82 (s, 3H, NCH3); 1313C NMR (101 MHz, DMSO-d6) δ 164.9, 151.4, 145.0 (t, J = 27.7 Hz), 141.4, 131.4, 130.7 (2C), 121.1 (2C), 120.0 (q, J = 257.6 Hz), 111.0 (t, J = 233.7 Hz), 110.8, 92.5, 37.3; HRMS (ESI) m / z [M+Na] + : calcd for C 14 H9F5N4NaO2S, 415.0259, found, 415.0264.

[0208] Example 48

[0209] Preparation of Compound I-46, the chemical formula of Compound I-46 is as follows:

[0210]

[0211] The specific preparation method of Compound I-46 in this example is as follows: Using the method described in Example 39, replace o-chlorobenzoyl chloride with 3,4-dichlorobenzoyl chloride, and the other steps are the same as those in Example 39. The obtained Compound I-46 is a light yellow solid (271.6 mg, yield 72%), m.p. = 182.6–184.2 °C; 1H NMR (400 MHz, DMSO-d6) δ 11.13 (s, 1H, CONH-H), 8.27 (d, J = 2.0 Hz, 1H, Ph-H), 7.99 (dd, J = 8.4, 2.0 Hz, 1H, Ph-H), 7.90 (d, J = 8.4 Hz, 1H, Ph-H), 7.14 (t, J = 53.0 Hz, 1H, CHF2), 3.82 (s, 3H, NCH3); 13 13C NMR (101 MHz, DMSO-d6) δ 164.0, 145.0 (t, J = 27.7 Hz), 141.2, 135.7, 132.6, 131.7, 131.2, 130.1, 128.4, 110.9 (t, J = 233.8 Hz) 110.7, 92.4, 37.3.

[0212] Example 49

[0213] Preparation of Compound I-47, the chemical formula of Compound I-47 is as follows:

[0214]

[0215] The preparation method of compound I-47 in this example is as follows: Using the method described in Example 39, replace o-chlorobenzoyl chloride with 3,5-dichlorobenzoyl chloride, and the other steps are the same as those in Example 39. The obtained compound I-47 is a pale yellow solid (256.5 mg, yield 68%), m.p. = 151.6–154.1 °C; H NMR (400 MHz, DMSO-d6) δ 11.17 (s, 1H, CONH-H), 8.03 (d, J = 1.8 Hz, 2H, Ph-H), 7.99 (t, J = 1.9 Hz, 1H, Ph-H), 7.14 (t, J = 53.0 Hz, 1H, CHF2), 3.83 (s, 3H, NCH3); 13 C NMR (101 MHz, DMSO-d6) δ 163.6, 145.0 (t, J = 27.7 Hz), 141.0, 135.6, 134.7 (2C), 132.1, 127.0 (2C), 110.9 (t, J = 233.8 Hz), 110.8, 92.4, 37.3.

[0216] Example 50

[0217] Preparation of compound I-48. The chemical formula of compound I-48 is as follows:

[0218]

[0219] The preparation method of compound I-48 in this example is as follows: Using the method described in Example 39, replace o-chlorobenzoyl chloride with 3-trifluoromethyl-4-chlorobenzoyl chloride, and the other steps are the same as those in Example 39. The obtained compound I-48 is a pale yellow solid (308.0 mg, yield 75%), m.p. = 137.1–139.9 °C; 1 H NMR (400 MHz, DMSO-d6) δ 11.25 (s, 1H, CONH-H), 8.46 (s, 1H, Ph-H), 8.31 (dd, J = 8.4, 1.6 Hz, 2H, Ph-H), 8.01 (d, J = 8.4 Hz, 1H, Ph-H), 7.14 (t, J = 53.0 Hz, 1H, CHF2), 3.83 (s, 3H, NCH3); 13 C NMR (101 MHz, DMSO-d6) δ 164.0, 145.0 (t, J = 27.7 Hz), 141.1, 135.2, 133.8, 132.4, 131.7, 127.5 (q, J = 5.2 Hz), 127.0 (d, J = 31.5 Hz), 122.6 (d, J = 273.3 Hz), 110.9 (t, J = 233.8 Hz), 110.7, 92.5, 37.3.

[0220] Example 51

[0221] Preparation of Compound I-49, the chemical formula of Compound I-49 is as follows:

[0222]

[0223] The preparation method of Compound I-49 in this example is as follows: Dissolve thiocyanato-5-pyrazolamine compound (R1 = methyl) (168.2 mg, 1 mmol) and triethylamine (0.55 mL) in anhydrous dichloromethane (2 mL), and then slowly add p-trifluoromethylbenzoyl chloride dropwise under an ice bath. After reacting for 30 minutes under the ice bath, transfer it to room temperature and continue to react at room temperature for about 3 hours. Monitor by TLC until the thiocyanato-5-pyrazolamine (III) reaction is complete. Extract with ethyl acetate (3 × 10 mL), combine the organic phases and wash with saturated brine, and finally dry with anhydrous magnesium sulfate, filter, and rotary evaporate the solvent under reduced pressure to obtain the crude product. Purify by silica gel column chromatography (petroleum ether / ethyl acetate = 2:1) to obtain the light yellow solid Compound I-49 (238.2 mg, yield 70%), m.p. = 187.0–189.6 °C; 1 H NMR (400 MHz, DMSO-d6) δ 10.98 (s, 1H, CONH-H), 8.22 (d, J = 8.1 Hz, 2H, Ph-H), 7.99 (d, J = 8.1 Hz, 2H, Ph-H), 3.70 (s, 3H, NCH3), 2.29 (s, 3H, CH3); 13 C NMR (101 MHz, DMSO-d6) δ 164.8, 149.1, 139.3, 136.3, 132.3 (q, J = 31.9 Hz), 130.1, 129.0 (2C), 125.8 (q, J = 3.6 Hz), 123.8 (q, J = 272.6 Hz), 111.2, 91.7, 36.4, 12.1.

[0224] Example 52

[0225] Preparation of Compound I-50, the chemical formula of Compound I-50 is as follows:

[0226]

[0227] The preparation method of Compound I-50 in this example is as follows: Adopt the method described in Example 51, replace p-trifluoromethylbenzoyl chloride with 3,5-dichlorobenzoyl chloride, and the other steps are the same as those in Example 51. The obtained Compound I-50 is a light yellow solid (242.3 mg, yield 71%), m.p. = 212.4–214.8 °C; 11H NMR (400 MHz, DMSO-d6) δ 10.95 (s, 1H, CONH-H), 8.02 (s, 2H, Ph-H), 7.97 (s, 1H, Ph-H), 3.69 (s, 3H, NCH3), 2.28 (s, 3H, CH3); 13 13C NMR (101 MHz, DMSO-d6) δ 163.4, 149.1, 139.0, 135.7, 134.6 (2C), 132.0, 126.9 (2C), 111.2, 91.6, 36.5, 12.1.

[0228] Example 53

[0229] Preparation of Compound I-51. The chemical formula of Compound I-51 is as follows:

[0230]

[0231] The preparation method of Compound I-51 in this example is as follows: Using the method described in Example 51, replace p-trifluoromethylbenzoyl chloride with 3-trifluoromethyl-4-chlorobenzoyl chloride, and the other steps are the same as those in Example 51. The obtained Compound I-51 is a light yellow solid (236.1 mg, yield 63%), m.p. = 188.8–191.1 °C; 1 1H NMR (400 MHz, DMSO-d6) δ 11.04 (s, 1H, CONH-H), 8.44 (s, 1H, Ph-H), 8.30 (d, J = 8.3 Hz, 1H, Ph-H), 7.99 (d, J = 8.4 Hz, 1H, Ph-H), 3.70 (s, 3H, NCH3), 2.28 (s, 3H, CH3); 13 13C NMR (101 MHz, DMSO-d6) δ 163.7, 149.1, 139.1, 135.0, 133.7, 132.3, 131.8, 127.4 (q, J = 5.3 Hz), 127.0 (q, J = 31.3 Hz), 122.6 (q, J = 273.3 Hz), 111.2, 91.6, 36.4, 12.1.

[0232] Example 54

[0233] Inhibitory effects of the thiocyanatopyrazole-structured benzamide derivatives (Compound Nos. I-1 to I-51) synthesized in Examples 1–53 against the tested phytopathogenic fungi and oomycetes.

[0234] 1. Experimental subjects

[0235] The thiocyanatopyrazole-structured benzamide derivatives synthesized in Examples I-1 to I-51

[0236] 2. Experimental methods

[0237] The in vitro inhibitory activities of compounds 1–51 against the tested plant pathogenic fungi and oomycetes were determined at a concentration of 20 mg / L using the mycelial linear growth rate method. The selected fungi and oomycetes were provided by the Institute of Pesticide Science, Northwest A&F University.

[0238] Using the fluxapyroxad solution at 20 mg / L as the positive control and 5% DMSO aqueous solution as the blank control, the accurately weighed test compound was completely dissolved in 5% DMSO (v / v) aqueous solution. 10 mL of the test solution or control solution was quickly mixed with 90 mL of sterile PDA medium at 50 °C to obtain a medicated solution with a mass concentration of 20 mg / L. It was then poured into a sterilized petri dish while it was still hot, 10 mL per dish, and cooled for later use. The tested plant pathogenic fungi (mycelial disc with a diameter of 5 mm) were inoculated into the above petri dishes, and three replicates were set for each test group. After culturing in a constant temperature incubator at 25 °C for 72 h, the colony diameter (mm) was measured using the cross method, and the mycelial growth inhibition rate (IR) was calculated according to formula (1): IR (%) = [(d c -d0)-(ds-d0)] / (d c -d0)×100 (1);

[0239] In the formula: d0 is the diameter of the mycelial disc (5 mm), d c is the average colony diameter (mm) of the blank control group, and ds is the average colony diameter (mm) of the sample group.

[0240] 3. The experimental results are shown in Table 1

[0241] Table 1 In vitro antibacterial activities of benzamide derivatives containing thiocyanopyrazole structures synthesized in Examples 1–53 a (Inhibition rate, %) (20 mg / L)

[0242]

[0243]

[0244] a The data in the table are the average values of three data; V.m. b V.mali; B.c. c B cinerea; R.s d R.solani; S.s e S.sclerotiorum; G.g f G.graminis; p.c g .P.capsica

[0245] As can be seen from Table 1, most of the compounds have inhibitory effects on 6 kinds of pathogenic bacteria. Among them, compounds I-26 and I-27 have the most excellent activity against Sclerotinia sclerotiorum of rapeseed, with an inhibition rate of 100%; compounds I-7 and I-10 have the most excellent activity against Valsa mali of apple, with an inhibition rate as high as 100%; compound I-48 has the most excellent activity against Gaeumannomyces graminis of wheat, with an inhibition rate of 85.14%; compound I-26 has the most excellent activity against Rhizoctonia solani of rice, with an inhibition rate reaching 90.01%; compounds I-42 and I-49 have the most excellent activity against Phytophthora capsici of pepper, with an inhibition rate of 100%; compound I-7 has the best activity against Botrytis cinerea of grape, with an inhibition rate of 95.65%.

[0246] In summary, the 51 kinds of thiocyanatopyrazolecarboxamide compounds prepared by chemical synthesis in this application all have significant antifungal and anti-oomycete activities, especially showing outstanding inhibitory activities against Valsa mali and Phytophthora capsici of pepper, which provides a basis for the development of novel fungicides with benzamide derivatives containing thiocyanatopyrazole structure as the active ingredient.

[0247] What is described in the above specification is only the specific implementation manners of the present invention. Various examples do not constitute a limitation to the essence of the present invention. Those of ordinary skill in the technical field can make modifications or variations to the previously described specific implementation manners after reading the specification without departing from the essence and scope of the invention.

Claims

1. A benzamide derivative containing a thiocyanatopyrazole structure, characterized in that: The benzamide derivatives containing a thiocyanatopyrazole structure are selected from the following compounds:

2. Use of a benzamide derivative containing a thiocyanatopyrazole structure as described in claim 1, characterized in that: The benzamide derivatives containing a thiocyanatopyrazole structure are used as agricultural fungicides.

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