Pyrazoles containing n1-heterocycles, processes for their preparation and uses thereof

Abstract

The application discloses a pyrazole compound containing N1-heterocycle, and a structural formula of the compound is shown as formula (I). The pyrazole compound containing N1-heterocycle of formula (I) has a novel molecular structure, and the chemical structural formula has distinct characteristics. In the structural formula, the N1-heterocycle can be thiazole, oxazole or thiophene, Ar can be a benzene ring or a pyridine ring, and generally, the compound can be an amide or a hydrazide. The preparation method of the compound is simple, raw materials are easy to obtain, reaction conditions are easy to control, and the yield is high. The compound has obvious activity of inhibiting or killing agricultural harmful fungi and the effect of preventing and treating fungal diseases of crops, and has the use as a pesticide fungicide.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of pesticides, and particularly relates to a pyrazole compound containing N1-heterocycle and a preparation method and application thereof. BACKGROUND

[0002] Agriculture has many problems in the development process, such as plant disease problems, especially a large number of fungal diseases, fast development, and difficult prevention and treatment.

[0003] Succinate dehydrogenase inhibitors are a kind of fungicides developed early, and have a long application time and a wide range of fungal control, such as thifluzamide, boscalid, fluxapyroxad, and the like. Although the succinate dehydrogenase inhibitors have good fungicidal activity and play a great role in the prevention and treatment of agricultural fungal diseases, the succinate dehydrogenase inhibitors have the following shortcomings: a single type, only the same type of compounds; a complicated preparation method, raw materials are not easy to obtain, and reaction conditions are relatively complex, and a low yield; and an unobvious effect of inhibiting or killing harmful fungi with long-term and large-scale use. SUMMARY

[0004] The present application aims to provide a pyrazole compound containing N1-heterocycle and a preparation method and application thereof to solve the problems in the background.

[0005] In order to achieve the above-mentioned purpose, the present application provides the following technical scheme: a pyrazole compound containing N1-heterocycle and a preparation method and application thereof, the structure of the compound is shown in formula (I),

[0006]

[0007] wherein, R 1 is selected from one of H, CH3, C2H5, n-C3H 7、 i-C3H7, c-C3H5, CF3, CHF2, t-buty (tert-butyl); R 2 is selected from one of H, Cl, Br; R 3 is selected from one of H, OCH3, c-C3H5; Het is selected from one of thiazole, oxazole, thiophene; X is selected from one of NH, CH2, CH2CH2; Ar is selected from a benzene ring, a pyridine ring; Y (n) is selected from H, 2-Cl, 3-Cl, 4-Cl, 2-F, 3-F, 4-F, 2-Br, 3-Br, 4-CH3, 4-CF3, 4-OCH3, 4-OCF3, 4-NO2, 4-CN, 2,4-Cl2, 2,4-F2, 2-CH3-5F, 2,3,4,5,6-F5.

[0008] Preferably, R 1 one of CH3, C2H5, i-C3H7, c-C3H5, CF3, CHF2;

[0009] Preferably, R 2 is H; R 3 is H; Het is thiazole; X is one of NH, CH2; Ar is selected from benzene ring, pyridine ring;

[0010] Preferably, Y(n) is selected from H, 2-Cl, 3-Cl, 4-Cl, 2-F, 3-F, 4-F, 4-Br, 4-CH3, 2,4-Cl2, 2,4-F2, 2-CH3-5F.

[0011] Preferably, the compound of general formula (I) is obtained from N1-heterocycle-containing pyrazole carboxylic acid of general formula (II) and intermediate of general formula (III) through the following two paths A and B:

[0012]

[0013] R 2 , R 3 , X, Ar, Y(n) are defined as above.

[0014] Preferably, the appropriate solvent used for the reaction can be selected from dichloromethane, dichloroethane, tetrahydrofuran, acetonitrile, etc.

[0015] The appropriate base can be selected from triethylamine, N,N-diisopropyl ethylamine, pyridine, sodium hydroxide, lithium hydroxide, sodium carbonate, potassium carbonate, etc.

[0016] Preferably, the temperature condition of the reaction is -10℃ to the boiling point of the solvent; the time condition of the reaction is 1-8 hours.

[0017] Preferably, the condensing agent used in synthesis path B can be TBTU, HOBT, EDCI, DMAP, PyBOP.

[0018] Preferably, the N1-heterocycle-containing pyrazole compound is used for inhibiting or killing harmful fungi in agricultural prevention and control operations.

[0019] Preferably, the agricultural fungal diseases include but are not limited to wheat scab, tomato gray mold, rice sheath blight, tomato early blight, rice blast.

[0020] The beneficial effects of the present application are as follows: the present application applies the active substructure splicing method, introduces thiazole, oxazole, thiophene and other five-membered heterocycles into the 1-position of the pyrazole ring to construct a pyrazole carboxylic acid containing N1 heterocycle as a new carboxylic acid fragment on the basis of retaining the core fragment pyrazole-4-carboxamide; then an amine, hydrazine fragment is introduced into the molecular structure to form a new pyrazole amide, hydrazide derivative containing N1 heterocycle; the derivative has obvious fungicidal (inhibitory) activity, especially the rice sheath blight fungus, tomato gray mold fungus, rice blast fungus and the like have more obvious inhibitory activity; the pyrazole compound containing N1 heterocycle of formula (I) described in the present application has a novel molecular structure, and the chemical structural formula has distinct characteristics; the N1 heterocycle in the structural formula can be thiazole, oxazole, thiophene and the like, Ar can be a benzene ring, a pyridine ring and the like, and overall the compound can be an amide or a hydrazide; the preparation method of the compound is simple, the raw materials are easy to obtain, the reaction conditions are easy to control, and the yield is high; the compound has obvious inhibitory or fungicidal activity on agricultural harmful fungi and the effect of preventing and treating fungal diseases of crops, and has the use as a fungicide. DETAILED DESCRIPTION

[0021] The technical solutions in the embodiments of the present application will be clearly and completely described below in combination with the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of protection of the present application.

[0022] The present application provides a pyrazole compound containing N1-heterocycle and a preparation method and application thereof, and the structural formula of the compound is shown as formula (I),

[0023]

[0024] In formula (I), each group has the following particularly preferred definitions: in the structural formula of compounds Ib1-Ib19, Ia1-Ia44, Het is Ar is

[0025]

[0026]

[0027]

[0028] In implementation 1, the preparation of N-phenyl-3-methyl-1-(thiazol-2-yl)-1-hydrogen-pyrazole-4-carboxamide (Ib1), the compound (Ib1) is prepared by the method shown below:

[0029]

[0030] Place (0.003 mol, 0.63 g) 3-methyl-l-(thiazol-2-yl)-l-hydro-pyrazole-4- carboxylic acid in 100 mL round bottom flask, add 15 mL of thionyl chloride, stir and reflux for 2-4 hours after adding a magnetic bar, evaporate excess thionyl chloride under reduced pressure. Add 20 mL of dichloromethane to the round bottom flask containing 3-methyl-l-(thiazol-2-yl)-l-hydro-pyrazole-4-carboxylic acid chloride, place in ice-salt bath and stir to cool to -10 to 0 °C after adding a magnetic bar, add aniline (0.003 mol, 0.28 g), slowly add triethylamine (0.0045 mol, 0.45 g) and stir the reaction for 0.5-1 hour, allow to warm to room temperature and continue stirring for 4-6 hours. Monitor the completion of the reaction by TLC, place the reaction mixture in 100 mL separating funnel, add 20 mL of dichloromethane, wash with water 3 times (3*30 mL), wash with saturated brine 2 times (2*30 mL), dry over anhydrous sodium sulfate, concentrate, column chromatography to get the product 0.69 g, yield 81.1%.

[0031] Example 2: Preparation of N-phenyl-3-methyl-l-(thiazol-2-yl)-l-hydro-pyrazole-4- carboxamide (Ib1), compound (Ib1) is prepared by the method shown below:

[0032]

[0033] Place (0.003 mol, 0.63 g) 3-methyl-l-(thiazol-2-yl)-l-hydro-pyrazole-4- carboxylic acid in 100 mL round bottom flask, add 20 mL of dichloromethane, O- benzotriazolyl-N,N,N',N'-tetramethyluronium tetrafluoroborate (TBTU) (0.0045 mol, 1.44 g), triethylamine (0.006 mol, 0.60 g), stir for 15-30 minutes at room temperature, add aniline (0.003 mol, 0.28 g) and continue stirring for 4-10 hours. Monitor the completion of the reaction by TLC, if there is solid, directly suction filter to get the product, then place the reaction mixture in 100 mL separating funnel, add 20 mL of dichloromethane, wash with water 3 times (3*30 mL), wash with saturated brine 2 times (2*30 mL), dry over anhydrous sodium sulfate, concentrate, column chromatography to get the product 0.62 g, yield 72.9%.

[0034] Example 3: Preparation of N'-phenyl-3-methyl-l-(thiazol-2-yl)-l-hydro-pyrazole-4- carbohydrazide (Ia1), compound (Ia1) is prepared by the method shown below in formula (A5):

[0035]

[0036] 0.003 mol (0.63 g) of 3-methyl-1-(thiazol-2-yl)-1-hydro-pyrazole-4-carboxylic acid was placed in a 100 mL round-bottom flask, and 15 mL of thionyl chloride was added. After adding a rotor, the mixture was stirred and refluxed for 2–4 hours. Excess thionyl chloride was evaporated under reduced pressure. 20 mL of dichloromethane and a rotor were added to a round-bottom flask containing 3-methyl-1-(thiazol-2-yl)-1-hydro-pyrazole-4-carboxylic acid. The flask was then placed in an ice-salt bath and stirred until cooled to -10–0 °C. Phenyhydrazine (0.003 mol, 0.32 g) was added, followed by slow dropwise addition of triethylamine (0.0045 mol, 0.45 g). The mixture was stirred and reacted for 0.5–1 hour. The mixture was then allowed to warm naturally to room temperature and stirred for another 4–6 hours. After the reaction was completed by TLC monitoring, the reaction mixture was placed in a 100 mL separatory funnel, 20 mL of dichloromethane was added, and the mixture was washed three times with water (3 x 30 mL), washed twice with saturated saline (2 x 30 mL), dried over anhydrous sodium sulfate, concentrated, and subjected to column chromatography to obtain 0.86 g of product, with a yield of 95.5%.

[0037] Example 4: Preparation of N'-phenyl-3-methyl-1-(thiazolyl-2-yl)-1-hydropyrazole-4-carboxylhydrazide (Ia1), compound (Ia1) was prepared by the method represented by the following formula (A5):

[0038]

[0039] 0.003 mol (0.63 g) of 3-methyl-1-(thiazol-2-yl)-1-hydropyrazole-4-carboxylic acid was placed in a 100 mL round-bottom flask, and 20 mL of dichloromethane, O-benzotriazole-N,N,N',N'-tetramethylurea tetrafluoroborate (TBTU) (0.0045 mol, 1.44 g), and triethylamine (0.006 mol, 0.60 g) were added. After stirring at room temperature for 15–30 minutes, phenylhydrazine (0.003 mol, 0.32 g) was added, and the reaction was continued with stirring for 4–10 hours. After the reaction was completed by TLC monitoring, if there was any solid, it was directly filtered to obtain the product. Then, the reaction mixture was placed in a 100 mL separatory funnel, 20 mL of dichloromethane was added, and the mixture was washed three times with water (3 x 30 mL), washed twice with saturated saline (2 x 30 mL), dried over anhydrous sodium sulfate, concentrated, and subjected to column chromatography. The solids obtained by filtration were combined to obtain a total of 0.76 g of product, with a yield of 84.4%.

[0040] Using the methods described in Examples 1-4 above, pyrazole compounds Ib1-Ib19, Ia1-Ia45 containing the N1 heterocycle of formula (I) were prepared:

[0041] The structural formula and NMR data of the compound are as follows:

[0042]

[0043] phenyl-3-methyl-1-(thiazol-2-yl)-1H-pyrazole-4-carboxamide (Ib1): white solid, yield 81.1%; 1 H NMR (400 MHz, DMSO-d6) δ: 10.01 (s, 1H), 9.28 (s, 1H), 7.77 - 7.65 (m, 3H), 7.61 (d, J = 3.4 Hz, 1H), 7.35 (t, J = 7.8 Hz, 2H), 7.09 (t, J = 7.3 Hz, 1H), 2.49 (s, 3H). 13 C NMR (101 MHz, DMSO-d6) δ: 161.00, 160.69, 153.55, 140.87, 139.52, 129.11, 123.90, 120.36, 118.51, 118.25, 13.88.

[0044]

[0045] N-(o-tolyl)-3-methyl-1-(thiazol-2-yl)-1H-pyrazole-4-carboxamide (Ib2): white solid, yield 65.5%; 1 H NMR (400 MHz, DMSO-d6) δ: 9.63 (s, 1H), 9.21 (s, 1H), 7.69 (t, J = 4.8 Hz, 1H), 7.60 (d, J = 3.4 Hz, 1H), 7.34 (t, J = 6.7 Hz, 1H), 7.27 (d, J = 7.2 Hz, 1H), 7.18 (dt, J = 22.0, 6.8 Hz, 2H), 2.47 (s, 3H), 2.25 (s, 3H). 13 C NMR (101 MHz, DMSO-d6) δ: 161.02, 160.70, 153.40, 140.88, 136.37, 133.82, 130.80, 129.09, 126.90, 126.42, 126.31, 118.51, 118.13, 18.39, 13.82.

[0046]

[0047] N-(m-tolyl)-3-methyl-1-(thiazol-2-yl)-1H-pyrazole-4-carboxamide (Ib3): white solid, yield 87.6%;1 H NMR (400 MHz, DMSO-d6) δ: 9.92 (s, 1H), 9.28 (s, 1H), 7.71 (d, J = 3.4 Hz, 1H), 7.63 - 7.57 (m, 2H), 7.52 (d, J = 8.1 Hz, 1H), 7.22 (t, J = 7.8 Hz, 1H), 6.91 (d, J = 7.4 Hz, 1H), 2.48 (s, 3H), 2.31 (s, 3H). 13 C NMR (101 MHz, DMSO-d6) δ: 160.94, 160.70, 153.55, 140.87, 139.46, 138.26, 129.06, 128.94, 124.57, 120.87, 118.49, 118.27, 117.49, 21.67, 13.89.

[0048]

[0049] N-(p-tolyl)-3-methyl-1-(thiazol-2-yl)-1H-pyrazole-4-carboxamide (Ib4): white solid, yield 80.9%; 1 H NMR (400 MHz, DMSO-d6) δ: 9.95 (s, 1H), 9.26 (s, 1H), 7.71 (d, J = 3.5 Hz, 1H), 7.61 (dd, J = 9.9, 2.6 Hz, 3H), 7.15 (d, J = 8.3 Hz, 2H), 2.49 (s, 3H), 2.28 (s, 3H). 13 C NMR (101 MHz, DMSO-d6) δ: 160.82, 160.70, 153.51, 140.89, 136.97, 132.83, 129.51, 128.99, 120.36, 118.51, 118.31, 20.94, 13.89.

[0050]

[0051] N-(3-fluorophenyl)-3-methyl-1-(thiazol-2-yl)-1H-pyrazole-4-carboxamide (Ib6): white solid, yield 79.1%; 1H NMR (400 MHz, DMSO-d6) δ: 10.18 (d, J = 8.6 Hz, 1H), 9.29 (s, 1H), 7.73 (dd, J = 13.2, 2.9 Hz, 2H), 7.62 (d, J = 3.4 Hz, 1H), 7.54 - 7.44 (m, 1H), 7.38 (dd, J = 15.2, 8.1 Hz, 1H), 6.92 (td, J = 8.5, 2.5 Hz, 1H), 2.49 (s, 3H). 13 C NMR (101 MHz, DMSO-d6) δ: 163.74, 161.35, 161.20, 160.61, 153.62, 141.30 (d, J = 11.0 Hz), 140.87, 130.70 (d, J = 9.5 Hz), 129.21, 118.57, 117.88, 115.88 (d, J = 2.4 Hz), 110.27 (d, J = 21.1 Hz), 106.96 (d, J = 26.5 Hz), 13.89.

[0052]

[0053] N-(4-fluorophenyl)-3-methyl-1-(thiazol-2-yl)-1H-pyrazole-4-carboxamide (Ib7): white solid, yield 76.9%; 1 H NMR (400 MHz, DMSO-d6) δ: 10.07 (s, 1H), 9.25 (s, 1H), 7.75 (dd, J = 7.5, 5.3 Hz, 2H), 7.71 (d, J = 3.3 Hz, 1H), 7.62 - 7.55 (m, 1H), 7.19 (t, J = 8.3 Hz, 2H), 2.49 (s, 3H). 19 F NMR (377 MHz, DMSO-d6) δ: -119.17. 13 C NMR (101 MHz, DMSO-d6) δ: 160.92, 160.66, 159.81, 157.42, 153.52, 140.88, 135.85 (d, J = 2.3 Hz), 129.09, 122.13 (d, J = 7.7 Hz), 118.55, 118.10, 115.80, 115.58, 13.85.

[0054]

[0055] N-(3-chlorophenyl)-3-methyl-1-(thiazol-2-yl)-1H-pyrazole-4-carboxamide (Ib8): white solid, yield 55.2%; 1 H NMR (400 MHz, DMSO-d6) δ: 10.16 (d, J = 11.5 Hz, 1H), 9.29 (s, 1H), 7.94 (t, J = 5.6 Hz, 1H), 7.74 (dd, J = 13.7, 3.4 Hz, 1H), 7.64 (dd, J = 17.0, 5.5 Hz, 2H), 7.38 (t, J = 8.1 Hz, 1H), 7.15 (dd, J = 8.0, 1.2 Hz, 1H), 2.49 (s, 3H). 13 C NMR (101 MHz, DMSO-d6) δ: 161.20, 160.60, 153.63, 141.01, 140.90, 133.46, 130.84, 129.25, 123.54, 119.65, 118.64, 118.51, 117.85, 13.90.

[0056]

[0057] N-(2,4-difluorophenyl)-3-methyl-1-(thiazol-2-yl)-1H-pyrazole-4-carboxamide (Ib9): white solid, yield 36.4%; 1 H NMR (400 MHz, DMSO-d6) δ: 9.95 (s, 1H), 9.25 (s, 1H), 7.71 (d, J = 3.4 Hz, 1H), 7.65 - 7.57 (m, 2H), 7.42 - 7.28 (m, 1H), 7.12 (t, J = 8.6 Hz, 1H), 2.46 (s, 3H). 19 F NMR (377 MHz, DMSO-d6) δ: -113.51 (d, J = 5.7 Hz), -116.65 (d, J = 5.8 Hz). 13C NMR (101 MHz, DMSO-d6) d: 161.15, 160.59, 153.52, 140.95, 129.42, 128.54 (d, J = 9.8 Hz), 122.34, 118.64, 117.36, 111.79, 111.76, 111.68 (d, J = 22.0 Hz) 111.58, 111.54, 105.09, 104.84, 104.82, 104.58, 13.84.

[0058]

[0059] N-(5-fluoro-2-methylphenyl)-3-methyl-1-(thiazol-2-yl)-1H-pyrazole-4-carboxamide (Ib10): white solid, yield 44.7%; 1 H NMR (400 MHz, CDC13) δ: 8.68 (s, 1H), 7.88 (dt, J = 14.8, 7.4 Hz, 1H), 7.57 (d, J = 3.5 Hz, 1H), 7.41 - 7.31 (m, 1H), 7.19 - 7.08 (m, 2H), 6.80 (td, J = 8.2, 2.7 Hz, 1H), 2.62 (s, 3H), 2.29 (s, 3H). 19 F NMR (377 MHz, DMSO-d6) δ: -117.02. 13 C NMR (101 MHz, DMSO-d6) d: 161.72, 161.07, 160.64, 159.33, 153.45, 140.90, 137.62 (d, J = 10.4 Hz), 131.90 (d, J = 9.0 Hz), 129.00 (d, J = 3.2 Hz), 128.99, 118.60, 117.89, 112.80 (dd, J = 43.1, 22.2 Hz), 17.65, 13.82.

[0060]

[0061] N-phenyl-1-(thiazol-2-yl)-3-ethyl-1H-pyrazole-4-carboxamide (Ib11): white solid, yield 44.1%; 1H NMR (400 MHz, CDC13) δ: 8.65 (s, 1H), 7.66 (s, 1H), 7.57 (d, J = 8.0 Hz, 2H), 7.54 (d, J = 3.4 Hz, 1H), 7.34 (t, J = 7.7 Hz, 2H), 7.17 - 7.07 (m, 2H), 3.01 (q, J = 7.5 Hz, 2H), 1.35 (t, J = 7.5 Hz, 3H). 13 C NMR (101 MHz, CDC13) δ: 160.83, 158.30, 140.25, 137.67, 129.10, 127.25, 124.57, 120.20, 118.04, 116.53, 21.18, 13.05.

[0062]

[0063] 3-ethyl-1-(thiazol-2-yl)-N-(o-tolyl)-1H-pyrazole-4-carboxamide (Ib12): white solid, yield 48.7%; 1 H NMR (400 MHz, CDC13) δ: 8.64 (s, 1H), 7.88 (d, J = 7.9 Hz, 1H), 7.55 (d, J = 3.5 Hz, 1H), 7.34 (s, 1H), 7.23 (dd, J = 7.6, 3.7 Hz, 2H), 7.16 - 7.08 (m, 2H), 3.03 (q, J = 7.5 Hz, 2H), 2.32 (s, 3H), 1.37 (t, J = 7.5 Hz, 3H). 13 C NMR (101 MHz, CDC13) δ: 160.92, 160.80, 158.10, 140.27, 135.47, 130.62, 129.18, 127.35, 126.91, 125.46, 123.36, 118.14, 116.56, 21.27, 17.89, 13.11.

[0064]

[0065] N-(m-tolyl)-3-ethyl-1-(thiazol-2-yl)-1H-pyrazole-4-carboxamide (Ib13): white solid, yield 52.5%; 1H NMR (400 MHz, DMSO-d6) δ: 9.95 (s, 1H), 9.28 (s, 1H), 7.70 (t, J = 8.6 Hz, 1H), 7.61 (d, J = 3.3 Hz, 2H), 7.51 (t, J = 11.1 Hz, 1H), 7.22 (t, J = 7.8 Hz, 1H), 6.91 (d, J = 7.5 Hz, 1H), 2.95 (q, J = 7.5 Hz, 2H), 2.31 (s, 3H), 1.25 (t, J = 7.5 Hz, 3H). 13 C NMR (101 MHz, DMSO-d6) δ: 160.85, 160.75, 158.68, 140.89, 139.46, 138.26, 129.26, 128.95, 124.57, 120.85, 118.50, 117.67, 117.48, 21.68, 21.11, 13.50.

[0066]

[0067] N-(2-fluorophenyl)-3-ethyl-1-(thiazol-2-yl)-1H-pyrazole-4-carboxamide (Ib14): white solid, yield 48.1 %; 1 H NMR (400 MHz, DMSO-d6) δ: 9.90 (s, 1H), 9.28 (s, 1H), 7.70 (dd, J = 9.4, 3.1 Hz, 1H), 7.64 - 7.50 (m, 3H), 7.41 - 7.34 (m, 1H), 7.32 - 7.22 (m, 1H), 2.93 (q, J = 7.5 Hz, 2H), 1.24 (t, J = 7.5 Hz, 3H). 13 C NMR (101 MHz, DMSO-d6) δ: 161.04, 160.67, 158.65, 140.93, 135.02, 130.05, 129.57, 129.51, 128.92, 127.87, 127.79, 118.60, 117.02, 21.09, 13.45. 19 F NMR (377 MHz, DMSO-d6) δ: -117.02.

[0068]

[0069] N-(3-fluorophenyl)-3-ethyl-1-(thiazol-2-yl)-1H-pyrazole-4-carboxamide (Ib15): white solid, yield 51.2%; 1 H NMR (400 MHz, CDC13) δ: 8.66 (s, 1H), 7.68 (s, 1H), 7.60 - 7.53 (m, 2H), 7.33 - 7.25 (m, 1H), 7.20 (d, J = 8.2 Hz, 1H), 7.15 (d, J = 3.4 Hz, 1H), 6.83 (td, J = 8.3, 2.4 Hz, 1H), 3.01 (q, J = 7.5 Hz, 2H), 1.35 (t, J = 7.5 Hz, 3H). 19 F NMR (377 MHz, CDC13) δ: -111.16. 13 C NMR (101 MHz, CDC13) δ: 164.26, 161.82, (160.77, 158.39,), 140.25, 139.20 (d, J = 10.9 Hz), 130.18 (d, J = 9.4 Hz), 127.23, 117.70, 116.67, 115.21 (d, J = 2.9 Hz), 111.36, 111.15, 107.73, 107.46, 21.19, 13.02.

[0070]

[0071] N-(3-chlorophenyl)-3-ethyl-1-(thiazol-2-yl)-1H-pyrazole-4-carboxamide (Ib16): white solid, yield 45.4%; 1 H NMR (400 MHz, CDC13) δ: 8.67 (s, 1H), 7.72 (d, J = 9.1 Hz, 2 H), 7.54 (d, J = 3.0 Hz, 1H), 7.39 (d, J = 7.9 Hz, 1H), 7.25 (dd, J = 10.3, 5.1 Hz, 1H), 7.12 (dd, J = 16.5, 5.4 Hz, 2H), 3.01 (dd, J = 14.9, 7.4 Hz, 2H), 1.35 (t, J = 7.4 Hz, 3H). 13C NMR (101 MHz, CDC13) δ: 160.82, 158.39, 140.24, 138.82, 134.79, 130.03, 127.31, 124.65, 120.24, 118.03, 117.64, 116.67, 21.19, 13.00.

[0072]

[0073] N-(4-chlorophenyl)-3-ethyl-1-(thiazol-2-yl)-1H-pyrazole-4-carboxamide (Ib17): white solid, yield 56.1 %; 1 H NMR (400 MHz, DMSO-d6) δ: 10.15 (s, 1H), 9.27 (s, 1H), 7.76 (t, J = 11.4 Hz, 2H), 7.71 (d, J = 3.0 Hz, 1H), 7.61 (d, J = 3.0 Hz, 1H), 7.40 (d, J = 8.5 Hz, 2H), 2.94 (q, J = 7.4 Hz, 2H), 1.24 (t, J = 7.4 Hz, 3H). 13 C NMR (101 MHz, DMSO-d6) δ: 160.97, 160.69, 158.70, 140.90, 138.50, 129.39, 129.04, 127.45, 121.81, 118.59, 117.39, 21.11, 13.44.

[0074]

[0075] N-(2,4-dichlorophenyl)-3-ethyl-1-(thiazol-2-yl)-1H-pyrazole-4-carboxamide (Ib18): white solid, yield 41.5 %; 1 H NMR (400 MHz, CDC13) δ: 8.71 (s, 1H), 8.45 (t, J = 6.7 Hz, 1H), 8.00 (s, 1H), 7.56 (t, J = 5.7 Hz, 1H), 7.41 (d, J = 2.3 Hz, 1H), 7.27 (dd, J = 8.8, 2.3 Hz, 1H), 7.16 (d, J = 3.4 Hz, 1H), 3.04 (q, J = 7.5 Hz, 2H), 1.38 (t, J = 7.5 Hz, 3H). 13C NMR (101 MHz, CDC13) δ: 160.66, 160.36, 157.82, 140.33, 133.32, 129.20, 128.74, 127.97, 127.82, 123.25, 122.32, 117.70, 116.78, 21.34, 13.00.

[0076]

[0077] N-phenyl-1-(thiazol-2-yl)-3-(trifluoromethyl)-1H-pyrazole-4-carboxamide (Ib19): white solid, yield 70.1 %; 1 H NMR (400 MHz, DMSO-d6) δ: 10.37 (s, 1H), 9.50 (s, 1H), 7.80 (d, J = 13.6 Hz, 2H), 7.73 (d, J = 7.7 Hz, 2H), 7.38 (t, J = 7.3 Hz, 2H), 7.13 (t, J = 6.9 Hz, 1H). 19 F NMR (377 MHz, DMSO-d6) δ: -60.64. 13 C NMR (101 MHz, DMSO-d6) δ: 159.61, 157.98, 142.91 (d, J = 38.4 Hz), 141.20, 139.05, 131.38, 129.25, 124.43, 120.56, 120.40, 119.07.

[0078]

[0079] N'-phenyl-3-methyl-1-(thiazol-2-yl)-1H-pyrazole-4-carbohydrazide (Ia1): white solid, yield 95.5 %; 1 H NMR (400 MHz, DMSO-d6) δ: 10.22 (d, J = 2.4 Hz, 1H), 9.18 (s, 1H), 7.88 (d, J = 2.6 Hz, 1H), 7.70 (d, J = 3.5 Hz, 1H), 7.61 (d, J = 3.5 Hz, 1H), 7.16 (t, J = 7.9 Hz, 2H), 6.80 (d, J = 7.7 Hz, 2H), 6.72 (t, J = 7.3 Hz, 1H), 2.44 (s, 3H). 13F NMR (376 MHz, DMSO-d6) d: -126.46, -148.31.

[0080]

[0081] N'-(4-chlorophenyl)-3-methyl-1-(thiazol-2-yl)-1H-pyrazole-4-carbohydrazide (Ia3): white solid, yield 79.1 %; 1 H NMR (400 MHz, DMSO-d6) d: 10.26 (s, 1H), 9.19 (s, 1H), 7.88 (s, 1H), 7.70 (s, 1H), 7.61 (d, J = 2.0 Hz, 1H), 7.00 (t, J = 8.3 Hz, 2H), 6.82 (s, 2H), 2.44 (s, 3H). 19 F NMR (376 MHz, DMSO-d6) d: -126.46, -148.31. 13 C NMR (101 MHz, DMSO-d6) d: 162.54, 160.60, 157.52, 155.20, 153.25, 146.57, 140.89, 128.73, 118.53, 116.12, 115.72, 115.50, 113.99 (d, J = 7.5 Hz), 13.72.

[0082]

[0083] N'-(4-chlorophenyl)-3-methyl-1-(thiazol-2-yl)-1H-pyrazole-4-carbohydrazide (Ia3): white solid, yield 79.1 %; 1 H NMR (400 MHz, DMSO-d6) d: 10.26 (s, 1H), 9.19 (s, 1H), 7.88 (s, 1H), 7.70 (s, 1H), 7.61 (d, J = 2.0 Hz, 1H), 7.00 (t, J = 8.3 Hz, 2H), 6.82 (s, 2H), 2.44 (s, 3H). 13C NMR (101 MHz, DMSO-d6) δ: 162.49, 160.59, 153.28, 149.01, 140.91, 128.98, 128.73, 122.33, 118.56, 116.01, 114.25, 13.71.

[0084]

[0085] N'-(4-bromophenyl)-3-methyl-1-(thiazol-2-yl)-1H-pyrazole-4-carbohydrazide (Ia4): white solid, yield 81.4%; 1 H NMR (400 MHz, DMSO-d6) δ: 10.29 (d, J = 3.7 Hz, 1H), 9.19 (d, J = 2.3 Hz, 1H), 8.12 (d, J = 2.2 Hz, 1H), 7.70 (d, J = 3.4 Hz, 1H), 7.61 (d, J = 3.4 Hz, 1H), 7.31 (d, J = 8.7 Hz, 2H), 6.77 (d, J = 8.8 Hz, 2H), 2.44 (s, 3H). 13 CNMR (101 MHz, DMSO-d6) δ: 162.48, 160.58, 153.29, 149.42, 140.90, 131.80, 128.77, 118.56, 115.98, 114.76, 109.81, 13.74.

[0086]

[0087] N'-(p-tolyl)-3-methyl-1-(thiazol-2-yl)-1H-pyrazole-4-carbohydrazide (Ia5): white solid, yield 70.2%; 1 H NMR (400 MHz, DMSO-d6) δ: 10.12 (d, J = 2.9 Hz, 1H), 9.12 (s, 1H), 7.70 (t, J = 3.1 Hz, 2H), 7.60 (d, J = 3.4 Hz, 1H), 6.98 (t, J = 10.2 Hz, 3H), 6.71 (d, J = 8.3 Hz, 2H), 2.43 (s, 3H), 2.19 (s, 3H). 13C NMR (101 MHz, DMSO-d6) d: 162.43, 160.62, 153.25, 147.73, 140.90, 129.61, 128.52, 127.70, 118.51, 116.22, 112.99, 20.62, 13.72.

[0088]

[0089] N'-(2,4-dichlorophenyl)-3-methyl-1-(thiazol-2-yl)-1H-pyrazole-4-carbohydrazide (Ia6): white solid, yield 51.9%; 1 H NMR (400 MHz, DMSO-d6) d: 10.32 (d, J = 1.5 Hz, 1H), 9.15 (s, 1H), 7.82 (s, 1H), 7.70 (t, J = 5.7 Hz, 1H), 7.61 (d, J = 3.4 Hz, 1H), 7.44 (d, J = 2.3 Hz, 1H), 7.22 (dd, J = 8.8, 2.3 Hz, 1H), 6.87 (t, J = 6.5 Hz, 1H), 2.44 (s, 3H). 13 C NMR (101 MHz, DMSO-d6) d: 162.43, 160.55, 153.35, 144.62, 140.94, 128.89, 128.79, 128.25, 122.54, 118.65, 118.12, 115.77, 114.68, 13.73.

[0090]

[0091] N'-(2-chlorophenyl)-3-methyl-1-(thiazol-2-yl)-1H-pyrazole-4-carbohydrazide (Ia7): white solid, yield 60.5%; 1 H NMR (400 MHz, DMSO-d6) d: 10.30 (d, J = 1.8 Hz, 1H), 9.16 (s, 1H), 7.71 (d, J = 3.4 Hz, 1H), 7.61 (d, J = 3.6 Hz, 2H), 7.31 (dd, J = 7.9, 1.1 Hz, 1H), 7.17 (dd, J = 11.3, 4.1 Hz, 1H), 6.91 - 6.86 (m, 1H), 6.81 - 6.74 (m, 1H), 2.44 (s, 3H). 13C NMR (101 MHz, DMSO-d6) δ: 162.42, 160.58, 153.34, 145.38, 140.93, 129.63, 128.73, 128.30, 120.10, 118.62, 117.71, 115.89, 113.61, 13.73.

[0092]

[0093] N'-phenyl-3-ethyl-1-(thiazol-2-yl)-1H-pyrazole-4-carbohydrazide (Ia8): white solid, yield 76.6%; 1 H NMR (400 MHz, DMSO-d6) δ: 10.26 (d, J = 2.6 Hz, 1H), 9.19 (s, 1H), 7.90 (d, J = 2.5 Hz, 1H), 7.70 (d, J = 3.4 Hz, 1H), 7.61 (d, J = 3.4 Hz, 1H), 7.16 (t, J = 7.8 Hz, 2H), 6.80 (d, J = 7.8 Hz, 2H), 6.72 (t, J = 7.3 Hz, 1H), 2.89 (q, J = 7.5 Hz, 2H), 1.21 (t, J = 7.5 Hz, 3H). 13 C NMR (101 MHz, DMSO-d6) δ: 162.42, 160.58, 153.34, 145.38, 140.93, 129.63, 128.73, 128.30, 120.10, 118.62, 117.71, 115.89, 113.61, 13.73.

[0094]

[0095] 3-ethyl-N'-(4-fluorophenyl)-1-(thiazol-2-yl)-1H-pyrazole-4-carbohydrazide (Ia9): white solid, yield 64.6%; 1H NMR (400 MHz, DMSO-d6) δ: 10.28 (d, J = 2.8 Hz, 1H), 9.19 (d, J = 3.0 Hz, 1H), 7.90 (d, J = 2.8 Hz, 1H), 7.70 (d, J = 3.4 Hz, 1H), 7.61 (d, J = 3.4 Hz, 1H), 7.00 (t, J = 8.9 Hz, 2H), 6.85 - 6.75 (m, 2H), 2.88 (q, J = 7.5 Hz, 2H), 1.20 (t, J = 7.5 Hz, 3H). 19 F NMR (376 MHz, DMSO-d6) δ: -126.51. 13 C NMR (101 MHz, DMSO-d6) δ: 162.44, 160.66, 158.46, 157.50, 155.18, 146.58, 140.90, 128.90, 118.52, 115.72, 115.50, 113.93 (d, J = 7.5 Hz), 21.07, 13.52.

[0096]

[0097] N'-(4-chlorophenyl)-3-ethyl-1-(thiazol-2-yl)-1H-pyrazole-4-carbohydrazide (Ia10): white solid, yield 69.3%; 1 H NMR (400 MHz, DMSO-d6) δ: 10.32 (s, 1H), 9.20 (s, 1H), 8.12 (s, 1H), 7.70 (s, 1H), 7.61 (s, 1H), 7.19 (d, J = 7.7 Hz, 2H), 6.81 (d, J = 7.7 Hz, 2H), 2.88 (d, J = 7.0 Hz, 2H), 1.21 (d, J = 6.4 Hz, 3H). 13 C NMR (101 MHz, DMSO-d6) δ: 162.41, 160.65, 158.49, 149.04, 140.90, 128.96, 122.27, 118.55, 115.40, 114.21, 20.98, 13.52.

[0098]

[0099] N'-(4-bromophenyl)-3-ethyl-1-(thiazol-2-yl)-1H-pyrazole-4-carbohydrazide (Ia11): white solid, yield 67.5%; 1 H NMR (400 MHz, DMSO-d6) δ: 10.31 (d, J = 2.2 Hz, 1H), 9.19 (s, 1H), 8.13 (d, J = 2.1 Hz, 1H), 7.70 (d, J = 3.4 Hz, 1H), 7.61 (d, J = 3.4 Hz, 1H), 7.30 (d, J = 8.8 Hz, 2H), 6.76 (d, J = 8.8 Hz, 2H), 2.88 (q, J = 7.5 Hz, 2H), 1.23 - 1.17 (m, 3H). 13 C NMR (101 MHz, DMSO-d6) δ: 162.39, 160.64, 158.49, 149.44, 140.91, 131.80, 128.96, 118.55, 115.38, 114.73, 109.78, 20.98, 13.52.

[0100]

[0101] N'-(p-tolyl)-3-ethyl-1-(thiazol-2-yl)-1H-pyrazole-4-carbohydrazide (Ia12): white solid, yield 59.1%; 1 H NMR (400 MHz, DMSO-d6) δ: 10.18 (s, 1H), 9.15 (s, 1H), 7.71 (dd, J = 8.3, 3.0 Hz, 2H), 7.60 (d, J = 3.4 Hz, 1H), 6.96 (d, J = 8.1 Hz, 2H), 6.71 (d, J = 8.2 Hz, 2H), 2.88 (q, J = 7.4 Hz, 2H), 2.18 (s, 3H), 1.20 (t, J = 7.5 Hz, 3H). 13 C NMR (101 MHz, DMSO-d6) δ: 162.35, 160.68, 158.45, 147.75, 140.90, 129.60, 128.75, 127.64, 118.50, 115.62, 112.96, 20.97, 20.61, 13.54.

[0102]

[0103] N'-(2,4-dichlorophenyl)-3-ethyl-1-(thiazol-2-yl)-1H-pyrazole-4-carbohydrazide (Ia13): light yellow solid, yield 48.1%; 1 H NMR (400 MHz, DMSO-d6) δ: 10.33 (d, J = 1.6 Hz, 1H), 9.15 (s, 1H), 7.82 (s, 1H), 7.71 (d, J = 3.4 Hz, 1H), 7.61 (d, J = 3.4 Hz, 1H), 7.44 (d, J = 2.3 Hz, 1H), 7.21 (dt, J = 12.6, 6.3 Hz, 1H), 6.88 (d, J = 8.8 Hz, 1H), 2.88 (q, J = 7.5 Hz, 2H), 1.21 (t, J = 7.5 Hz, 3H). 13 CNMR (101 MHz, DMSO-d6) δ: 162.33, 160.62, 158.56, 144.63, 140.93, 128.96, 128.90, 128.25, 122.52, 118.61, 118.11, 115.17, 114.61, 20.98, 13.50.

[0104]

[0105] N'-(2-chlorophenyl)-3-ethyl-1-(thiazol-2-yl)-1H-pyrazole-4-carbohydrazide (Ia14): grey white solid, yield 50.7%; 1 H NMR (400 MHz, DMSO-d6) δ: 10.31 (s, 1H), 9.16 (s, 1H), 7.71 (d, J = 3.4 Hz, 1H), 7.61 (d, J = 4.5 Hz, 2H), 7.31 (d, J = 7.8 Hz, 1H), 7.17 (dd, J = 11.3, 4.1 Hz, 1H), 6.88 (d, J = 8.1 Hz, 1H), 6.77 (dd, J = 11.1, 4.0 Hz, 1H), 2.89 (q, J = 7.5 Hz, 2H), 1.21 (t, J = 7.5 Hz, 3H). 13CNMR (101 MHz, DMSO-d6) δ: 162.33, 160.64, 158.54, 145.38, 140.93, 129.64, 128.90, 128.29, 120.08, 118.58, 117.71, 115.30, 113.55, 20.99, 13.52.

[0106]

[0107] N'-phenyl-3-isopropyl-1-(thiazol-2-yl)-1H-pyrazole-4-carbohydrazide(Ia15):white solid,yield61.2%; 1 H NMR (400 MHz, DMSO-d6) δ: 10.19 (s, 1H), 9.13 (d, J = 3.2 Hz, 1H), 7.91 (d, J = 2.0 Hz, 1H), 7.70 (d, J = 3.3 Hz, 1H), 7.60 (d, J = 3.3 Hz, 1H), 7.16 (t, J = 7.7 Hz, 2H), 6.78 (t, J = 11.7 Hz, 2H), 6.72 (t, J = 7.2 Hz, 1H), 3.55 (dt, J = 13.7, 6.8 Hz, 1H), 1.26 (d, J = 6.9 Hz, 6H). 13 C NMR (101 MHz, DMSO-d6) δ: 162.48, 162.19, 160.75, 150.04, 140.90, 129.20, 128.90, 119.03, 118.47, 115.21, 112.70, 26.89, 22.05.

[0108]

[0109] N'-(4-fluorophenyl)-3-isopropyl-1-(thiazol-2-yl)-1H-pyrazole-4-carbohydrazide(Ia16):whitesolid,yield 54.4%; 1H NMR (400 MHz, DMSO-d6) δ: 10.24 (d, J = 2.4 Hz, 1H), 9.15 (s, 1H), 7.90 (d, J = 2.7 Hz, 1H), 7.70 (d, J = 3.4 Hz, 1H), 7.60 (d, J = 3.4 Hz, 1H), 7.00 (t, J = 8.9 Hz, 2H), 6.88 - 6.74 (m, 2H), 3.61 - 3.51 (m, 1H), 1.26 (d, J = 6.9 Hz, 6H). 19 F NMR (376 MHz, DMSO-d6) δ: -126.49. 13 C NMR (101 MHz, DMSO-d6) δ: 162.52, 162.17, 160.74, 157.51, 155.19, 146.59, 140.89, 128.97, 118.47, 115.74, 115.51, 115.14, 113.91 (d, J = 7.6 Hz), 26.89, 22.04.

[0110]

[0111] N'-(4-chlorophenyl)-3-isopropyl-1-(thiazol-2-yl)-1H-pyrazole-4-carbohydrazide (Ia17): white solid, yield 67.6%; 1 H NMR (400 MHz, DMSO-d6) δ: 10.24 (s, 1H), 9.14 (s, 1H), 8.11 (s, 1H), 7.70 (d, J = 3.1 Hz, 1H), 7.60 (d, J = 3.1 Hz, 1H), 7.19 (d, J = 8.5 Hz, 2H), 6.80 (d, J = 8.5 Hz, 2H), 3.54 (dt, J = 13.6, 6.8 Hz, 1H), 1.25 (d, J = 6.8 Hz, 6H). 13 C NMR (101 MHz, DMSO-d6) δ: 162.48, 162.20, 160.72, 149.03, 140.90, 128.99, 122.31, 118.51, 115.03, 114.20, 26.90, 22.03.

[0112]

[0113] N'-(4-bromophenyl)-3-isopropyl-1-(thiazol-2-yl)-1H-pyrazole-4-carbohydrazide (Ia18): white solid, yield 66.1 %; 1 H NMR (400 MHz, DMSO-d6) δ: 10.22 (s, 1H), 9.13 (s, 1H), 8.13 (d, J = 2.3 Hz, 1H), 7.70 (t, J = 5.7 Hz, 1H), 7.60 (d, J = 3.4 Hz, 1H), 7.31 (d, J = 8.8 Hz, 2H), 6.77 (d, J = 8.8 Hz, 2H), 3.56 (dq, J = 13.8, 6.9 Hz, 1H), 1.26 (d, J = 6.9 Hz, 6H). 13 C NMR (101 MHz, DMSO-d6) δ: 162.47, 162.21, 160.72, 149.43, 140.90, 131.83, 128.97, 118.49, 115.01, 114.72, 109.85, 26.91, 22.03.

[0114]

[0115] 3-isopropyl-1-(thiazol-2-yl)-N'-(p-tolyl)-1H-pyrazole-4-carbohydrazide (Ia19): white solid, yield 56.9 %; 1 H NMR (400 MHz, DMSO-d6) δ: 10.18 (s, 1H), 9.12 (s, 1H), 7.73 (d, J = 3.0 Hz, 1H), 7.70 (d, J = 3.5 Hz, 1H), 7.60 (d, J = 3.5 Hz, 1H), 6.97 (d, J = 8.2 Hz, 2H), 6.71 (d, J = 8.4 Hz, 2H), 3.54 (dq, J = 13.8, 6.9 Hz, 1H), 2.19 (s, 3H), 1.25 (d, J = 6.9 Hz, 6H). 13 C NMR (101 MHz, DMSO-d6) δ: 162.43, 162.16, 160.75, 147.76, 140.89, 129.59, 128.86, 127.62, 118.45, 115.27, 112.94, 26.87, 22.04, 20.61.

[0116]

[0117] N'-(2,4-dichlorophenyl)-3-isopropyl-1-(thiazol-2-yl)-1H-pyrazole-4-carbohydrazide(Ia20): grey white solid, yield 65.8 %; 1 H NMR (400 MHz, DMSO-d6) δ: 10.32 (s, 1H), 9.13 (s, 1H), 7.82 (s, 1H), 7.70 (d, J = 3.3 Hz, 1H), 7.63 - 7.57 (m, 1H), 7.49 - 7.38 (m, 1H), 7.22 (dd, J = 8.8, 2.3 Hz, 1H), 6.88 (d, J = 8.8 Hz, 1H), 3.54 (hept, J = 6.8 Hz, 1H), 1.26 (d, J = 6.9 Hz, 6H). 13 C NMR (101 MHz, DMSO-d6) δ: 162.38, 162.29, 160.69, 144.63, 140.93, 129.08, 128.91, 128.25, 122.51, 118.58, 118.11, 114.79, 114.59, 26.91, 22.05.

[0118]

[0119] N'-(2-chlorophenyl)-3-isopropyl-1-(thiazol-2-yl)-1H-pyrazole-4-carbohydrazide (Ia21): white solid, yield 54.6 %; 1 H NMR (400 MHz, DMSO-d6) δ: 10.31 (s, 1H), 9.14 (s, 1H), 7.71 (d, J = 3.4 Hz, 1H), 7.61 (dd, J = 5.1, 2.8 Hz, 2H), 7.32 (dd, J = 7.8, 0.9 Hz, 1H), 7.16 (dd, J = 11.4, 4.1 Hz, 1H), 6.89 (d, J = 8.1 Hz, 1H), 6.81 - 6.73 (m, 1H), 3.55 (dq, J = 13.7, 6.8 Hz, 1H), 1.27 (d, J = 6.9 Hz, 6H). 13C NMR (101 MHz, DMSO-d6) d: 162.39, 162.28, 160.71, 145.39, 140.92, 129.64, 129.01, 128.29, 120.07, 118.54, 117.71, 114.93, 113.52, 26.91, 22.06.

[0120]

[0121] N'-phenyl-3-cyclopropyl-1-(thiazol-2-yl)-1H-pyrazole-4-carbohydrazide (Ia22): white solid, yield 84.5%; 1 H NMR (400 MHz, DMSO-d6) d: 10.15 (s, 1H), 9.10 (s, 1H), 7.90 (s, 1H), 7.63 (d, J = 44.9 Hz, 2H), 7.16 (s, 2H), 6.91 - 6.66 (m, 3H), 2.66 (s, 1H), 0.94 (d, J = 21.4 Hz, 4H). 13 C NMR (101 MHz, DMSO-d6) d: 162.61, 160.57, 158.69, 150.03, 140.90, 129.23, 128.69, 119.09, 118.45, 116.40, 112.76, 9.80, 8.12.

[0122]

[0123] N'-(4-fluorophenyl)-3-cyclopropyl-1-(thiazol-2-yl)-1H-pyrazole-4-carbohydrazide (Ia23): white solid, yield 95.1%; 1 H NMR (400 MHz, DMSO-d6) d: 10.18 (d, J = 2.8 Hz, 1H), 9.10 (s, 1H), 7.90 (d, J = 2.8 Hz, 1H), 7.69 (d, J = 3.5 Hz, 1H), 7.57 (d, J = 3.4 Hz, 1H), 7.01 (t, J = 8.9 Hz, 2H), 6.86 - 6.79 (m, 2H), 2.66 (ddd, J = 13.3, 8.3, 5.1 Hz, 1H), 1.02 - 0.95 (m, 2H), 0.94 - 0.87 (m, 2H). 19FNMR (376 MHz, DMSO-d6) δ: -126.41. 13 C NMR (101 MHz, DMSO-d6) δ: 162.65, 160.64, 158.67, 157.54, 155.22, 146.57, 140.76, 128.75, 118.29, 116.34, 115.76, 115.54, 113.98 (d, J = 7.5 Hz), 9.80, 8.12.

[0124]

[0125] N'-(4-chlorophenyl)-3-cyclopropyl-1-(thiazol-2-yl)-1H-pyrazole-4-carbohydrazide (Ia24): white solid, yield 75.7%; 1 H NMR (400 MHz, DMSO-d6) δ: 10.19 (s, 1H), 9.10 (s, 1H), 8.11 (s, 1H), 7.63 (d, J = 42.7 Hz, 2H), 7.20 (d, J = 8.1 Hz, 2H), 6.82 (d, J = 8.1 Hz, 2H), 2.65 (s, 1H), 1.06 - 0.82 (m, 4H). 13 C NMR (101 MHz, DMSO-d6) δ: 162.61, 160.62, 158.70, 149.01, 140.90, 129.01, 128.78, 122.38, 118.47, 116.24, 114.26, 9.81, 8.12.

[0126]

[0127] N'-(4-chlorophenyl)-3-cyclopropyl-1-(thiazol-2-yl)-1H-pyrazole-4-carbohydrazide (Ia24): white solid, yield 75.7%; 1H NMR (400 MHz, DMSO-d6) δ: 10.20 (d, J = 2.1 Hz, 1H), 9.10 (s, 1H), 8.13 (d, J = 2.2 Hz, 1H), 7.69 (d, J = 3.4 Hz, 1H), 7.57 (d, J = 3.4 Hz, 1H), 7.32 (d, J = 8.8 Hz, 2H), 6.78 (d, J = 8.8 Hz, 2H), 2.71 - 2.59 (m, 1H), 1.03 - 0.95 (m, 2H), 0.94 - 0.87 (m, 2H). 13 C NMR (101 MHz, DMSO-d6) δ: 162.60, 160.62, 158.71, 149.42, 140.89, 131.85, 128.79, 118.47, 116.22, 114.77, 109.88, 9.81, 8.13.

[0128]

[0129] N'-(p-tolyl)-3-cyclopropyl-1-(thiazol-2-yl)-1H-pyrazole-4-carbohydrazide (Ia26): white solid, yield 65.3%; 1 H NMR (400 MHz, DMSO-d6) δ: 10.20 (d, J = 2.1 Hz, 1H), 9.10 (s, 1H), 8.13 (d, J = 2.2 Hz, 1H), 7.69 (d, J = 3.4 Hz, 1H), 7.57 (d, J = 3.4 Hz, 1H), 7.32 (d, J = 8.8 Hz, 2H), 6.78 (d, J = 8.8 Hz, 2H), 2.71 - 2.59 (m, 1H), 1.03 - 0.95 (m, 2H), 0.94 - 0.87 (m, 2H). 13 C NMR (101 MHz, DMSO-d6) δ: 162.60, 160.62, 158.71, 149.42, 140.89, 131.85, 128.79, 118.47, 116.22, 114.77, 109.88, 9.81, 8.13.

[0130]

[0131] N'-(2,4-dichlorophenyl)-3-cyclopropyl-1-(thiazol-2-yl)-1H-pyrazole-4-carbohydrazide (Ia27): yellow-white solid, yield 66.9%; 1 H NMR (400 MHz, DMSO-d6) δ: 10.32 (d, J = 1.4 Hz, 1H), 9.11 (s, 1H), 7.83 (s, 1H), 7.69 (d, J = 3.4 Hz, 1H), 7.58 (d, J = 3.4 Hz, 1H), 7.47 - 7.41 (m, 1H), 7.23 (dd, J = 8.8, 2.3 Hz, 1H), 6.91 (d, J = 8.8 Hz, 1H), 2.70 - 2.60 (m, 1H), 1.03 - 0.94 (m, 2H), 0.94 - 0.86 (m, 2H). 13 C NMR (101 MHz, DMSO-d6) δ: 162.56, 160.59, 158.78, 144.65, 140.92, 128.93, 128.89, 128.27, 122.54, 118.55, 118.13, 116.00, 114.70, 9.82, 8.14.

[0132]

[0133] N'-(2-chlorophenyl)-3-cyclopropyl-1-(thiazol-2-yl)-1H-pyrazole-4-carbohydrazide (Ia28): yellow-white solid, yield 69.3%; 1 H NMR (400 MHz, DMSO-d6) δ: 10.32 (s, 1H), 9.13 (s, 1H), 7.70 (d, J = 3.4 Hz, 1H), 7.63 (s, 1H), 7.61 - 7.54 (m, 1H), 7.34 - 7.29 (m, 1H), 7.20 - 7.14 (m, 1H), 6.94 - 6.89 (m, 1H), 6.81 - 6.74 (m, 1H), 2.73 - 2.61 (m, 1H), 1.03 - 0.86 (m, 4H). 13C NMR (101 MHz, DMSO-d6) δ: 162.55, 160.62, 158.77, 145.41, 140.91, 129.63, 128.87, 128.31, 120.09, 118.51, 117.72, 116.13, 113.64, 9.81, 8.15.

[0134]

[0135] N'-phenyl-1-(thiazol-2-yl)-3-(trifluoromethyl)-1H-pyrazole-4-carbohydrazide (Ia29): white solid, yield 80.5%; 1 H NMR (400 MHz, DMSO-d6) δ: 10.51 (d, J = 12.5 Hz, 1H), 9.44 (d, J = 6.5 Hz, 1H), 8.04 (d, J = 1.8 Hz, 1H), 7.80 (dd, J = 14.7, 3.1 Hz, 2H), 7.17 (t, J = 7.8 Hz, 2H), 6.83 (d, J = 7.7 Hz, 2H), 6.74 (t, J = 7.3 Hz, 1H). 13 C NMR (101 MHz, DMSO-d6) δ: 160.83, 160.04, 149.70, 148.54 (t, J = 23.7 Hz), 141.16, 129.62, 129.22, 120.07, 119.24, 116.93, 112.84, 109.68 (t, J = 236.3 Hz).

[0136]

[0137] N'-(4-fluorophenyl)-1-(thiazol-2-yl)-3-(trifluoromethyl)-1H-pyrazole-4-carbohydrazide (Ia30): white solid, yield 90.5%; 1 H NMR (400 MHz, DMSO-d6) δ: 10.53 (s, 1H), 9.44 (s, 1H), 8.03 (d, J = 1.8 Hz, 1H), 7.80 (dd, J = 14.8, 3.4 Hz, 2H), 7.01 (t, J = 8.8 Hz, 2H), 6.84 (dt, J = 16.0, 7.0 Hz, 2H). 19F NMR (376 MHz, DMSO-d6) δ: -60.64, -126.23. 13 C NMR (101 MHz, DMSO-d6) δ: 159.57, 157.63, 146.17, 142.84 (d, J = 38.4 Hz), 141.20, 131.12, 116.95, 115.77, 115.54, 114.05 (d, J = 7.5 Hz).

[0138]

[0139] N'-(4-chlorophenyl)-1-(thiazol-2-yl)-3-(trifluoromethyl)-1H-pyrazole-4-carbohydrazide (Ia31): white solid, yield 62.9%; 1 H NMR (400 MHz, DMSO-d6) δ: 10.56 (s, 1H), 9.45 (s, 1H), 8.24 (s, 1H), 7.80 (d, J = 11.3 Hz, 2H), 7.20 (d, J = 8.4 Hz, 2H), 6.84 (d, J = 8.4 Hz, 2H). 19 F NMR (376 MHz, DMSO-d6) δ: -60.65. 13 C NMR (101 MHz, DMSO-d6) δ: 159.54, 142.85 (d, J = 38.4 Hz), 148.62, 141.21, 131.17, 129.01, 122.58, 116.83, 114.31, 120.59 (t, J = 32.1 Hz).

[0140]

[0141] N'-(4-bromophenyl)-1-(thiazol-2-yl)-3-(trifluoromethyl)-1H-pyrazole-4-carbohydrazide (Ia32): white solid, yield 72.1%; 1 H NMR (400 MHz, DMSO-d6) δ: 10.55 (s, 1H), 9.45 (s, 1H), 8.26 (d, J = 1.3 Hz, 1H), 7.80 (dd, J = 15.3, 3.4 Hz, 2H), 7.32 (d, J = 8.7 Hz, 2H), 6.81 (d, J = 8.8 Hz, 2H). 19F NMR (376 MHz, DMSO-d6) δ: -60.66. 13 C NMR (101 MHz, DMSO-d6) δ: 160.81, 160.01, 149.08, 148.54 (t, J = 23.9 Hz), 141.16, 131.85, 129.69, 120.07, 116.71, 114.84, 110.07, 109.66 (t, J = 237.4 Hz).

[0142]

[0143] N'-(p-tolyl)-3-(trifluoromethyl)-1-(thiazol-2-yl)-1H-pyrazole-4-carbohydrazide (Ia33): white solid, yield 69.1%; 1 H NMR (400 MHz, DMSO-d6) δ: 10.47 (d, J = 19.7 Hz, 1H), 9.42 (d, J = 12.0 Hz, 1H), 7.86 (d, J = 2.7 Hz, 1H), 7.83 - 7.79 (m, 1H), 7.79 - 7.75 (m, 1H), 6.97 (d, J = 8.2 Hz, 2H), 6.74 (d, J = 6.8 Hz, 2H), 2.19 (s, 3H). 19 F NMR (376 MHz, DMSO-d6) δ: -60.62. 13 C NMR (101 MHz, DMSO-d6) δ: 159.50 (d, J = 7.9 Hz), 147.34, 141.19, 131.00, 129.61, 127.87, 120.55 (t, J = 139.68 Hz), 117.07, 113.03, 20.61.

[0144]

[0145] N'-(2,4-dichlorophenyl)-1-(thiazol-2-yl)-3-(trifluoromethyl)-1H-pyrazole-4-carbohydrazide (Ia34): yellow-white solid, yield 58.3%; 1H NMR (400 MHz, DMSO-d6) δ: 10.61 (s, 1H), 9.43 (s, 1H), 7.97 (s, 1H), 7.83 (d, J = 3.4 Hz, 1H), 7.79 (d, J = 3.4 Hz, 1H), 7.46 (d, J = 2.3 Hz, 1H), 7.23 (dd, J = 8.8, 2.3 Hz, 1H), 6.95 (d, J = 8.8 Hz, 1H). 19 F NMR (376 MHz, DMSO-d6) δ: -60.69. 13 C NMR (101 MHz, DMSO-d6) δ: 159.48, 144.25, 142.94 (q, J = 38.5 Hz), 141.21, 131.21, 128.96, 128.23, 127.96, 122.78, 120.63, 118.23, 116.52, 114.65, 114.01.

[0146]

[0147] N'-(2-chlorophenyl)-1-(thiazol-2-yl)-3-(trifluoromethyl)-1H-pyrazole-4-carbohydrazide (Ia35): white solid, yield 40.3%; 1 H NMR (400 MHz, DMSO-d6) δ: 10.57 (s, 1H), 9.41 (s, 1H), 7.85 - 7.81 (m, 1H), 7.77 (dd, J = 8.3, 6.1 Hz, 2H), 7.32 (d, J = 7.9 Hz, 1H), 7.17 (t, J = 7.7 Hz, 1H), 6.93 (d, J = 8.1 Hz, 1H), 6.78 (dd, J = 10.9, 4.2 Hz, 1H). 19 F NMR (376 MHz, DMSO-d6) δ: -60.67. 13 C NMR (101 MHz, DMSO-d6) δ: 159.51, 159.46, 144.99, 141.22, 131.14, 129.70, 128.31, 121.89, 120.63, 120.27, 119.21, 117.77, 116.66, 113.57.

[0148]

[0149] N'-phenyl-3-(difluoromethyl)-1-(thiazol-2-yl)-1H-pyrazole-4-carbohydrazide (Ia36): white solid, yield 71.5%; 1 H NMR (400 MHz, DMSO-d6) δ: 10.60 (s, 1H), 9.45 (s, 1H), 8.01 (d, J = 2.1 Hz, 1H), 7.79 (d, J = 3.4 Hz, 1H), 7.74 (d, J = 3.4 Hz, 1H), 7.42 (t, J = 69.6 Hz, 1H), 7.17 (t, J = 7.8 Hz, 2H), 6.82 (d, J = 7.8 Hz, 2H), 6.74 (t, J = 7.3 Hz, 1H). 19 F NMR (376 MHz, DMSO-d6) δ: -60.62. 13 CNMR (101 MHz, DMSO-d6) δ: 159.53, 149.63, 142.87 (d, J = 38.2 Hz), 141.20, 131.07, 129.22, 121.94, 120.57, 119.25, 117.01, 112.80.

[0150]

[0151] N'-(4-fluorophenyl)-3-(difluoromethyl)-1-(thiazol-2-yl)-1H-pyrazole-4-carbohydrazide (Ia37): white solid, yield 85.7%; 1 H NMR (400 MHz, DMSO-d6) δ: 10.60 (s, 1H), 9.42 (s, 1H), 8.00 (d, J = 1.9 Hz, 1H), 7.78 (t, J = 5.7 Hz, 1H), 7.74 (d, J = 3.4 Hz, 1H), 7.39 (t, J = 53.6 Hz, 1H), 7.01 (t, J = 8.8 Hz, 2H), 6.87 - 6.79 (m, 2H). 19 F NMR (376 MHz, DMSO-d6) δ: -116.37, -126.21, -148.29. 13CNMR (101 MHz, DMSO-d6) δ: 160.85, 160.03, 157.62, 155.30, 148.52 (t, J = 23.8 Hz), 146.24, 141.16, 129.65, 120.06, 116.83, 115.77, 115.55, 114.08 (d, J = 7.5 Hz), 109.68 (t, J = 236.3 Hz).

[0152]

[0153] N'-(4-chlorophenyl)-3-(difluoromethyl)-1-(thiazol-2-yl)-1H-pyrazole-4-carbohydrazide (Ia38): white solid, yield 78.1 %; 1 HNMR (400 MHz, DMSO-d6) δ: 10.60 (s, 1H), 9.41 (s, 1H), 8.21 (s, 1H), 7.87 - 7.70 (m, 2H), 7.40 (t, J = 53.6 Hz, 1H), 7.19 (d, J = 8.4 Hz, 2H), 6.82 (d, J = 8.4 Hz, 2H). 19 FNMR (376 MHz, DMSO-d6) δ: -116.40. 13 CNMR (101 MHz, DMSO-d6) δ: 160.82, 160.02, 148.68, 141.17, 129.68, 129.01, 122.55, 120.09, 116.73, 114.32, 109.67 (t, J = 236.5 Hz).

[0154]

[0155] N'-(4-bromophenyl)-3-(difluoromethyl)-1-(thiazol-2-yl)-1H-pyrazole-4-carbohydrazide (Ia39): white solid, yield 89.5 %; 1H NMR (400 MHz, DMSO-d6) δ: 10.61 (d, J = 17.5 Hz, 1H), 9.41 (d, J = 9.7 Hz, 1H), 8.23 (s, 1H), 7.79 (d, J = 3.3 Hz, 1H), 7.74 (d, J = 3.3 Hz, 1H), 7.40 (t, J = 53.6 Hz, 1H), 7.31 (d, J = 8.7 Hz, 2H), 6.78 (d, J = 8.7 Hz, 2H). 19 F NMR (376 MHz, DMSO-d6) δ: -116.39, -148.28. 13 C NMR (101 MHz, DMSO-d6) δ: 159.51, 149.02, 142.67 (t, J = 38.4 Hz), 141.20, 131.84, 131.16, 121.91, 120.58, 119.23, 116.81, 114.82, 110.10.

[0156]

[0157] N'-(p-tolyl)-3-(difluoromethyl)-1-(thiazol-2-yl)-1H-pyrazole-4-carbohydrazide (Ia40): white solid, yield 72.1 %; 1 H NMR (400 MHz, DMSO-d6) δ: 10.51 (d, J = 12.6 Hz, 1H), 9.39 (d, J = 8.8 Hz, 1H), 7.83 (d, J = 2.8 Hz, 1H), 7.79 (d, J = 3.4 Hz, 1H), 7.73 (d, J = 3.4 Hz, 1H), 7.41 (t, J = 53.6 Hz, 1H), 6.97 (d, J = 8.2 Hz, 2H), 6.73 (d, J = 8.3 Hz, 2H), 2.19 (s, 3H). 19 F NMR (376 MHz, DMSO-d6) δ: -116.36, -148.30. 13 C NMR (101 MHz, DMSO-d6) δ: 160.76, 160.04, 148.40 (d, J = 23.7 Hz), 147.39, 141.15, 129.63, 129.48, 127.90, 120.04, 116.91, 113.07, 109.66 (t, J = 236.4 Hz), 20.61.

[0158]

[0159] N'-(2,4-dichlorophenyl)-3-(difluoromethyl)-1-(thiazol-2-yl)-1H-pyrazole-4-carbohydrazide(Ia41):yellow-white solid,yield 83.7%; 1 H NMR (400 MHz, DMSO-d6) δ: 10.61 (s, 1H), 9.36 (s, 1H), 7.94 (s, 1H), 7.80 (d, J = 3.4 Hz, 1H), 7.74 (d, J = 3.4 Hz, 1H), 7.45 (t, J = 4.9 Hz, 1H), 7.40 (t, J = 53.2 Hz, 1H), 7.22 (dd, J = 8.8, 2.3 Hz, 1H), 6.92 (d, J = 8.8 Hz, 1H). 19 F NMR (376 MHz, DMSO-d6) δ: -116.34. 13 C NMR (101 MHz, DMSO-d6) δ: 160.80, 159.98, 148.58 (t, J = 23.9 Hz), 144.32, 141.17, 129.66, 128.95, 128.25, 122.79, 120.13, 118.22, 116.49, 114.72, 109.61 (t, J = 236.5 Hz).

[0160]

[0161] N'-(2-chlorophenyl)-3-(difluoromethyl)-1-(thiazol-2-yl)-1H-pyrazole-4-carbohydrazide(Ia42):white solid,yield 58.1%; 1 H NMR (400 MHz, DMSO-d6) δ: 10.59 (s, 1H), 9.36 (s, 1H), 7.80 (d, J = 3.4 Hz, 1H), 7.76 - 7.72 (m, 2H), 7.41 (t, J = 53.6 Hz, 1H), 7.32 (dd, J = 7.9, 1.3 Hz, 1H), 7.20 - 7.14 (m, 1H), 6.91 (dd, J = 8.2, 1.2 Hz, 1H), 6.79 (td, J = 7.7, 1.4 Hz, 1H). 19 F NMR (376 MHz, DMSO-d6) δ: -116.34. 13C NMR (101 MHz, DMSO-d6) d: 160.79, 160.01, 148.57 (t, J = 23.9 Hz), 145.07, 141.18, 129.69, 129.59, 128.32, 120.29, 120.12, 117.77, 116.61, 113.65, 109.62 (t, J = 236.5 Hz).

[0162]

[0163] N-benzyl-1-(thiazol-2-yl)-3-(trifluoromethyl)-1H-pyrazole-4-carboxamide (Ia43): white solid, yield 65.7%; 1 H NMR (400 MHz, DMSO-d6) d: 9.33 (s, 1H), 9.10 (t, J = 5.7 Hz, 1H), 7.79 (d, J = 3.4 Hz, 1H), 7.75 (d, J = 3.4 Hz, 1H), 7.37 - 7.33 (m, 4H), 7.31 - 7.20 (m, 1H), 4.47 (d, J = 5.9 Hz, 2H). 19 F NMR (376 MHz, DMSO-d6) d: -60.54. 13 C NMR (101 MHz, DMSO-d6) d: 159.63, 159.27, 142.73 (d, J = 38.3 Hz), 141.16, 139.45, 130.92, 128.82, 127.86, 127.41, 120.40, 118.85, 42.83.

[0164]

[0165] N-(4-chlorobenzyl)-1-(thiazol-2-yl)-3-(trifluoromethyl)-1H-pyrazole-4-carboxamide (Ia44): white solid, yield 68.1%; 1 H NMR (400 MHz, DMSO-d6) d: 9.32 (s, 1H), 9.17 - 9.07 (m, 1H), 7.78 (t, J = 4.9 Hz, 1H), 7.75 (d, J = 3.4 Hz, 1H), 7.39 (q, J = 8.5 Hz, 4H), 4.44 (d, J = 5.8 Hz, 2H). 19F NMR (376 MHz, DMSO-d6) δ: -60.56. 13 C NMR (101 MHz, DMSO-d6) δ: 159.61, 159.33, 142.70 (d, J = 38.1 Hz), 141.16, 138.53, 131.98, 130.97, 129.73, 128.77, 120.43, 118.73, 42.18.

[0166]

[0167] O-((6-chloropyridin-3-yl)methyl)-1-(thiazol-2-yl)-3-(trifluoromethyl)-1H-pyrazole-4-carboxami de(Ia45):white solid,yield 81.8%; 1 H NMR (400 MHz, DMSO-d6) δ: 9.32 (s, 1H), 9.17 (t, J = 5.7 Hz, 1H), 8.42 (d, J = 2.3 Hz, 1H), 7.84 (dd, J = 8.2, 2.4 Hz, 1H), 7.79 (t, J = 4.6 Hz, 1H), 7.76 (d, J = 3.4 Hz, 1H), 7.52 (d, J = 8.2 Hz, 1H), 4.49 (d, J = 5.7 Hz, 2H). 19 F NMR (376 MHz, DMSO-d6) δ: -60.60. 13 C NMR (101 MHz, DMSO-d6) δ: 159.59, 159.51, 149.54, 149.37, 142.66 (d, J = 38.2 Hz), 141.16, 139.57, 134.62, 131.11, 124.51, 120.44, 118.54.

[0168] Example 5: fungicidal activity of the N1 -containing heterocyclic pyrazoles of formula (I) Ia1 -Ia45, Ib1 -Ib19 of the present application;

[0169] The fungicidal activity of the N1-heterocycle-containing pyrazoles of formula (I) Ia1-Ia45, Ib1-Ib19 of the present application was determined by using Magnaporthe grisea, Rhizoctonia solani, Botrytis cinerea, Fusarium graminearum, Alternaria solani, and Sclerotinia sclerotiorum as test strains, and the inhibition rate was determined at different concentrations of 100 μg / mL, 25 μg / mL, etc. by the mycelium growth rate method.

[0170] The specific determination method is as follows:

[0171] Accurately weigh 18 mg of the target compound into 1 mL of DMSO to prepare a stock solution with a concentration of 18000 μg / mL. Accurately take 0.25 mL of the stock solution with a pipette, add it to 45 mL of sterilized molten PDA medium (solvent concentration is 0.55%, less than 1%), shake well, prepare a drug-containing medium with a concentration of 100 μg / mL, and pour it evenly into 3 disposable sterile plastic culture dishes. The medium with the same amount of solvent added is used as a blank control. Use a puncher (inner diameter 0.5 cm) to punch the activated colonies growing normally to prepare a bacterial disease, and use an inoculation needle to inoculate the bacterial cake to the center of the above-mentioned medium, and place it in a 25±1℃ constant temperature incubator for dark culture. When the diameter of the colonies on the control medium reaches about 2 / 3 of the diameter of the culture dish, measure the diameter, measure twice with the cross method, and calculate the average value. Each concentration and the blank control are repeated 3 times. The growth inhibition rate of the drug is calculated according to the following formula:

[0172] I(%)=(C-T) / (C-0.5)×100%

[0173] In the above formula, I is the mycelium growth inhibition rate, C is the average value of the diameter of the control colonies, and T is the average value of the diameter of the drug-treated colonies.

[0174] Table 1, fungicidal activity (inhibition rate, %) of N1-heterocycle-containing pyrazoles of formula (I) Ib1-Ib19 and Ia43-45 at a concentration of 100 μg / mL

[0175]

[0176] Table 2, fungicidal activity (inhibition rate, %) of some compounds against Sclerotinia sclerotiorum at a concentration of 100 μg / mL

[0177]

[0178] The inventors further studied the effect of the combination of these compounds and found that the combination of Ib3 (50 μg / mL) and Ib11 (50 μg / mL) had a synergistic effect on the inhibition rate of R. solani, which was 78.45 ± 0.67%, the combination of Ib12 (50 μg / mL) and Ib14 (50 μg / mL) had a synergistic effect on the inhibition rate of B. cinerea, which was 89.76 ± 0.98%, the combination of Ib2 (50 μg / mL) and Ib10 (50 μg / mL) had a synergistic effect on the inhibition rate of F. graminearum, which was 95.72 ± 0.58%, and the combination of Ib6 (50 μg / mL) and Ib7 (50 μg / mL) had a synergistic effect on the inhibition rate of S. sclerotiorum, which was 58.45 ± 0.76%.

[0179] The N1-containing heterocyclic pyrazole compounds Ib1-Ib19, Ia43-Ia45 of formula (I) of the present application had a bactericidal activity of 100 μg / mL, and the results are shown in Tables 1 and 2. Overall, the target compounds had moderate to significant bactericidal (bacteriostatic) activity. For the rice sheath blight fungus, the compound Ib8 had an activity comparable to the control agent hymexazol at the test concentration, and the compounds Ib1, Ib2, and Ib15 had an inhibition activity higher than the commercial agent hymexazol at the test concentration. For the tomato gray mold, the compounds Ib12 and Ib15 had an inhibition activity comparable to azoxystrobin at the test concentration. For the wheat scab fungus, the compound Ib10 had an inhibition activity comparable to hymexazol at the test concentration, and Ib2 had an inhibition activity higher than hymexazol and comparable to azoxystrobin. For the tomato early blight fungus, the compounds Ib6, Ib8, and Ia45 had an inhibition activity comparable to hymexazol at the test concentration, the compounds Ib1, Ib2, Ib3, Ib10, Ib11, and Ib15 had an inhibition activity higher than hymexazol, and Ib2 had an inhibition activity higher than boscalid. For the rice blast fungus, the compounds Ib1-Ib8, Ib10-Ib12, Ib15, Ia44, and Ia45 all had an inhibition activity higher than the commercial agent boscalid at the test concentration. For the rapeseed sclerotinia fungus, the eight compounds tested all had a low activity at the test concentration.

[0180] Table 3, the bactericidal activity (inhibition rate, %) of the N1-containing heterocyclic pyrazole compounds Ia1-Ia42 of formula (I) at a concentration of 25 μg / mL

[0181]

[0182]

[0183] The N1-containing heterocyclic pyrazoles of formula (I) of the present application Ia1-Ia42 have the results of the fungicidal activity determination at 25 μg / mL concentration listed in Table 3, and overall, the target compounds have significant fungicidal (bacteriostatic) activity. For the Rhizoctonia solani, the inhibitory activities of the compounds Ia1-Ia42 at the test concentration are all higher than hymexazol, and the activities of the compounds Ia2-Ia7, Ia13, Ia14, Ia27, Ia28, Ia31, Ia32, Ia34, Ia35, Ia37-Ia42 are also higher than the commercial agent boscalid. For the Botrytis cinerea, the activities of the compounds at the test concentration are all higher than hymexazol except for the compounds Ia8, Ia12, Ia17-Ia19, Ia22-Ia26, and the activities of the compounds Ia6, Ia7, Ia13, Ia14, Ia15, Ia20, Ia21, Ia27, Ia28, Ia32, Ia34, Ia41, Ia42 are also higher than the commercial agent boscalid. For the Gibberella zeae, the activities of the target compounds are all higher than the commercial agents boscalid and hymexazol except for the compounds Ia1, Ia8, Ia17, Ia18, Ia20-Ia26, Ia35. For the Magnaporthe grisea, the inhibitory activities of all the compounds are higher than the commercial agent boscalid except for the compounds Ia1, Ia18, Ia22, Ia25, Ia26.

[0184] In order to further explore the compounds with significant bacteriostatic activity, the EC 50 values of the compounds against 5 kinds of pathogenic fungi were tested, and the results are shown in Table 4. It can be seen from the table that for the Magnaporthe grisea, the EC 50 values of the compounds Ia3, Ia4, Ia6, Ia7, Ia11, Ia13, Ia24, Ia27, Ia31, Ia32, Ia34, Ia39, Ia41 are all lower than the commercial control agent boscalid, that is, the activities are all better than boscalid. For the Botrytis cinerea, the EC 50 values of the compounds Ia4, Ia6, Ia13, Ia15, Ia17, Ia20, Ia24, Ia32, Ia34, Ia41 are all lower than the commercial control agent boscalid, that is, the activities are all better than boscalid.

[0185] Table 4, the EC 50 values (μg / mL) of the target compounds against 5 kinds of plant pathogens

[0186]

[0187]

[0188] While embodiments of the application have been shown and described, it is to be understood that the embodiments described are merely exemplary of the principles and application of the present application. Numerous modifications and adaptions can be effected without departing from the spirit and scope of the present application, which is not limited to the exact construction and arrangement described. It is intended, therefore, to cover all modifications and adaptions that fall within the scope of the claims and their equivalents.

Claims

1. Use of N1-heterocycle-containing pyrazoles for inhibiting or killing plant harmful pathogenic fungi, characterized in that, The plant harmful pathogenic fungi are Gibberella zeae, Botrytis cinerea, Pellicularia sasakii, Alternaria solani, Sclerotinia sclerotiorum or Magnaporthe grisea; The plant harmful pathogenic fungi are Gibberella zeae, Botrytis cinerea, Pellicularia sasakii, Alternaria solani, Sclerotinia sclerotiorum or Magnaporthe grisea; The N1-heterocyclic pyrazoles are of the formula

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