Novel pyrazole ester compound and its preparation method and application

Abstract

The present invention discloses a novel pyrazole ester compound, the structural formula of the compound is shown in formula (I). The novel pyrazole ester compound of formula (I) described in the present invention has a novel molecular structure, and its chemical structural formula has distinct characteristics. In the structural formula, Q can be a common pharmacophore such as pyridyl, benzyl, chrysanthemic acid, pyrazolyl, thiazolyl, thienyl, oxazolyl, thiazolyl and pyrazole. Overall, the compound is an ester. The preparation method of the compound of formula (I) described in the present invention is simple, the raw materials are easily available, the reaction conditions are easily controlled, and the yield is high. The compound of formula (I) described in the present invention has obvious activity in inhibiting or killing agricultural harmful fungi and the effect of preventing and treating fungal diseases of crops, and has the purpose of being used as a pesticide bactericide.

Description

Technical Field

[0001] The present invention belongs to the technical field of pesticides, and specifically relates to a novel pyrazole ester compound and a preparation method and application thereof. Background Art

[0002] There are many types of plant fungal diseases, which spread quickly and are difficult to prevent and control. Some types of pathogens have a wide host range and cause serious damage, seriously affecting the growth and storage of plants, and thus affecting the yield and quality of agricultural products. Chemical control still occupies a major position in the prevention and control of agricultural diseases, but there are also some problems. Some existing fungicides have relatively single targets, and long-term single or large-scale use has made the problem of microbial resistance increasingly prominent, seriously affecting the effectiveness and sustainable application of fungicides. Therefore, the development of new, highly efficient, low-toxic and environmentally friendly fungicides is of great significance for preventing and controlling agricultural diseases, ensuring agricultural production safety, and protecting the yield and quality of agricultural products.

[0003] Ester compounds occupy a place in chemistry and pesticide science. Some ester compounds also have important pharmacological activities, some have anti-tumor activity, some have antioxidant activity, and some have antibacterial activity. For example, the agricultural fungicides carbendazim, bupirimate, azoxystrobin, kresoxim-methyl, pyraclostrobin, etc. in the methoxyacrylate class all contain ester groups. Summary of the Invention

[0004] The object of the present invention is to provide a novel pyrazole ester compound to solve the problems raised in the above background technology.

[0005] In order to achieve the above-mentioned object, the present invention provides the following technical solution: a novel pyrazole ester compound, the structural formula of which is shown in formula (I),

[0006] Wherein, Q is selected from one of substituted pyridyl, substituted benzyl, chrysanthemic acid, substituted pyrazolyl, substituted thiazolyl, substituted thienyl, substituted oxazolyl, and substituted thiazolyl-pyrazolyl.

[0007] Preferably, Q is selected from 2-chloropyridyl, 6-chloropyridyl, 2-chlorobenzyl, 4-chlorobenzyl, 2,4-dichlorobenzyl, 2-methylbenzyl, 4-methylbenzyl, chrysanthemic acid, 1-methyl-3-trifluoromethylpyrazolyl, 1-methyl-3-difluoromethylpyrazolyl, 1,3-dimethyl-5-chloro-pyrazolyl, 2,4-dimethylthiazolyl, 2-methyl-4-trifluoromethylthiazolyl, 2-methyl-4-difluoromethylthiazolyl, thiophene-2 -methyl, thiophene-3-methyl, 5-oxazolyl, 4-oxazolyl, 1-(thiazol-2-yl)-3-methyl-pyrazolyl, 1-(thiazol-2-yl)-3-ethyl-pyrazolyl, 1-(thiazol-2-yl)-3-cyclopropyl-pyrazolyl, 1-(thiazol-2-yl)-3-isopropyl-pyrazolyl, 1-(thiazol-2-yl)-3-trifluoromethyl-pyrazolyl, 1-(thiazol-2-yl)-3-difluoromethyl-pyrazolyl.

[0008] Preferably, the structural formula of Q is

[0009] One of them.

[0010] Preferably, Q is selected from 1-methyl-3-difluoromethyl-pyrazolyl, 1,3-dimethyl-5-chloro-pyrazolyl, 2-methyl-4-trifluoromethylthiazole, 1-(thiazol-2-yl)-3-cyclopropyl-pyrazolyl, 1-(thiazol-2-yl)-3-isopropyl-pyrazolyl, 1-(thiazol-2-yl)-3-trifluoromethyl-pyrazolyl, 1-(thiazol-2-yl)-3-difluoromethyl-pyrazolyl.

[0011] Preferably, the compound represented by general formula (I) is obtained from various carboxylic acid groups represented by general formula (II) and 1-(4-chlorophenyl)-3-pyrazolol represented by general formula (III) through the following two routes A and B:

[0012]

[0013] The appropriate solvent used in the reaction can be selected from dichloromethane, chloroform, tetrahydrofuran, acetonitrile, etc.;

[0014] The base used in the reaction includes triethylamine, N,N-diisopropylethylamine, pyridine, sodium hydroxide, lithium hydroxide, sodium carbonate, and potassium carbonate.

[0015] Preferably, it is characterized in that: the temperature condition of the reaction is -15°C to the boiling point of the solvent;

[0016] The reaction time condition is 30 minutes to 16 hours.

[0017] Preferably, the reaction temperature is -5 to 75°C;

[0018] The reaction time condition is 1 to 8 hours.

[0019] Preferably, the application of the novel pyrazole ester compound in inhibiting or killing harmful fungi is suitable for use in the agricultural field as a fungicide.

[0020] Preferably, the fungal diseases include but are not limited to wheat fusarium wilt, tomato gray mold, rice sheath blight, tomato early blight, and rice blast.

[0021] The beneficial effects of the present invention are as follows:

[0022] 1. The novel pyrazole ester compound of formula (I) described in the present invention has a novel molecular structure and a distinct chemical structure. In the structural formula, Q can be a common pharmacological group such as pyridyl, benzyl, chrysanthemic acid, pyrazolyl, thiazolyl, thiazolyl, pyrazole-containing pyrazole, etc. Overall, the compound is an ester.

[0023] 2. The preparation method of the compound of formula (I) described in the present invention is simple, the raw materials are readily available, the reaction conditions are easily controlled, and the yield is high.

[0024] 3. The compound of formula (I) described in the present invention has obvious activity in inhibiting or killing agricultural harmful fungi and preventing and treating fungal diseases of crops, and has the use as a pesticide fungicide.

[0025] The present invention uses an active substructure splicing method to construct pyrazole ester compounds by splicing various carboxylic acid groups such as thiazolecarboxylic acid, pyrazolecarboxylic acid, phenylacetic acid, chrysanthemic acid, and thiazole-pyrazolecarboxylic acid with 1-(4-chlorophenyl)-3-pyrazolol. The compounds have obvious fungal killing (inhibition) activity, especially having more significant inhibitory activity against rice blast fungus, rice sheath blight fungus, tomato gray mold fungus, etc. DETAILED DESCRIPTION

[0026] The following is a clear and complete description of the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making any creative efforts are within the scope of protection of the present invention.

[0027] The present invention provides a structural formula of the compound as shown in formula (I),

[0028]

[0029] Wherein, Q is selected from one of substituted pyridyl, substituted benzyl, chrysanthemic acid, substituted pyrazolyl, substituted thiazolyl, and substituted thiazolyl-pyrazolyl.

[0030] wherein Q is selected from 2-chloropyridyl, 6-chloropyridyl, 2-chlorobenzyl, 4-chlorobenzyl, 2,4-dichlorobenzyl, 2-methylbenzyl, 4-methylbenzyl, chrysanthemic acid, 1-methyl-3-trifluoromethylpyrazolyl, 1-methyl-3-difluoromethylpyrazolyl, 1,3-dimethyl-5-chloro-pyrazolyl, 2,4-dimethylthiazolyl, 2-methyl-4-trifluoromethylthiazole, 2-methyl-4- Difluoromethylthiazolyl, 1-(thiazol-2-yl)-3-methyl-pyrazolyl, 1-(thiazol-2-yl)-3-ethyl-pyrazolyl, 1-(thiazol-2-yl)-3-cyclopropyl-pyrazolyl, 1-(thiazol-2-yl)-3-isopropyl-pyrazolyl, 1-(thiazol-2-yl)-3-trifluoromethyl-pyrazolyl, 1-(thiazol-2-yl)-3-difluoromethyl-pyrazolyl.

[0031] In formula (I), the Q group has the following particularly preferred definitions:

[0032]

[0033]

[0034] In Example 1, the preparation of 1-(4-chlorophenyl)-1-hydrogen-pyrazol-3-yl-2-chloronicotinate (I 1), compound (I 1) was prepared by the following method:

[0035]

[0036] Place (0.003 mol, 0.47 g) 2-chloronicotinic acid in a 100 mL round-bottom flask, add 15 mL thionyl chloride, add a rotor, stir and reflux for 2-4 hours, evaporate the excess thionyl chloride under reduced pressure, add 20 mL dichloromethane and a rotor to the round-bottom flask containing 2-chloronicotinyl chloride, place in an ice-salt bath, stir and cool to -10-0 ° C, add 1-(4-chlorophenyl)-3-pyrazolol (0.003 mol, 0.58 g), and slowly add triethylamine (0.0045 mol) dropwise. l, 0.45 g) was stirred for reaction for 0.5 to 1 hour, and the temperature was naturally raised to room temperature and the stirring reaction was continued for 4 to 6 hours. After the completion of the reaction monitored by TLC, the reaction mixture was placed in a 100-mL separatory funnel, and 20 mL of dichloromethane was added. The mixture was washed with water three times (3*30 mL) and twice with saturated brine (2*30 mL). The mixture was dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 0.85 g of the product with a yield of 85.1%.

[0037] In Example 2, the preparation of 1-(4-chlorophenyl)-1-hydrogen-pyrazol-3-yl-2-chloronicotinate (I 1), compound (I 1) was prepared by the following method:

[0038]

[0039] 3-Methyl-1-(thiazol-2-yl)-1-hydrogen-pyrazole-4-carboxylic acid (0.003 mol, 0.47 g) was placed in a 100 mL round-bottom flask, and 20 mL of dichloromethane, O-benzotriazole-N,N,N',N'-tetramethyluronium 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 to 30 minutes, 1-(4-chlorophenyl)-3-pyrazolol (0.003 mol) was added. l, 0.58 g) was stirred and reacted for 4 to 10 hours. After the completion of the reaction monitored by TLC, if any solid was found, it was the product by direct filtration. The reaction mixture was then placed in a 100 mL separatory funnel, added with 20 mL of dichloromethane, washed with water three times (3*30 mL), washed twice with saturated brine (2*30 mL), dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography. The filtered solids were combined to obtain 0.45 g of the product with a yield of 45.1%.

[0040] In Example 3, the methods of Examples 1-2 above were used to prepare novel pyrazole ester compounds I1-I22 of formula (I). The structural formulas and NMR data of the compounds are as follows:

[0041]

[0042] 1-(4-chlorophenyl)-1H-pyrazol-3-yl2-chloronicotinate(I1): Yellow-white solid, yield 85.1%; 1 H NMR(400MHz, DMSO-d6)δ:8.71(dd,J=4.7,1.8Hz,1H),8.61(d,J=2.6Hz,1H),8.57(dd,J=7.7,1.8Hz, 1H),7.86(d,J=8.9Hz,2H),7.69(dd,J=7.7,4.8Hz,1H),7.59(d,J=8.9Hz,2H),6.62(d,J=2.6Hz,1H). 13 C NMR (101MHz, DMSO-d6) δ: 161.60, 156.26, 153.87, 149.32, 141.95, 138.46, 131.05, 130.40, 130.01, 125.23, 123.92, 120.14, 100.13.

[0043]

[0044] 1-(4-chlorophenyl)-1H-pyrazol-3-yl6-chloronicotinate(I2):Yellow-whitesolid,yield 44.1%; 1 H NMR(400MHz,CDCl3)δ:9.21(d,J=1.9Hz,1H),8.43(dd,J=8.3,2.2Hz,1H),7.89(d,J=2.5Hz,1H),7.61(d,J=8.8Hz,2H),7.50(t,J=10.1Hz,1H),7.43(d,J=8.8Hz,2H),6.53(d,J=2.4Hz,1H). 13 C NMR(101MHz,CDCl3)δ:161.69,156.77,156.17,151.89,140.15,138.14,132.33,129.65,128.06,124.51,123.79,119.97,99.42.

[0045]

[0046] 1-(4-chlorophenyl)-1H-pyrazol-3-yl2-(2-chlorophenyl)acetate(I3):Yellow-white solid,yield 43.3%; 1 H NMR(400 MHz,CDCl3)δ:7.79(d,J=2.6 Hz,1H),7.56(d,J=8.8 Hz,2H),7.44–7.35(m,4H),7.30–7.25(m,2H),6.42(d,J=2.6 Hz,1H),4.07(s,2H). 13 C NMR(101 MHz,CDCl3)δ:167.63,156.64,138.20,134.69,132.01,131.63,131.32,129.65,129.54,129.16,127.72,127.10,119.83,99.30,38.95.

[0047]

[0048] 1-(4-chlorophenyl)-1H-pyrazol-3-yl2-(4-chlorophenyl)acetate(I4):Yellow-white solid,yield 31.8%; 1H NMR(400 MHz,CDCl3)δ:7.79(d,J=2.5 Hz,1H),7.56(d,J=8.7 Hz,2H),7.40(d,J=8.7 Hz,2H),7.37–7.27(m,4H),6.38(d,J=2.5Hz,1H),3.88(s,2H). 13 C NMR(101 MHz,CDCl3)δ:168.19,156.54,138.16,133.55,132.10,131.20,130.83,129.57,128.93,127.77,119.85,99.23,40.31.

[0049]

[0050] 1-(4-chlorophenyl)-1H-pyrazol-3-yl2-(2,4-dichlorophenyl)acetate(I5):Yellow-white solid,yield 57.9%; 1 H NMR(400 MHz,CDCl3)δ:7.80(d,J=2.5 Hz,1H),7.56(d,J=8.7 Hz,2H),7.45(d,J=1.9 Hz,1H),7.40(d,J=8.7 Hz,2H),7.32(d,J=8.3Hz,1H),7.26(dd,J=7.5,2.5 Hz,1H),6.41(d,J=2.5 Hz,1H),4.03(s,2H). 13 C NMR(101MHz,CDCl3)δ:167.21,156.50,138.17,135.40,134.35,132.38,132.10,129.91,129.56,129.53,127.78,127.44,119.86,99.24,38.36.

[0051]

[0052] 1-(4-chlorophenyl)-1H-pyrazol-3-yl2-(o-tolyl)acetate(I6):Yellowsolid,yield46.9%; 1H NMR(400 MHz,CDCl3)δ:7.77(d,J=2.6 Hz,1H),7.54(t,J=8.6Hz,2H),7.41–7.34(m,2H),7.29(d,J=6.1 Hz,1H),7.23–7.17(m,3H),6.37(d,J=2.6 Hz,1H),3.92(s,2H),2.39(s,3H). 13 C NMR(101 MHz,CDCl3)δ:168.47,156.72,138.23,137.00,132.00,131.60,130.53,130.36,129.53,127.83,127.68,126.33,119.83,99.30,38.92,19.68.

[0053]

[0054] 1-(4-chlorophenyl)-1H-pyrazol-3-yl2-(p-tolyl)acetate(I7):Yellowsolid,yield41.8%; 1 H NMR(400 MHz,CDCl3)δ:7.78(d,J=2.6 Hz,1H),7.58–7.53(m,2H),7.43–7.36(m,2H),7.25(d,J=2.0 Hz,2H),7.20–7.13(m,2H),6.38(d,J=2.6 Hz,1H),3.87(s,2H),2.34(s,3H). 13 C NMR(101 MHz,CDCl3)δ:168.78,156.74,138.23,137.17,131.99,129.73,129.53,129.46,129.30,127.67,119.82,99.32,40.62,21.10.

[0055]

[0056] 1-(4-chlorophenyl)-1H-pyrazol-3-yl-(Z)-3-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethylcyclopropane-1-carboxylate(I8):Yellowsolid,yield 67.2%; 1HNMR(400 MHz,CDCl3)δ:7.81(d,J=2.6 Hz,1H),7.57(d,J=8.8Hz,2H),7.41(d,J=8.8 Hz,2H),6.91(d,J=9.1 Hz,1H),6.38(d,J=2.6 Hz,1H),2.35(t,J=8.7 Hz,1H),2.26(d,J=8.3 Hz,1H),1.39(s,3H),1.35(s,3H).19F NMR(376MHz,CDCl3)δ:-68.76. 13 C NMR(101 MHz,CDCl3)δ:167.42,156.45,138.22,132.09,129.57,127.75,119.85,99.45,32.43,31.79,29.96,28.25,14.83.

[0057]

[0058] 1-(4-chlorophenyl)-1H-pyrazol-3-yl-2-(4-chlorophenyl)-3-methylbutanoate(I9):Brown liquid,yield 50.5%; 1 H NMR(400 MHz,CDCl3)δ:7.76(d,J=2.6 Hz,1H),7.58–7.51(m,2H),7.44–7.29(m,6H),6.34(t,J=4.1 Hz,1H),3.42(d,J=10.4 Hz,1H),2.48–2.36(m,1H),1.16(d,J=6.5 Hz,3H),0.78(d,J=6.7 Hz,3H). 13 C NMR(101 MHz,CDCl3)δ:170.62,156.64,138.22,135.77,133.56,132.03,129.99,129.52,128.87,127.64,119.89,99.15,59.14,32.11,21.42,20.07.

[0059]

[0060] 1-(4-chlorophenyl)-1H-pyrazol-3-yl-2-phenylpropanoate(I10):Brownliquid,yield 64.3%; 1H NMR(400 MHz,CDCl3)δ:7.75(d,J=2.4 Hz,1H),7.54(d,J=8.7Hz,2H),7.43–7.32(m,6H),7.29(t,J=7.0 Hz,1H),6.34(d,J=2.5 Hz,1H),4.01(q,J=7.2 Hz,1H),1.64(d,J=7.2 Hz,3H). 13 C NMR(101 MHz,CDCl3)δ:171.58,156.83,139.48,138.24,131.96,129.51,128.86,127.63,127.52,119.89,99.23,45.55,18.60.

[0061]

[0062] 1-(4-chlorophenyl)-1H-pyrazol-3-yl-1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-carboxylate(I11):Yellow solid,yield 36.5%; 1 H NMR(400 MHz,DMSO-d6)δ:8.89(s,1H),8.58(d,J=2.7 Hz,1H),7.90–7.79(m,2H),7.63–7.54(m,2H),6.56(d,J=2.6 Hz,1H),4.02(d,J=6.7 Hz,3H). 19 F NMR(376 MHz,DMSO-d6)δ:-60.87. 13 C NMR(101MHz,DMSO-d6)δ:157.75,156.14,140.98(d,J=38.1Hz),139.49,138.49,130.94,130.26,129.98,129.70,120.05,118.77,109.99,100.26,40.00.

[0063]

[0064] 1-(4-chlorophenyl)-1H-pyrazol-3-yl3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylate(I12):Yellow solid,yield 55.7%; 1H NMR(400 MHz,DMSO-d6)δ:8.75(s,1H),8.57(d,J=2.6 Hz,1H),7.83(t,J=5.9 Hz,2H),7.64–7.51(m,2H),7.25(t,J=53.6 Hz,1H),6.54(d,J=2.6 Hz,1H),3.99(s,3H). 19 F NMR(376MHz,DMSO-d6)δ:-115.11. 13 C NMR(101 MHz,DMSO-d6)δ:158.85,156.23,146.37(t,J=25.1 Hz),138.51,138.04,130.90,130.19,129.98,120.02,110.17,110.07,100.32,39.94.

[0065]

[0066] 1-(4-chlorophenyl)-1H-pyrazol-3-yl5-chloro-1,3-dimethyl-1H-pyrazole-4-carboxylate(I13):Yellow solid,yield 57.1%; 1 H NMR(400 MHz,DMSO-d6)δ:8.56(d,J=2.7 Hz,1H),7.89–7.77(m,2H),7.61–7.50(m,2H),6.53(d,J=2.6 Hz,1H),3.83(s,3H),2.42(s,3H). 13 C NMR(101 MHz,DMSO-d6)δ:159.20,156.28,151.12,138.53,132.29,130.83,130.11,129.95,120.01,106.67,100.50,36.96,14.86.

[0067]

[0068] 1-(4-chlorophenyl)-1H-pyrazol-3-yl2,4-dimethylthiazole-5-carboxylate(I14):Yellow solid,yield 42.4%; 1H NMR(400 MHz,DMSO-d6)δ:8.58(d,J=2.7 Hz,1H),7.88–7.81(m,2H),7.60–7.53(m,2H),6.56(d,J=2.6 Hz,1H),2.72(s,3H),2.67(s,3H). 13 CNMR(101 MHz,DMSO-d6)δ:171.57,162.46,159.10,156.12,138.46,130.96,130.24,129.96,120.07,119.18,100.29,19.71,17.70.

[0069]

[0070] 1-(4-chlorophenyl)-1H-pyrazol-3-yl2-methyl-4-(trifluoromethyl)thiazole-5-carboxylate(I15):Yellow solid,yield 43.1%; 1 H NMR(400 MHz,DMSO-d6)δ:8.60(d,J=2.7 Hz,1H),7.89–7.82(m,2H),7.62–7.55(m,2H),6.61(d,J=2.6 Hz,1H),2.83(s,3H). 19 F NMR(376 MHz,DMSO-d6)δ:-59.98. 13 C NMR(101 MHz,DMSO-d6)δ:173.15,155.98,155.75,146.13(d,J=37.2 Hz),138.38,131.15,130.48,130.00,120.21,100.01,19.75.

[0071]

[0072] 1-(4-chlorophenyl)-1H-pyrazol-3-yl4-(difluoromethyl)-2-methylthiazole-5-carboxylate(I16):Yellow solid,yield 49.3%; 1H NMR(400 MHz,DMSO-d6)δ:8.60(d,J=2.6 Hz,1H),7.86(dd,J=6.9,5.0 Hz,2H),7.62–7.53(m,2H),7.43(t,J=53.2 Hz,1H)6.60(d,J=2.6 Hz,1H),2.83(s,3H). 19 F NMR(376 MHz,DMSO-d6)δ:-114.79. 13 C NMR(101 MHz,DMSO-d6)δ:173.58,163.38,157.42,155.76,153.25(t,J=23.1Hz),138.38,131.12,130.37,129.98,129.69,120.15,118.76,108.74(t,J=237.0 Hz),100.09,19.89.

[0073]

[0074] 1-(4-chlorophenyl)-1H-pyrazol-3-yl3-methyl-1-(thiazol-2-yl)-1H-pyrazole-4-carboxylate(I17):Yellow solid,yield 37.6%; 1 H NMR(400 MHz,DMSO-d6)δ:9.07(s,1H),8.58(d,J=2.7 Hz,1H),7.88–7.82(m,2H),7.74(d,J=3.4 Hz,1H),7.68(d,J=3.4 Hz,1H),7.60–7.53(m,2H),6.55(d,J=2.6 Hz,1H),2.52(s,3H). 13 C NMR(101MHz,DMSO-d6)δ:159.94,159.86,156.32,154.09,141.14,138.53,132.56,130.87,130.16,129.98,120.00,119.50,113.22,100.43,13.70.

[0075]

[0076] 1-(4-chlorophenyl)-1H-pyrazol-3-yl3-ethyl-1-(thiazol-2-yl)-1H-pyrazole-4-carboxylate(I18):Yellow solid,yield 44.3%; 1 H NMR(400 MHz,DMSO-d6)δ:9.04(s,1H),8.57(d,J=2.6 Hz,1H),7.85(d,J=8.9 Hz,2H),7.73(t,J=5.6 Hz,1H),7.68(t,J=3.7 Hz,1H),7.60–7.52(m,2H),6.56(d,J=2.6 Hz,1H),2.94(q,J=7.5 Hz,2H),1.28(t,J=7.5 Hz,3H). 13 C NMR(101 MHz,DMSO-d6)δ:159.98,159.66,159.06,156.31,141.11,138.51,132.68,130.85,130.09,129.93,119.96,119.42,112.46,100.39,21.05,12.94.

[0077]

[0078] 1-(4-chlorophenyl)-1H-pyrazol-3-yl3-isopropyl-1-(thiazol-2-yl)-1H-pyrazole-4-carboxylate(I19):Yellow solid,yield 45.9%; 1 H NMR(400 MHz,DMSO-d6)δ:9.07(s,1H),8.58(d,J=2.7 Hz,1H),7.85(d,J=8.9 Hz,2H),7.75(d,J=3.4 Hz,1H),7.68(d,J=3.4 Hz,1H),7.58(d,J=8.9 Hz,2H),6.56(d,J=2.6 Hz,1H),3.52(dq,J=13.7,6.9 Hz,1H),1.33(d,J=6.9 Hz,6H). 13C NMR(101 MHz,DMSO-d6)δ:162.88,160.04,159.65,156.32,141.14,138.53,132.91,130.87,130.16,129.97,120.01,119.47,111.93,100.46,27.16,21.73.

[0079]

[0080] 1-(4-chlorophenyl)-1H-pyrazol-3-yl3-cyclopropyl-1-(thiazol-2-yl)-1H-pyrazole-4-carboxylate(I20):Yellow solid,yield 62.1%; 1 H NMR(400 MHz,DMSO-d6)δ:9.03(s,1H),8.59(d,J=2.7 Hz,1H),7.89–7.82(m,2H),7.73(d,J=3.4 Hz,1H),7.66(d,J=3.4 Hz,1H),7.62–7.55(m,2H),6.57(d,J=2.6 Hz,1H),2.60–2.52(m,1H),1.13–1.05(m,2H),1.02–0.95(m,2H). 13 C NMR(101 MHz,DMSO-d6)δ:159.98,159.37,156.34,141.13,138.54,132.65,130.87,130.18,129.98,120.01,119.44,113.23,100.50,9.86,8.23.

[0081]

[0082] 1-(4-chlorophenyl)-1H-pyrazol-3-yl1-(thiazol-2-yl)-3-(trifluoromethyl)-1H-pyrazole-4-carboxylate(I21):Yellow solid,yield 57.4%; 1 HNMR(400 MHz,DMSO-d6)δ:9.44(s,1H),8.60(d,J=2.7 Hz,1H),7.89–7.78(m,4H),7.64–7.53(m,2H),6.59(d,J=2.6 Hz,1H). 19F NMR (376 MHz, DMSO-d6) δ: -61.52. 13 C NMR (101MHz, DMSO-d6) δ: 158.97, 157.33, 155.94, 143.10 (d, J = 39.2 Hz)141.39,138.47,135.48,131.03,130.40,130.01,121.29,120.11,112.97,100.24.

[0083]

[0084] 1-(4-chlorophenyl)-1H-pyrazol-3-yl3-(difluoromethyl)-1-(thiazol-2-yl)-1H-pyrazole-4-carboxylate(I22): Yellow solid, yield 61.9%; 1 H NMR (400 MHz, DMSO-d6) δ: 9.33 (s, 1H), 8.60 (d, J = 2.7 Hz, 1H), 7.90–7.83 (m, 2H), 7.82 (d, J = 3.4 Hz, 1H), 7.79 (d, J = 3.4 Hz,1H),7.61–7.55(m,2H),7.40(t,J=53.2 Hz,1H),6.57(d,J=2.6Hz,1H). 19 F NMR (376 MHz, DMSO-d6) δ: -117.09. 13 CNMR(101 MHz, DMSO-d6)δ:159.41,158.37,156.02,148.70,141.34,138.48,134.00, 130.99,130.33,130.01,120.79,120.08,113.40,112.04,109.69,100.30..

[0085] In Example 4, the fungicidal activity of the novel pyrazole ester compounds I1-I22 of formula (I) of the present invention was determined using Magnaporthe grisea, Rhizoctonia solani, Botrytis cinerea, Fusarium graminearum, and Alternaria solani as test strains, and the inhibition rate at a concentration of 100 μg / mL was determined by the mycelial growth rate method;

[0086] The specific measurement method is as follows:

[0087] 18 mg of the target compound was accurately weighed and dissolved in 1 mL of DMSO to prepare a stock solution with a concentration of 18,000 μg / mL. 0.25 mL of the stock solution was accurately measured with a pipette and added to 45 mL of sterilized molten PDA medium (solvent concentration was 0.55%, less than 1%). The mixture was shaken thoroughly to prepare a drug-containing medium with a concentration of 100 μg / mL. The medium was evenly poured into three disposable sterile plastic Petri dishes. A medium with an equal amount of solvent was used as a blank control. A microbial plate was punched out of a normally growing activated colony using a puncher (inner diameter 0.5 cm). The bacterial cake was inoculated into the center of the above culture medium using an inoculating needle. The culture was incubated upside down in a constant temperature incubator at 25±1°C in the dark. The diameter of the colony on the control culture medium was measured when it grew to about 2 / 3 of the culture dish. Each colony diameter was measured twice using the cross-sectional method, and the average value was calculated. Three replicates were set for each concentration and the blank control. The growth inhibition rate of the drug was calculated as follows:

[0088] I(%)=(C-T) / (C-0.5)×100%

[0089] In the above formula, I is the mycelial growth inhibition rate, C is the average diameter of the control colony, and T is the average diameter of the drug-treated colony.

[0090] Table 1 Bactericidal activity (inhibition rate, %) of the novel pyrazole ester compounds I1-I22 of formula (I) at a concentration of 100 μg / mL

[0091]

[0092]

[0093] The fungicidal activity test results of the novel pyrazole ester compounds I1-I22 of formula (I) of the present invention at a concentration of 100 μg / mL are listed in Table 1. Overall, the target compounds have moderate to significant fungicidal (inhibitory) activity. For rice sheath blight, compounds I10, I11, I12, I15, and I16 are more active than the control agent benomyl at the test concentration, and compound I16 is equivalent to azoxystrobin in activity. Compounds I10 and Ib15 have higher inhibitory activity at the test concentration than the commercial agent azoxystrobin. For tomato gray mold, compound I16 has a higher inhibitory activity at the test concentration than the commercial agent azoxystrobin. The inhibitory activity of compounds I15 and I16 at the tested concentrations was higher than that of oxadiazon at the tested concentrations. Against wheat ergot pathogen, the inhibitory activity of compounds I1, I3, I4, I6, I7, I10, I11, I12, I15, I16, and I20 was higher than that of oxadiazon at the tested concentrations. Against rice blast pathogen, the inhibitory activity of compounds I1, I3, I4, I6, I7, I10, I11, I12, I15, I16, and I20 was higher than that of oxadiazon at the tested concentrations. Against rice blast pathogen, except for compounds I8-I9 and I18-I22, the inhibitory activity of the compounds was higher than that of the commercial agent boscalid at the tested concentrations, and the activity of compounds I10 and I16 was comparable to that of oxadiazon.

[0094] The inventors further studied the effects of the combination of these compounds and found that the combination of I11 (50 μg / mL) and I14 (50 μg / mL) had an inhibition rate of 91.81±0.56% on R.solani, showing synergistic synergy; the combination of I7 (50 μg / mL) and I10 (50 μg / mL) had an inhibition rate of 84.34±0.89% on B.cinerea, showing synergistic synergy; the combination of I15 (50 μg / mL) and I16 (50 μg / mL) had an inhibition rate of 89.93±1.45% on F.graminearum, showing synergistic synergy.

[0095] In order to further explore the compounds with significant antibacterial activity, the EC50 values ​​of the compounds against 5 pathogenic fungi were tested. The results are shown in Table 2. As can be seen from the table, for rice blast fungus, the EC50 values ​​of compounds I1, I2, I3, I4, I6, I7, I11, I12, I14, I15, and I16 are 50 The values ​​are all lower than those of the commercial control agent boscalid, which means that the activity is better than boscalid. For tomato early blight fungus, the EC values ​​of compounds I3, I4, I6, I10, I11, I12, I15, and I16 are 50 The values ​​were all lower than those of the commercial control agent, carbendazim, which means that the activities were better than carbendazim.

[0096] Table 2. EC of the novel pyrazole ester compounds I1-I22 of formula (I) against five plant pathogens 50

[0097]

[0098]

[0099] It should be noted that, in this document, relational terms such as first and second, etc., are used only to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any actual relationship or order between these entities or operations. Moreover, the terms "comprises," "comprising," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that includes a list of elements includes not only those elements but also other elements not explicitly listed, or elements inherent to such process, method, article, or apparatus.

[0100] While embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions, and variations may be made to these embodiments without departing from the principles and spirit of the invention, and that the scope of the invention is defined by the appended claims and their equivalents.

Claims

1. A novel pyrazole ester compound, characterized in that: The structural formula of the compound is shown in formula (I), , wherein the structural formula of Q is One of them.

2. The method for preparing the novel pyrazole ester compound according to claim 1, characterized in that: The compound represented by general formula (I) is obtained by the following two reactions A and B of general formula (II) and general formula (III): ； The organic solvent used in the reaction is selected from dichloromethane, chloroform, tetrahydrofuran, and acetonitrile; The base used in the reaction is selected from triethylamine, N,N-diisopropylethylamine, pyridine, sodium hydroxide, lithium hydroxide, sodium carbonate, and potassium carbonate.

3. The method for preparing the novel pyrazole ester compound according to claim 2, wherein: The reaction temperature ranges from -15°C to the boiling point of the solvent; and the reaction time ranges from 30 minutes to 16 hours.

4. The method for preparing the novel pyrazole ester compound according to claim 3, wherein: The reaction temperature is -5 to 75° C., and the reaction time is 1 to 8 hours.

5. Use of the novel pyrazole ester compound according to claim 1 in inhibiting or killing harmful fungi in plant diseases.

6. The use according to claim 5, characterized in that The plant diseases are wheat fusarium head blight, tomato gray mold, rice sheath blight, tomato early blight, rice blast, rapeseed sclerotinia or apple leaf spot.

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