CN114957124B - 3- (trifluoromethyl) -pyrazole-4-carboxylic ester derivative and preparation method and application thereof - Google Patents

3- (trifluoromethyl) -pyrazole-4-carboxylic ester derivative and preparation method and application thereof Download PDF

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CN114957124B
CN114957124B CN202210595056.0A CN202210595056A CN114957124B CN 114957124 B CN114957124 B CN 114957124B CN 202210595056 A CN202210595056 A CN 202210595056A CN 114957124 B CN114957124 B CN 114957124B
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CN114957124A (en
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姚孟孟
陈委婷
韩亮
刘幸海
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Zhejiang University of Technology ZJUT
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Abstract

The invention discloses a 3- (trifluoromethyl) -pyrazole-4-carboxylic acid ester derivative, a preparation method and application thereof, wherein the structural formula of the 3- (trifluoromethyl) -pyrazole-4-carboxylic acid ester derivative is shown as the formula (I):

Description

3- (trifluoromethyl) -pyrazole-4-carboxylic ester derivative and preparation method and application thereof
Technical Field
The invention belongs to the technical field of chemical synthesis, and particularly relates to a 3- (trifluoromethyl) -pyrazole-4-carboxylic ester derivative, and a preparation method and application thereof.
Background
The pyrazole oxime compounds mainly have insecticidal and acaricidal activities. Typical compounds are Fenpyroximate (Fenpyroximate) developed by Nihon Nohyaku company in 1985, and have been playing an important role in crop protection as agricultural insecticidal acaricides for many years. The fenpyroximate has two configurations of E and Z, and the E body has high acaricidal activity and high speed. The acaricide has strong contact killing effect on various mites, is mainly used for preventing and controlling phytophagous mites, and has activity on the whole growth period, especially young mites. Has good control effect on insect pests such as prodenia litura, chilo suppressalis, rice planthoppers and the like and diseases such as rice blast, powdery mildew, downy mildew and the like.
As the pyrazole oxime ester compound contains active structural groups such as pyrazole, benzyl and the like, the pyrazole oxime ester compound has the characteristics of high efficiency, low toxicity, good environmental compatibility and the like, and also has wide biological activity such as anti-tumor, antibacterial, insecticidal, weeding and the like.
The design and synthesis of novel pyrazoloxime lipid bactericides and herbicides have important significance for developing novel pesticides with high efficiency, low toxicity and low residue, and have advantages in pesticide creation.
Disclosure of Invention
Aiming at the technical problems, the invention aims to provide a 3- (trifluoromethyl) -pyrazole-4-carboxylic ester derivative, and a preparation method and application thereof. The invention is based on Fluxapyroxad (Fluxapyroxad) and synthesizes pyrazole amide ester compounds by introducing a fatty chain extension middle part. Then introducing substituted benzaldoxime on the pyrazole acyl to examine the influence on the biological activity of the compound, and designing and synthesizing the pyrazole oxime ester compound.
In order to achieve the above purpose, the following technical scheme is provided:
a3- (trifluoromethyl) -pyrazole-4-carboxylic acid ester derivative has a structural formula shown in a formula (I):
h on the benzene ring in formula (I) is mono-substituted, poly-substituted or unsubstituted by substituent R, which is independently alkyl, methoxy, halogen, nitro or trifluoromethyl.
Preferably, R in formula (I) is 2-methyl, 4-methyl, 2,4, 6-trimethyl, 2-methoxy, 4-methoxy, 3,4, 5-trimethoxy, 2-bromo, 4-bromo, 2-nitro, 3-nitro, 4-fluoro, 4-trifluoromethyl, 4-chloro or 2, 4-dichloro.
A preparation method of 3- (trifluoromethyl) -pyrazole-4-carboxylic acid ester derivatives, which comprises the following steps:
1) Adding acetic anhydride into a mixed solution of trifluoro acetoacetic acid ethyl ester and triethyl orthoformate, heating to reflux, reacting for 6-12h, stopping heating, cooling the reaction liquid to room temperature, and evaporating under reduced pressure to remove low boiling point substances to obtain (E) -2- (ethoxymethylene) -4, 4-trifluoro-3-oxo-ethyl butyrate shown in a formula (II);
2) Adding the ethyl (E) -2- (ethoxymethylene) -4, 4-trifluoro-3-oxobutyrate shown in the formula (II) obtained in the step (1) into absolute ethyl alcohol, uniformly stirring, then dropwise adding the ethyl (E) -2- (ethoxymethylene) -4, 4-trifluoro-3-oxobutyrate into a mixed solution of methyl hydrazine aqueous solution and absolute ethyl alcohol under the ice salt bath condition, heating to 40-60 ℃ after the dropwise adding, carrying out TLC tracking reaction, removing a solvent by reduced pressure evaporation after the reaction is finished, adding ethyl acetate and water for extraction, washing an organic layer with saturated saline water for three times, drying through anhydrous magnesium sulfate, filtering, concentrating the filtrate, and removing the solvent to obtain a crude product of the ethyl 1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboxylate shown in the formula (III);
3) Adding sodium hydroxide aqueous solution into the crude product of the 1-methyl-3-trifluoromethyl-1H-pyrazole-4-ethyl formate shown in the formula (III) obtained in the step (2), heating to 50-70 ℃, stirring, performing TLC tracking reaction, cooling to room temperature after the reaction is finished, adding concentrated hydrochloric acid to adjust pH, precipitating a large amount of solids, filtering, washing with water, and drying to obtain the crude product of the 1-methyl-3-trifluoromethyl-1H-pyrazole-4-formic acid shown in the formula (IV);
4) Adding thionyl chloride into the crude product of the 1-methyl-3-trifluoromethyl-1H-pyrazole-4-formic acid shown in the formula (IV) obtained in the step (3), heating and refluxing until the reaction liquid becomes clear and transparent from turbidity, continuing to react for 10-60 minutes, stopping heating, and removing redundant thionyl chloride by reduced pressure rotary evaporation to obtain 1-methyl-3-trifluoromethyl-1H-pyrazole-4-formyl chloride shown in the formula (V);
5) Dissolving the 1-methyl-3-trifluoromethyl-1H-pyrazole-4-formyl chloride shown in the formula (V) obtained in the step (4) in dichloromethane, dropwise adding the dichloromethane in which the substituted benzaldehyde oxime shown in the formula (VI) and triethylamine are dissolved under the ice salt bath condition, stirring the solution while dropwise adding, stirring the solution at normal temperature after the dropwise adding, performing TLC tracking reaction, adding column chromatography silica gel after the reaction is finished, removing the solvent by reduced pressure rotary evaporation, and purifying the solution by column chromatography to obtain the 3- (trifluoromethyl) -pyrazole-4-carboxylate derivative shown in the formula (I);
when H on the benzene ring is substituted or not substituted by a substituent R, the substituent R is 2-methyl, 4-methyl, 2,4, 6-trimethyl, 2-methoxy, 4-methoxy, 3,4, 5-trimethoxy, 2-bromo, 4-bromo, 2-nitro, 3-nitro, 4-fluoro, 4-trifluoromethyl, 4-chloro or 2, 4-dichloro.
Further, in the step 3), concentrated hydrochloric acid is added to adjust the pH to 1-4.
Further, in the step 1), the feeding mole ratio of the acetic anhydride, the trifluoro acetoacetic acid ethyl ester and the triethyl orthoformate is 3:1-2:3-6; in the step 2), the feeding mole ratio of the (E) -2- (ethoxymethylene) -4, 4-trifluoro-3-oxo-ethyl butyrate and methyl hydrazine shown in the formula (II) is 1:1-2; in the step 3), the feeding mole ratio of the 1-methyl-3-trifluoromethyl-1H-pyrazole-4-ethyl formate shown in the formula (III) to the sodium hydroxide is 1:1-3; in the step 4), the dosage of the thionyl chloride is excessive; in the step 5), the feeding mole ratio of the 1-methyl-3-trifluoromethyl-1H-pyrazole-4-formyl chloride shown in the formula (V) to the substituted benzaldehyde oxime shown in the formula (VI) is 1:1.1-1.5.
Further, the volume amount of absolute ethyl alcohol in which ethyl (E) -2- (ethoxymethylene) -4, 4-trifluoro-3-oxobutanoate represented by the formula (II) is dissolved in the step 2) is 0.1 to 0.4mL/mmol in terms of the amount of the substance of ethyl (E) -2- (ethoxymethylene) -4, 4-trifluoro-3-oxobutanoate represented by the formula (II), and the volume amount of thionyl chloride in the step 4) is 0.1 to 0.5mL/mmol in terms of the amount of the substance of 1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid represented by the formula (IV).
Further, the volume amount of methylene chloride used for dissolving 1-methyl-3-trifluoromethyl-1H-pyrazole-4-carbonyl chloride in the step 5) is 1 to 3mL/mmol based on the amount of the substance of 1-methyl-3-trifluoromethyl-1H-pyrazole-4-carbonyl chloride represented by the formula (V).
Further, the eluent separated by column chromatography in the step 5) adopts a mixed solution of ethyl acetate and petroleum ether in a volume ratio of 2:3.
The synthetic process route of the 3- (trifluoromethyl) -pyrazole-4-carboxylic acid ester derivative is as follows:
when H on the benzene ring is substituted or not substituted by a substituent R, the substituent R is 2-methyl, 4-methyl, 2,4, 6-trimethyl, 2-methoxy, 4-methoxy, 3,4, 5-trimethoxy, 2-bromo, 4-bromo, 2-nitro, 3-nitro, 4-fluoro, 4-trifluoromethyl, 4-chloro or 2, 4-dichloro.
Application of 3- (trifluoromethyl) -pyrazole-4-carboxylic ester derivative in preparing bactericide is provided.
Application of 3- (trifluoromethyl) -pyrazole-4-carboxylic ester derivative in preparing herbicide.
Compared with the prior art, the invention has the beneficial effects that: the invention provides a 3- (trifluoromethyl) -pyrazole-4-carboxylate derivative, a preparation method and application thereof in preparing bactericides and herbicides, the preparation method is simple and convenient to operate, the obtained compound has the best inhibition rate to rice blast germs at 50ppm effective concentration, and has moderate inhibition activity to lettuce and strand-cutting, and the compound provides a basis for research and development of new pesticides.
Detailed Description
The invention will be further illustrated with reference to specific examples, but the scope of the invention is not limited thereto.
The synthetic process route of the 3- (trifluoromethyl) -pyrazole-4-carboxylic ester derivative is as follows:
when H on the benzene ring is substituted or not substituted by a substituent R, the substituent R is 2-methyl, 4-methyl, 2,4, 6-trimethyl, 2-methoxy, 4-methoxy, 3,4, 5-trimethoxy, 2-bromo, 4-bromo, 2-nitro, 3-nitro, 4-fluoro, 4-trifluoromethyl, 4-chloro or 2, 4-dichloro.
Example 1 preparation of (E) -benzaldehyde O- (1-methyl-3- (trifluoromethyl) -1H-pyrazole-4-carbonyl) oxime
1) Preparation of (E) -2- (ethoxymethylene) -4, 4-trifluoro-3-oxobutanoic acid ethyl ester:
acetic anhydride (15.3 g,150.0 mmol) was added into a 100mL reaction flask, then ethyl trifluoroacetoacetate (9.2 g,50.0 mmol) and triethyl orthoformate (22.2 g,150.0 mmol) were added, the temperature was raised to reflux, after the reaction was carried out for 8 hours, the heating was stopped, and after the reaction solution cooled to room temperature, the low boilers were removed by rotary evaporation under reduced pressure to obtain a crude product of ethyl (E) -2- (ethoxymethylene) -4, 4-trifluoro-3-oxobutyrate represented by the formula (II);
2) Synthesis of 1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid ethyl ester (III):
absolute ethyl alcohol (10 mL) was added to a crude product containing 48.0mmol of ethyl 4, 4-trifluoro-2- (methoxymethylene) -3-oxobutyrate of formula (II), and the mixture was stirred uniformly, then added dropwise to a mixed solution of 40% by mass methyl hydrazine aqueous solution (methylhydrazine 72.0 mmol) and absolute ethyl alcohol (15 mL) under ice salt bath conditions, and after the addition was completed, the mixture was heated to 50℃and TLC (V) EA /V PE =1/2) tracking the reaction, removing the solvent by reduced pressure rotary evaporation after the reaction is finished, then adding ethyl acetate (20 mL) and water for extraction, washing the organic layer with saturated saline water three times, drying the organic layer with anhydrous magnesium sulfate, and then performing reduced pressure rotary evaporation to obtain a crude product of the 1-methyl-3-trifluoromethyl-1H-pyrazole-4-ethyl formate shown in the formula (iii);
3) Synthesis of 1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid (IV):
a reaction flask of 100mL was charged with 41mmol of ethyl 1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboxylate of formula (III), followed by addition of 10% strength by mass sodium hydroxide solution (82.0 mmol) and stirring at 60℃and TLC (V) EA /V PE =1/1) tracking reaction, cooling to room temperature after the reaction is finished, adding concentrated hydrochloric acid to adjust the pH to about 2.0, precipitating a large amount of solids, carrying out suction filtration, washing with water and drying to obtain a crude product of 1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid shown in a formula (IV);
4) Synthesis of 1-methyl-3-trifluoromethyl-1H-pyrazole-4-carbonyl chloride (V):
adding a crude product containing 27.0mmol of 1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid shown in a formula (IV) into a 100mL reaction bottle, adding thionyl chloride (10 mL), heating and refluxing until the reaction liquid becomes clear and transparent from turbidity, continuing to react for 30 minutes, stopping heating, and removing redundant thionyl chloride by reduced pressure rotary evaporation to obtain 1-methyl-3-trifluoromethyl-1H-pyrazole-4-formyl chloride shown in a formula (V);
5) Synthesis of (E) -benzaldehyde O- (1-methyl-3- (trifluoromethyl) -1H-pyrazole-4-carbonyl) oxime (A1):
dichloromethane (10 mL) was added to 1-methyl-3-trifluoromethyl-1H-pyrazole-4-carbonyl chloride (6.0 mmol) shown in (V), benzaldehyde oxime (7.5 mmol) was added to a 50mL reaction flask, dichloromethane (10 mL) and triethylamine (1 mL) were then added, and after stirring uniformly, the dichloromethane solution of 1-methyl-3-trifluoromethyl-1H-pyrazole-4-carbonyl chloride shown in (V) was added dropwise to the reaction flask under ice salt bath conditions, stirring was carried out while dropwise addition was carried out, stirring was carried out at room temperature after dropwise addition was completed, TLC (V) EA /V PE =1/2) tracking reaction, adding column chromatography silica gel after the reaction is finished, removing solvent by reduced pressure rotary evaporation, purifying by column chromatography to obtain a compound (A1), and eluting with a mixed solution of ethyl acetate and petroleum ether in a volume ratio of 2:3;
wherein H on the benzene ring in the structural formula (I) is not substituted, and the molecular structure of the compound of the formula (A1) is formed.
(E) -benzaldehyde O- (1-methyl-3- (trifluoromethyl) -1H-pyrazole-4-carbonyl) oxime: white solid, yield: 71.9%, melting point: 190-194 ℃; 1 H NMR(CDCl 3 ,500MHz),δ:8.47(s,1H,CH),8.14(s,1H,Pyrazole),7.80(d,J＝6.9Hz,2H,Ph),7.53-7.50(m,1H,Ph),7.48-7.45(m,2H,Ph),4.03(s,3H,CH 3 )；HRMS(ESI)for C 13 H 10 F 3 N 3 O 2 m/z:Calculated,298.0798,Found,298.0803[M+H] + .
example 2 preparation of (E) -2-methylbenzaldehyde O- (1-methyl-3- (trifluoromethyl) -1H-pyrazole-4-carbonyl) oxime (A2)
The compound (A2) was produced by the same procedure of example 1, except that the benzaldehyde oxime in step 5) of example 1 was replaced with an equivalent molar amount of 2-methylbenzaldehyde oxime.
(E) -2-methylbenzaldehyde O- (1-methyl-3- (trifluoromethyl) -1H-pyrazole-4-carbonyl) oxime: white solid, yield: 70.2%, melting point: 134-137 ℃; 1 H NMR(CDCl 3 ,500MHz),δ:8.72(s,1H,CH),8.14(s,1H,Pyrazole),7.90(d,J＝7.8Hz,1H,Ph),7.39(t,J＝7.5Hz,1H,Ph),7.29-7.25(m,2H,Ph),4.03(s,3H,CH 3 ),2.53(s,3H,CH 3 )；HRMS(ESI)for C 14 H 12 F 3 N 3 O 2 m/z:Calculated,312.0954,Found,312.0960[M+H] + .
example 3 preparation of (E) -4-methylbenzaldehyde O- (1-methyl-3- (trifluoromethyl) -1H-pyrazole-4-carbonyl) oxime (A3)
The compound (A3) was produced in the same manner as in example 1 except that the benzaldehyde oxime in step 5) of example 1 was replaced with an equivalent molar amount of 4-methylbenzaldehyde oxime.
(E) -4-methylbenzaldehyde O- (1-methyl-3- (trifluoromethyl) -1H-pyrazole-4-carbonyl) oxime: white solid, yield: 70.5%, melting point: 169-174 ℃; 1 H NMR(CDCl 3 ,500MHz),δ:8.43(s,1H,CH),8.13(s,1H,Pyrazole),7.69(d,J＝8.2Hz,2H,Ph),7.27(d,J＝7.7Hz,2H,Ph),4.02(s,3H,CH 3 ),2.42(s,3H,CH 3 )；HRMS(ESI)for C 14 H 12 F 3 N 3 O 2 m/z:Calculated,312.0954,Found,312.0960[M+H] + .
example 4 preparation of (E) -2,4, 6-trimethylbenzaldehyde O- (1-methyl-3- (trifluoromethyl) -1H-pyrazole-4-carbonyl) oxime (A4)
The compound (A4) was produced by substituting the benzaldehyde oxime in step 5) of example 1 with an equivalent molar amount of 2,4, 6-trimethylbenzaldehyde oxime in the same manner as in example 1.
(E) -2,4, 6-trimethylbenzaldehyde O- (1-methyl-3- (trifluoromethyl) -1H-pyrazole-4-carbonyl) oxime: pale yellow solid, yield: 69.3%, melting point: 138-144 ℃; 1 H NMR(CDCl 3 ,500MHz),δ:8.77(s,1H,CH),8.13(s,1H,Pyrazole),6.94(s,2H,Ph),4.03(s,3H,CH 3 ),2.49(s,6H,CH 3 ),2.32(s,3H,CH 3 )；HRMS(ESI)for C 16 H 16 F 3 N 3 O 2 m/z:Calculated,340.1267,Found,340.1273[M+H] + .
example 5 preparation of (E) -2-methoxybenzaldehyde O- (1-methyl-3- (trifluoromethyl) -1H-pyrazole-4-carbonyl) oxime (A5)
The compound (A5) was produced by the same procedure of example 1 except that the benzaldehyde oxime in step 5) of example 1 was replaced with an equivalent molar amount of 2-methoxybenzaldehyde oxime.
(E) -2-methoxybenzaldehyde O- (1-methyl-3- (trifluoromethyl) -1H-pyrazole-4-carbonyl) oxime: white solid, yield: 69.7%, melting point: 131-133 ℃; 1 H NMR(CDCl 3 ,500MHz),δ:8.86(s,1H,CH),8.12(s,1H,Pyrazole),8.03(d,J＝6.0Hz,1H,Ph),7.46(t,J＝8.4Hz,1H,Ph),7.01(t,J＝7.6Hz,1H,Ph),6.95(d,J＝8.5Hz,1H,Ph),4.02(s,3H,CH 3 ),3.90(s,3H,OCH 3 )；HRMS(ESI)for C 14 H 12 F 3 N 3 O 3 m/z:Calculated,328.0904,Found,328.0909[M+H] + .
example 6 preparation of (E) -4-methoxybenzaldehyde O- (1-methyl-3- (trifluoromethyl) -1H-pyrazole-4-carbonyl) oxime (A6)
The compound (A6) was produced in the same manner as in example 1 except that the benzaldehyde oxime in step 5) of example 1 was replaced with an equivalent molar amount of 4-methoxybenzaldehyde oxime.
(E) -4-methoxybenzaldehyde O- (1-methyl-3- (trifluoromethyl) -1H-pyrazole-4-carbonyl) oxime: pale yellow solid, yield: 69.5%, melting point: 142-148 ℃; 1 H NMR(CDCl 3 ,500MHz),δ:8.40(s,1H,CH),8.12(s,1H,Pyrazole),7.74(d,J＝8.8Hz,2H,Ph),6.96(d,J＝8.8Hz,2H,Ph),4.02(s,3H,CH 3 ),3.87(s,3H,OCH 3 )；HRMS(ESI)for C 14 H 12 F 3 N 3 O 3 m/z:Calculated,338.0904,Found,338.0909[M+H] + .
example 7 preparation of (E) -3,4, 5-trimethoxybenzaldehyde O- (1-methyl-3- (trifluoromethyl) -1H-pyrazole-4-carbonyl) oxime (A7)
The compound (A7) was produced by the same procedure of example 1, except that the benzaldehyde oxime in step 5) of example 1 was replaced with 3,4, 5-trimethoxybenzaldehyde oxime in an equivalent molar amount.
(E) -3,4, 5-trimethoxybenzaldehyde O- (1-methyl-3- (trifluoromethyl) -1H-pyrazole-4-carbonyl) oxime: white solid, yield: 70.1%, melting point: 135-140 ℃; 1 H NMR(CDCl 3 ,500MHz),δ:8.37(s,1H,CH),8.13(s,1H,Pyrazole),7.02(s,2H,Ph),4.03(s,3H,CH 3 ),3.92(s,6H,OCH 3 ),3.91(s,3H,OCH 3 )；HRMS(ESI)for C 16 H 16 F 3 N 3 O 5 m/z:Calculated,388.1115,Found,388.1120[M+H] + ..
example 8 preparation of (E) -2-bromobenzaldehyde O- (1-methyl-3- (trifluoromethyl) -1H-pyrazole-4-carbonyl) oxime (A8)
The compound (A8) was produced in the same manner as in example 1 except that the benzaldehyde oxime in step 5) of example 1 was replaced with 2-bromobenzaldehyde oxime in an equivalent molar amount.
(E) -2-bromobenzaldehyde O- (1-methyl-3- (trifluoromethyl) -1H-pyrazole-4-carbonyl) oxime as a pale yellow solid in yield: 68.3%, melting point: 135-139 ℃; 1 H NMR(CDCl 3 ,500MHz),δ:8.88(s,1H,CH),8.15(s,1H,Pyrazole),8.13(d,J＝7.7Hz,1H,Ph),7.64(d,J＝7.8Hz,1H,Ph),7.40(t,J＝6.8Hz,1H,Ph),7.36(t,J＝7.6Hz,1H,Ph),4.04(s,3H,CH 3 )；HRMS(ESI)for C 13 H 9 BrF 3 N 3 O 2 m/z:Calculated,375.9903,Found,375.9908[M+H] + .
example 9 preparation of (E) -4-bromobenzaldehyde O- (1-methyl-3- (trifluoromethyl) -1H-pyrazole-4-carbonyl) oxime (A9)
The compound (A9) was produced in the same manner as in example 1 except that the benzaldehyde oxime in step 5) of example 1 was replaced with an equivalent molar amount of 4-bromobenzaldehyde oxime.
(E) -4-bromobenzaldehyde O- (1-methyl-3- (trifluoromethyl) -1H-pyrazole-4-carbonyl) oxime as a pale yellow solid in yield: 69.2%, melting point: 189-191 ℃; 1 H NMR(CDCl 3 ,500MHz),δ:8.42(s,1H,CH),8.14(s,1H,Pyrazole),7.68(d,J＝8.5Hz,2H,Ph),7.61(d,J＝8.5Hz,2H,Ph),4.03(s,3H,CH 3 )；HRMS(ESI)for C 13 H 9 BrF 3 N 3 O 2 m/z:Calculated,375.9903,Found,375.9908[M+H] + .
example 10 preparation of (E) -2-nitrobenzaldehyde O- (1-methyl-3- (trifluoromethyl) -1H-pyrazole-4-carbonyl) oxime (A10)
The compound (a 10) was produced in the same manner as in example 1 except that the benzaldehyde oxime in step 5) of example 1 was replaced with 2-nitrobenzaldehyde oxime in the same molar amount.
(E) -2-nitrobenzaldehyde O- (1-methyl-3- (trifluoromethyl) -1H-pyrazole-4-carbonyl) oxime: pale yellow solid, yield: 71.1%, melting point: 154-159℃； 1 H NMR(CDCl 3 ,500MHz),δ:9.09(s,1H,CH),8.21(d,J＝8.2Hz,1H,Ph),8.17(d,J＝9.2Hz,1H,Ph),8.16(s,1H,Pyrazole),7.77(t,J＝6.9Hz,1H,Ph),7.70(t,J＝7.8Hz,1H,Ph),4.05(s,3H,CH 3 )；HRMS(ESI)for C 13 H 9 F 3 N 4 O 4 m/z:Calculated,343.0649,Found,343.0654[M+H] + ..
Example 11 preparation of (E) -3-nitrobenzaldehyde O- (1-methyl-3- (trifluoromethyl) -1H-pyrazole-4-carbonyl) oxime (A11)
The compound (a 11) was produced in the same manner as in example 1 except that the benzaldehyde oxime in step 5) of example 1 was replaced with 3-nitrobenzaldehyde oxime in the same molar amount.
(E) -3-nitrobenzaldehyde O- (1-methyl-3- (trifluoromethyl) -1H-pyrazole-4-carbonyl) oxime: white solid, yield: 71.8%, melting point: 171-172 ℃; 1 H NMR(CDCl 3 ,500MHz),δ:8.61(s,1H,Ph),8.56(s,1H,CH),8.37(d,J＝8.2Hz,1H,Ph),8.21(d,J＝7.8Hz,1H,Ph),8.17(s,1H,Pyrazole),7.68(t,J＝8.0Hz,1H,Ph),4.05(s,3H,CH 3 )；HRMS(ESI)for C 13 H 9 F 3 N 4 O 4 m/z:Calculated,343.0649,Found,343.0654[M+H] + .
example 12 preparation of (E) -4-fluorobenzaldehyde O- (1-methyl-3- (trifluoromethyl) -1H-pyrazole-4-carbonyl) oxime (A12)
The compound (a 12) was produced in the same manner as in example 1 except that the benzaldehyde oxime in step 5) of example 1 was replaced with 4-fluorobenzaldehyde oxime in the same molar amount.
(E) -4-fluorobenzaldehyde O- (1-methyl-3- (trifluoromethyl) -1H-pyrazole-4-carbonyl) oxime: white solid, yield: 69.5%, melting point: 140-143 ℃; 1 H NMR(CDCl 3 ,500MHz),δ:8.44(s,1H,CH),8.14(s,1H,Pyrazole),7.82(d,J＝5.3Hz,1H,Ph),7.80(d,J＝5.3Hz,1H,Ph),7.16(t,J＝8.6Hz,2H,Ph),4.03(s,3H,CH 3 )；HRMS(ESI)for C 13 H 9 F 4 N 3 O 2 m/z:Calculated,316.0704,Found,316.0709[M+H] + .
example 13 preparation of (E) -4- (trifluoromethyl) benzaldehyde O- (1-methyl-3- (trifluoromethyl) -1H-pyrazole-4-carbonyl) oxime (A13)
The compound (a 13) was produced in the same manner as in example 1 except that the benzaldehyde oxime in step 5) of example 1 was replaced with 4-trifluoromethylbenzaldehyde oxime in the same molar amount.
(E) -4- (trifluoromethyl) benzaldehyde O- (1-methyl-3- (trifluoromethyl) -1H-pyrazole-4-carbonyl) oxime: white solid, yield: 68.1%, melting point: 135-138 ℃; 1 H NMR(CDCl 3 ,500MHz),δ:8.51(s,1H,CH),8.16(s,1H,Pyrazole),7.94(d,J＝8.1Hz,2H,Ph),7.73(d,J＝8.1Hz,2H,Ph),4.04(s,3H,CH 3 )；HRMS(ESI)for C 14 H 9 F 6 N 3 O 2 m/z:Calculated,366.0672,Found,366.0677[M+H] + .
example 14 preparation of (E) -2, 4-dichlorobenzaldehyde O- (1-methyl-3- (trifluoromethyl) -1H-pyrazole-4-carbonyl) oxime (A14)
The compound (a 14) was produced in the same manner as in example 1 except that the benzaldehyde oxime in step 5) of example 1 was replaced with 2, 4-dichlorobenzaldehyde oxime in the same molar amount.
(E) -2, 4-dichlorobenzaldehyde O- (3- (trifluoromethyl) -1l 2-pyrazole-4-carbonyl) oxime: white solid, yield: 68.4%, melting point: 157-159 ℃; 1 H NMR(CDCl 3 ,500MHz),δ:8.84(s,1H,CH),8.15(s,1H,Pyrazole),8.10(d,J＝8.5Hz,1H,Ph),7.48(s,1H,Ph),7.35(d,J＝8.5Hz,1H,Ph),4.04(s,3H,CH 3 )；HRMS(ESI)for C 13 H 8 Cl 2 F 3 N 3 O 2 m/z:Calculated,366.0018,Found,366.0024[M+H] + .
EXAMPLE 15 bactericidal Activity test
Test object: tomato early blight (Alternaria solani), wheat scab (Gibberella zeae), rice blast (Pyrazolericularia oryae), pepper epidemic (Phytophthora capsici), sclerotinia sclerotiorum (Sclerotinia sclerotiorum), cucumber gray mold (Botrytis cinerea), sheath blight (Riziocotinia solani), cucumber fusarium wilt (Fusarium oxysporum), peanut brown spot (Cercospora arachidicola) and apple ring rot (Physalospora piricola).
The compounds (A1) to (a 14) prepared in examples 1 to 14 were labeled as test compounds, respectively, and the bactericidal activity test was performed in the following manner:
test treatment: each compound was dissolved in DMSO to 1% master batch for use. And testing the indoor bactericidal activity of each compound on 10 germs at a dosage of 50ppm by adopting a bacteriostasis circle method.
A test method; 150. Mu.L of the mother solution was aspirated by a pipette, and 3mL of 500ppm of the solution was prepared by dissolving the mother solution in distilled water. 1mL of the liquid medicine is sucked by a pipette, placed in a sterilized culture dish, placed in 9mL of PDA culture medium, shaken well and cooled. The puncher is fully burnt in the outer flame of an alcohol lamp, a round fungus cake is picked after cooling (the incision must be ensured to be cooled), then a sterilization inoculation needle is used for picking the fungus cake, the mycelium surface is downwards attached to the center of a culture dish, the culture dish is placed in a culture box for culture at 27 ℃, the pure growth quantity of the colony with the colony diameter is measured after 48 hours and is the difference value between the average colony diameter and the diameter of the fungus cake, and the bacteriostasis rate (%) is calculated by referring to the following formula.
The pure growth amount of the control colony in the calculation formula refers to the pure growth amount of the colony under the clear water control test.
The bactericidal activity test results are shown in table 1.
TABLE 1 bactericidal activity (% control) of each compound at 50ppm
The surface shows that the compounds have certain bactericidal activity, but the bactericidal effects on wheat gibberella, phytophthora capsici, cucumber botrytis cinerea and cucumber fusarium wilt are not good, and are lower than 30%; the sterilizing effect on the brown spot germ of the peanut is lower than 50 percent. The inhibition rate of A9 to the sheath blight of rice reaches 51.7 percent. In general, the A5 compound has the best inhibition rate to rice blast germ, up to 85.7%, more than 65% to Rhizoctonia solani and Rhizoctonia cerealis, and more than 50% to Alternaria solani and Sclerotinia sclerotiorum, no matter the sterilization type or the effect is the best in the series.
EXAMPLE 16 herbicidal Activity test
Herbicidal activity test subjects: lettuce, cutting the strands.
The weeding activity test method comprises the following steps: all seeds were mixed with 5 high Le Shi bleach water for about 10min prior to bioassay and surface sterilized. The seeds were thoroughly rinsed with deionized water (Millipore system) and air dried in a sterile environment. Bioassays were performed on sterile non-pyrolyzed polystyrene 24-well cell culture plates, with 200 μl of sterile water for the control group, and with 180 μl of water and 20 μl of the samples of the invention appropriately diluted. 5 lettuce or glume seeds are put into each hole, and the cover is sealed by a sealing film. After continuous light cultivation for 7 days in an incubator at 26 ℃, the growth of seedlings in the control group and the sample group is observed. The weeding effect of the medicine to be tested is tested by inhibiting the growth of the compound on lettuce, the height of the glume-cutting seedling under the illumination condition. Test concentration of drug to be tested: 1mM, repeated twice. The weeding activity index: plant height growth inhibition (%). Activity classification index: 4 stages: the inhibition rate is more than or equal to 80 percent; 3 stages: the inhibition rate is 60-79%; 2 stages: the inhibition rate is 40-59%; stage 1: the inhibition rate is less than or equal to 20 to 39 percent, and the inhibition rate is less than or equal to 20 at the level 0.
TABLE 2 herbicidal Activity of the test Compounds (growth inhibition, 1 mM)
Compounds A1, A4 have moderate inhibitory activity against lettuce and agrostis, respectively.
What has been described in this specification is merely an enumeration of possible forms of implementation for the inventive concept and may not be considered limiting of the scope of the present invention to the specific forms set forth in the examples.

Claims (7)

1. The application of 3- (trifluoromethyl) -pyrazole-4-carboxylic ester derivatives in preparing herbicides is characterized in that the structural formula is shown in the formula (I):
in the formula (I), R is 2,4, 6-trimethyl.
2. The use according to claim 1, wherein the preparation method of the 3- (trifluoromethyl) -pyrazole-4-carboxylic acid ester derivative comprises the following steps:
1) Adding acetic anhydride into a mixed solution of trifluoro acetoacetic acid ethyl ester and triethyl orthoformate, heating to reflux, reacting for 6-12h, stopping heating, cooling the reaction liquid to room temperature, and evaporating under reduced pressure to remove low boiling point substances to obtain (E) -2- (ethoxymethylene) -4, 4-trifluoro-3-oxo-ethyl butyrate shown in a formula (II);
2) Adding the ethyl (E) -2- (ethoxymethylene) -4, 4-trifluoro-3-oxobutyrate shown in the formula (II) obtained in the step (1) into absolute ethyl alcohol, uniformly stirring, then dropwise adding the ethyl (E) -2- (ethoxymethylene) -4, 4-trifluoro-3-oxobutyrate into a mixed solution of methyl hydrazine aqueous solution and absolute ethyl alcohol under the ice salt bath condition, heating to 40-60 ℃ after the dropwise adding, carrying out TLC tracking reaction, removing a solvent by reduced pressure evaporation after the reaction is finished, adding ethyl acetate and water for extraction, washing an organic layer with saturated saline water for three times, drying through anhydrous magnesium sulfate, filtering, concentrating the filtrate, and removing the solvent to obtain a crude product of the ethyl 1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboxylate shown in the formula (III);
3) Adding sodium hydroxide aqueous solution into the crude product of the 1-methyl-3-trifluoromethyl-1H-pyrazole-4-ethyl formate shown in the formula (III) obtained in the step (2), heating to 50-70 ℃, stirring, performing TLC tracking reaction, cooling to room temperature after the reaction is finished, adding concentrated hydrochloric acid to adjust the pH to 1-4, precipitating a large amount of solid, filtering, washing with water, and drying to obtain the crude product of the 1-methyl-3-trifluoromethyl-1H-pyrazole-4-formic acid shown in the formula (IV);
4) Adding thionyl chloride into the crude product of the 1-methyl-3-trifluoromethyl-1H-pyrazole-4-formic acid shown in the formula (IV) obtained in the step (3), heating and refluxing until the reaction liquid becomes clear and transparent from turbidity, continuing to react for 10-60 minutes, stopping heating, and removing redundant thionyl chloride by reduced pressure rotary evaporation to obtain 1-methyl-3-trifluoromethyl-1H-pyrazole-4-formyl chloride shown in the formula (V);
5) Dissolving the 1-methyl-3-trifluoromethyl-1H-pyrazole-4-formyl chloride shown in the formula (V) obtained in the step (4) in dichloromethane, dropwise adding the dichloromethane in which the substituted benzaldehyde oxime shown in the formula (VI) and triethylamine are dissolved under the ice salt bath condition, stirring the solution while dropwise adding, stirring the solution at normal temperature after the dropwise adding, performing TLC tracking reaction, adding column chromatography silica gel after the reaction is finished, removing the solvent by reduced pressure rotary evaporation, and purifying the solution by column chromatography to obtain the 3- (trifluoromethyl) -pyrazole-4-carboxylate derivative shown in the formula (I);
the substituent R is 2,4, 6-trimethyl.
3. The use according to claim 2, wherein concentrated hydrochloric acid is added in step 3) to adjust the pH to 2.0.
4. The use according to claim 2, wherein in step 1), the molar ratio of acetic anhydride, ethyl trifluoroacetoacetate and triethyl orthoformate is 3:1-2:3-6; in the step 2), the feeding mole ratio of the (E) -2- (ethoxymethylene) -4, 4-trifluoro-3-oxo-ethyl butyrate and methyl hydrazine shown in the formula (II) is 1:1-2; in the step 3), the feeding mole ratio of the 1-methyl-3-trifluoromethyl-1H-pyrazole-4-ethyl formate shown in the formula (III) to the sodium hydroxide is 1:1-3; in the step 4), the dosage of the thionyl chloride is excessive; in the step 5), the feeding mole ratio of the 1-methyl-3-trifluoromethyl-1H-pyrazole-4-formyl chloride shown in the formula (V) to the substituted benzaldehyde oxime shown in the formula (VI) is 1:1.1-1.5.
5. The use according to claim 2, wherein the amount by volume of absolute ethanol in which the ethyl (E) -2- (ethoxymethylene) -4, 4-trifluoro-3-oxobutanoate of formula (II) is dissolved in step 2) is from 0.1 to 0.4mL/mmol based on the amount of ethyl (E) -2- (ethoxymethylene) -4, 4-trifluoro-3-oxobutanoate of formula (II), and the amount by volume of thionyl chloride in step 4) is from 0.1 to 0.5mL/mmol based on the amount of 1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid of formula (IV).
6. The use according to claim 2, wherein the volume amount of dichloromethane used in step 5) for dissolving 1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid chloride is 1 to 3mL/mmol based on the amount of the substance of 1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid chloride of formula (v).
7. The use according to claim 2, wherein the eluent from the column chromatography in step 5) is a mixture of ethyl acetate and petroleum ether in a volume ratio of 2:3.
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