A pyridazine derivative, its preparation method and application

Abstract

The present application relates to the field of compound synthesis technology and pesticides, and in particular to a pyridazine derivative, a preparation method and application thereof, the pyridazine derivative is an aromatic ether and an N-substituted phenylcarboxamide group; the aromatic ether is a substituted pyridazine group substituted phenyl ether; the substituted phenyl group is trifluoromethyl or halogen substitution, and the phenyl group containing the N-substituted phenylcarboxamide group is substituted by different halogen groups; the derivative has effective pre-emergence and post-emergence herbicidal activity, and can be applied as a herbicide; the structure of the derivative is simple, the production cost is low, and the application prospect is wide.

Description

Technical Field

[0001] This invention belongs to the fields of compound synthesis technology and pesticides, specifically relating to a pyridazine derivative, its preparation method, and its application. Background Technology

[0002] With the increasing global population, food security has become increasingly important, and ensuring a steady increase in food production has always been a key goal of agricultural development. Herbicides are one of the important measures to ensure food production, and their use in agricultural production has been increasing year by year. The use of herbicides can improve agricultural productivity, save labor costs, protect the environment, improve crop quality, and promote sustainable agricultural development. However, with the large-scale use of herbicides, weeds are gradually developing resistance to them. At the same time, with the improvement of living standards, the requirements for herbicides are also increasing. The continuous development of new, highly efficient, low-toxicity, and environmentally friendly herbicides is an urgent need in current agricultural production, and also provides opportunities for the development of the herbicide industry.

[0003] Small molecules containing pyridazine rings are widely used in pharmaceuticals, pesticides, and materials. In the pesticide field, herbicides based on pyridazines are already on the market, such as pyridazine alcohol, pyridaben, fluazinam, and flupyridazine ester. In addition, research on pyridazine-containing herbicides has made some progress in recent years. For example, applications 201811035345.5, 201811035352.5, 201811035457.0, and 201880076904.9 disclose the preparation and herbicidal activity of pyridazine herbicides. However, these herbicides still have drawbacks such as high toxicity, high production costs, and large dosage requirements. Meanwhile, with the improvement of living standards, environmental protection requirements, and the emergence of weed resistance, there is a need to continuously develop new, efficient, safe, economical herbicides with different modes of action. Summary of the Invention

[0004] This invention addresses the shortcomings of existing technologies by proposing a pyridazine derivative, its preparation method, and its application.

[0005] Specifically, this is achieved through the following technical solutions:

[0006] One of the pyridazine derivatives is a pyridazine derivative containing an N-substituted arylformyl group or a pyridazine derivative containing an aryl ether;

[0007] A pyridazine derivative is a substituted aryloxy group and an N-substituted aryl formamide introduced onto a pyridazine ring, wherein the general structural formula of the pyridazine derivative is as shown in formula (I):

[0008]

[0009] In the formula: R1 is a halogen atom;

[0010] R2 is a halogen or a trifluoromethyl or trifluoromethoxy;

[0011] X is hydrogen or halogen;

[0012] The pyridazine derivatives include the following compounds:

[0013] Compound A1: 3-(3-trifluoromethylphenoxy)-4-N-(2,4-difluorophenyl)formamide pyridazine;

[0014] Compound A2: 3-(3-trifluoromethylphenoxy)-4-N-phenylcarbamate pyridazine;

[0015] Compound A3: 3-(3-trifluoromethylphenoxy)-4-N-(2-chlorophenyl)carbamate;

[0016] Compound A4: 3-(3-trifluoromethylphenoxy)-4-N-(3-chlorophenyl)carbamate;

[0017] Compound A5: 3-(3-trifluoromethylphenoxy)-4-N-(4-chlorophenyl)carbamate;

[0018] Compound A6: 3-(3-trifluoromethylphenoxy)-4-N-(2,3-dichlorophenyl)carbamate;

[0019] Compound A7: 3-(3-trifluoromethylphenoxy)-4-N-(2,4-dichlorophenyl)formamide pyridazine;

[0020] Compound A8: 3-(3-trifluoromethylphenoxy)-4-N-(2,5-dichlorophenyl)formamide pyridazine;

[0021] Compound A9: 3-(3-trifluoromethylphenoxy)-4-N-(2,6-dichlorophenyl)carbamate;

[0022] Compound A10: 3-(3-trifluoromethylphenoxy)-4-N-(3,4-dichlorophenyl)formamide pyridazine;

[0023] Compound A11: 3-(3-trifluoromethylphenoxy)-4-N-(3,5-dichlorophenyl)formamide pyridazine;

[0024] Compound A12: 3-(3-trifluoromethylphenoxy)-4-N-(2-fluorophenyl)carbamate;

[0025] Compound A13: 3-(3-trifluoromethylphenoxy)-4-N-(3-fluorophenyl)carbamate;

[0026] Compound A14: 3-(3-trifluoromethylphenoxy)-4-N-(4-fluorophenyl)carbamate;

[0027] Compound A15: 3-(3-trifluoromethylphenoxy)-4-N-(2,3-difluorophenyl)formamide pyridazine;

[0028] Compound A16: 3-(3-trifluoromethylphenoxy)-4-N-(2,5-difluorophenyl)formamide pyridazine;

[0029] Compound A17: 3-(3-trifluoromethylphenoxy)-4-N-(2,6-difluorophenyl)formamide pyridazine;

[0030] Compound A18: 3-(3-trifluoromethylphenoxy)-4-N-(3,4-difluorophenyl)formamide pyridazine;

[0031] Compound A19: 3-(3-trifluoromethylphenoxy)-4-N-(3,5-difluorophenyl)formamide pyridazine;

[0032] Compound A20: 3-(3-trifluoromethylphenoxy)-4-N-(2-chloro-3-fluorophenyl)carboxamide pyridazine; Compound A21: 3-(3-trifluoromethylphenoxy)-4-N-(2-chloro-4-fluorophenyl)carboxamide pyridazine; Compound A22: 3-(3-trifluoromethylphenoxy)-4-N-(2-chloro-5-fluorophenyl)carboxamide pyridazine;

[0033] Compound A23: 3-(3-trifluoromethylphenoxy)-4-N-(2-chloro-6-fluorophenyl)formamide pyridazine; Compound A24: 3-(3-trifluoromethylphenoxy)-4-N-(3-chloro-4-fluorophenyl)formamide pyridazine; Compound A25: 3-(3-trifluoromethylphenoxy)-4-N-(3-chloro-5-fluorophenyl)formamide pyridazine; Compound A26: 3-(3-trifluoromethylphenoxy)-4-N-(3-chloro-6-fluorophenyl)formamide pyridazine; Compound A27: 3-(3-trifluoromethylphenoxy)-4-N-(2-fluoro-4-chlorophenyl)formamide pyridazine; Compound A28: 3-(3-trifluoromethylphenoxy)-4-N-(2,3,4-trifluorophenyl)formamide pyridazine; Compound A29: 3-(3-trifluoromethylphenoxy)- 4-N-(2,3,5-trifluorophenyl)carbamopyridazine; Compound A30: 3-(3-trifluoromethylphenoxy)-4-N-(2,3,6-trifluorophenyl)carbamopyridazine; Compound A31: 3-(3-trifluoromethylphenoxy)-4-N-(3,4,5-trifluorophenyl)carbamopyridazine; Compound A32: 3-(3-trifluoromethylphenoxy)-4-N-(2,4,5-trifluorophenyl)carbamopyridazine; Compound A33: 3-(3-trifluoromethylphenoxy)-4-N-(2,4,6-trifluorophenyl)carbamopyridazine; Compound B1: 3-(3-trifluoromethylphenoxy)-4-N-(2,4-difluorophenyl)carbamopyridazine; Compound B2: 3-(3-trifluoromethylphenoxy)-4-N-phenylcarbamopyridazine;

[0034] Compound B3: 3-(3-trifluoromethylphenoxy)-4-N-(2-chlorophenyl)carboxamide-6-chloropyridazine;

[0035] Compound B4: 3-(3-trifluoromethylphenoxy)-4-N-(3-chlorophenyl)carboxamide-6-chloropyridazine;

[0036] Compound B5: 3-(3-trifluoromethylphenoxy)-4-N-(4-chlorophenyl)carboxamide-6-chloropyridazine;

[0037] Compound B6: 3-(3-trifluoromethylphenoxy)-4-N-(2,3-dichlorophenyl)formamide-6-chloropyridazine; Compound B7: 3-(3-trifluoromethylphenoxy)-4-N-(2,4-dichlorophenyl)formamide-6-chloropyridazine; Compound B8: 3-(3-trifluoromethylphenoxy)-4-N-(2,5-dichlorophenyl)formamide-6-chloropyridazine; Compound B9: 3-(3-trifluoromethylphenoxy)-4- N-(2,6-dichlorophenyl)formamide-6-chloropyridazine; Compound B10: 3-(3-trifluoromethylphenoxy)-4-N-(3,4-dichlorophenyl)formamide-6-chloropyridazine; Compound B11: 3-(3-trifluoromethylphenoxy)-4-N-(3,5-dichlorophenyl)formamide-6-chloropyridazine; Compound B12: 3-(3-trifluoromethylphenoxy)-4-N-(2-fluorophenyl)formamide-6-chloropyridazine;

[0038] Compound B13: 3-(3-trifluoromethylphenoxy)-4-N-(3-fluorophenyl)carboxamide-6-chloropyridazine;

[0039] Compound B14: 3-(3-trifluoromethylphenoxy)-4-N-(4-fluorophenyl)carboxamide-6-chloropyridazine;

[0040] Compound B15: 3-(3-trifluoromethylphenoxy)-4-N-(2,3-difluorophenyl)formamide-6-chloropyridazine; Compound B16: 3-(3-trifluoromethylphenoxy)-4-N-(2,5-difluorophenyl)formamide-6-chloropyridazine; Compound B17: 3-(3-trifluoromethylphenoxy)-4-N-(2,6-difluorophenyl)formamide-6-chloropyridazine; Compound B18: 3-(3-trifluoromethylphenoxy)-4-N-(3,4-difluorophenyl)formamide-6-chloropyridazine; Compound B19: 3-(3-trifluoromethylphenoxy)-4-N -(3,5-Difluorophenyl)formamide-6-chloropyridazine; Compound B20: 3-(3-trifluoromethylphenoxy)-4-N-(2-chloro-3-fluorophenyl)formamide-6-chloropyridazine; Compound B21: 3-(3-trifluoromethylphenoxy)-4-N-(2-chloro-4-fluorophenyl)formamide-6-chloropyridazine; Compound B22: 3-(3-trifluoromethylphenoxy)-4-N-(2-chloro-5-fluorophenyl)formamide-6-chloropyridazine; Compound B23: 3-(3-trifluoromethylphenoxy)-4-N-(2-chloro-6-fluorophenyl)formamide-6-chloropyridazine;

[0041] Compound B24: 3-(3-trifluoromethylphenoxy)-4-N-(3-chloro-4-fluorophenyl)carboxamide-6-chloropyridazine;

[0042] Compound B25: 3-(3-trifluoromethylphenoxy)-4-N-(3-chloro-5-fluorophenyl)carboxamide-6-chloropyridazine;

[0043] Compound B26: 3-(3-trifluoromethylphenoxy)-4-N-(3-chloro-6-fluorophenyl)carboxamide-6-chloropyridazine;

[0044] Compound B27: 3-(3-trifluoromethylphenoxy)-4-N-(2-fluoro-4-chlorophenyl)carboxamide-6-chloropyridazine;

[0045] Compound B28: 3-(3-trifluoromethylphenoxy)-4-N-(2,3,4-trifluorophenyl)formamide-6-chloropyridazine;

[0046] Compound B29: 3-(3-trifluoromethylphenoxy)-4-N-(2,3,5-trifluorophenyl)formamide-6-chloropyridazine;

[0047] Compound B30: 3-(3-trifluoromethylphenoxy)-4-N-(2,3,6-trifluorophenyl)carboxamide-6-chloropyridazine;

[0048] Compound B31: 3-(3-trifluoromethylphenoxy)-4-N-(3,4,5-trifluorophenyl)carboxamide-6-chloropyridazine;

[0049] Compound B32: 3-(3-trifluoromethylphenoxy)-4-N-(2,4,5-trifluorophenyl)carboxamide-6-chloropyridazine;

[0050] Compound B33: 3-(3-trifluoromethylphenoxy)-4-N-(2,4,6-trifluorophenyl)carboxamide-6-chloropyridazine.

[0051] Another object of the present invention is to provide a method for preparing the pyridazine derivative, wherein the pyridazine derivative is synthesized by using pyridazine 3,6-dichloro-4-carboxylic acid, iodomethane, 3-trifluoromethylphenol and substituted aniline as main raw materials, and by esterification, etherification, hydrolysis, dehalogenation and amidation reactions, respectively; wherein the aniline is substituted with halogen.

[0052] The preparation method of the pyridazine derivatives, the synthesis of A1-A33 includes the following steps:

[0053] (1) Preparation of compound methyl 3,6-dichloro-4-carboxylate pyridazine (intermediate 2):

[0054] Compound 1 (3,6-dichloro-4-carboxypyridazine) was dissolved in an organic solvent, sodium carbonate was added, and iodomethane was added dropwise at a certain temperature. After the reaction of compound 1 was completed, the solid was obtained by extraction with ethyl acetate, drying and column chromatography, which is intermediate 2.

[0055] (2) Preparation of methyl 3-(3-trifluoromethylphenoxy)-4-carboxylate-6-chloropyridazine (intermediate 3):

[0056] Take 3-trifluoromethylphenol and an inorganic base in an organic solvent, stir at room temperature for 1 hour, add the organic solution of intermediate 2 dropwise, after the reaction is complete, filter, extract the organic layer with ethyl acetate, wash with saturated sodium chloride, dry and then column chromatography to obtain the solid, which is intermediate 3.

[0057] (3) Preparation of 3-(3-trifluoromethylphenoxy)-4-carboxylic acid-6-chloropyridazine (intermediate 4):

[0058] Intermediate 3 was placed in a mixed solvent of methanol and water, and sodium hydroxide or lithium hydroxide was added at room temperature. The mixture was stirred at room temperature. After the reaction was complete, the pH was adjusted to acidic with 1N HCl, extracted with ethyl acetate, washed with saturated sodium chloride, dried, and filtered to remove the organic solvent to obtain intermediate 4.

[0059] (4) Preparation of pyridazine 3-(3-trifluoromethylphenoxy)-4-carboxylic acid (intermediate 5)

[0060] Take intermediate 4 in ethanol, then add Pd / C and ammonium formate or pass hydrogen gas, heat to reflux, after the reaction is complete, adjust the pH to acidic, extract with ethyl acetate, wash with saturated sodium chloride, dry and column chromatography to obtain solid, which is intermediate 5.

[0061] (5) Preparation of target compounds A1-A33:

[0062] Intermediate 5 was placed in dichloromethane, DMF was added, and oxalyl chloride was added dropwise at room temperature. After reacting for 2 hours, dichloromethane was removed under reduced pressure, and then dichloromethane was added. Next, amine compounds and triethylamine were added dropwise. After reacting for 2 hours at room temperature, water was added to quench the reaction. The mixture was extracted with dichloromethane, washed with saturated sodium chloride, dried, and then subjected to column chromatography to obtain the solid, which was the target compound A1-A33.

[0063] The preparation method of the pyridazine derivatives, the synthesis of B1-B33 includes the following steps:

[0064] Steps (1) to (3) are the same as steps (1) to (3) of the target compound A1-A33;

[0065] (4) Preparation of target compounds B1-B33:

[0066] Intermediate 4 was placed in dichloromethane, DMF was added, and oxalyl chloride was added dropwise at room temperature. After reacting for 2 hours, dichloromethane was removed under reduced pressure, and then dichloromethane was added. Next, amine compounds and triethylamine were added dropwise. After reacting for 2 hours at room temperature, water was added to quench the reaction. The mixture was extracted with dichloromethane, washed with saturated sodium chloride, dried, and then subjected to column chromatography to obtain the solid, which was the target compound B1-B33.

[0067] Among the steps mentioned above:

[0068] In step (1), the reaction temperature is 0-25℃.

[0069] In step (2), the inorganic base is sodium carbonate, lithium carbonate, potassium carbonate or cesium carbonate.

[0070] In step (3), the amount of formic acid used is 5-10 times the mass of 3 or 5 moles of the intermediate.

[0071] The preparation route of the pyridazine derivative is as follows:

[0072]

[0073] Another object of the present invention is the use of the pyridazine derivative in the preparation of herbicides.

[0074] Specifically, the application of the pyridazine derivatives in the preparation of herbicides for barnyard grass, velvetleaf, amaranth, lambsquarters, ryegrass, purslane, bermudagrass, rapeseed, speedwell, amaranth, black nightshade, bitter lettuce, dandelion, sage, clover, chickweed, goosegrass, goosegrass, and foxtail grass.

[0075] Beneficial effects:

[0076] This invention is based on the pyridazine structure and introduces trifluoromethylphenoxy and N-halogen-substituted phenylformamide groups to form herbicidal active pharmacophores. Therefore, it creates a small molecule pyridazine herbicide pesticide containing aromatic ethers and N-halogen-substituted phenylformamide groups with relatively stable physicochemical properties and excellent drug-like properties. This type of derivative has a particularly significant post-emergence inhibition effect on dicotyledonous weeds and a significant pre-emergence inhibition effect on monocotyledonous and dicotyledonous weeds.

[0077] Pre-emergence activity studies showed that, at a concentration of 100 μg / mL, most compounds in series A and B exhibited better pre-emergence herbicidal activity compared to the positive control pyfluquat, particularly compounds A19, B1, and B19, which showed 100% inhibition against the roots and stems of barnyardgrass. Similarly, compounds A28, A29, B23, and B31 also showed 100% inhibition against the roots and stems of purslane. Some compounds showed 100% inhibition only against the roots or stems. At a concentration of 10 μg / mL, compounds B1, B19, and B20 showed higher inhibition rates against the roots and stems of both barnyardgrass and purslane compared to the positive control pyfluquat, exceeding those of the positive control. Among these, B19 showed the best pre-emergence herbicidal activity, followed by B1. Notably, B1 and B20 caused complete whitening of barnyardgrass, similar to pyfluquat. Furthermore, compounds A5, A7, B3, B4, B6, B11, B13, B16, B22, B25, B29, B31, and B33 also showed better inhibition rates against barnyardgrass roots than pyrfluthrin. For purslane, most of these compounds exhibited higher activity than pyrfluthrin, both against roots and stems.

[0078] Post-emergence herbicidal activity tests showed that most pyridazine compounds exhibited good herbicidal activity against *Abutilon theophrasti*, *Amaranthus retroflexus*, *Amaranthus urinaria*, and *Veronica persica* at a dosage of 300 g ai / ha. In particular, at a dosage of 75 g ai / ha, compound B1 was comparable to the positive control herbicide pyrifluquinazon, and compared to the positive control fluroxypyr, it showed superior inhibitory activity against *Amaranthus retroflexus* and *Abutilon theophrasti*.

[0079] This invention relates to pyridazine derivatives with simple structure, simple preparation process, low production cost, high yield, low toxicity, easy degradation, good environmental compatibility, high safety in use, and non-toxic and harmless preparation process. Attached Figure Description

[0080] Figure 1 This is a route diagram for the preparation of pyridazine derivatives. Detailed Implementation

[0081] The specific embodiments of the present invention will be described in further detail below, but the present invention is not limited to these embodiments. Any improvements or substitutions based on these embodiments are still within the scope of protection claimed by the claims of the present invention.

[0082] Example 1: A method for preparing 3-(3-trifluoromethylphenoxy)-4-N-(2,4-difluorophenyl)formamide pyridazine (i.e., compound A1), comprising the following steps:

[0083] (1) Preparation of methyl 3,6-dichloro-4-carboxylate pyridazine (intermediate 2):

[0084] 19.3 g (0.1 mol) of 3,6-dichloro-4-carboxypyridazine was dissolved in 70 mL of N,N-dimethylformamide. Sodium carbonate (31.8 g, 0.3 mol) was added with stirring at room temperature. After no more bubbles were generated, iodomethane (21.3 g, 0.15 mol) was added dropwise at room temperature. After the addition was complete, stirring was continued at room temperature until the 3,6-dichloro-4-carboxypyridazine was completely eliminated. Stirring was then stopped, the solid was removed by filtration, 150 mL of water was added to the organic layer, and the mixture was extracted with ethyl acetate, dried, and subjected to column chromatography to obtain 18 g of solid methyl 3,6-dichloro-4-carboxypyridazine intermediate, with a yield of 87%.

[0085] (2) Preparation of methyl 3-(3-trifluoromethylphenoxy)-4-carboxylate-6-chloropyridazine (intermediate 3):

[0086] 3-Trifluoromethylphenol (1.62 g, 10 mmol) was dissolved in N,N-dimethylformamide, and Cs₂CO₃ (6.52 g, 20 mmol) was added. The reaction was carried out at room temperature for 2 h, and then 3 mL of a solution of 3,6-dichloro-4-carboxypyridazine (2.07 g, 10 mmol) dissolved in DMF was added dropwise. The mixture was stirred at room temperature for 1 h. After filtration, the organic layer was extracted with ethyl acetate, dried, and subjected to column chromatography to obtain 2.9 g of solid methyl 3-(3-trifluoromethylphenoxy)-4-carboxylate-6-chloropyridazine intermediate, with a yield of 88%.

[0087] (3) Preparation of 3-(3-trifluoromethylphenoxy)-4-carboxylic acid-6-chloropyridazine (intermediate 4):

[0088] 3.3 g (10 mmol) of methyl 3-(3-trifluoromethylphenoxy)-4-carboxylic acid-6-chloropyridazine was added to 20 mL of methanol and 4 mL of water, along with 0.6 g of NaOH. The mixture was stirred at room temperature. After the starting material reacted, 1 N HCl was added to adjust the pH to 4-5. The mixture was extracted with ethyl acetate, dried, and subjected to column chromatography to obtain 2.9 g of the solid intermediate 3-(3-trifluoromethylphenoxy)-4-carboxylic acid-6-chloropyridazine, with a yield of 90%.

[0089] (4) Preparation of pyridazine 3-(3-trifluoromethylphenoxy)-4-carboxylic acid (intermediate 5)

[0090] 3-(3-trifluoromethylphenoxy)-4-carboxylic acid-6-chloropyridazine (3.19 g, 10 mmol), 5% Pd / C (15 mg), and ammonium formate (6.3 g, 100 mmol) were heated to reflux in 50 mL of ethanol. After the reactants disappeared, the mixture was filtered, and the organic layer was extracted with ethyl acetate, dried, and subjected to column chromatography to obtain 2.8 g of the solid intermediate 3-(3-trifluoromethylphenoxy)-4-carboxylic acid-pyridazine, with a yield of 95%.

[0091] (5) Preparation of the target compound 3-(3-trifluoromethylphenoxy)-4-N-(2,4-difluorophenyl)formamide pyridazine (A1):

[0092] Dissolve 2.84 g (10 mmol) of 3-(3-trifluoromethylphenoxy)-4-carboxylic acid pyridazine in 20 mL of dichloromethane. Add 1.5 g (12 mmol) of oxalyl chloride dropwise at room temperature, followed by one drop of DMF. Continue stirring at room temperature for 1 hour. Then add 1.4 g (11 mmol) of 2,4-difluoroaniline and 1.2 g (12 mmol) of triethylamine. React for 1 hour, add 20 mL of water, extract with dichloromethane, dry, and perform column chromatography to obtain 2.4 g of solid 3-(3-trifluoromethylphenoxy)-4-N-(2,4-difluorophenyl)carboxamide pyridazine, yield 60%.

[0093] The target compounds A2-A33 are prepared using the method described in A1, but differ from A1 in that 2,4-difluoroaniline is successively replaced with aniline, 2-chloroaniline, 3-chloroaniline, 4-chloroaniline, 2,3-dichloroaniline, 2,4-dichloroaniline, 2,5-dichloroaniline, 2,6-dichloroaniline, 3,4-dichloroaniline, 3,5-dichloroaniline, 2-fluoroaniline, 3-fluoroaniline, 4-fluoroaniline, 2,3-difluoroaniline, 2,5-difluoroaniline, 2,6-difluoroaniline, 3,4-dichloroaniline, 3,5-dichloroaniline, 2-fluoroaniline, 3-fluoroaniline, 4-fluoroaniline, 2,3-difluoroaniline, 2,5-difluoroaniline, 2,6-difluoroaniline, and 2,4-dichloroaniline. Fluoroaniline, 3,4-difluoroaniline, 3,5-difluoroaniline, 2-chloro-3-fluoroaniline, 2-chloro-4-fluoroaniline, 2-chloro-5-fluoroaniline, 2-chloro-6-fluoroaniline, 3-chloro-4-fluoroaniline, 3-chloro-5-fluoroaniline, 3-chloro-6-fluoroaniline, 4-chloro-6-fluoroaniline, 2,3,4-trifluoroaniline, 2,3,5-trifluoroaniline, 2,3,6-trifluoroaniline, 3,4,5-trifluoroaniline, 2,4,5-trifluoroaniline, 2,4,6-trifluoroaniline.

[0094] Example 2: A method for preparing 3-(3-trifluoromethylphenoxy)-4-N-(2,4-difluorophenyl)formamide-6-chloropyridazine (B1), comprising the following steps:

[0095] Steps (1)-(3): Refer to steps (1)-(3) of Example 1;

[0096] (4) Preparation of 3-(3-trifluoromethylphenoxy)-4-N-(2,4-difluorophenyl)formamide-6-chloropyridazine (B1):

[0097] Dissolve 3-(3-trifluoromethylphenoxy)-4-carboxylic acid-6-chloropyridazine (3.18 g, 10 mmol) in 20 mL of dichloromethane. Add oxalyl chloride (1.5 g, 12 mmol) dropwise at room temperature, followed by one drop of DMF. Continue stirring at room temperature for 1 hour. Then add 2,4-difluoroaniline (1.4 g, 11 mmol) and triethylamine (1.2 g, 12 mmol). React for 1 hour, add 20 mL of water, extract with dichloromethane, dry and perform column chromatography to obtain 3.1 g of solid 3-(3-trifluoromethylphenoxy)-4-N-(2,4-difluorophenyl)carboxamide-6-chloropyridazine, yield 70%.

[0098] The target compounds B2-B33 are prepared using the method described in B1, but differ in that 2,4-difluoroaniline is successively replaced with aniline, 2-chloroaniline, 3-chloroaniline, 4-chloroaniline, 2,3-dichloroaniline, 2,4-dichloroaniline, 2,5-dichloroaniline, 2,6-dichloroaniline, 3,4-dichloroaniline, 3,5-dichloroaniline, 2-fluoroaniline, 3-fluoroaniline, 4-fluoroaniline, 2,3-difluoroaniline, 2,5-difluoroaniline, 2,6-difluoroaniline, 3,4-dichloroaniline, 3,5-dichloroaniline, 2-fluoroaniline, 3-fluoroaniline, 4-fluoroaniline, 2,3-difluoroaniline, 2,5-difluoroaniline, 2,6-difluoroaniline, and 2,4-dichloroaniline. Fluoroaniline, 3,4-difluoroaniline, 3,5-difluoroaniline, 2-chloro-3-fluoroaniline, 2-chloro-4-fluoroaniline, 2-chloro-5-fluoroaniline, 2-chloro-6-fluoroaniline, 3-chloro-4-fluoroaniline, 3-chloro-5-fluoroaniline, 3-chloro-6-fluoroaniline, 4-chloro-6-fluoroaniline, 2,3,4-trifluoroaniline, 2,3,5-trifluoroaniline, 2,3,6-trifluoroaniline, 3,4,5-trifluoroaniline, 2,4,5-trifluoroaniline, 2,4,6-trifluoroaniline.

[0099] The structural formulas and physicochemical data of the target compounds prepared in the above embodiments are shown below:

[0100]

[0101]

[0102] (A1): 3-(3-trifluoromethylphenoxy)-4-N-(2,4-difluorophenyl)carbamate; Whitesolid. Yield: 81%.mp 145–146℃. 1 HNMR (500MHz, CDCl3) δ9.89 (s, 1H), 9.26 (d, J = 4.8Hz, 1H), 8.54–8.42 (m, 1H), 8.39 ( d,J=4.8Hz,1H),7.78–7.59(m,3H),7.54(dt,J=7.3,2.2Hz,1H),7.06–6.82(m,2H). 13C NMR (101MHz, CDCl3) δ160.61,159.27(dd,J=249.3,11.8Hz),158.91,152.92(dd,J=248.7,12. 5Hz),151.86(d,J=22.6Hz),150.40,132.70(q,J=33.1Hz),130.93,130.74,125.22,123.43(q, J=3.8Hz),123.42(q,J=273.3Hz),123.04(d,J=9.5Hz),122.19(dd,J=10.2,3.8Hz),121.02,11 8.89(q,J=4.0Hz),111.62(dd,J=21.8,3.8Hz),103.88(dd,J=26.8,23.1Hz).HRMS(ESI):Calcd for C 18 H 11 O2N3F5[M+H] + 396.07578, found: 396.07659. (A2): 3-(3-trifluoromethylphenoxy)-4-N-phenylcarbamate pyridazine; Whitesolid. Yield: 85%. mp 110-111℃. 1 H NMR (500MHz, CDCl3) δ9.50 (s, 1H), 9.23 (d, J = 4.8Hz, 1H), 8.38 (d, J = 4.8Hz, 1H), 7.70 –7.61(m,4H),7.60(s,1H),7.55–7.49(m,1H),7.45–7.36(m,2H),7.24–7.18(m,1H). 13 C NMR (101MHz, CDCl3) δ160.84,158.96,152.15,150.37,136.89,132.75(q,J=33.3Hz),131.02,130.81,129.31,125 .70,125.50,123.47(q,J=3.8Hz),123.43(q,J=273.4Hz),121.63,120.80,119.12(q,J=4.0Hz).HRMS(ESI):Calcd for C 18 H13O2N3F3[M+H] + 360.09544, found: 360.09476.

[0103] (A3): 3-(3-trifluoromethylphenoxy)-4-N-(2-chlorophenyl)carbamate; White solid. Yield: 75%. mp 136–137℃. 1 H NMR (500MHz, CDCl3) δ10.36(s,1H),9.26(d,J=4.8Hz,1H),8.64(dd,J=8.3,1.6Hz,1H),8.41(d,J=4.9Hz,1H ),7.69–7.57(m,3H),7.57–7.51(m,1H),7.42(dd,J=8.0,1.4Hz,1H),7.40–7.34(m,1H),7.17–7.11(m,1H). 13 C NMR (101MHz, CDCl3) δ160.70,159.01,152.12,150.34,134.41,132.68(q,J=33.0Hz),131.04,130.73,129.32,128.02,125 .80,125.37,123.48,123.44(q,J=273.7Hz),123.38(q,J=3.7Hz),122.01,121.32,119.08(q,J=4.0Hz).HRMS(ESI):Calcd for C 18 H 12 O2N3ClF3[M+H] + 394.05647, found: 394.05554.

[0104] (A4): 3-(3-trifluoromethylphenoxy)-4-N-(3-chlorophenyl)carbamate; White solid. Yield: 77%. mp 151–152℃. 1 H NMR (500MHz, CDCl3) δ9.51 (s, 1H), 9.24 (d, J = 4.8Hz, 1H), 8.37 (d, J = 4.8Hz, 1H), 7.80 (t, J = 2.1Hz, 1H),7.70–7.62(m,2H),7.59(s,1H),7.53–7.47(m,2H),7.31(t,J=8.1Hz,1H),7.22–7.15(m,1H). 13CNMR(101MHz, CDCl3)δ160.75,159.15,152.04,150.38,137.99,134.97,132.77(q,J=33.4Hz),123.40(q,J=273.8Hz),131.0 2,130.86,130.27,125.72,125.53,123.57(q,J=3.8Hz),121.20,120.88,119.17(q,J=3.9Hz),118.78.HRMS(ESI):Calcdfor C 18 H 12 O2N3ClF3[M+H] + 394.05647, found: 394.05566.

[0105] (A5): 3-(3-trifluoromethylphenoxy)-4-N-(4-chlorophenyl)carbamate; White solid. Yield: 80%. mp 149–150℃. 1 H NMR (500MHz, CDCl3) δ9.50 (s, 1H), 9.25 (d, J = 4.7Hz, 1H), 8.38 (d, J = 4.5Hz, 1 H),7.71–7.61(m,5H),7.59(s,1H),7.54–7.48(m,1H),7.36(d,J=8.8Hz,1H). 13 C NMR (126MHz, CDCl3) δ160.83, 159.10, 152.11, 150.47, 135.52, 132.87 (q, J = 33.2Hz), 131.10, 130.93, 130.83, 129. 42,125.60,123.65(q,J=4.0Hz),123.46(q,J=273.2Hz),122.09,121.32,119.fz22(q,J=3.9Hz).HRMS(ESI):Calcd for C 18 H 12 O2N3ClF3[M+H] + 394.05647, found: 394.05554.

[0106] (A6): 3-(3-trifluoromethylphenoxy)-4-N-(2,3-dichlorophenyl)carbamate; Whitesolid. Yield: 65%.mp 165–167℃. 1H NMR (500MHz, CDCl3) δ10.46 (s, 1H), 9.27 (d, J = 4.8Hz, 1H), 8.68–8.53 (m, 1H), 8.41 (d ,J=4.8Hz,1H),7.72–7.62(m,2H),7.60(s,1H),7.56–7.51(m,1H),7.34–7.29(m,2H). 13 C NMR (126MHz, CDCl3) δ160.68,159.26,152.10,150.43,136.10,133.22,132.82(q,J=33.2Hz),131.11,130.89,128.22,126.46,12 5.41,123.57(q,J=4.1Hz),123.47(q,J=273.0Hz),122.29(q,J=24.3Hz),121.11,120.00,119.11(q,J=3.9Hz).HRMS(ESI):Calcd for C 18 H 11 O2N3Cl2F3[M+H] + 428.01749, found: 428.01678.

[0107] (A7): 3-(3-trifluoromethylphenoxy)-4-N-(2,4-dichlorophenyl)carbamate; Whitesolid. Yield: 72%.mp 170–171℃. 1 H NMR (400MHz, CDCl3) δ10.35(s,1H),9.27(d,J=4.8Hz,1H),8.62(d,J=8.9Hz,1H),8.40(d,J=4.8Hz,1H) ,7.70–7.61(m,2H),7.60(s,1H),7.55–7.50(m,1H),7.44(d,J=2.4Hz,1H),7.34(dd,J=8.9,2.4Hz,1H). 13 C NMR (101MHz, CDCl3) δ160.60,159.06,151.99,150.38,133.17,132.72(q,J=33.4Hz),131.02,130.81,130.36,129.07,128 .22,125.36,123.98,123.51(q,J=3.9Hz),123.40(q,J=273.3Hz).122.63,120.96,119.07(q,J=3.8Hz).HRMS(ESI):Calcd for C 18 H11 O2N3Cl2F3[M+H] + 428.01749, found: 428.01666.

[0108] (A8): 3-(3-trifluoromethylphenoxy)-4-N-(2,5-dichlorophenyl)carbamate; Whitesolid. Yield: 65%.mp 233–234℃. 1 H NMR (500MHz, CDCl3) δ10.38(s,1H),9.28(d,J=4.5Hz,1H),8.75(d,J=2.4Hz,1H),8.41(d,J=4.4Hz,1H),7 .70–7.62(m,2H),7.60(s,1H),7.54(d,J=7.3Hz,1H),7.35(d,J=8.6Hz,1H),7.13(dd,J=8.6,2.4Hz,1H). 13 C NMR(126MHz, CDCl3)δ160.63,159.23,152.07,150.47,135.27,133.91,132.78(q,J=33.0Hz),131.12,130.86,130.00,125 .76,125.43,123.56(q,J=3.9Hz),123.47(q,J=273.2Hz),121.93,121.52,120.95,119.13(q,J=4.0Hz).HRMS(ESI):Calcd for C 18 H 11 O2N3Cl2F3[M+H] + 428.01749, found: 428.01675. (A9): 3-(3-trifluoromethylphenoxy)-4-N-(2,6-dichlorophenyl)carbamate; White solid. Yield: 60%. mp 183–185℃. 1 H NMR(500MHz, CDCl3)δ9.30(s,1H),9.26(d,J=4.8Hz,1H),8.39(d,J=4.8Hz,1H),7 .68–7.59(m,3H),7.56–7.51(m,1H),7.44(d,J=8.2Hz,2H),7.27(t,J=8.2Hz,1H). 13C NMR (126MHz, CDCl3) δ161.18,159.42,152.17,150.27,133.49,132.73(q,J=33.2Hz),131.48,131.34,130.84,129 .35,128.76,125.60,123.52(q,J=3.8Hz),123.49(q,J=273.0Hz).120.72,119.29(q,J=4.0Hz).HRMS(ESI):Calcd for C 18 H 11 O2N3Cl2F3[M+H] + 428.01749, found: 428.01654.

[0109] (A10): 3-(3-trifluoromethylphenoxy)-4-N-(3,4-dichlorophenyl)carbamate; Whitesolid. Yield: 73%. mp 120–122℃. 1 H NMR (500MHz, CDCl3) δ9.51 (s, 1H), 9.22 (d, J = 4.8Hz, 1H), 8.33 (d, J = 4.8Hz, 1H), 7.92 (d, J = 2.4Hz, 1H), 7.69–7.61(m,2H),7.57(s,1H),7.53–7.48(m,1H),7.47(dd,J=8.7,2.4Hz,1H),7.42(d,J=8.8Hz,1H). 13 C NMR (126MHz, CDCl3) δ160.75,159.30,152.05,150.41,136.37,133.17,132.80(q,J=33.2Hz),131.03,130.95,130.82,129 .00,125.60,123.67(q,J=3.8Hz),123.45(q,J=273.0Hz),122.51,121.09,120.06,119.22(q,J=3.9Hz).HRMS(ESI):Calcd for C 18 H 11 O2N3Cl2F3[M+H] + 428.01749, found: 428.01657.

[0110] (A11): 3-(3-trifluoromethylphenoxy)-4-N-(3,5-dichlorophenyl)carbamate; Whitesolid. Yield: 70%. mp 188–189℃. 1H NMR (500MHz, CDCl3) δ9.52 (s, 1H), 9.24 (d, J = 4.8Hz, 1H), 8.35 (d, J = 4.8Hz, 1 H),7.69–7.60(m,4H),7.58(s,1H),7.54–7.47(m,1H),7.19(t,J=2.0Hz,1H). 13 CNMR(126MHz, CDCl3)δ160.73,159.38,151.95,150.49,138.66,135.63,132.90(q,J=33.4Hz),131.16,131.01,12 5.70,125.65,123.81(q,J=4.0Hz),123.44(q,J=273.0Hz),120.82,119.32(q,J=3.8Hz),119.10.HRMS(ESI):Calcd forC 18 H 11 O2N3Cl2F3[M+H] + 428.01749, found: 428.01678.

[0111] (A12): 3-(3-trifluoromethylphenoxy)-4-N-(2-fluorophenyl)carbamate; Whitesolid. Yield: 81%. mp 126–127℃. 1 HNMR(500MHz, CDCl3)δ9.99(s,1H),9.26(d,J=4.8Hz,1H),8.63–8.44(m,1H),8.39(d,J= 4.8Hz,1H),7.69–7.59(m,3H),7.58–7.52(m,1H),7.25–7.19(m,1H),7.17–7.11(m,2H). 13 C NMR (126MHz, CDCl3) δ160.69, 158.95, 152.88 (d, J = 244.9Hz), 152.08, 150.46, 132 .72(q,J=33.2Hz),131.03,130.77,125.90(d,J=10.0Hz),125.71(d,J=7.7Hz),12 5.29,124.98(d,J=3.7Hz),123.51(q,J=273.2Hz),123.44(q,J=4.0Hz),122.25(d ,J=45.4Hz),121.33,118.97(q,J=4.0Hz),115.09(d,J=19.0Hz).HRMS(ESI):Calcd for C 18 H11 O2N3F4Na[M+Na] + 400.06796, found: 400.06732.

[0112] (A13): 3-(3-trifluoromethylphenoxy)-4-N-(3-fluorophenyl)carbamate; Whitesolid. Yield: 72%. mp 110–111℃. 1 HNMR(500MHz, CDCl3)δ9.54(s,1H),9.24(d,J=4.8Hz,1H),8.38(d,J=4.7Hz,1H),7.73–7.61(m ,3H),7.58(s,1H),7.55–7.47(m,1H),7.38–7.29(m,1H),7.29–7.23(m,1H),6.96–6.85(m,1H). 13 C NMR (126MHz, CDCl3) δ163.10 (d, J = 246.0Hz), 160.81, 159.16, 152.10, 150.48, 138. 39(d,J=10.8Hz),132.87(q,J=33.1Hz),131.13,130.93,130.47(d,J=9.5Hz),125. 57,123.65(q,J=3.8Hz),123.46(q,J=273.3Hz),121.30,119.21(q,J=3.8Hz),116. 10(d,J=3.0Hz),112.52(d,J=21.3Hz),108.42(d,J=26.5Hz).HRMS(ESI):Calcdfor C 18 H 11 O2N3F4Na[M+Na] + 400.06796, found: 400.06796.

[0113] (A14): 3-(3-trifluoromethylphenoxy)-4-N-(4-fluorophenyl)carbamate; Brownsolid. Yield: 75%. mp 120–121℃. 1 H NMR (400MHz, CDCl3) δ9.48 (s, 1H), 9.22 (d, J = 4.8Hz, 1H), 8.36 (d, J = 4.9Hz, 1 H),7.71–7.60(m,4H),7.58(s,1H),7.53–7.44(m,1H),7.08(t,J=8.6Hz,2H). 13CNMR(101MHz, CDCl3)δ160.83,160.10(d,J=246.2Hz),159.03,152.08,150.37,132.92,132.73(q,J=33.2Hz),131.02,130.84,125.54,12 3.53(q,J=3.9Hz),123.40(q,J=273.4Hz),122.68(d,J=8.0Hz),121.39,119.14(q,J=3.9Hz),116.05(d,J=22.7Hz).HRMS(ESI):Calcdfor C 18 H 11 O2N3F4Na[M+Na] + 400.06796, found: 400.06702.

[0114] (A15): 3-(3-trifluoromethylphenoxy)-4-N-(2,3-difluorophenyl)carbamate; Whitesolid. Yield: 71%. mp 142–143℃. 1 HNMR (500MHz, CDCl3) δ10.02(s,1H),9.27(d,J=4.7Hz,1H),8.39(d,J=4.8Hz,1H),8.29(t,J=7.4Hz,1H) ,7.74–7.60(m,3H),7.54(d,J=7.4Hz,1H),7.16(dd,J=8.3,5.3,2.1Hz,1H),7.00(dd,J=8.6,1.0Hz,1H). 13 CNMR(101MHz,CDCl3)δ160.56,159.09,151.90,150.41,150.21(dd,J=249.1,10.6Hz), 141.53(dd,J=247.0,15.2Hz),132.70(q,J=33.0Hz),130.98,130.80,127.53(d,J=7.5 Hz), 125.22, 124.72–124.42 (m, 1C), 123.50 (q, J = 3.8Hz), 123.41 (q, J = 273.6Hz), 120. 89,118.91(q,J=3.9Hz),117.00(d,J=3.7Hz),113.26(d,J=16.9Hz).HRMS(ESI):Calcd forC 18 H 10 O2N3F5Na[M+Na] +418.05854, found: 418.05771. (A16): 3-(3-trifluoromethylphenoxy)-4-N-(2,5-difluorophenyl)carbamate; White solid. Yield: 69%. mp 153–154℃. 1 H NMR (500MHz, CDCl3) δ10.56 (s, 1H), 9.26 (d, J = 4.8Hz, 1H), 8.52–8.08 (m, 2H) ,7.70–7.57(m,3H),7.55–7.50(m,1H),7.17–7.02(m,1H),6.89–6.78(m,1H). 13 C NMR (101MHz, CDCl3) δ 160.49, 158.66 (dd, J = 243.11, 2.2Hz), 159.03, 151.89, 150.44, 148. 75(dd,J=240.2,3.1Hz),132.66(q,J=33.2Hz),130.98,130.76,126.64(t,J=11.8Hz),125 .20,123.45(q,J=3.7Hz),123.42(q,J=273.9Hz),120.85,118.86(q,J=3.9Hz),115.46(dd ,J=21.9,9.6Hz),111.48(dd,J=24.6,7.9Hz),109.23(d,J=30.3Hz).HRMS(ESI):Calcdfor C 18 H 10 O2N3F5Na[M+Na] + 418.05854, found: 418.05759.

[0115] (A17): 3-(3-trifluoromethylphenoxy)-4-N-(2,6-difluorophenyl)carbamate; Whitesolid. Yield: 68%.mp 158–159℃. 1 H NMR(500MHz, CDCl3)δ9.24(d,J=4.9Hz,1H),9.08(s,1H),8.38(d,J=4.8Hz,1H), 7.69–7.58(m,2H),7.56–7.50(m,3H),7.36–7.27(m,1H),7.03(t,J=8.1Hz,1H). 13C NMR (101MHz, CDCl3) δ161.00,159.68,157.72(dd,J=251.7,4.7Hz),152.05,150.25,132.63(q,J=33.3Hz),131.27,130.73,128.63(t,J=9.7Hz),1 25.60,123.44(q,J=3.8Hz),123.43(q,J=273.4Hz),120.34,119.23(q,J=3.7Hz),113.05(t,J=16.4Hz),112.51–110.85(m,1C).HRMS(ESI):Calcd for C 18 H 10 O2N3F5Na[M+Na] + 418.05854, found: 418.05801.

[0116] (A18): 3-(3-trifluoromethylphenoxy)-4-N-(3,4-difluorophenyl)carbamate; Whitesolid. Yield: 78%. mp 149–150℃. 1 H NMR(500MHz, CDCl3)δ9.51(s,1H),9.26(d,J=4.8Hz,1H),8.39(d,J=4.7Hz,1H),7.93–7.77(m, 1H),7.73–7.61(m,2H),7.59(s,1H),7.53–7.49(m,1H),7.25–7.21(m,1H),7.21–7.14(m,1H). 13 C NMR (101MHz, CDCl3) δ160.73, 159.11, 151.95, 150.44, 150.17 (dd, J = 248.4, 13.7Hz), 147. 78(dd,J=248.3,12.5Hz),133.29(dd,J=8.7,3.5Hz),132.82(d,J=33.6Hz),131.06,130.9 0,125.55,123.66(q,J=3.8Hz),123.37(q,J=273.3Hz),120.98,116.55(dd,J=8.7,3.5Hz) ,119.17(q,J=3.7Hz),117.59(d,J=18.5Hz),110.71(d,J=22.0Hz).HRMS(ESI):CalcdforC 18 H 10 O2N3F5Na[M+Na] +418.05854, found: 418.05854.

[0117] (A19): 3-(3-trifluoromethylphenoxy)-4-N-(3,5-difluorophenyl)carbamate; Whitesolid. Yield: 78%.mp 105–106℃. 1 H NMR(500MHz, CDCl3)δ9.57(s,1H),9.27(d,J=4.9Hz,1H),8.38(d,J=4.8Hz,1H),7.73–7.6 2(m,2H),7.59(s,1H),7.51(dt,J=7.0,2.5Hz,1H),7.38–7.28(m,2H),6.74–6.61(m,1H). 13 C NMR (101MHz, CDCl3) δ 163.22 (dd, J = 247.5, 14.4Hz), 160.64, 159.28, 151.88, 150.45, 138.89 (t, J = 13.2Hz), 133.37 (q, J = 273.4Hz), 132.82 (q, J = 33. 0Hz),131.10,130.95,125.53,123.73(q,J=3.8Hz),120.83,119.17(q,J=3.8Hz),104.27–103.31(m,1C),100.97(t,J=25.5Hz).HRMS(ESI):Calcdfor C 18 H 10 O2N3F5Na[M+Na] + 418.05854, found: 418.05762.

[0118] (A20): 3-(3-trifluoromethylphenoxy)-4-N-(2-chloro-3-fluorophenyl)carbamate; Whitesolid. Yield: 75%.mp 163–164℃. 1 H NMR (500MHz, CDCl3) δ10.40(s,1H),9.27(d,J=5.0Hz,1H),8.46(d,J=8.3Hz,1H),8.41(d,J=4.8Hz,1H),7. 71–7.62(m,2H),7.61(s,1H),7.57–7.51(m,1H),7.34(td,J=8.4,5.9Hz,1H),7.01(td,J=8.4,1.4Hz,1H). 13CNMR (101MHz, CDCl3) δ160.60, 159.20, 158.22 (d, J = 249.6Hz), 151.99, 150.38, 135.98,132.72(q,J=33.3Hz),131.06,130.84,128.39(d,J=8.5Hz),125.35,123 .52(q,J=3.8Hz),119.05(q,J=273.8Hz),121.00,119.05(q,J=3.9Hz),117.03( d,J=3.2Hz),112.57(d,J=20.6Hz),111.05(d,J=20.5Hz).HRMS(ESI):CalcdforC 18 H 10 O2N3ClF4Na[M+Na] + 434.02899, found: 434.02823.

[0119] (A21): 3-(3-trifluoromethylphenoxy)-4-N-(2-chloro-4-fluorophenyl)carbamate; Whitesolid. Yield: 75%.mp 162–163℃. 1 H NMR (500MHz, CDCl3) δ10.26(s,1H),9.26(d,J=4.8Hz,1H),8.61(dd,J=9.2,5.5Hz,1H),8.40(d,J= 4.8Hz,1H),7.71–7.57(m,3H),7.55–7.50(m,1H),7.18(dd,J=7.9,2.8Hz,1H),7.14–7.03(m,1H). 13 C NMR(101MHz, CDCl3)δ160.66,158.97,158.96(d,J=249.7Hz),152.03,150.36,132 .67(q,J=33.2Hz),131.01,130.89(d,J=3.5Hz),130.80,125.37,124.19(d,J=10. 3Hz),123.47(q,J=3.8Hz),123.42(q,J=273.4Hz),123.13(d,J=8.2Hz),121.08,1 19.06(q,J=3.9Hz),116.71(d,J=25.8Hz),114.96(d,J=21.7Hz).HRMS(ESI):Calcd for C 18 H 10 O2N3ClF4Na[M+Na] +434.02899, found: 434.02811.

[0120] (A22): 3-(3-trifluoromethylphenoxy)-4-N-(2-chloro-5-fluorophenyl)carbamate; Whitesolid. Yield: 72%.mp 200–201℃. 1 HNMR (500MHz, CDCl3) δ10.43(s,1H),9.28(d,J=4.8Hz,1H),8.50(dd,J=10.7,3.0Hz,1H),8.41(d,J=4.8H z,1H),7.71–7.61(m,2H),7.60(s,1H),7.57–7.50(m,1H),7.37(dd,J=8.9,5.5Hz,1H),6.93–6.82(m,1H). 13 C NMR (101MHz, CDCl3) δ160.57, 161.56 (d, J = 246.7Hz), 159.20, 151.98, 150.39, 135. 42(d,J=12.2Hz),132.70(q,J=33.3Hz),131.07,130.79,129.96(d,J=9.4Hz),125. 37,123.49(q,J=3.7Hz),123.41(q,J=273.4Hz),120.90,119.06(q,J=4.0Hz),118. 11(d,J=3.5Hz),112.60(d,J=23.5Hz),109.50(d,J=29.9Hz).HRMS(ESI):CalcdforC 18 H 10 O2N3ClF4Na[M+Na] + 434.02899, found: 434.02814.

[0121] (A23): 3-(3-trifluoromethylphenoxy)-4-N-(2-chloro-6-fluorophenyl)carbamate; Whitesolid. Yield: 70%. mp 142–143℃. 1 H NMR(500MHz, CDCl3)δ9.25(d,J=4.8fHz,2H),8.39(d,J=4.8Hz,1H),7.70–7.59( m,3H),7.58–7.50(m,1H),7.34–7.27(m,2H),7.16(ddd,J=9.5,7.3,2.3Hz,1H). 13C NMR(101MHz, CDCl3)δ161.03,159.35,158.04(d,J=255.5Hz),152.07,150.28,132 .67(q,J=33.1Hz),131.54(d,J=2.9Hz),131.33,130.77,128.91(d,J=9.2Hz),125 .52,125.31(d,J=3.6Hz),123.46(q,J=3.6Hz),123.42(q,J=273.5Hz),122.11(d, J=15.5Hz),120.44,119.19(q,J=3.8Hz),115.34(d,J=20.6Hz).HRMS(ESI):Calcd for C 18 H 10 O2N3ClF4Na[M+Na] + 434.02899, found: 434.02859.

[0122] (A24): 3-(3-trifluoromethylphenoxy)-4-N-(3-chloro-4-fluorophenyl)carbamate; Whitesolid. Yield: 79%. mp 141–143℃. 1 H NMR (500MHz, CDCl3) δ9.48 (s, 1H), 9.24 (d, J = 5.0Hz, 1H), 8.37 (d, J = 4.8Hz, 1H), 7.88 (dd, J = 6. 4,2.6Hz,1H),7.71–7.62(m,2H),7.58–7.57(m,1H),7.53–7.44(m,2H),7.15(t,J=8.7Hz,1H). 13 C NMR(101MHz, CDCl3)δ160.74,159.15,155.55(d,J=248.0Hz),151.95,150.43,1 33.44(d,J=3.2Hz),132.82(q,J=33.3Hz),131.07,130.91,125.57,123.67(q,J =3.7Hz),123.38(q,J=273.9Hz),123.12,121.60(d,J=19.0Hz),120.95,120.58 (d,J=7.2Hz),119.21(q,J=3.9Hz),116.97(d,J=22.5Hz).HRMS(ESI):Calcdfor C 18 H 10 O2N3ClF4Na[M+Na] +434.02899, found: 434.02820.

[0123] (A25): 3-(3-trifluoromethylphenoxy)-4-N-(3-chloro-5-fluorophenyl)carbamate; Whitesolid. Yield: 78%.mp 138–139℃. 1 H NMR(500MHz, CDCl3)δ9.55(s,1H),9.25(d,J=4.7Hz,1H),8.36(d,J=4.8Hz,1H),7.72–7.62(m,2H),7 .58(s,1H),7.54(t,J=2.1Hz,1H),7.53–7.48(m,1H),7.43–7.37(m,1H),6.94(dt,J=8.2,2.1Hz,1H). 13 CNMR (101MHz, CDCl3) δ162.86 (d, J = 248.8Hz), 160.65, 159.29, 151.88, 150.45, 138 .85(d,J=11.9Hz),135.60(d,J=12.0Hz),132.85(q,J=33.3Hz),131.09,130.94,125 .55,123.72(t,J=4.0Hz),123.37(q,J=273.4Hz),120.76,119.23(q,J=4.1Hz),116. 40(d,J=3.6Hz),113.29(d,J=24.9Hz),106.68(d,J=26.5Hz).HRMS(ESI):CalcdforC 18 H 10 O2N3ClF4Na[M+Na] + 434.02899, found: 434.02823.

[0124] (A26): 3-(3-trifluoromethylphenoxy)-4-N-(3-chloro-6-fluorophenyl)carbamate; Whitesolid. Yield: 80%.mp 193–195℃. 1 H NMR (500MHz, CDCl3) δ10.02(d,J=3.6Hz,1H),9.27(d,J=4.8Hz,1H),8.61(dd,J=6.7,2.5 Hz,1H),8.38(d,J=4.8Hz,1H),7.67–7.59(m,1H),7.57–7.50(m,1H),7.18–7.02(m,1H). 13C NMR(101MHz, CDCl3)δ160.48,159.01,151.88,151.16(d,J=245.2Hz),149.9 4,132.68(q,J=33.1Hz),131.00,130.76,130.10(d,J=3.5Hz),126.73(d,J= 11.1Hz), 125.28, 125.20, 123.48 (q, J = 3.7Hz), 123.41 (q, J = 273.4Hz), 121. 83,120.81,118.87(q,J=4.0Hz),115.90(d,J=20.6Hz).HRMS(ESI):Calcdfor C 18 H 10 O2N3ClF4Na[M+Na] + 434.02899, found: 434.02811.

[0125] (A27): 3-(3-trifluoromethylphenoxy)-4-N-(2-fluoro-4-chlorophenyl)carbamate; Whitesolid. Yield: 79%.mp 168–169℃. 1 H NMR (400MHz, CDCl3) δ9.90 (s, 1H), 9.19 (d, J = 4.8Hz, 1H), 8.42 (t, J = 8.6Hz, 1H), 8.30 (d,J=4.8Hz,1H),7.66–7.52(m,3H),7.47(dt,J=7.1,2.4Hz,1H),7.17–7.06(m,2H). 13 C NMR (101MHz, CDCl3) δ160.53, 158.94, 152.47 (d, J = 249.0Hz), 151.93, 150. 41,132.70(q,J=33.3Hz),130.92,130.75,130.23(d,J=10.2Hz),125.19,12 5.16,124.65(d,J=10.0Hz),123.46(q,J=3.7Hz),123.41(q,J=273.4Hz),12 2.61,120.91,118.88(q,J=3.9Hz),115.88(d,J=22.6Hz).HRMS(ESI):Calcd forC 18 H 10 O2N3ClF4Na[M+Na] + 434.02899, found: 434.02795.

[0126] (A28): 3-(3-trifluoromethylphenoxy)-4-N-(2,3,4-trifluorophenyl)carbamate; Whitesolid. Yield: 80%. mp 120–121℃. 1 H NMR(500MHz, CDCl3)δ9.90(s,1H),9.28(d,J=4.8Hz,1H),8.38(d,J=4.8Hz,1H),8.32–8.1 5(m,1H),7.70–7.62(m,2H),7.61(d,J=2.4Hz,1H),7.57–7.50(m,1H),7.13–7.00(m,1H). 13 C NMR (101MHz, CDCl3) δ160.55,159.21,151.83,150.42,149.77–146.30(m,1C),142.68( d,J=248.7Hz),141.35–138.25(m,1C),132.73(q,J=33.3Hz),130.98,130.84,125.24,1 23.58(q,J=3.7Hz),123.39(q,J=273.6Hz),123.25(dd,J=7.6,3.7Hz),120.69,118.92 (q,J=4.0Hz),116.08(dd,J=7.4,4.4Hz),112.10(dd,J=18.0,3.9Hz).HRMS(ESI):Calcd for C 18 H 10 O2N3F6[M+H] + 414.06717, found: 414.06680.

[0127] (A29): 3-(3-trifluoromethylphenoxy)-4-N-(2,3,5-trifluorophenyl)carbamate; Whitesolid. Yield: 78%.mp 124–125℃. 1 H NMR (500MHz, CDCl3) δ10.11(s,1H),9.28(d,J=4.8Hz,1H),8.38(d,J=4.8Hz,1H),8.2 6–8.08(m,1H),7.74–7.62(m,2H),7.61(s,1H),7.57–7.51(m,1H),6.90–6.67(m,1H). 13CNMR(101MHz, CDCl3)δ160.42,159.31,159.21–156.60(m,1C),151.78,151.22–148.47(m,1 C),150.45,140.17–136.09(m,1C),132.71(q,J=33.3Hz),130.99,130.84,128.03–127.62(m ,1C),124.96(d,J=44.8Hz),123.58(q,J=3.7Hz),123.39(q,J=273.9Hz),120.50,118.87(q ,J=4.0Hz),104.37(dd,J=30.1,3.6Hz),101.18(dd,J=28.0,20.7Hz).HRMS(ESI):CalcdforC 18 H 10 O2N3F6[M+H] + 414.06717, found: 414.06616.

[0128] (A30): 3-(3-trifluoromethylphenoxy)-4-N-(2,3,6-trifluorophenyl)carbamate; Whitesolid. Yield: 75%.mp 143–145℃. 1 H NMR (500MHz, CDCl3) δ9.26(d,J=4.8Hz,1H),9.13(s,1H),8.38(d,J=4.8Hz,1H),7. 69–7.58(m,3H),7.53(dt,J=7.4,2.3Hz,1H),7.21–7.09(m,1H),7.02–6.93(m,1H). 13 C NMR(101MHz, CDCl3)δ160.90,159.67,154.41–51.89(m,1C),151.94(d,J=5.7Hz),150.24, 148.97–146.86(m,1C),146.50–144.32(m,1C),132.62(q,J=33.3Hz),131.25,130.76,125. 56,123.49(q,J=3.8Hz),123.40(q,J=273.3Hz),120.07,119.18(q,J=3.9Hz),115.53(dd,J =19.4,9.2Hz),114.65(dd,J=17.1,13.8Hz),111.11–109.78(m,1C).HRMS(ESI):CalcdforC 18 H 10O2N3F6[M+H] + 414.06717, found: 414.06619.

[0129] (A31): 3-(3-trifluoromethylphenoxy)-4-N-(3,4,5-trifluorophenyl)carbamate; Whitesolid. Yield: 78%.mp 181–183℃. 1 H NMR (500MHz, CDCl3) δ9.50 (s, 1H), 9.26 (d, J = 4.9Hz, 1H), 8.37 (d, J = 4.8Hz, 1H), 7.72–7.61 (m, 2H), 7.58 (s, 1H), 7.50 (m, 1H), 7.47–7.37 (m, 2H). 13 CNMR(101MHz, CDCl3)δ166.84,166.03,158.45,156.69–154.10(m,3C),142.02–139.26(m,2C),136.39,135.71(q,J=32.3Hz),134.13(d,J= 4.3Hz),131.36,130.21,128.93(q,J=273.3Hz),127.61(d,J=6.0Hz),124.43–123.43(m,1C),110.08–107.76(m,2C).HRMS(ESI):Calcdfor C 18 H 10 O2N3F6[M+H] + 414.06717, found: 414.06656.

[0130] (A32): 3-(3-trifluoromethylphenoxy)-4-N-(2,4,5-trifluorophenyl)carbamate; Brownsolid. Yield: 76%.mp 157–158℃. 1 H NMR(500MHz, CDCl3)δ9.96(s,1H),9.26(d,J=4.8Hz,1H),8.65–8.44(m,1H),8.37(d,J= 4.9Hz,1H),7.66–7.60(m,2H),7.60–7.57(m,1H),7.55–7.51(m,1H),7.15–6.93(m,1H). 13C NMR(101MHz,CDCl3)δ160.48,158.98,151.84,150.44,149.14–144.94(m,3C ),132.67(q,J=33.2Hz),130.95,130.79,125.21,123.51(q,J=3.8Hz),123. 40(q,J=273.8Hz),122.74–121.29(m,1C),120.66,118.85(q,J=4.0Hz),110.76(dd,J=25.0,1.9Hz),105.12(dd,J=24.9,22.2Hz).HRMS(ESI):Calcdfor C 18 H 10 O2N3F6[M+H] + 414.06717, found: 414.06622.

[0131] (A33): 3-(3-trifluoromethylphenoxy)-4-N-(2,4,6-trifluorophenyl)carbamate; Whitesolid. Yield: 78%.mp 147–148℃. 1 H NMR (500MHz, CDCl3) δ9.23(d,J=4.8Hz,1H),8.95(s,1H),8.35(d,J=4.6Hz,1H),7.79–7.57(m,3H),7.54–7.44(m,1H),6.91–6.67(m,2H). 13 CNMR (101MHz, CDCl3) δ160.97, f162.82–159.98 (m, 1C), 159.98, 158.12 (m, 2C), 152.01, 150.23, 132.63 (q, J = 33.1Hz), 131.25, 130.75, 125.60, 123.47(q,J=3.8Hz),123.41(q,J=273.9Hz),120.13,119.21(q,J=3.9Hz),109.71(td,J=16.8,5.1Hz),101.20–100.66(m,2C).HRMS(ESI):Calcd for C 18 H 10 O2N3F6[M+H] + 414.06717, found: 414.06555.

[0132] (B1): 3-(3-trifluoromethylphenoxy)-4-N-(2,4-difluorophenyl)formamide-6-chloropyridazine; Whitesolid. Yield: 80%.mp 140–142℃. 1 HNMR(500MHz, CDCl3)δ9.84(s,1H),8.52–8.41(m,1H),8.38(s,1H),7.68–7.61(m,2H),7.60(s,1H),7.56–7.50(m,1H),7.04–6.87(m,2H). 13 C NMR (101MHz, CDCl3) δ 159.87, 159.43 (dd, J = 249.8, 11.8Hz), 157.61, 154.78, 151.75, 152. 94(dd,J=248.3,12.4Hz),132.76,132.75(q,J=33.3Hz),130.80,125.02,123.67(q,J=3.7H z),123.41,123.67(q,J=273.2Hz),123.08(d,J=8.8Hz),121.92(dd,J=10.2,3.7Hz),118.7 5(q,J=3.8Hz),111.72(dd,J=22.0,3.8Hz),103.94(dd,J=26.8,23.0Hz).HRMS(ESI):Calcd for C 18 H 10 ClO2N3F5[M+H] + 430.03762, found: 430.03598.

[0133] (B2): 3-(3-trifluoromethylphenoxy)-4-N-phenylformamide-6-chloropyridazine; White solid. Yield: 81%. mp 162–163℃. 1 H NMR (500MHz, CDCl3) δ9.41(s,1H),8.39(s,1H),7.75–7.59(m,4H),7.58(s,1H),7.53–7.46(m,1H),7.45–7.36(m,2H),7.24–7.19(m,1H). 13C NMR (101MHz, CDCl3) δ160.13,157.66,154.77,151.90,136.59,132.84,132.83(q,J=33.2Hz),130.88,129.38,125.9 7,125.32,123.98,123.73(q,J=3.7Hz),123.34(q,J=273.7Hz),120.83,119.01(q,J=3.8Hz).HRMS(ESI):CalcdforC 18 H 11 O2N3ClF3Na[M+Na] + 416.03841, found: 416.03757.

[0134] (B3): 3-(3-trifluoromethylphenoxy)-4-N-(2-chlorophenyl)carboxamide-6-chloropyridazine; Whitesolid. Yield: 68%.mp 158–160℃. 1 H NMR(400MHz, CDCl3)δ10.30(s,1H),8.60(dd,J=8.3,1.5Hz,1H),8.40(s,1H),7.67–7.61(m,2H),7.60( s,1H),7.56–7.49(m,1H),7.42(dd,J=8.0,1.5Hz,1H),7.39–7.33(m,1H),7.15(td,J=7.8,1.6Hz,1H). 13 C NMR (101MHz, CDCl3) δ159.98,157.70,154.71,151.86,134.11,132.88,132.72(q,J=33.1Hz),130.82,129.37,128.10, 126.09,125.20,123.80–123.58(m,2C),132.52,123.37(q,J=273.0Hz),122.02,118.96(q,J=3.9Hz).HRMS(ESI):Calcd for C18H11O2N3Cl2F3[M+H] + 428.01749, found: 428.01694.

[0135] (B4): 3-(3-trifluoromethylphenoxy)-4-N-(3-chlorophenyl)carboxamide-6-chloropyridazine; Whitesolid. Yield: 78%.mp 150–152℃. 1H NMR (500MHz, CDCl3) δ9.43 (s, 1H), 8.35 (s, 1H), 7.77 (t, J = 2.1Hz, 1H), 7.69–7.62 (m,2H),7.58(s,1H),7.53–7.46(m,2H),7.32(t,J=8.1Hz,1H),7.23–7.17(m,1H). 13 C NMR (101MHz, CDCl3) δ160.03,157.86,154.76,151.80,137.68,135.03,132.84(q,J=33.7Hz),132.82,130.93,130.33,126 .00,125.33,123.82(q,J=3.7Hz),123.57,123.32(q,J=273.3Hz),120.91,119.03(q,J=3.9Hz),118.83.HRMS(ESI):Calcd for C 18 H 11 O2N3Cl2F3[M+H] + 428.01749, found: 428.01721.

[0136] (B5): 3-(3-trifluoromethylphenoxy)-4-N-(4-chlorophenyl)carboxamide-6-chloropyridazine; Whitesolid. Yield: 80%.mp 175–177℃. 1 H NMR (500MHz, CDCl3) δ9.44(s,1H),8.37(s,1H),7.69–7.63(m,2H),7.63–7.60(m,2fH),7.57(s,1H),7.51–7.48(m,1H),7.38–7.35(m,2H). 13 C NMR (126MHz, CDCl3) δ160.12,157.81,154.86,151.85,135.22,132.93,132.92(q,J=31.1Hz),131.14,131.01,129 .50,125.43,123.91(q,J=3.9Hz),123.68,123.38(q,J=273.2Hz).122.13,119.10(q,J=3.9Hz).HRMS(ESI):Calcd for C 18 H 11 O2N3Cl2F3[M+H] + 428.01749, found: 428.01675.

[0137] (B6): 3-(3-trifluoromethylphenoxy)-4-N-(2,3-dichlorophenyl)formamide-6-chloropyridazine; Whitesolid. Yield: 70%.mp 196–198℃. 1 H NMR(500MHz, CDCl3)δ10.40(s,1H),8.71–8.48(m,1H),8.41(s,1H),7.70–7.6 1(m,2H),7.59(s,1H),7.55–7.50(m,1H),7.33(s,1H),7.32(d,J=1.0Hz,1H). 13 C NMR (101MHz, CDCl3) δ159.89,157.90,154.76,151.79,135.73,133.23,132.95(d,J=8.4Hz),132.82(q,J=33.7Hz).130.90,128. 23,126.67,125.15,123.77(q,J=3.7Hz),123.41,123.32(q,J=273.9Hz).122.20,119.97,118.91(q,J=4.0Hz).HRMS(ESI):Calcd for C 18 H 10 O2N3Cl3F3[M+H] + 461.97852, found: 461.97745.(B7): 3-(3-trifluoromethylphenoxy)-4-N-(2,4-dichlorophenyl)carboxamide-6-chloropyridazine; White solid. Yield: 77%. mp 185–187℃. 1 HNMR(500MHz, CDCl3)δ10.28(s,1H),8.59(d,J=8.9Hz,1H),8.40(s,1H),7.69–7.62(m, 2H),7.59(s,1H),7.55–7.49(m,1H),7.44(d,J=2.4Hz,1H),7.35(dd,J=9.0,2.4Hz,1H). 13CNMR(101MHz, CDCl3)δ159.89,157.77,154.77,151.79,132.88,132.85,132.81(q,J=33.7Hz),130.87,130.71,129.12,12 8.30,125.15,124.06,123.74(q,J=3.8Hz),123.35,123.32(q,J=273.5Hz),122.69,118.93(q,J=3.8Hz).HRMS(ESI):Calcd forC 18 H 10 O2N3Cl3F3[M+H] + 461.97852, found: 461.97711.

[0138] (B8): 3-(3-trifluoromethylphenoxy)-4-N-(2,5-dichlorophenyl)formamide-6-chloropyridazine; Whitesolid.Yield: 78%.mp 202–204℃. 1 H NMR(500MHz, CDCl3)δ10.31(s,1H),8.70(d,J=2.5Hz,1H),8.39(s,1H),7.67–7.62(m,2 H),7.59(s,1H),7.53–7.51(m,1H),7.35(d,J=8.6Hz,1H),7.13(dd,J=8.5,2.5Hz,1H). 13 C NMR (126MHz, CDCl3) δ159.92,157.93,154.85,151.81,134.97,133.98,132.98,132.85(q,J=33.6Hz),130.95,130.06,126 .06,125.25,123.83(q,J=4.0Hz),123.39(q,J=273.3Hz),123.30,121.97,121.59,119.00(q,J=3.9Hz).HRMS(ESI):Calcd for C 18 H9O2N3Cl3F3Na[M+Na] + 483.96047, found: 483.96063.

[0139] (B9): 3-(3-trifluoromethylphenoxy)-4-N-(2,6-dichlorophenyl)formamide-6-chloropyridazine; Whitesolid. Yield: 68%.mp 183–184℃. 1H NMR (500MHz, CDCl3) δ9.24(s,1H),8.40(s,H),7.66–7.62(m,2H),7.60(s,1H),7.54–7.51(m,1H),7.45(d,J=8.1Hz,1H),7.30–7.26(m,2H). 13 CNMR(126MHz, CDCl3)δ160.42,158.23,154.69,151.92,133.43,133.32,133.09,132.77(q,J=33.2Hz ),131.03,130.92,128.83,125.43,123.77,123.42(q,J=273.2Hz),123.01,119.17.HRMS(ESI):Calcd for C 18 H9O2N3Cl3F3Na[M+Na] + 483.96047, found: 483.95880.

[0140] (B10): 3-(3-trifluoromethylphenoxy)-4-N-(3,4-dichlorophenyl)formamide-6-chloropyridazine; Whitesolid. Yield: 79%.mp 150–152℃. 1 HNMR (500MHz, CDCl3) δ9.44 (s, 1H), 8.35 (s, 1H), 7.90 (d, J = 2.4Hz, 1H), 7.67–7.64 (m, 2H), 7.57 (s, 1H), 7.53–7.40 (m, 3H). 13 C NMR (126MHz, CDCl3) δ160.04, 157.97, 154.89, 151.76, 136.02, 133.32, 132.95 (q, J = 33.4Hz), 132.81, 131.07, 130.94, 129 .41,125.45,124.01(d,J=3.8Hz),123.36(q,J=273.2Hz),123.29,122.57,120.09,119.15(q,J=3.9Hz).HRMS(ESI):Calcd for C 18 H9O2N3Cl3F3Na[M+Na] + 483.96047, found: 483.95889.

[0141] (B11): 3-(3-trifluoromethylphenoxy)-4-N-(3,5-dichlorophenyl)formamide-6-chloropyridazine; Whitesolid. Yield: 80%. mp 170–171℃. 1 H NMR (500MHz, CDCl3) δ9.43(s,1H),8.32(s,1H),7.69–7.63(m,2H),7.60(d,J=1.9Hz,2H),7.56(s,1H),7.51–7.45(m,1H),7.20(t,J=1.9Hz,1H). 13 CNMR(126MHz, CDCl3)δ160.03,158.11,154.85,151.74,138.36,135.70,132.94,132.93(q,J=33.3Hz),13 1.07,125.96,125.44,124.02(q,J=4.0Hz),123.36(q,J=273.3Hz),123.24,119.15(2C).HRMS(ESI):Calcd for C 18 H9O2N3Cl3F3Na[M+Na] + 483.96047, found: 483.95926.

[0142] (B12): 3-(3-trifluoromethylphenoxy)-4-N-(2-fluorophenyl)carboxamide-6-chloropyridazine; Whitesolid. Yield: 72%.mp 167–168℃. 1 H NMR (500MHz, CDCl3) δ9.94(s,1H),8.50–8.46(m,1H),8.39(s,1H),7.65–7.60(m,3H),7.54–7.52(m,1H),7.24–7.20(m,1H),7.18–7.11(m,2H). 13 C NMR (101MHz, CDCl3) δ159.89, 157.58, 154.77, 152.82 (d, J = 245.94Hz), 151.80, 132.77, 132.72 (q, J = 33.22Hz), 130.76, 125.94 (d, J = 7.6Hz), 125. 57(d,J=9.7Hz),125.01,124.97,123.37(q,J=274.72Hz),123.59(q,J=3.9Hz),122.02,118.76(q,J=3.9Hz),115.16,114.97.HRMS(ESI):Calcdfor C 18 H10 O2N3ClF4Na[M+Na] + 434.02899, found: 434.02795.

[0143] (B13): 3-(3-trifluoromethylphenoxy)-4-N-(3-fluorophenyl)carboxamide-6-chloropyridazine; Whitesolid. Yield: 80%.mp 136–137℃. 1 H NMR(500MHz, CDCl3)δ9.49(s,1H),8.38(s,1H),7.67–7.64(m,3H),7.58(s,0H ),7.51–7.49(m,1H),7.37–7.32(m,1H),7.27–7.25(m,1H),6.95–6.91(m,1H). 13 C NMR (126MHz, CDCl3) δ163.06 (d, J = 246.3Hz), 160.10, 157.90, 154.82, 151.85, 138.09 (d,J=10.7Hz),132.96(d,J=13.9Hz),132.88(q,J=33.3Hz),131.01,130.55(d,J=9.2 Hz),125.40,123.88(q,J=3.8Hz),123.70,123.39(q,J=273.2Hz),119.07(q,J=3.9Hz ),116.16(d,J=3.1Hz),112.79(d,J=21.2Hz),108.46(d,J=26.5Hz).HRMS(ESI):Calcd for C 18 H 10 O2N3ClF4Na[M+Na] + 434.02899, found: 434.02841.

[0144] (B14): 3-(3-trifluoromethylphenoxy)-4-N-(4-fluorophenyl)carboxamide-6-chloropyridazine; Whitesolid. Yield: 81%.mp 134–136℃. 1 H NMR (500MHz, CDCl3) δ9.40(s,1H),8.38(s,1H),7.66–7.61(m,4H),7.58–7.57(m,1H),7.51–7.48(m,1H),7.12–7.07(m,2H). 13C NMR (101MHz, CDCl3) δ160.25 (d, J = 247.3Hz), 160.11, 157.73, 154.79, 151.85, 132.86 (q, J = 34.1Hz), 132.84, 132.61 (d, J = 3.1Hz), 130.91 ,125.33,123.32(q,J=273.8Hz),124.81–123.7(m,2C),122.74(d,J=8.0Hz),119.01(q,J=3.8Hz),116.14(d,J=22.7Hz).HRMS(ESI):Calcd for C 18 H 10 O2N3ClF4Na[M+Na] + 434.02899, found: 434.02792.

[0145] (B15): 3-(3-trifluoromethylphenoxy)-4-N-(2,3-difluorophenyl)formamide-6-chloropyridazine; Whitesolid. Yield: 70%. mp 169–171℃. 1 H NMR (500MHz, CDCl3) δ10.31(s,1H),8.74(s,1H),8.68–8.53(m,1H),8.19–7.95(m,3H),7.93–7.80(m,1H),7.56–7.48(m,1H),7.48–7.29(m,1H). 13 CNMR(126MHz, CDCl3)δ159.90,157.85,154.85,151.73,150.26(dd,J=248.2,10.8Hz),1 41.61(dd,J=246.5,15.1Hz),132.90,132.82(q,J=33.0Hz),130.94,127.30(d,J=6.5Hz ), 125.10, 124.73 (dd, J = 7.6, 4.9Hz), 123.82 (q, J = 4.0Hz), 123.40 (q, J = 273.2Hz), 123. 31`,118.84(q,J=3.8Hz),117.09(d,J=3.8Hz),113.63(d,J=16.6Hz).HRMS(ESI):Calcd for C 18 H 10 O2N3ClF5[M+H] + 430.03762, found: 430.03830.

[0146] (B16): 3-(3-trifluoromethylphenoxy)-4-N-(2,5-difluorophenyl)formamide-6-chloropyridazine; Whitesolid. Yield: 78%.mp 152–154℃. 1 HNMR(500MHz, CDCl3)δ10.00(m,1H),8.39(s,1H),8.37–8.31(m,1H),7.73–7.62(m, 2H),7.61(s,1H),7.54(dt,J=6.5,2.7Hz,1H),7.17–7.06(m,1H),6.91–6.82(m,1H). 13 C NMR(101MHz, CDCl3)δ159.77,148.77(dd,J=243.4,3.0Hz),157.72,154.84,151.67,148.77( dd,J=240.6,3.0Hz),132.84,132.75(q,J=33.1Hz),130.83,126.37(t,J=12.0Hz),124.85(d ,J=31.6Hz),123.71(q,J=3.7Hz),123.34(q,J=273.4Hz),123.19,118.73(q,J=3.9Hz),115. 55(dd,J=21.4,9.6Hz),111.83(dd,J=24.8,7.9Hz),109.31(d,J=30.4Hz).HRMS(ESI):Calcd for C 18 H9O2N3ClF5Na[M+Na] + 452.01957, found: 452.01944.

[0147] (B17): 3-(3-trifluoromethylphenoxy)-4-N-(2,6-difluorophenyl)formamide-6-chloropyridazine; Whitesolid. Yield: 70%. mp 157–158℃. 1 H NMR (500MHz, CDCl3) δ9.01(s,1H),8.38(s,1H),7.66–7.61(m,2H),7.60(s,1H),7.53–7.51(m,1H),7.35–7.28(m,1H),7.04(t,J=8.1Hz,2H). 13C NMR(126MHz, CDCl3)δ160.35,158.50,157.75(dd,J=252.1,0.1Hz),154.71,151.88,133.19,132.81(d,J=33.4Hz),130.88,128.94(t,J=9.7Hz),125 .47,123.79(q,J=4.2Hz),123.41(q,J=273.5Hz),122.77,119.18(q,J=4.2Hz),112.76(t,J=16.3Hz),112.13(dd,J=19.4,4.0Hz).HRMS(ESI):Calcd for C 18 H9O2N3ClF5Na[M+Na] + 452.01957, found: 452.01825.

[0148] (B18): 3-(3-trifluoromethylphenoxy)-4-N-(3,4-difluorophenyl)carboxamide-6-chloropyridazine; Yellowsolid. Yield: 78%. mp 153–154℃. 1 H NMR (500MHz, CDCl3) δ9.42(s,1H),8.31(s,1H),7.80–7.70(m,1H),7.67–7.58(m,2H),7.54(s,1H),7.50–7.41(m,1H),7.23–7.08(m,2H). 13 CNMR(101MHz,CDCl3)δ160.03,157.87,154.73,151.77,150.29(dd,J=230.8,13.1Hz),1 47.82(dd,J=230.6,12.9Hz),133.16–132.92(m,1C),132.81(q,J=33.1Hz),132.78,130. 94,125.31,123.82(q,J=3.9Hz),123.51,123.31(q,J=273.4Hz),118.96(q,J=3.9Hz),1 17.63(d,J=18.3Hz),116.66(dd,J=6.3,3.4Hz),110.76(d,J=21.9Hz).HRMS(ESI):Calcd for Calcd for C 18 H9O2N3ClF5Na[M+Na] + 452.01957, found: 452.01885.

[0149] (B19): 3-(3-trifluoromethylphenoxy)-4-N-(3,5-difluorophenyl)formamide-6-chloropyridazine; Whitesolid. Yield: 80%. mp 145–146℃. 1 H NMR (400MHz, CDCl3) δ9.50(s,1H),8.37(s,1H),7.72–7.63(m,2H),7.57(d,J=1.7Hz,1H),7.53–7.44(m,1H),7.33–7.21(m,2H),6.79–6.60(m,1H). 13 CNMR (101MHz, CDCl3) δ163.25 (dd, J=248.0, 14.5Hz), 159.93, 157.98, 154.87 ,151.66,138.58(t,J=12.9Hz),132.94,132.93(q,J=33.3Hz),131.01,125.32 ,124.64,123.95(q,J=3.7Hz),123.29(q,J=273.4Hz),123.14,121.93,119.04 (q,J=4.0Hz),106.07–102.51(m,1C),101.27(t,J=25.4Hz).HRMS(ESI):Calcd for Calcd forC 18 H9O2N3ClF5Na[M+Na] + 452.01957, found: 452.01957.

[0150] (B20): 3-(3-trifluoromethylphenoxy)-4-N-(2-chloro-3-fluorophenyl)carboxamide-6-chloropyridazine; Whitesolid. Yield: 70%.mp 174–175℃. 1 H NMR(400MHz, CDCl3)δ10.34(s,1H),8.49–8.42(m,1H),8.41(s,1H),7.70–7.63 (m,2H),7.60(s,1H),7.56–7.49(m,1H),7.40–7.30(m,1H),7.09–6.96(m,1H). 13C NMR(101MHz, CDCl3)δ159.89,158.22(d,J=249.7Hz),157.91,154.78,151.76,1 35.69,132.92,132.81(d,J=33.6Hz),130.91,128.49(d,J=8.3Hz),125.16,123 .78(q,J=3.8Hz),123.36,123.32(q,J=273.7Hz),118.92(q,J=3.9Hz),117.10( d,J=3.6Hz),112.87(d,J=20.6Hz),111.15(d,J=20.5Hz).HRMS(ESI):Calcdfor C 18 H9O2N3Cl2F4Na[M+Na] + 467.99002, found: 467.98984.

[0151] (B21): 3-(3-trifluoromethylphenoxy)-4-N-(2-chloro-4-fluorophenyl)carboxamide-6-chloropyridazine; Whitesolid. Yield: 75%.mp 162–164℃. 1 H NMR(400MHz, CDCl3)δ10.21(s,1H),8.60(dd,J=9.2,5.5Hz,1H),8.41(s,1H),7.70–7.62 (m,2H),7.59(s,1H),7.55–7.49(m,1H),7.20(dd,J=7.9,2.8Hz,1H),7.15–7.05(m,1H). 13 C NMR (101MHz, CDCl3) δ159.95, 159.14 (d, J = 250.4Hz), 157.69, 154.76, 151.79, 132.91 (d,J=8.0Hz),132.79(q,J=33.5Hz),130.87,130.61(d,J=3.6Hz),125.17,124.29(d, J=10.3Hz),123.73(q,J=3.7Hz),123.46,123.33(q,J=274.0Hz),123.22(d,J=8.3Hz) ,118.91(q,J=3.7Hz),116.79(d,J=26.3Hz),115.08(d,J=21.9Hz).HRMS(ESI):Calcd for C 18 H9O2N3Cl2F4Na[M+Na] + 467.99002, found: 467.98834.

[0152] (B22): 3-(3-trifluoromethylphenoxy)-4-N-(2-chloro-5-fluorophenyl)carboxamide-6-chloropyridazine; Whitesolid. Yield: 75%.mp 153–154℃. 1 H NMR(500MHz, CDCl3)δ10.36(s,1H),8.47(dd,J=10.5,2.9Hz,1H),8.40(s,1H),7.67–7.6 2(m,2H),7.59(s,1H),7.54–7.50(m,1H),7.38(dd,J=8.9,5.5Hz,1H),6.90–6.86(m,1H). 13 C NMR (126MHz, CDCl3) δ161.61 (d, J = 246.3Hz), 159.93, 157.97, 154.84, 151.82, 135 .19(d,J=11.9Hz),132.99,132.84(q,J=33.3Hz),130.94,130.10(d,J=9.3Hz),12 5.25,123.81(q,J=4.0Hz),123.40(q,J=273.0Hz),123.32,119.00(q,J=4.0Hz),1 18.25(d,J=3.6Hz),112.98(d,J=23.4Hz),109.64(d,J=29.6Hz).HRMS(ESI):Calcd for C 18 H 10 O2N3Cl2F4[M+H] + 446.00807, found: 446.00809.

[0153] (B23): 3-(3-trifluoromethylphenoxy)-4-N-(2-chloro-6-fluorophenyl)carboxamide-6-chloropyridazine; Whitesolid. Yield: 70%.mp 178–180℃. 1 H NMR (500MHz, CDCl3) δ9.18(s,1H),8.39(s,1H),7.69–7.58(m,3H),7.55–7.50(m,1H),7.34–7.27(m,2H),7.22–7.13(m,1H). 13C NMR (101MHz, CDCl3) δ160.30, 158.14, 157.99 (d, J = 255.6Hz), 154.65, 151.85, 133.12,132.74(q,J=33.0Hz),131.53(d,J=2.9Hz),130.84,129.13(d,J=9.2H z),125.37,125.33,123.70(q,J=4.0Hz),123.35(q,J=273.4Hz),122.84,121. 82(d,J=15.4Hz),119.06(q,J=3.9Hz),115.40(d,J=20.6Hz).HRMS(ESI):Calcd for C 18 H 10 O2N3Cl2F4[M+H] + 446.00807, found: 446.00818.

[0154] (B24): 3-(3-trifluoromethylphenoxy)-4-N-(3-chloro-4-fluorophenyl)carboxamide-6-chloropyridazine; Whitesolid. Yield: 78%.mp 132–134℃. 1 HNMR (400MHz, CDCl3) δ9.41 (s, 1H), 8.37 (s, 1H), 7.85 (dd, J = 6.5, 2.7Hz, 1H ),7.72–7.63(m,2H),7.57(s,1H),7.52–7.41(m,2H),7.17(t,J=8.7Hz,1H). 13 CNMR (101MHz, CDCl3) δ160.03, 157.87, 155.71 (d, J = 249.7Hz), 154.84, 151.73, 133.15(d,J=3.6Hz),132.90(d,J=33.7Hz),132.89,130.98,125.38,123.92(q,J =3.8Hz),123.30,123.29(q,J=273.9Hz),123.18,121.71(d,J=19.0Hz),120.65 (d,J=7.2Hz),119.08(q,J=4.0Hz),117.06(d,J=22.6Hz).HRMS(ESI):CalcdforC 18 H9O2N3Cl2F4Na[M+Na] + 467.99002, found: 467.99005.

[0155] (B25): 3-(3-trifluoromethylphenoxy)-4-N-(3-chloro-5-fluorophenyl)carboxamide-6-chloropyridazine; Whitesolid. Yield: 78%.mp 176–178℃. 1 H NMR (500MHz, CDCl3) δ9.47(s,1H),8.37(s,1H),7.71–7.65(m,2H),7.57(s,1H),7.55–7.47(m,2H),7.40–7.36(m,1H),7.00–6.93(m,1H). 13 CNMR (126MHz, CDCl3) δ162.93 (d, J = 249.2Hz), 160.01, 158.07, 154.93, 151.73, 13 8.61(d,J=12.0Hz),135.76(d,J=12.2Hz),133.01,131.09,133.05(q,J=33.4Hz),1 25.43,124.06(q,J=3.9Hz),123.3(q,J=276.4Hz),123.16,119.17(q,J=3.9Hz),1 16.53(d,J=3.3Hz),113.66(d,J=25.1Hz),106.84(d,J=26.5Hz).HRMS(ESI):Calcd forC 18 H9O2N3Cl2F4Na[M+Na] + 467.99002, found: 467.98969.

[0156] (B26): 3-(3-trifluoromethylphenoxy)-4-N-(3-chloro-6-fluorophenyl)carboxamide-6-chloropyridazine; Whitesolid. Yield: 75%.mp 189–191℃. 1 HNMR (500MHz, CDCl3) δ9.97 (d, J=3.3Hz, 1H), 8.58 (dd, J=6.7, 2.5Hz, 1H), 8.38 (s,1H),7.67–7.63(m,2H),7.60(s,1H),7.54–7.52(m,1H),7.15–7.07(m,2H). 13C NMR (126MHz, CDCl3) δ159.83, 157.77, 154.91, 151.72, 151.24 (d, J = 244.9Hz), 132.91,130.90,132.83(q,J=33.3Hz),130.25(d,J=3.4Hz),126.52(d,J=11.0 Hz),125.63(d,J=7.8Hz),125.08,123.80(q,J=3.8Hz),123.40(q,J=273.2Hz) ,123.23,121.94,118.81(q,J=4.1Hz),116.04(d,J=20.7Hz).HRMS(ESI):Calcd forC 18 H9O2N3Cl2F4Na[M+Na] + 467.99002, found: 467.99020.

[0157] (B27): 3-(3-trifluoromethylphenoxy)-4-N-(2-fluoro-4-chlorophenyl)carboxamide-6-chloropyridazine; Whitesolid. Yield: 78%.mp 165–166℃. 1 H NMR(500MHz, CDCl3)δ9.92(s,1H),8.47(t,J=8.6Hz,1H),8.38(s,1H),7.68–7.62(m,2H),7.60 (d,J=2.5Hz,1H),7.56–7.50(m,1H),7.22(dt,J=9.0,1.7Hz,1H),7.19(dd,J=10.5,2.3Hz,1H). 13 C NMR (101MHz, CDCl3) δ159.81, 157.64, 154.82, 152.48 (d, J = 249.2Hz), 151.70, 132.81(q,J=33.1Hz),132.78,130.82,130.59(d,J=10.2Hz),125.26(d,J=3.7H z),125.01,124.37(d,J=10.2Hz),123.71(q,J=3.7Hz),123.33(q,J=273.9Hz) ,123.28,122.65,118.75(q,J=3.9Hz),115.94(d,J=22.2Hz).HRMS(ESI):Calcd for C 18 H9O2N3Cl2F4Na[M+Na] + 467.99002, found: 467.98999.

[0158] (B28): 3-(3-trifluoromethylphenoxy)-4-N-(2,3,4-trifluorophenyl)formamide-6-chloropyridazine; Whitesolid. Yield: 80%.mp 134–136℃. 1 H NMR (400MHz, CDCl3) δ9.84(s,1H),8.38(s,1H),8.30–8.16(m,1H),7.70–7.63(m,2H),7.59(s,1H),7.56–7.47(m,1H),7.12–6.98(m,1H). 13 CNMR(101MHz,CDCl3)δ159.82,157.93,154.79,151.61,149.57–146.99(m,1C),1 43.95–138.45(m,2C),132.82(q,J=33.3Hz),132.80,130.91,125.04,123.81(q, J=3.8Hz),123.31(q,J=273.8Hz),123.04,123.00–122.92(m,1C),118.77(q,J=3 .98Hz),116.14(dd,J=7.4,4.4Hz),112.20(dd,J=17.9,3.9Hz).HRMS(ESI):Calcd for C 18 H8O2N3ClF6Na[M+Na] + 470.01014, found: 470.00876.

[0159] (B29): 3-(3-trifluoromethylphenoxy)-4-N-(2,3,5-trifluorophenyl)carboxamide-6-chloropyridazine; Whitesolid. Yield: 78%.mp 130–132℃. 1H NMR (500MHz, CDCl3) δ 10.05 (s, 1H), 8.38 (s, 1H), 8.20–8.11 (m, 1H), 7.68–7.63 (m, 2H), 7.60 (s, 1H), 7.56–7.49 (m, 1H), 6.86–6.71 (m, 1H). 13C NMR (101MHz, CDCl3) δ 159.70, 159.20–156.61 (m, 2C). ),154.86,151.56,151.12–148.49(m,1C),139.42–136.80(m,1C),132. 86,132.78(q,J=33.8Hz),130.91,127.61–126.38(m,1C),124.98,123.8 1(q,J=3.7Hz),123.31(q,J=273.5Hz),122.83,118.73(q,J=4.0Hz),104.43(dd,J=30.0,3.7Hz),101.50(dd,J=28.0,21.0Hz).HRMS(ESI):Calcd forC18H8O2N3ClF6Na[M+Na] + 470.01014, found: 470.00854.

[0160] (B30): 3-(3-trifluoromethylphenoxy)-4-N-(2,3,6-trifluorophenyl)formamide-6-chloropyridazine; Whitesolid. Yield: 70%.mp 113–115℃. 1 H NMR (400MHz, CDCl3) δ9.07(s,1H),8.38(s,1H),7.73–7.61(m,2H),7.59(s,1H),7.56–7.48(m,1H),7.23–7.12(m,1H),7.05–6.93(m,1H). 13CNMR(101MHz, CDCl3)δ160.19,158.44,154.62,153.09(dt,J=248.0,2.9Hz),151.73,1 48.74–147.23(m,1C),146.29–144.69(m,1C),133.09,132.71(q,J=33.6Hz),130.85,12 5.38,123.76(q,J=3.8Hz),123.32(q,J=327.4Hz),122.42,119.06(q,J=3.8Hz),115.8 0(dd,J=19.3,9.3Hz),114.49–114.18(m,1C),111.03–110.70(m,1C).HRMS(ESI):Calcd for C 18 H8O2N3ClF6Na[M+Na] + 470.01014, found: 470.00876.

[0161] (B31): 3-(3-trifluoromethylphenoxy)-4-N-(3,4,5-trifluorophenyl)formamide-6-chloropyridazine; Whitesolid. Yield: 78%.mp 138–140℃. 1 H NMR (400MHz, CDCl3) δ9.42 (s, 1H), 8.36 (s, 1H), 7.72–7.61 (m, 2H), 7.56 (d, J = 0.9Hz, 1H), 7.48 (td, J = 5.5, 4.9, 2.8Hz, 1H), 7.46–7.34 (m, 2H). 13 CNMR(101MHz, CDCl3)δ159.92,158.05,154.84,152.58–149.94(m,1C),151.62,138.86–136.06(m,1C),132.95(q,J=33.5Hz),132.90,132.18–13 2.00(m,1C),131.03,125.34,124.01(q,J=3.8Hz),123.27(q,J=273.9Hz),123.03,119.04(q,J=3.8Hz),105.58–105.33(m,1C).HRMS(ESI):Calcd for C 18 H8O2N3ClF6Na[M+Na] + 470.01014, found: 470.00894.

[0162] (B32): 3-(3-trifluoromethylphenoxy)-4-N-(2,4,5-trifluorophenyl)carboxamide-6-chloropyridazine; Whitesolid. Yield: 77%.mp 148–150℃. 1 H NMR (500MHz, CDCl3) δ9.99(s,1H),8.55–8.44(m,1H),8.37(s,1H),7.69–7.61(m,2H),7.58(s,1H),7.54–7.49(m,1H),7.08–7.00(m,1H). 13 CNMR(101MHz, CDCl3)δ159.76,157.68,154.84,151.61,149.14–145.33(m,3C),132.81,132.76(q,J=33.5Hz),130.87,125.01,123.78(q,J=3.7H z),123.32(q,J=273.7Hz),122.99,121.93–121.68(m,1C),118.72(q,J=3.8Hz),110.84(d,J=24.9Hz),105.45–104.98(m,1C).HRMS(ESI):Calcd for C 18 H8O2N3ClF6Na[M+Na] + 470.01014, found: 470.00830.

[0163] (B33): 3-(3-trifluoromethylphenoxy)-4-N-(2,4,6-trifluorophenyl)formamide-6-chloropyridyl; Whitesolid. Yield: 70%. mp 145–146℃. 1 H NMR (400MHz, CDCl3) δ8.90(s,1H),8.36(s,1H),7.68–7.61(m,2H),7.58(s,1H),7.54–7.50(m,1H),6.85–6.79(m,2H). 13C NMR(101MHz, CDCl3)δ163.18–160.25(m,1C),160.25,159.45–156.72(m,1C),158.72,154.57,151.77,133.11,132.69(q,J=33.1Hz),130.83,125 .41,123.71(q,J=3.8Hz),123.33(q,J=273.3Hz),122.44,119.10(q,J=3.8Hz),109.55–109.43(m,1C),101.30–100.76(m,1C).HRMS(ESI):Calcd for C 18 H8O2N3ClF6Na[M+Na] + 470.01014, found: 470.00879.

[0164] Pre-seeding activity assay of target compounds:

[0165] This experiment used the petri dish method, with various weeds as test subjects. Weed seeds were germinated in an incubator until they showed signs of germination. Two sheets of filter paper were then placed in each petri dish (12-well plate), with 4-6 identical germinating seeds in each well. A compound was dissolved in DMF to prepare a 100 μg / mL concentration, which was then added to the wells. Each treatment was repeated three times. After treatment, the petri dishes were placed in an artificial climate incubator and cultured for 5 days at 25-30℃, 5000 lx light, a day:night ratio of 16:8, and a relative humidity of 70%-80%. The root and stem lengths of four seeds with similar growth were measured. The growth inhibition rate of each treatment group on weed seeds was calculated, with L representing the root and stem length of the weeds. The formula is as follows:

[0166] Growth inhibition rate (%) = L (空白组) –L (处理组) / L (空白组) ×100%

[0167] Pre-emergence herbicidal activity is shown in Tables 1 and 2.

[0168] Table 1. Pre-emergence herbicidal activity (100 μg / mL)

[0169]

[0170] a Albinism. b The amaranth was dead and inactive.

[0171]

[0172]

[0173] Post-seeding activity test of target compound:

[0174] This experiment used a spraying method with various weeds as test subjects. Weed seeds were germinated in an incubator until they showed white sprouts. All sprouted seeds were evenly scattered in 8×8cm plastic pots filled two-thirds full with organic substrate and placed in a greenhouse for growth. When both grasses and broadleaf weeds reached the three-leaf stage, they were ready for testing. Compounds were dissolved in 100 μL DMF and diluted with 0.1% Tween-80 to doses of 300, 150, or 75 g ai / ha. Pyrifluquinazon and flufenoxuron were used as positive controls and target compounds, respectively, for spraying all weeds. After 25 days in the greenhouse, the herbicidal activity of the treated weeds was evaluated visually, using a control group (CK). Crop safety testing also used this post-emergence testing method. Results are shown in Tables 3, 4, and 5.

[0175] Table 3. Post-emergence herbicidal activity of series A compounds

[0176]

[0177]

[0178] Table 4. Post-emergence herbicidal activity of B-series compounds

[0179]

[0180]

[0181] Table 5. Herbicidal activity of B1 (75g ai / ha)

[0182]

[0183]

[0184] Table 6. Crop Safety Assessment

[0185]

[0186] As shown in Tables 1 and 2, at a dosage of 100 μg / mL, most compounds exhibited superior inhibitory effects compared to pyrifluquinazon, especially compounds A19, B1, and B19, which showed 100% inhibition rates against the roots and stems of barnyardgrass. Compounds A28, A29, B23, and B31 also showed 100% inhibition rates against the roots and stems of purslane. Some of these compounds showed 100% inhibition rates only against the roots or stems. At a concentration of 10 μg / mL, only compounds B1, B19, and B20 showed higher inhibition rates against the roots and stems of both barnyardgrass and purslane than the positively charged pyrifluquinazon. Among these, B19 showed the best pre-emergence herbicidal activity, followed by B1. In addition, compounds A5, A7, B3, B4, B6, B11, B13, B16, B22, B25, B29, B31 and B33 showed better root inhibition rates against barnyardgrass than pyrfluthrin, and most of the compounds showed higher activity than pyrfluthrin against the roots or stems of purslane.

[0187] As can be seen from Tables 3, 4 and 5, some compounds showed herbicidal activity comparable to that of the positive control pyfluquat chloride against broadleaf weeds, especially compound B1, which showed the most outstanding performance. When the application concentration was 75 gai / ha, B1 had better activity against broadleaf weeds than the positive control pyfluquat chloride and fluroxypyr.

[0188] Table 6 shows that compound B1 is safer than the positive control BF in spinach, pepper, soybean, and corn. Other crops also showed similar activities to B1 and BF.

[0189] In summary, this series of pyridazine derivatives exhibits excellent herbicidal and inhibitory activity. Therefore, this series of compounds can be further developed as novel pre- and post-emergence herbicides for application in a wider range of farmlands.

[0190] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Any simple modifications, equivalent changes, and alterations made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention shall still fall within the scope of the present invention.

Claims

1. A pyridazine derivative, characterized in that, The general structural formula is as shown in formula (I): In formula (I): R1 is fluorine or chlorine; R2 is trifluoromethyl; X is halogen or hydrogen atom.

2. The pyridazine derivative as described in claim 1, characterized in that, Selected from the following compounds: Compound A1: 3-(3-trifluoromethylphenoxy)-4- N -(2,4-difluorophenyl)formamide pyridazine; Compound A3: 3-(3-trifluoromethylphenoxy)-4- N -(2-chlorophenyl)formamide pyridazine; Compound A4: 3-(3-trifluoromethylphenoxy)-4- N -(3-Chlorophenyl)formamide pyridazine; Compound A5: 3-(3-trifluoromethylphenoxy)-4- N -(4-chlorophenyl)formamide pyridazine; Compound A6: 3-(3-trifluoromethylphenoxy)-4- N -(2,3-dichlorophenyl)formamide pyridazine; Compound A7: 3-(3-trifluoromethylphenoxy)-4- N -(2,4-dichlorophenyl)formamide pyridazine; Compound A8: 3-(3-trifluoromethylphenoxy)-4- N -(2,5-dichlorophenyl)formamide pyridazine; Compound A9: 3-(3-trifluoromethylphenoxy)-4- N -(2,6-dichlorophenyl)formamide pyridazine; Compound A10: 3-(3-trifluoromethylphenoxy)-4- N -(3,4-dichlorophenyl)formamide pyridazine; Compound A11: 3-(3-trifluoromethylphenoxy)-4- N -(3,5-dichlorophenyl)formamide pyridazine; Compound A12: 3-(3-trifluoromethylphenoxy)-4- N -(2-Fluorophenyl)formamide pyridazine; Compound A13: 3-(3-trifluoromethylphenoxy)-4- N -(3-Fluorophenyl)formamide pyridazine; Compound A14: 3-(3-trifluoromethylphenoxy)-4- N -(4-Fluorophenyl)formamide pyridazine; Compound A15: 3-(3-trifluoromethylphenoxy)-4- N -(2,3-difluorophenyl)formamide pyridazine; Compound A16: 3-(3-trifluoromethylphenoxy)-4- N -(2,5-difluorophenyl)formamide pyridazine; Compound A17: 3-(3-trifluoromethylphenoxy)-4- N -(2,6-difluorophenyl)formamide pyridazine; Compound A18: 3-(3-trifluoromethylphenoxy)-4- N -(3,4-difluorophenyl)formamide pyridazine; Compound A19: 3-(3-trifluoromethylphenoxy)-4- N -(3,5-difluorophenyl)formamide pyridazine; Compound A20: 3-(3-trifluoromethylphenoxy)-4- N -(2-chloro-3-fluorophenyl)formamide pyridazine; Compound A21: 3-(3-trifluoromethylphenoxy)-4- N -(2-chloro-4-fluorophenyl)formamide pyridazine; Compound A22: 3-(3-trifluoromethylphenoxy)-4- N -(2-chloro-5-fluorophenyl)formamide pyridazine; Compound A23: 3-(3-trifluoromethylphenoxy)-4- N -(2-chloro-6-fluorophenyl)formamide pyridazine; Compound A24: 3-(3-trifluoromethylphenoxy)-4- N -(3-chloro-4-fluorophenyl)formamide pyridazine; Compound A25: 3-(3-trifluoromethylphenoxy)-4- N -(3-chloro-5-fluorophenyl)formamide pyridazine; Compound A26: 3-(3-trifluoromethylphenoxy)-4- N -(3-chloro-6-fluorophenyl)formamide pyridazine; Compound A27: 3-(3-trifluoromethylphenoxy)-4- N -(2-fluoro-4-chlorophenyl)formamide pyridazine; Compound A28: 3-(3-trifluoromethylphenoxy)-4- N -(2,3,4-trifluorophenyl)formamide pyridazine; Compound A29: 3-(3-trifluoromethylphenoxy)-4- N -(2,3,5-trifluorophenyl)formamide pyridazine; Compound A30: 3-(3-trifluoromethylphenoxy)-4- N -(2,3,6-trifluorophenyl)formamide pyridazine; Compound A31: 3-(3-trifluoromethylphenoxy)-4- N -(3,4,5-trifluorophenyl)formamide pyridazine; Compound A32: 3-(3-trifluoromethylphenoxy)-4- N -(2,4,5-trifluorophenyl)formamide pyridazine; Compound A33: 3-(3-trifluoromethylphenoxy)-4- N -(2,4,6-trifluorophenyl)formamide pyridazine; Compound B1: 3-(3-trifluoromethylphenoxy)-4- N -(2,4-difluorophenyl)formamide-6-chloropyridazine; Compound B3: 3-(3-trifluoromethylphenoxy)-4- N -(2-Chlorophenyl)formamide-6-chloropyridazine; Compound B4: 3-(3-trifluoromethylphenoxy)-4- N -(3-Chlorophenyl)formamide-6-chloropyridazine; Compound B5: 3-(3-trifluoromethylphenoxy)-4- N -(4-Chlorophenyl)formamide-6-chloropyridazine; Compound B6: 3-(3-trifluoromethylphenoxy)-4- N -(2,3-dichlorophenyl)formamide-6-chloropyridazine; Compound B7: 3-(3-trifluoromethylphenoxy)-4- N -(2,4-dichlorophenyl)formamide-6-chloropyridazine; Compound B8: 3-(3-trifluoromethylphenoxy)-4- N -(2,5-dichlorophenyl)formamide-6-chloropyridazine; Compound B9: 3-(3-trifluoromethylphenoxy)-4- N -(2,6-dichlorophenyl)formamide-6-chloropyridazine; Compound B10: 3-(3-trifluoromethylphenoxy)-4- N -(3,4-dichlorophenyl)formamide-6-chloropyridazine; Compound B11: 3-(3-trifluoromethylphenoxy)-4- N -(3,5-dichlorophenyl)formamide-6-chloropyridazine; Compound B12: 3-(3-trifluoromethylphenoxy)-4- N -(2-Fluorophenyl)formamide-6-chloropyridazine; Compound B13: 3-(3-trifluoromethylphenoxy)-4- N -(3-Fluorophenyl)formamide-6-chloropyridazine; Compound B14: 3-(3-trifluoromethylphenoxy)-4- N -(4-Fluorophenyl)formamide-6-chloropyridazine; Compound B15: 3-(3-trifluoromethylphenoxy)-4- N -(2,3-difluorophenyl)formamide-6-chloropyridazine; Compound B16: 3-(3-trifluoromethylphenoxy)-4- N -(2,5-difluorophenyl)formamide-6-chloropyridazine; Compound B17: 3-(3-trifluoromethylphenoxy)-4- N -(2,6-difluorophenyl)formamide-6-chloropyridazine; Compound B18: 3-(3-trifluoromethylphenoxy)-4- N -(3,4-difluorophenyl)formamide-6-chloropyridazine; Compound B19: 3-(3-trifluoromethylphenoxy)-4- N -(3,5-difluorophenyl)formamide-6-chloropyridazine; Compound B20: 3-(3-trifluoromethylphenoxy)-4- N -(2-chloro-3-fluorophenyl)formamide-6-chloropyridazine; Compound B21: 3-(3-trifluoromethylphenoxy)-4- N -(2-chloro-4-fluorophenyl)formamide-6-chloropyridazine; Compound B22: 3-(3-trifluoromethylphenoxy)-4- N -(2-chloro-5-fluorophenyl)formamide-6-chloropyridazine; Compound B23: 3-(3-trifluoromethylphenoxy)-4- N -(2-chloro-6-fluorophenyl)formamide-6-chloropyridazine; Compound B24: 3-(3-trifluoromethylphenoxy)-4- N -(3-chloro-4-fluorophenyl)formamide-6-chloropyridazine; Compound B25: 3-(3-trifluoromethylphenoxy)-4- N -(3-chloro-5-fluorophenyl)formamide-6-chloropyridazine; Compound B26: 3-(3-trifluoromethylphenoxy)-4- N -(3-chloro-6-fluorophenyl)formamide-6-chloropyridazine; Compound B27: 3-(3-trifluoromethylphenoxy)-4- N -(2-fluoro-4-chlorophenyl)formamide-6-chloropyridazine; Compound B28: 3-(3-trifluoromethylphenoxy)-4- N -(2,3,4-trifluorophenyl)formamide-6-chloropyridazine; Compound B29: 3-(3-trifluoromethylphenoxy)-4- N -(2,3,5-trifluorophenyl)formamide-6-chloropyridazine; Compound B30: 3-(3-trifluoromethylphenoxy)-4- N -(2,3,6-trifluorophenyl)formamide-6-chloropyridazine; Compound B31: 3-(3-trifluoromethylphenoxy)-4- N -(3,4,5-trifluorophenyl)formamide-6-chloropyridazine; Compound B32: 3-(3-trifluoromethylphenoxy)-4- N -(2,4,5-trifluorophenyl)formamide-6-chloropyridazine; Compound B33: 3-(3-trifluoromethylphenoxy)-4- N -(2,4,6-trifluorophenyl)formamide-6-chloropyridazine.

3. The method for preparing the pyridazine derivative as described in claim 1, characterized in that, Includes the following steps: (1) Preparation of compound methyl 3,6-dichloro-4-carboxylate pyridazine (intermediate 2): Compound 1 was dissolved in an organic solvent, sodium carbonate was added, and iodomethane was added dropwise at room temperature. After the reaction of compound 1 was completed, the solid was obtained by extraction with ethyl acetate, drying and column chromatography, which is intermediate 2. The compound 1 is 3,6-dichloro-4-carboxypyridazine. (2) Preparation of methyl 3-(3-trifluoromethylphenoxy)-4-carboxylate-6-chloropyridazine (intermediate 3): 3-Trifluoromethylphenol and cesium carbonate were placed in an organic solvent and stirred at room temperature for 1 hour. Then, an organic solution of intermediate 2 was added dropwise. After the reaction was complete, the mixture was filtered, and the organic layer was extracted with ethyl acetate, washed with saturated sodium chloride, dried, and then subjected to column chromatography to obtain a solid, which was intermediate 3. (3) Preparation of 3-(3-trifluoromethylphenoxy)-4-carboxylic acid-6-chloropyridazine (intermediate 4): Intermediate 3 was placed in a mixed solvent of methanol and water, and sodium hydroxide or lithium hydroxide was added at room temperature. The mixture was stirred at room temperature. After the reaction was complete, the pH was adjusted to acidic with 1 N HCl, extracted with ethyl acetate, washed with saturated sodium chloride, dried, and filtered to remove the organic solvent to obtain intermediate 4. (4) Preparation of pyridazine 3-(3-trifluoromethylphenoxy)-4-carboxylic acid (intermediate 5): Take intermediate 4 in ethanol, then add Pd / C and ammonium formate or pass hydrogen gas, heat to reflux, after the reaction is complete, adjust the pH to acidic, extract with ethyl acetate, wash with saturated sodium chloride, dry and column chromatography to obtain solid, which is intermediate 5. (5) Preparation of target compounds A1, A3-A33: Intermediate 5 was placed in dichloromethane, DMF was added, and oxalyl chloride was added dropwise at room temperature. After reacting for 2 hours, dichloromethane was removed under reduced pressure. Then, dichloromethane was added, followed by the dropwise addition of amine compounds and triethylamine. After reacting for 2 hours at room temperature, the reaction was quenched with water. The mixture was extracted with dichloromethane, washed with saturated sodium chloride, dried, and then subjected to column chromatography to obtain the solid, which was the target compound A1, A3-A33. (6) Preparation of target compounds B1, B3-B33: Intermediate 4 was placed in dichloromethane, DMF was added, and oxaloyl chloride was added dropwise at room temperature. After reacting for 2 hours, dichloromethane was removed under reduced pressure, and then dichloromethane was added. Next, amine compounds and triethylamine were added dropwise. After reacting for 2 hours at room temperature, the reaction was quenched with water, extracted with dichloromethane, washed with saturated sodium chloride, dried, and then column chromatography was performed to obtain the solid, which was the target compounds B1, B3-B33.

4. The application of the pyridazine derivative as described in claim 1 or 2, or the pyridazine derivative prepared by the preparation method as described in claim 3, in the preparation of herbicides.

5. The application of the pyridazine derivative as described in claim 4 in the preparation of herbicides, characterized in that, The weeds targeted are barnyard grass, velvetleaf, amaranth, lambsquarters, ryegrass, purslane, bermudagrass, rapeseed, speedwell, amaranth, black nightshade, sow thistle, dandelion, sage, clover, chickweed, goosegrass, and foxtail. 6,3-(3-trifluoromethylphenoxy)-4- N Application of phenylformamide pyridazine in the preparation of herbicides; the herbicides include barnyard grass, velvetleaf, amaranth, lambsquarters, ryegrass, purslane, bermudagrass, rapeseed, speedwell, amaranth, black nightshade, bitter lettuce, dandelion, sage, clover, chickweed, goosegrass, and foxtail. 7,3-(3-trifluoromethylphenoxy)-4- N Application of 6-chloropyridazine in the preparation of herbicides; the herbicides include barnyard grass, velvetleaf, amaranth, lambsquarters, ryegrass, purslane, bermudagrass, rapeseed, speedwell, amaranth, black nightshade, bitter lettuce, dandelion, sage, clover, chickweed, goosegrass, and foxtail.

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