CN101921244B - Derivative of 4-methyl-1,2,3-thiadiazole containing 4-(1,1,2,2-tetrafluoroethoxy)-3,5-dichlorobenzene amino and synthesis method and application thereof - Google Patents

Abstract

The invention provides a derivative of 4-methyl-1,2,3-thiadiazole containing 4-(1,1,2,2-tetrafluoroethoxy)-3,5-dichlorobenzene amino and a synthesis method and application thereof. The invention relates to heterocyclic compounds containing 1,2-diazole, in particular to 4-methyl-1,2,3-thiadiazole containing 1,1,2,2-tetrafluoroethoxy, which has the chemical structural general formula shown in the specification. The invention discloses a structural general formula and a synthesis method of the compounds, discloses an application of the compounds used as insecticide, bactericide, anti-plant virus agent and plant activator, discloses a process for mixing the compounds with agriculturally acceptable assistants or synergists to prepare the insecticide, the bactericide, the anti-plant virus agent and the plant activator, discloses an application of the combination of the compounds and commercial insecticide, bactericide, anti-plant virus agent or plant activator for preventing and treating diseases, insect pests and virus diseases in agriculture, forestry and horticulture, and discloses a preparation method of the compounds.

Description

Derivatives of 4-methyl-1,2,3-thiadiazole containing 4-(1,1,2,2-tetrafluoroethoxy)-3,5-dichloroanilino and their synthetic methods and use

technical field

The technical scheme of the present invention relates to heterocyclic compounds containing 1,2-oxadiazole, specifically to 1,2-dichloroanilino containing 4-(1,1,2,2-tetrafluoroethoxy)-3,5-dichloroanilino 2,3-Thiadiazole derivatives.

Background technique

Heterocyclic compounds are an important source of physiologically active lead compounds, and 1,2,3-thiadiazoles are heterocyclic compounds with a wide range of biological activities, among which, thiazamide (TDL) and benzothiadiazole ( BTH) are all commercialized 1,2,3-thiadiazole plant activators, and plant activators are "green pesticides" in the true sense. The inventor's previous research found that methionamide has good inducing activity (ZL 200610013185.5), currently in the process of industrialization.

The multi-component Ugi reaction is a directional four-component condensation reaction between aldehydes, amines, acids and isonitriles. It is widely used in combinatorial chemistry and has good stereoselectivity. Based on the functional group of the reaction components It is widely used in rational design, solid-state reaction and total synthesis. This reaction has good atom economy and is a green chemical reaction, which is of great significance in the discovery and optimization of lead structures. Our previous research used Ugi reaction to conduct exploratory research, and synthesized some new compounds. Some compounds have certain inductive activity, and some compounds have certain bactericidal activity. Considering the special physical and chemical properties of the F atom and its contribution to biological activity. The previous research also found that introducing 4-(1,1,2,2-tetrafluoroethoxy)-3,5-dichloroaniline into the lead compound also found a new compound with high insecticidal activity (201010198522.9), In order to broaden the scope of leading structure optimization, the present invention has carried out in-depth structural derivation of such compounds with the support of the National Natural Science Foundation of China (20872071 and 20911120069) and the Tianjin Natural Science Foundation of China (10JCZDJC17500), from the principle of active substructure splicing Starting, F atom (4-(1,1,2,2-tetrafluoroethoxy)-3,5-dichloroaniline) was introduced into the target molecule, and the insecticidal, bactericidal and antiviral and inducing activities were carried out determination.

Contents of the invention

The technical problem to be solved by the present invention is to provide new 4-methyl-1,2 , a synthetic method of 3-thiadiazole heterocyclic derivatives, which provides the activity of this type of compound to inhibit the growth of insects, the activity of inhibiting pathogenic fungi and the activity of inducing disease resistance, as well as the direct anti-plant virus activity such as the activity of half-leaf blotch method and protective activity as well as therapeutic activity, while providing the use of these compounds as agrochemicals for plant protection in the fields of agriculture, forestry, sanitation and horticulture.

The technical solution adopted by the present invention to solve the technical problem is: 4-(1,1,2,2-tetrafluoroethoxy)-3, which has insecticidal activity, bactericidal activity, direct antiviral activity and inducing activity, The general chemical structure formula of 4-methyl-1,2,3-thiadiazole heterocyclic derivatives of 5-dichloroanilino is as formula I, and the chemical structure of specific compounds is shown in Table 1:

Wherein: R ₁ is 4-(1,1,2,2-tetrafluoroethoxy)-3,5-dichloroaniline, R ₃ is cyclohexyl, R ₂ is selected from phenyl, o-chlorophenyl , m-chlorophenyl, p-chlorophenyl, o-fluorophenyl, m-fluorophenyl, p-fluorophenyl, o-trifluoromethylphenyl, m-trifluoromethylphenyl, p-trifluoromethylphenyl, o-nitrophenyl, m-nitrophenyl, p-nitrophenyl, o-methylphenyl, m-methylphenyl, p-methylphenyl, m-hydroxyphenyl, p-hydroxyphenyl, o-methoxy phenyl, m-methoxyphenyl, p-methoxyphenyl radicals;

R ₁ is 4-(1,1,2,2-tetrafluoroethoxy)-3,5-dichloroaniline, when R ₃ is isopropyl, R ₂ is selected from phenyl, o-chlorophenyl, m-chlorophenyl, p-chlorophenyl, o-fluorophenyl, m-fluorophenyl, p-fluorophenyl, o-trifluoromethylphenyl, m-trifluoromethylphenyl, p-trifluoromethylphenyl, ortho Nitrophenyl, m-nitrophenyl, p-nitrophenyl, o-methylphenyl, m-methylphenyl, p-methylphenyl, m-hydroxyphenyl, p-hydroxyphenyl, o-methoxybenzene group, m-methoxyphenyl group, p-methoxyphenyl group;

4-methyl-1,2,3-thiadiazole heterocyclic derivatives containing 4-(1,1,2,2-tetrafluoroethoxy)-3,5-dichloroanilino of the present invention The synthesis method is as follows:

Wherein: R ₁ is 4-(1,1,2,2-tetrafluoroethoxy)-3,5-dichlorophenyl; R ₂ is selected from phenyl, o-chlorophenyl, m-chlorophenyl, p-chlorophenyl, o-fluorophenyl, m-fluorophenyl, p-fluorophenyl, o-trifluoromethylphenyl, m-trifluoromethylphenyl, p-trifluoromethylphenyl, o-nitrophenyl, m-nitrophenyl, p-nitrophenyl, o-methylphenyl, m-methylphenyl, p-methylphenyl, m-hydroxyphenyl, p-hydroxyphenyl, o-methoxyphenyl, m-methoxy A group of phenyl, p-methoxyphenyl; _R3 is a group selected from cyclohexyl, isopropyl.

Specifically divided into the following steps:

A. Preparation of 4-methyl-1,2,3-thiadiazole heterocyclic derivatives containing 4-(1,1,2,2-tetrafluoroethoxy)-3,5-dichloroanilino :

Add 10 ml of methanol to a 50 ml round bottom flask, then add 4-methyl-1,2,3-thiadiazole-5-carboxylic acid II, amine compound R ₁ NH ₂ III and aldehyde compound R ₂ CHO VI and isonitrile compound R ₃ NC V each 2 mmoles, the reaction system was stirred at room temperature for 0.5 hours and then left to stand still, TCL monitored the reaction, after two days of reaction, if a solid was formed in the reaction, the solid product was obtained by filtration , the solid product is washed with methanol, or with 200-300 mesh silica gel column chromatography, the eluent is petroleum ether at 60-90 degrees Celsius: ethyl acetate, and the volume ratio is between 8:1-1:5 depending on the product During this period, the obtained pure product was used to calculate the yield, determine the melting point, and perform MS and ¹ H NMR measurements to synthesize 4-(1,1,2,2-tetrafluoroethoxy)-3,5-dichloroanilino The amount of 4-methyl-1,2,3-thiadiazole heterocyclic derivatives is enlarged or reduced according to the corresponding ratio;

B. 4-Methyl-1,2,3-thiadiazole heterocyclic derivatives containing 4-(1,1,2,2-tetrafluoroethoxy)-3,5-dichloroanilino group have the effect on pathogens Determination of effect on fungal growth activity:

Bactericidal 4-methyl-1,2,3-thiadiazole heterocyclic derivatives containing 4-(1,1,2,2-tetrafluoroethoxy)-3,5-dichloroanilino of the present invention The assay method of activity or antibacterial activity is as follows:

The bacterial growth rate assay method is adopted, and the specific process is: take 5 mg of sample and dissolve it in an appropriate amount of dimethylformamide, then dilute it to 500 micrograms/ml with a medicament containing a certain amount of Tween 20 emulsifier aqueous solution, and prepare the test medicament Under sterile conditions, draw 1 ml each into the petri dish, then add 9 ml of medium, shake well and make a 50 μg/ml drug-containing plate, use the plate with 1 ml of sterilized water as the blank control, and use the diameter A 4 mm hole puncher cuts out the bacterial plate along the outer edge of the mycelia, moves it to the plate containing the medicine, and arranges it in an equilateral triangle. Each treatment is repeated 3 times, and the culture plate is cultivated in a constant temperature incubator at 24±1°C. After the diameter of the control colony expands to 2-3 cm, investigate the expanded diameter of the bacteria plate of each treatment, calculate the average value, and calculate the relative bacteriostatic rate by comparing with the blank control. The test bacteria include a variety of common plant pathogens in agriculture, and their names and codes Including AS: Alternaria solani; CA: Cercospora arachidicola; PP: Physalospora piricola; BC: Botrytiscinerea; PS: Rice sheath blight (Pelicularia sasakii); GZ: Gibberella zeae; PI: Phytophthora infestans (Mont.) de Bary; SS: Sclerotias clerotiorum; RC: Rhizoctonia graminearum (Rhizoctonia cerealis), these pathogenic fungi can represent most of the species of pathogenic fungi that actually occur in the field in agricultural production in China.

C. 4-Methyl-1,2,3-thiadiazole heterocyclic derivatization containing 4-(1,1,2,2-tetrafluoroethoxy)-3,5-dichloroanilino of the present invention Determination of drug-induced disease resistance activity:

4-methyl-1,2,3-thiadiazole heterocyclic derivatives containing 4-(1,1,2,2-tetrafluoroethoxy)-3,5-dichloroanilino of the present invention induce The screening method of tobacco anti-tobacco mosaic virus (TMV) activity is as follows: the mensuration of in vitro direct antiviral activity adopts half-leaf method to carry out; In vivo direct antiviral activity assay comprises the mensuration of protective activity and therapeutic activity and adopts rubbing inoculation method to carry out; Tobacco anti-tobacco mosaic virus activity was carried out by in vivo induction friction inoculation method; in vivo induction was common tobacco with the same seedling age, 3 pots as a group, respectively treated tobacco seedlings 7 days before inoculation, and the treatment methods included : Spray the test compound solution 2 to 3 times, 10 milliliters each time, or soil treatment, 10 milliliters each time, in the 7th day, friction inoculate TMV on the newly grown tobacco leaves, place the tobacco seedlings at its growth suitable temperature and After cultivating under light for 3 days, check the onset situation, and calculate the inductive antiviral effect of the test compound on TMV according to the comprehensive lesion number according to the formula, each treatment is set to repeat 3 times, and the control is divided into blank control and standard drug treatment control 2 kinds; Select thianil (TDL) (purity greater than 99.5%) as the standard plant-induced disease resistance activator, while referring to the literature Fan Z.J.; et al.J.Agric.Food Chem., 2010, 58 (5): 2630- 2636 and Zuo X.; et al.J.Agric.Food Chem., 2010, 58(5): 2755-2762 The method described in the compound to tobacco mosaic virus protection, inactivation, treatment and semi-leaf scab Biological activity:

Among them, R is the effect of the new compound on tobacco resistance to TMV, unit: %

CK is the average number of dead spots on the leaves of the clean water control, unit: piece

I is the average number of dead spots on leaves after chemical treatment, unit: piece;

D. Derivatization of 4-methyl-1,2,3-thiadiazole heterocycle containing 4-(1,1,2,2-tetrafluoroethoxy)-3,5-dichloroanilino of the present invention Thing I is to the mensuration of diamondback moth insecticidal activity:

4-methyl-1,2,3-thiadiazole heterocyclic derivative I containing 4-(1,1,2,2-tetrafluoroethoxy)-3,5-dichloroanilino of the present invention The screening method for the insecticidal activity of Plutella xylostella is as follows: the leaf drug film method is used; the sample is first screened with 200 mg/L for activity; the original drug is first dissolved with a small amount of acetone, then diluted with 0.5‰Triton-100, -100 water was used as the control, and each concentration was repeated 4 times, and each repetition treated about 10 test insects; take fresh and non-polluted cabbage leaves, soak them in a series of concentration-gradient medicinal solutions for 10 seconds, and dry them indoors for about 2 hours Finally, put them into a petri dish with a diameter of 9 cm, and insert the 2nd instar early larvae of diamondback moth that are basically the same size; tie them tightly with rubber bands and place them in a constant temperature insect culture room for diamondback moth, and check the results after 96 hours or 120 hours And calculate the corrected mortality rate; use a small brush or tweezers to lightly touch the worm body, can not coordinate the movement as death; use diflubenzuron as the positive control.

E. Derivatization of 4-methyl-1,2,3-thiadiazole heterocycle containing 4-(1,1,2,2-tetrafluoroethoxy)-3,5-dichloroanilino of the present invention Thing I is to the mensuration of mosquito larva insecticidal activity:

4-methyl-1,2,3-thiadiazole heterocyclic derivative I containing 4-(1,1,2,2-tetrafluoroethoxy)-3,5-dichloroanilino of the present invention The screening method to the insecticidal activity of mosquito larvae is as follows: Culex pipienspallens pale-coloured subspecies, its Latin name is: Culex pipienspallens, the normal colony of indoor rearing; Take by weighing 2.0 milligrams of test compounds in the penicillin medicine bottle, add 10 milliliters Acetone, shaking and dissolving the sample to prepare a 200 μg/ml mother solution; pipette 1 ml of the mother solution into a 150 ml beaker filled with 89 ml of water, select 10 4th instar larvae, and pour them into the beaker together with 10 ml of feeding solution In the drug solution, the concentration is 2 micrograms per milliliter. Put the treated solution together with the beaker of the mosquito larvae into the standard treatment room and keep the temperature at 25 degrees Celsius for cultivation. After 24 hours, start to check the results, add a small amount of mosquito feed every day and suck out the mosquito pupae, supplement the evaporated water in the beaker by 5 ml/day, Until all the mosquito larvae died or pupated; most larvae pupated within 8 days; the aqueous solution containing 1 ml of acetone was used as the blank control; and hexaflumuron was used as the positive control.

The beneficial effect of the present invention is: the present invention has carried out the optimization of the leading structure of the plant activator Methiamin-a derivative of 1,2,3-thiadiazole-with independent intellectual property rights, and utilizes the active substructure Based on the principle of splicing, a series of new compounds were designed and synthesized, and a wide range of biological activity assays were carried out on the synthesized new compounds. The assay activities included antibacterial activity, inducing disease resistance activity, and anti-plant virus activity (including protection, passivation, treatment and semi-leaf activity of dead spots) and the determination of insecticidal activity, this type of compound can be used in the prevention and control of diseases, insect pests and viral diseases in the agricultural field, forestry field, horticultural field and health field, that is, it can be used to prepare fungicides, antiviral agents, plant Activators, insecticides and sanitation insecticides can also be used in combination with commercial pesticides including insecticides, sanitation insecticides, fungicides, anti-phytoviral agents, and plant activators.

The present invention will more specifically illustrate 4-methyl-1 containing 4-(1,1,2,2-tetrafluoroethoxy)-3,5-dichloroanilino through specific preparation and biological activity assay examples. , the synthesis, biological activity and application of 2,3-thiadiazole heterocyclic derivatives, but the examples are only used to specifically illustrate the present invention and not limit the present invention, especially the research on its biological activity is only an illustration , rather than limiting this patent, the specific implementation is as follows:

Embodiment 1: Synthesis and structural identification of compound WH-C1

In a 50 ml round bottom flask was added 10 ml of methanol followed by 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, 4-(1,1,2,2-tetrafluoroethoxy) -3,5-Dichloroaniline and 2 mmoles of benzaldehyde, 1.9 mmoles of cyclohexyl isonitrile, the reaction system was stirred at room temperature for 8 hours, after standing overnight, the reaction system had solid precipitation, filtered and washed with methanol to obtain Crude product, the mother liquor is chromatographed with 200-300 mesh silica gel column, the eluent is volume ratio, petroleum ether at 60-90 degrees Celsius: ethyl acetate: dichloromethane is 10:3:2, yield: 40%, melting point : 178-181 degrees Celsius, HR MS (m/z): 619.0955 (M+H) ⁺ ; ¹ H NMR (solvent: CDCl ₃ , chemical shift): δ7.38-7.05 (m, 7H), 6.18 (s, 1H), 6.12-5.85(t, 1H), 5.372(d, 1H), 3.87-3.85(m, 1H), 2.88(s, 3H), 2.02-1.04(m, 10H), ^1H NMR of the compound and MS data showed consistency with its chemical structure.

Embodiment 2: Synthesis and structural identification of compound WH-C2

In a 50 ml round bottom flask was added 10 ml of methanol followed by 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, 4-(1,1,2,2-tetrafluoroethoxy) -3,5-dichloroaniline and 2 mmoles of p-chlorobenzaldehyde, 1.9 mmoles of cyclohexylisonitrile, the reaction system was stirred at room temperature for 8 hours, and after standing overnight, the reaction system became cloudy, and a small amount of white solid was precipitated , filter and wash the solid with methanol to obtain crude product, yield: 30%, melting point: 187-189 degrees Celsius, HR MS (m/z): 653.0565 (M+H) ⁺ ; ¹ H NMR (solvent: CDCl ₃ , chemical shift ): δ7.38-7.05(m, 6H), 6.09(s, 1H), 6.13-5.87(t, 1H), 5.38(d, 1H), 3.85-3.83(m, 1H), 2.87(s, 3H ), 2.01-1.08 (m, 10H), the ¹ H NMR and MS data of this compound showed that it was consistent with its chemical structure.

Embodiment 3: Synthesis and structural identification of compound WH-C3

In a 50 ml round bottom flask was added 10 ml of methanol followed by 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, 4-(1,1,2,2-tetrafluoroethoxy) -3,5-dichloroaniline and 2 mmoles of p-hydroxybenzaldehyde, 1.9 mmoles of cyclohexyl isonitrile, the reaction system was stirred at room temperature for 8 hours, and left standing overnight, no solid was precipitated in the reaction system, and the reaction mixture was concentrated Afterwards, the white crude product was obtained by 200-300 mesh silica gel column chromatography, and the eluent was volume ratio, petroleum ether at 60-90 degrees Celsius: ethyl acetate: dichloromethane was 3:2:1, yield: 24%, Melting point: 123-125 degrees Celsius, HR MS (m/z): 635.0904 (M+H) ⁺ ; ¹ H NMR (solvent: CDCl ₃ , chemical shift): δ7.41 (s, 1H), 6.97 (d, 2H ), 6.73(d, 2H), 6.09(s, 1H), 6.13-5.87(t, 1H), 5.63(s, 1H), 5.43(d, 1H), 3.85-3.83(m, 1H), 2.87( s, 3H), 1.99-1.25 (m, 10H), the ¹ H NMR and MS data of this compound showed that it was consistent with its chemical structure.

Embodiment 4: Synthesis and structural identification of compound WH-C4

In a 50 ml round bottom flask was added 10 ml of methanol followed by 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, 4-(1,1,2,2-tetrafluoroethoxy) -3,5-dichloroaniline and o-chlorobenzaldehyde each 2 mmol, cyclohexyl isonitrile 1.9 mmol, the reaction system was stirred at room temperature for 8 hours, after standing overnight, a small amount of white solid precipitated out in the reaction system, filtered And wash the solid with methanol to obtain a crude product, the mother liquor is chromatographed on a 200-300 mesh silica gel column, the eluent is a volume ratio, 60-90 degrees Celsius of petroleum ether: ethyl acetate: dichloromethane is 6: 2: 1, and the yield : 62%, melting point: 163-166 degrees Celsius, HR MS (m/z): 653.0570 (M+H) ⁺ ; ¹ H NMR (solvent: CDCl ₃ , chemical shift): δ7.43-7.02 (m, 6H) , 6.56(s, 1H), 6.10-5.84(t, 1H), 5.52(d, 1H), 3.91-3.87(m, 1H), 2.87(s, 3H), 2.06-1.09(m, 10H), the ¹ H NMR and MS data of the compound showed consistency with its chemical structure.

Embodiment 5: Synthesis and structural identification of compound WH-C5

In a 50 ml round bottom flask was added 10 ml of methanol followed by 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, 4-(1,1,2,2-tetrafluoroethoxy) -3,5-dichloroaniline and m-chlorobenzaldehyde each 2 mmol, cyclohexyl isonitrile 1.9 mmol, the reaction system was stirred at room temperature for 8 hours, after standing overnight, a small amount of white solid precipitated out in the reaction system, filtered And wash the solid with methanol to obtain a crude product, the mother liquor is chromatographed on a 200-300 mesh silica gel column, the eluent is a volume ratio, 60-90 degrees Celsius of petroleum ether: ethyl acetate: dichloromethane is 6: 1: 1, and the yield : 40%, melting point: 119-123 degrees Celsius, HRMS (m/z): 655.0539 (M+H) ⁺ ; ¹ H NMR (solvent: CDCl ₃ , chemical shift): δ7.72-7.00 (m, 6H), 6.09(s,1H), 6.13-5.87(t,1H), 5.43(d,1H), 3.89-3.83(m,1H), 2.88(s,3H), 2.02-1.12(m,10H), the compound The ¹ H NMR and MS data were consistent with its chemical structure.

Embodiment 6: Synthesis and structural identification of compound WH-C6

In a 50 ml round bottom flask was added 10 ml of methanol followed by 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, 4-(1,1,2,2-tetrafluoroethoxy) -3,5-dichloroaniline and o-nitrobenzaldehyde each 2 millimoles, cyclohexyl isonitrile 1.9 millimoles, the reaction system was stirred at room temperature for 8 hours, and a small amount of white solid was precipitated out in the reaction system after standing overnight. Filtrate and wash the solid with methanol to obtain a crude product, and the filtrate is chromatographed on a 200-300 mesh silica gel column, the eluent is a volume ratio, 60-90 degrees Celsius of petroleum ether: ethyl acetate: dichloromethane is 7: 1: 6, and the yield is Yield: 25%, melting point: 189-191 degrees Celsius, HR MS (m/z): 664.0806 (M+H) ⁺ ; ¹ H NMR (solvent: CDCl ₃ , chemical shift): δ7.97-7.28 (m, 6H ), 6.57(s, 1H), 6.10-5.84(t, 1H), 5.61(d, 1H), 3.87-3.84(m, 1H), 2.88(s, 3H), 2.05-1.09(m, 10H), ¹ H NMR and MS data for this compound showed consistency with its chemical structure.

Embodiment 7: Synthesis and structural identification of compound WH-C7

In a 50 ml round bottom flask was added 10 ml of methanol followed by 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, 4-(1,1,2,2-tetrafluoroethoxy) -3,5-dichloroaniline and 2 mmoles of m-nitrobenzaldehyde, 1.9 mmoles of cyclohexylisonitrile, the reaction system was stirred at room temperature for 8 hours, there was a small amount of white solid, filtered and washed with methanol, the mother liquor Use 200-300 mesh silica gel column chromatography, the eluent is volume ratio, petroleum ether at 60-90 degrees Celsius: ethyl acetate: dichloromethane is 4:1:2, yield: 40%, melting point: 214-216 Celsius, HR MS (m/z): 664.0812 (M+H) ⁺ ; ¹ H NMR (solvent: CDCl ₃ , chemical shift): δ8.19 (d, 1H), 8.14 (d, 1H), 7.67-7.31 (m, 4H), 6.19(s, 1H), 6.12-5.86(t, 1H), 5.54(d, 1H), 3.91-3.81(m, 1H), 2.90(s, 3H), 2.04-1.26(m , 10H), ^the1H NMR and MS data of this compound showed that it was consistent with its chemical structure.

Embodiment 8: Synthesis and structural identification of compound WH-C8

In a 50 ml round bottom flask was added 10 ml of methanol followed by 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, 4-(1,1,2,2-tetrafluoroethoxy) -3,5-dichloroaniline and 2 mmoles of p-nitrobenzaldehyde, 1.9 mmoles of cyclohexylisonitrile, the reaction system was stirred at room temperature for 8 hours, and a small amount of white solid was precipitated out in the reaction system after standing overnight. Filtrate and wash the solid with methanol to obtain a crude product, and the filtrate is chromatographed on a 200-300 mesh silica gel column, the eluent is a volume ratio, 60-90 degrees Celsius of petroleum ether: ethyl acetate: dichloromethane is 6: 2: 3, and the obtained Yield: 34%, melting point: 179-181 degrees Celsius, HR MS (m/z): 664.0818 (M+H) ⁺ ; ¹ H NMR (solvent: CDCl ₃ , chemical shift): δ8.17 (d, 2H), 7.43(d, 2H), 7.35(br, 1H), 7.12(br, 1H), 6.15(s, 1H), 6.12-5.86(t, 1H), 5.49(d, 1H), 3.88-3.86(m, 1H), 2.89 (s, 3H), 2.03-1.05 (m, 10H), ^{the 1} H NMR and MS data of this compound showed that it was consistent with its chemical structure.

Embodiment 9: Synthesis and structural identification of compound WH-C9

Add 10ml of methanol to a 50ml round bottom flask, then add 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, 4-(1,1,2,2-tetrafluoroethoxy)- 3,5-dichloroaniline and 2 mmoles of o-methylbenzaldehyde, 1.9 mmoles of cyclohexylisonitrile, the reaction system was stirred and reacted at room temperature for 8 hours, the reaction was stopped and the product was obtained by 200-300 mesh silica gel column chromatography , the eluent is a volume ratio, 60-90 degrees centigrade petroleum ether: ethyl acetate: dichloromethane is 6:1:3.

Embodiment 10: Synthesis and structural identification of compound WH-C10

In a 50 ml round bottom flask was added 10 ml of methanol followed by 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, 4-(1,1,2,2-tetrafluoroethoxy) -3,5-dichloroaniline and 2 mmoles of m-methylbenzaldehyde, 1.9 mmoles of cyclohexylisonitrile, the reaction system was stirred at room temperature for 8 hours, and a small amount of white solid was precipitated out in the reaction system after standing overnight. Filtrate and wash the solid with methanol to obtain a crude product, yield: 24%, melting point: 138-140 degrees Celsius, HR MS (m/z): 633.1112 (M+H) ⁺ ; ¹ H NMR (solvent: CDCl ₃ , chemical shift) : δ7.52-6.88(m, 6H), 6.14(s, 1H), 6.12-5.86(t, 1H), 5.36(d, 1H), 3.87-3.85(m, 1H), 2.89(s, 3H) , 2.25 (s, 3H), 2.01-1.10 (m, 10H), ^{the 1} H NMR and MS data of this compound showed that it was consistent with its chemical structure.

Example 11: Synthesis and structure identification of compound WH-C11

In a 50 ml round bottom flask was added 10 ml of methanol followed by 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, 4-(1,1,2,2-tetrafluoroethoxy) -3,5-dichloroaniline and 2 mmoles of p-tolualdehyde, 1.9 mmoles of cyclohexylisonitrile, the reaction system was stirred at room temperature for 8 hours, and a small amount of white solid was precipitated out in the reaction system after standing overnight. Filtrate and wash the solid with methanol to obtain a crude product. The filtrate is chromatographed on a 200-300-mesh silica gel column. The eluent is a volume ratio of petroleum ether at 60-90 degrees Celsius: ethyl acetate: dichloromethane is 16:1:4. Yield: 38%, melting point: 125-127 degrees Celsius, HRMS (m/z): 633.1118 (M+H) ⁺ ; ¹ HNMR (solvent: CDCl ₃ , chemical shift): δ7.52-6.97 (m, 6H), 6.13(s, 1H), 6.12-5.86(t, 1H), 5.36(d, 1H), 3.87-3.83(m, 1H), 2.88(s, 3H), 2.30(s, 3H), 2.00-1.00( m, 10H), ^the1HNMR and MS data of this compound showed that it was consistent with its chemical structure.

Example 12: Synthesis and structure identification of compound WH-C12

In a 50 ml round bottom flask was added 10 ml of methanol followed by 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, 4-(1,1,2,2-tetrafluoroethoxy) -3,5-dichloroaniline and 2 mmoles of o-fluorobenzaldehyde, 1.9 mmoles of cyclohexylisonitrile, the reaction system was stirred at room temperature for 8 hours, and a small amount of white solid precipitated out in the reaction system after standing overnight, filtered And wash the solid with methanol to obtain a crude product, the filtrate is chromatographed on a 200-300 mesh silica gel column, the eluent is a volume ratio, and petroleum ether at 60-90 degrees Celsius: ethyl acetate: dichloromethane is 18: 3: 5, and the yield : 36%, the product is a light yellow liquid, HR MS (m/z): 637.0861 (M+H) ⁺ ; ¹ H NMR (solvent: CDCl ₃ , chemical shift): δ7.31 (d, 1H), 7.08- 7.00(m, 3H), 6.64(s, 2H), 6.42(s, 1H), 6.15-5.85(t, 1H), 5.54(d, 1H), 3.88-3.87(m, 1H), 2.88(s, 3H), 2.04-1.18 (m, 10H), ¹ H NMR and MS data of this compound showed that it was consistent with its chemical structure.

Example 13: Synthesis and structure identification of compound WH-C13

In a 50 ml round bottom flask was added 10 ml of methanol followed by 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, 4-(1,1,2,2-tetrafluoroethoxy) -3,5-dichloroaniline and 2 mmoles of m-fluorobenzaldehyde, 1.9 mmoles of cyclohexylisonitrile, the reaction system was stirred at room temperature for 8 hours, and a small amount of white solid was precipitated in the reaction system after standing overnight, filtered And wash the solid with methanol to obtain a crude product, the filtrate is chromatographed on a 200-300 mesh silica gel column, the eluent is a volume ratio, and petroleum ether at 60-90 degrees Celsius: ethyl acetate: dichloromethane is 18: 3: 5, and the yield : 36%, melting point: 162-164 degrees Celsius, HR MS (m/z): 637.0862 (M+H) ⁺ ; ¹ H NMR (solvent: CDCl ₃ , chemical shift): δ7.52-6.92 (m, 3H) , 6.10(s, 1H), 6.13-5.87(t, 1H), 5.42(d, 1H), 3.88-3.84(m, 1H), 2.89(s, 3H), 2.02-1.040(m, 10H), the ¹ H NMR and MS data of the compound showed consistency with its chemical structure.

Example 14: Synthesis and structure identification of compound WH-C14

Add 10ml of methanol to a 50ml round bottom flask, then add 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, 4-(1,1,2,2-tetrafluoroethoxy)- 3,5-dichloroaniline and p-fluorobenzaldehyde each 2 millimoles, cyclohexyl isonitrile 1.9 millimoles, the reaction system was stirred and reacted at room temperature for 8 hours, the reaction was stopped and the product was obtained by 200-300 mesh silica gel column chromatography, The volume ratio of the eluent is petroleum ether at 60-90 degrees Celsius: ethyl acetate: dichloromethane is 2:1:1.

Example 15: Synthesis and structure identification of compound WH-C15

Add 10ml of methanol to a 50ml round bottom flask, then add 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, 4-(1,1,2,2-tetrafluoroethoxy)- 3,5-dichloroaniline and o-trifluoromethylbenzaldehyde each 2 mmoles, cyclohexyl isonitrile 1.9 mmoles, the reaction system was stirred and reacted at room temperature for 8 hours, the reaction was stopped and 200-300 mesh silica gel column chromatography To obtain the product, the eluent is a volume ratio of petroleum ether at 60-90 degrees Celsius: ethyl acetate: dichloromethane is 3:1:2.

Example 16: Synthesis and structure identification of compound WH-C16

In a 50 ml round bottom flask was added 10 ml of methanol followed by 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, 4-(1,1,2,2-tetrafluoroethoxy) -3,5-dichloroaniline and m-trifluoromethylbenzaldehyde 2 mmoles each, cyclohexyl isonitrile 1.9 mmoles, the reaction system was stirred at room temperature for 8 hours, and there was a small amount of white solid in the reaction system after standing overnight Precipitate, filter and wash the solid with methanol to obtain a crude product, the filtrate is chromatographed on a 200-300 mesh silica gel column, the eluent is a volume ratio, petroleum ether at 60-90 degrees Celsius: ethyl acetate = 5: 1, yield: 36% , melting point: 164-166 degrees Celsius, HR MS (m/z): 687.0829 (M+H) ⁺ ; ¹ H NMR (solvent: CDCl ₃ , chemical shift): δ7.60-7.26 (m, 6H), 6.20 ( s, 1H), 6.12-5.86(t, 1H), 5.46(d, 1H), 3.89-3.87(m, 1H), 2.90(s, 3H), 2.04-1.04(m, 10H), the ¹ H NMR and MS data showed consistency with its chemical structure.

Example 17: Synthesis and structure identification of compound WH-C17

In a 50 ml round bottom flask was added 10 ml of methanol followed by 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, 4-(1,1,2,2-tetrafluoroethoxy) -3,5-dichloroaniline and 2 mmoles of p-trifluoromethylbenzaldehyde, 1.9 mmoles of cyclohexylisonitrile, the reaction system was stirred at room temperature for 8 hours, and there was a small amount of white solid in the reaction system after standing overnight Precipitate, filter and wash the solid with methanol to obtain a crude product, the filtrate is chromatographed on a 200-300 mesh silica gel column, the eluent is a volume ratio, petroleum ether at 60-90 degrees Celsius: ethyl acetate = 6: 1, yield: 60% , melting point: 176-178 degrees Celsius, HR MS (m/z): 687.0828 (M+H) ⁺ ; ¹ H NMR (solvent: CDCl ₃ , chemical shift): δ7.57-6.96 (m, 6H), 6.15 ( s, 1H), 6.12-5.86(t, 1H), 5.42(d, 1H), 3.88-3.85(m, 1H), 2.89(s, 3H), 2.03-1.12(m, 10H), the ¹ H NMR and MS data showed consistency with its chemical structure.

Example 18: Synthesis and structure identification of compound WH-C18

In a 50 ml round bottom flask was added 10 ml of methanol followed by 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, 4-(1,1,2,2-tetrafluoroethoxy) -3,5-dichloroaniline and 2 mmoles of m-hydroxybenzaldehyde, 1.9 mmoles of cyclohexylisonitrile, the reaction system was stirred at room temperature for 8 hours, and a small amount of white solid was precipitated in the reaction system after standing overnight, filtered And wash the solid with methanol to obtain a crude product, the filtrate is chromatographed on a 200-300 mesh silica gel column, the eluent is a volume ratio, and petroleum ether at 60-90 degrees Celsius: ethyl acetate: dichloromethane is 12: 2: 5, and the yield : 39%, melting point: 191-194 degrees Celsius, HR MS (m/z): 635.0904 (M+H) ⁺ ; ¹ H NMR (solvent: CDCl ₃ , chemical shift): δ7.52-6.65 (m, 6H) , 6.07(s, 1H), 6.13-5.87(t, 1H), 5.47(d, 1H), 5.28(d, 1H), 3.85-3.83(m, 1H), 2.87(s, 3H), 2.002-1.10 (m, 10H), ^the1HNMR and MS data of this compound showed that it was consistent with its chemical structure.

Example 19: Synthesis and structure identification of compound WH-C19

In a 50 ml round bottom flask was added 10 ml of methanol followed by 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, 4-(1,1,2,2-tetrafluoroethoxy) -3,5-dichloroaniline and o-methoxybenzaldehyde each 2 mmol, cyclohexyl isonitrile 1.9 mmol, the reaction system was stirred at room temperature for 8 hours, after standing overnight, a small amount of white solid precipitated out of the reaction system , filter and wash the solid with methanol to obtain a crude product, yield: 33%, melting point: 144-145 degrees Celsius, HR MS (m/z): 649.1061 (M+H) ⁺ ; ¹ H NMR (solvent: CDCl ₃ , chemical shift ): δ7.30-6.79(m, 6H), 6.43(s, 1H), 6.11-5.84(t, 1H), 5.38(d, 1H), 3.89-3.87(m, 1H), 2.80(s, 3H ), 2.88 (s, 3H), 2.01-1.02 (m, 10H), ^{the 1} H NMR and MS data of this compound showed that it was consistent with its chemical structure.

Example 20: Synthesis and structure identification of compound WH-C20

In a 50 ml round bottom flask was added 10 ml of methanol followed by 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, 4-(1,1,2,2-tetrafluoroethoxy) -3,5-dichloroaniline and 2 mmoles of m-methoxybenzaldehyde, 1.9 mmoles of cyclohexylisonitrile, filtered and washed with methanol, the reaction system was stirred at room temperature for 8 hours, and after standing overnight, the reaction system A small amount of white solid was precipitated, filtered and washed with methanol to obtain a crude product, the filtrate was chromatographed on a 200-300 mesh silica gel column, the eluent was volume ratio, petroleum ether at 60-90 degrees Celsius: ethyl acetate = 5:1, and the Yield: 27%, melting point: 116-118 degrees Celsius, HRMS (m/z): 649.1063 (M+H) ⁺ ; ¹ H NMR (solvent: CDCl ₃ , chemical shift): δ7.52-6.61 (m, 6H) , 6.13(s, 1H), 6.13-5.86(t, 1H), 5.44(d, 1H), 3.89-3.85(m, 1H), 3.69(s, 3H), 2.88(s, 3H), 2.01-1.33 (m, 10H), ¹ H NMR and MS data of this compound showed that it was consistent with its chemical structure.

Example 21: Synthesis and structure identification of compound WH-C21

In a 50 ml round bottom flask was added 10 ml of methanol followed by 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, 4-(1,1,2,2-tetrafluoroethoxy) -3,5-dichloroaniline and 2 mmoles of p-methoxybenzaldehyde, 1.9 mmoles of cyclohexylisonitrile, the reaction system was stirred at room temperature for 8 hours, and a small amount of white solid precipitated out in the reaction system after standing overnight , filter and wash the solid with methanol to obtain a crude product, the filtrate is chromatographed on a 200-300 mesh silica gel column, the eluent is a volume ratio, and petroleum ether at 60-90 degrees Celsius: ethyl acetate: dichloromethane is 5: 1: 1, Yield: 74%, melting point: 152-155 degrees Celsius, HR MS (m/z): 649.1060 (M+H) ⁺ ; ¹ H NMR (solvent: CDCl ₃ , chemical shift): δ7.52-6.77 (m, 6H), 6.13(s, 1H), 6.13-5.87(t, 1H), 5.38(d, 1H), 3.86-3.83(m, 1H), 3.77(s, 3H), 2.88(s, 3H), 2.01 -1.07 (m, 10H), ^the1H NMR and MS data of this compound showed that it was consistent with its chemical structure.

Example 22: Synthesis and structure identification of compound WH-E1

In a 50 ml round bottom flask was added 10 ml of methanol followed by 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, 4-(1,1,2,2-tetrafluoroethoxy) -3,5-dichloroaniline and 2 mmoles of p-nitrobenzaldehyde, 1.9 mmoles of isopropyl isonitrile, the reaction system was stirred at room temperature for 8 hours, and a small amount of white solid was precipitated in the reaction system after standing overnight , filter and wash the solid with methanol to obtain a crude product, the filtrate is chromatographed on a 200-300 mesh silica gel column, the eluent is a volume ratio, and petroleum ether at 60-90 degrees Celsius: ethyl acetate: dichloromethane is 5: 1: 1, Yield: 34%, melting point: 153-155 degrees Celsius, HR MS (m/z): 646.0312 (M+Na) ⁺ ; ¹ H NMR (solvent: CDCl ₃ , chemical shift): δ8.17 (d, 2H, J=8.4Hz), 7.43(d, 2H, J=8.4Hz), 6.13(s, 1H), 6.00-5.46(t, 1H), 5.45(d, 1H, J=7.6Hz), 4.23-4.15( m, 1H), 2.90 (s, 3H), 1.24 (d, 2H, J = 6.4Hz), 1.14 (d, 2H, J = 6.4Hz), the ¹ H NMR and MS data of this compound were consistent with its chemical structure .

Example 23: Synthesis and structure identification of compound WH-E2

In a 50 ml round bottom flask was added 10 ml of methanol followed by 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, 4-(1,1,2,2-tetrafluoroethoxy) -3,5-dichloroaniline and 2 mmoles of o-tolualdehyde, 1.9 mmoles of isopropyl isonitrile, the reaction system was stirred at room temperature for 8 hours, and a small amount of white solid was precipitated in the reaction system after standing overnight , filter and wash the solid with methanol to obtain crude product, yield: 23%, melting point: 185-187 degrees Celsius, HRMS (m/z): 593.0799 (M+H) ⁺ ; ¹ H NMR (solvent: CDCl ₃ , chemical shift) : δ7.52-6.77(m, 6H), 6.50(s, 1H), 6.11-5.85(t, 1H), 5.31(d, 1H, J=7.6Hz), 4.23-4.18(m, 1H), 2.89 (s, 3H), 2.44 (s, 3H), 1.22 (d, 3H, J = 6.4Hz), 1.35 (d, 3H, J = 6.8Hz), the ¹ H NMR and MS data of this compound show that it is consistent with its chemical structure unanimous.

Example 24: Synthesis and structure identification of compound WH-E3

In a 50 ml round bottom flask was added 10 ml of methanol followed by 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, 4-(1,1,2,2-tetrafluoroethoxy) -3,5-dichloroaniline and 2 mmoles of m-tolualdehyde, 1.9 mmoles of isopropyl isonitrile, the reaction system was stirred at room temperature for 8 hours, and a small amount of white solid was precipitated in the reaction system after standing overnight , filter and wash the solid with methanol to obtain a crude product, the filtrate is chromatographed on a 200-300 mesh silica gel column, the eluent is a volume ratio, and petroleum ether at 60-90 degrees Celsius: ethyl acetate: dichloromethane is 4: 1: 2, Yield: 34%, melting point: 136-139 degrees Celsius, HR MS (m/z): 593.0807 (M+H) ⁺ ; ¹ H NMR (solvent: CDCl ₃ , chemical shift): δ7.52-6.88 (m, 6H), 6.13(s, 1H), 6.13-5.86(t, 1H), 5.33(d, 1H, J=7.6Hz), 4.20-4.15(m, 1H), 2.89(s, 3H), 2.45(s , 3H), 1.21 (d, 3H, J=6.4Hz), 1.114 (d, 3H, J=6.8Hz), the ¹ H NMR and MS data of this compound showed that it was consistent with its chemical structure.

Example 25: Synthesis and structure identification of compound WH-E4

In a 50 ml round bottom flask was added 10 ml of methanol followed by 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, 4-(1,1,2,2-tetrafluoroethoxy) -3,5-dichloroaniline and 2 mmoles of p-tolualdehyde, 1.9 mmoles of isopropyl isonitrile, the reaction system was stirred at room temperature for 8 hours, and a small amount of white solid was precipitated in the reaction system after standing overnight , filter and wash the solid with methanol to obtain a crude product, yield: 42%, melting point: 160-163 degrees Celsius, HR MS (m/z): 593.0808 (M+H) ⁺ ; ¹ H NMR (solvent: CDCl ₃ , chemical shift ): δ7.52-6.97(m, 6H), 6.13(s, 1H), 6.12-5.87(t, 1H), 5.35(d, 1H, J=7.6Hz), 4.19-4.14(m, 1H), 2.88(s, 3H), 2.30(s, 3H), 1.20(d, 3H, J=6.4Hz), 1.113(d, 3H, J=6.4Hz), the ¹ H NMR and MS data of this compound show that it is related to chemical consistent structure.

Example 26: Synthesis and structure identification of compound WH-E5

In a 50 ml round bottom flask was added 10 ml of methanol followed by 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, 4-(1,1,2,2-tetrafluoroethoxy) -3,5-Dichloroaniline and 2 mmoles of benzaldehyde, 1.9 mmoles of isopropyl isonitrile, the reaction system was stirred at room temperature for 8 hours, after standing overnight, a small amount of white solid precipitated out in the reaction system, filtered and used Wash the solid with methanol to obtain a crude product, and the filtrate is chromatographed on a 200-300-mesh silica gel column, the eluent is a volume ratio, and petroleum ether at 60-90 degrees Celsius: ethyl acetate: dichloromethane is 4: 1: 1, and the yield is: 31%, melting point: 144-146 degrees Celsius, HR MS (m/z): 579.0642 (M+H) ⁺ ; ¹ H NMR (solvent: CDCl ₃ , chemical shift): δ7.52-6.88 (m, 7H), 6.13(s, 1H), 6.13-5.86(t, 1H), 5.33(d, 1H, J=7.6Hz), 4.20-4.15(m, 1H), 2.89(s, 3H), 1.21(d, 3H, J = 6.4 Hz), 1.114 (d, 3H, J = 6.4 Hz), ¹ H NMR and MS data of this compound showed that it was consistent with its chemical structure.

Example 27: Synthesis and structure identification of compound WH-E6

In a 50 ml round bottom flask was added 10 ml of methanol followed by 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, 4-(1,1,2,2-tetrafluoroethoxy) -3,5-dichloroaniline and 2 mmoles of o-nitrobenzaldehyde, 1.9 mmoles of isopropyl isonitrile, the reaction system was stirred at room temperature for 8 hours, and a small amount of white solid was precipitated in the reaction system after standing overnight , filter and wash the solid with methanol to obtain a crude product, the filtrate is chromatographed on a 200-300 mesh silica gel column, the eluent is a volume ratio, and petroleum ether at 60-90 degrees Celsius: ethyl acetate: dichloromethane is 4: 1: 2, Yield: 25%, melting point: 103-105 degrees Celsius, HRMS (m/z): 624.0493 (M+H) ⁺ ; ¹ H NMR (solvent: CDCl ₃ , chemical shift): δ7.96-7.26 (m, 6H ), 6.56(s, 1H), 6.10-5.84(t, 1H), 5.63(d, 1H, J=7.6Hz), 4.19-4.14(m, 1H), 2.88(s, 3H), 1.24(d, 3H, J = 6.8 Hz) 1.12 (d, 3H, J = 6.4 Hz), ^{the 1} H NMR and MS data of this compound showed that it was consistent with its chemical structure.

Example 28: Synthesis and structure identification of compound WH-E7

In a 50 ml round bottom flask was added 10 ml of methanol followed by 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, 4-(1,1,2,2-tetrafluoroethoxy) -3,5-dichloroaniline and 2 mmoles of m-nitrobenzaldehyde, 1.9 mmoles of isopropyl isonitrile, a small amount of crystals were produced at the beginning, after the reaction system was stirred at room temperature, the crystals disappeared, and the reaction system Continue to stir at room temperature for 8 hours. After standing overnight, a white solid precipitates out of the reaction system. Filter and wash the solid with methanol to obtain a crude product. The filtrate is chromatographed on a 200-300 mesh silica gel column, and the eluent is volume ratio, 60-90 Petroleum ether in Celsius: ethyl acetate: dichloromethane is 3:1:2, yield: 31%, melting point: 127-130 degrees Celsius, HR MS (m/z): 624.0485 (M+H) ⁺ ; ¹ H NMR (solvent: CDCl ₃ , chemical shift): δ8.20-7.00 (m, 6H), 6.17 (s, 1H), 6.13-5.86 (t, 1H), 5.48 (d, 1H, J=7.6Hz), 4.21-4.16 (m, 1H), 2.91 (s, 3H), 1.25 (d, 3H, J=6.8Hz), 1.14 (d, 3H, J=6.4Hz), the ¹ H NMR and MS data of the compound showed consistent with its chemical structure.

Example 29: Synthesis and structure identification of compound WH-E8

In a 50 ml round bottom flask was added 10 ml of methanol followed by 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, 4-(1,1,2,2-tetrafluoroethoxy) -3,5-dichloroaniline and 2 mmoles of o-fluorobenzaldehyde, 1.9 mmoles of isopropyl isonitrile, the reaction system was stirred at room temperature for 8 hours, and a small amount of white solid was precipitated out in the reaction system after standing overnight. Filtrate and wash the solid with methanol to obtain a crude product, and the filtrate is chromatographed on a 200-300 mesh silica gel column, the eluent is a volume ratio, 60-90 degrees Celsius of petroleum ether: ethyl acetate: dichloromethane is 8:1:2, and the product is obtained. Yield: 31%, melting point: 145-148 degrees Celsius, HR MS (m/z): 597.0548 (M+H) ⁺ ; ¹ H NMR (solvent: CDCl ₃ , chemical shift): δ7.32-7.00 (m, 6H ), 6.40(s, 1H), 6.11-5.84(t, 1H), 5.48(d, 1H, J=7.6Hz), 4.21-4.17(m, 1H), 2.88(s, 3H), 1.24(d, 3H, J = 6.8 Hz), 1.151 (d, 3H, J = 6.8 Hz), ^{the 1} H NMR and MS data of this compound showed that it was consistent with its chemical structure.

Example 30: Synthesis and structure identification of compound WH-E9

In a 50 ml round bottom flask was added 10 ml of methanol followed by 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, 4-(1,1,2,2-tetrafluoroethoxy) -3,5-dichloroaniline and m-fluorobenzaldehyde each 2 mmoles, isopropyl isonitrile 1.9 mmoles, the reaction system was stirred at room temperature for 8 hours, and a small amount of white solid was precipitated out in the reaction system after standing overnight. Filtrate and wash the solid with methanol to obtain a crude product, and the filtrate is chromatographed on a 200-300 mesh silica gel column, the eluent is a volume ratio, 60-90 degrees Celsius of petroleum ether: ethyl acetate: dichloromethane is 8:1:2, and the product is obtained. Yield: 39%, melting point: 121-123 degrees Celsius, HRMS (m/z): 597.0552 (M+H) ⁺ ; ¹ H NMR (solvent: CDCl ₃ , chemical shift): δ7.30-6.92 (m, 6H) , 6.08(s, 1H), 6.13-5.87(t, 1H), 5.38(d, 1H, J=7.6Hz), 4.20-4.14(m, 1H), 2.89(s, 3H), 1.22(d, 3H , J=6.8Hz), 1.13 (d, 3H, J=6.8Hz), ^{the 1} H NMR and MS data of this compound showed that it was consistent with its chemical structure.

Example 31: Synthesis and structure identification of compound WH-E10

In a 50 ml round bottom flask was added 10 ml of methanol followed by 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, 4-(1,1,2,2-tetrafluoroethoxy) -3,5-dichloroaniline and 2 mmoles of p-fluorobenzaldehyde, 1.9 mmoles of isopropyl isonitrile, the reaction system was stirred at room temperature for 8 hours, and a small amount of white solid was precipitated out in the reaction system after standing overnight. Filtrate and wash the solid with methanol to obtain a crude product, and the filtrate is chromatographed on a 200-300 mesh silica gel column, the eluent is a volume ratio, 60-90 degrees Celsius of petroleum ether: ethyl acetate: dichloromethane is 8:1:2, and the product is obtained. Yield: 45%, melting point: 153-155 degrees Celsius, HR MS (m/z): 597.0546 (M+H) ⁺ ; ¹ H NMR (solvent: CDCl ₃ , chemical shift): δ7.30-6.97 (m, 6H ), 6.11(s, 1H), 6.11-5.86(t, 1H), 5.35(d, 1H, J=7.6Hz), 4.19-4.13(m, 1H), 2.88(s, 3H), 1.22(d, 3H, J = 6.8 Hz), 1.12 (d, 3H, J = 6.4 Hz), ^{the 1} H NMR and MS data of this compound showed that it was consistent with its chemical structure.

Example 32: Synthesis and structure identification of compound WH-E11

Add 10ml of methanol to a 50ml round bottom flask, then add 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, 4-(1,1,2,2-tetrafluoroethoxy)- 3,5-dichloroaniline and o-trifluoromethylbenzaldehyde 2 mmoles each, isopropyl isonitrile 1.9 mmoles, the reaction system was stirred at room temperature for 8 hours, the reaction was stopped and a 200-300 mesh silica gel column layer The product was separated, and the volume ratio of the eluent was 60-90 degrees centigrade petroleum ether: ethyl acetate: dichloromethane was 6:2:3.

Example 33: Synthesis and structure identification of compound WH-E12

In a 50 ml round bottom flask was added 10 ml of methanol followed by 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, 4-(1,1,2,2-tetrafluoroethoxy) -3,5-dichloroaniline and m-trifluoromethylbenzaldehyde each 2 mmoles, isopropyl isonitrile 1.9 mmoles, the reaction system was stirred at room temperature for 8 hours, and there was a small amount of white in the reaction system after standing overnight The solid was precipitated, filtered and washed with methanol to obtain a crude product, the filtrate was chromatographed on a 200-300 mesh silica gel column, the eluent was a volume ratio, petroleum ether at 60-90 degrees Celsius: ethyl acetate = 6: 1, yield: 53 %, melting point: 134-135 degrees Celsius, HR MS (m/z): 669.0335 (M+Na) ⁺ ; ¹ H NMR (solvent: CDCl ₃ , chemical shift): δ7.30-6.92 (m, 6H), 6.08 (s, 1H), 6.13-5.87(t, 1H), 5.38(d, 1H, J=7.6Hz), 4.20-4.14(m, 1H), 2.89(s, 3H), 1.22(d, 3H, J = 6.4 Hz), 1.13 (d, 3H, J = 6.8 Hz), ^{the 1} H NMR and MS data of this compound showed that it was consistent with its chemical structure.

Example 34: Synthesis and structure identification of compound WH-E13

In a 50 ml round bottom flask was added 10 ml of methanol followed by 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, 4-(1,1,2,2-tetrafluoroethoxy) -3,5-dichloroaniline and 2 mmoles of p-trifluoromethylbenzaldehyde, 1.9 mmoles of isopropyl isonitrile, the reaction system was stirred at room temperature for 8 hours, and there was a small amount of white in the reaction system after standing overnight The solid was precipitated, filtered and washed with methanol to obtain a crude product, the filtrate was chromatographed on a 200-300 mesh silica gel column, the eluent was a volume ratio, petroleum ether at 60-90 degrees Celsius: ethyl acetate = 6: 1, yield: 48 %, melting point: 126-128 degrees Celsius, HR MS (m/z): 669.0335 (M+Na) ⁺ ; ¹ H NMR (solvent: CDCl ₃ , chemical shift): δ7.56 (d, 2H, J=8.4Hz ), 7.31(d, 2H, J=8.0Hz), 6.13(s, 1H), 6.00-5.86(t, 1H), 5.39(d, 1H, J=7.6Hz), 4.22-4.16(m, 1H) , 2.90 (s, 3H), 1.23 (d, 3H, J=6.8Hz), 1.134 (d, 3H, J=6.4Hz), the ¹ H NMR and MS data of this compound showed that it was consistent with its chemical structure.

Example 35: Synthesis and structure identification of compound WH-E14

In a 50 ml round bottom flask was added 10 ml of methanol followed by 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, 4-(1,1,2,2-tetrafluoroethoxy) -3,5-dichloroaniline and 2 mmoles of m-hydroxyformaldehyde, 1.9 mmoles of isopropyl isonitrile, the reaction system was stirred at room temperature for 8 hours, and a small amount of white solid precipitated out in the reaction system after standing overnight, filtered The solid was washed with methanol to obtain a crude product, and the filtrate was chromatographed on a 200-300-mesh silica gel column, the eluent was volume ratio, petroleum ether at 60-90 degrees Celsius: ethyl acetate=4:1, yield: 54%, melting point: 140-142 degrees Celsius, HR MS (m/z): 617.0411 (M+Na) ⁺ ; ¹ H NMR (solvent: CDCl ₃ , chemical shift): δ7.15 (t, 3H), 6.79 (m, 1H), 6.67(m, 2H), 6.13-5.87(t, 1H), 6.04(s, 1H), 5.45(d, 1H, J=7.6Hz), 4.22-4.13(m, 1H), 2.99(s, 1H) , 2.87 (s, 1H), 1.20 (d, 3H, J=6.4Hz), 1.11 (d, 3H, J=6.4Hz), ^{the 1} H NMR and MS data of this compound showed that it was consistent with its chemical structure.

Example 36: Synthesis and structure identification of compound WH-E15

In a 50 ml round bottom flask was added 10 ml of methanol followed by 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, 4-(1,1,2,2-tetrafluoroethoxy) -3,5-dichloroaniline and 2 mmoles of p-hydroxybenzaldehyde, 1.9 mmoles of isopropyl isonitrile, the reaction system was stirred at room temperature for 8 hours, and a small amount of white solid was precipitated out in the reaction system after standing overnight. Filtrate and wash the solid with methanol to obtain a crude product, the filtrate is chromatographed on a 200-300 mesh silica gel column, the eluent is a volume ratio, petroleum ether at 60-90 degrees Celsius: ethyl acetate = 3: 1, yield: 43%, melting point : 106-108 degrees Celsius, HR MS (m/z): 617.0411 (M+Na) ⁺ ; ¹ H NMR (solvent: CDCl ₃ , chemical shift): δ6.97 (d, 2H, J=8.4Hz), 6.73 (d, 2H, J=8.4Hz), 6.13-5.87(t, 1H), 6.08(s, 1H), 5.38(d, 1H, J=7.6Hz), 5.36(s, 1H), 4.18-4.13( m, 1H) 2.88 (s, 3H), 1.20 (d, 3H, J=6.4Hz), 1.11 (d, 3H, J=6.4Hz), ¹ H NMR and MS data of this compound showed that it was consistent with its chemical structure.

Example 37: Synthesis and structure identification of compound WH-E16

In a 50 ml round bottom flask was added 10 ml of methanol followed by 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, 4-(1,1,2,2-tetrafluoroethoxy) -3,5-dichloroaniline and o-chlorobenzaldehyde each 2 millimoles, isopropyl isonitrile 1.9 millimoles, the reaction system was stirred at room temperature for 8 hours, and a small amount of white solid was precipitated out in the reaction system after standing overnight. Filtrate and wash the solid with methanol to obtain a crude product, the filtrate is chromatographed on a 200-300 mesh silica gel column, the eluent is a volume ratio, petroleum ether at 60-90 degrees Celsius: ethyl acetate=10:1, yield: 17%, melting point : 163-165 degrees Celsius, HR MS (m/z): 613.0249 (M+H) ⁺ ; ¹ H NMR (solvent: CDCl ₃ , chemical shift): δ7.30-6.92 (m, 6H), 6.08 (s, 1H), 6.13-5.87(t, 1H), 5.38(d, 1H, J=7.6Hz), 4.20-4.14(m, 1H), 2.89(s, 3H), 1.22(d, 3H, J=6.8Hz ) 1.13 (d, 3H, J = 6.8 Hz), the ¹ H NMR and MS data of this compound showed that it was consistent with its chemical structure.

Example 38: Synthesis and structure identification of compound WH-E17

In a 50 ml round bottom flask was added 10 ml of methanol followed by 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, 4-(1,1,2,2-tetrafluoroethoxy) -3,5-dichloroaniline and m-chlorobenzaldehyde each 2 mmoles, isopropyl isonitrile 1.9 mmoles, the reaction system was stirred at room temperature for 8 hours, and a small amount of white solid was precipitated out in the reaction system after standing overnight. Filtrate and wash the solid with methanol to obtain a crude product, the filtrate is chromatographed on a 200-300 mesh silica gel column, the eluent is a volume ratio, petroleum ether at 60-90 degrees Celsius: ethyl acetate=10:1, yield: 17%, melting point : 128-130 degrees Celsius, HR MS (m/z): 635.0072 (M+Na) ⁺ ; ¹ H NMR (solvent: CDCl ₃ , chemical shift): δ7.31 (d, 2H, J=8Hz), 7.22 ( t, 2H), 7.00(d, 2H, J=7.6Hz), 6.14-5.86(t, 1H), 6.07(s, 1H), 5.39(d, 2H, J=7.6Hz), 4.19-4.14(m , 1H) 2.89 (s, 3H), 1.22 (d, 3H, J=6.8Hz), 1.13 (d, 3H, J=6.8Hz), the ¹ H NMR and MS data of this compound showed that it was consistent with its chemical structure.

Example 39: Synthesis and structure identification of compound WH-E18

In a 50 ml round bottom flask was added 10 ml of methanol followed by 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, 4-(1,1,2,2-tetrafluoroethoxy) -3,5-dichloroaniline and p-chlorobenzaldehyde each 2 millimoles, isopropyl isonitrile 1.9 millimoles, the reaction system was stirred at room temperature for 8 hours, and a small amount of white solid was precipitated out in the reaction system after standing overnight. Filtrate and wash the solid with methanol to obtain a crude product. The filtrate is chromatographed on a 200-300-mesh silica gel column, the eluent is a volume ratio, petroleum ether at 60-90 degrees Celsius: ethyl acetate = 3: 1, yield: 21%, melting point : 177-179 degrees Celsius, HR MS (m/z): 613.0252 (M+H) ⁺ ; ¹ H NMR (solvent: CDCl ₃ , chemical shift): δ7.30-6.92 (m, 6H), 6.08 (s, 1H), 6.13-5.87(t, 1H), 5.38(d, 1H, J=7.6Hz), 4.20-4.14(m, 1H), 2.89(s, 3H), 1.22(d, 3H, J=6.4Hz ), 1.13 (d, 3H, J=6.4Hz), the ¹ H NMR and MS data of this compound showed that it was consistent with its chemical structure.

Example 40: Synthesis and structure identification of compound WH-E19

In a 50 ml round bottom flask was added 10 ml of methanol followed by 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, 4-(1,1,2,2-tetrafluoroethoxy) -3,5-dichloroaniline and o-methoxy formaldehyde each 2 mmol, isopropyl isonitrile 1.9 mmol, the reaction system was stirred at room temperature for 8 hours, after standing overnight, a small amount of white solid precipitated out of the reaction system , filter and wash the solid with methanol to obtain a crude product, the filtrate is chromatographed on a 200-300 mesh silica gel column, the eluent is a volume ratio, petroleum ether at 60-90 degrees Celsius: ethyl acetate=3: 1, yield: 42%, Melting point: 184-185 degrees Celsius, HR MS (m/z): 609.0748 (M+H) ⁺ ; ¹ H NMR (solvent: CDCl ₃ , chemical shift): δ7.30-6.79 (m, 6H), 6.41 (s , 1H), 6.10-5.84(t, 1H), 5.35(d, 1H, J=7.6Hz), 4.23-4.14(m, 1H), 3.79(s, 3H), 2.88(s, 3H), 1.20( d, 3H, J = 6.4 Hz), 1.12 (d, 3H, J = 6.4 Hz), ¹ H NMR and MS data of this compound showed that it was consistent with its chemical structure.

Example 41: Synthesis and structure identification of compound WH-E20

In a 50 ml round bottom flask was added 10 ml of methanol followed by 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, 4-(1,1,2,2-tetrafluoroethoxy) -3,5-dichloroaniline and m-methoxy formaldehyde 2 mmoles each, isopropyl isonitrile 1.9 mmoles, after stirring the reaction system at room temperature for 8 hours, the solid precipitated after standing, filtered and washed with methanol to obtain the product , yield: 22%, melting point: 121-122 degrees Celsius, HR MS (m/z): 609.0748 (M+H) ⁺ ; ¹ H NMR (solvent: CDCl ₃ , chemical shift): δ7.21 (t, 3H ), 6.84(m, 1H), 6.71(d.1H, J=7.6Hz), 6.61(s, 1H), 6.14-5.86(t, 1H), 5.36(d, 1H, J=7.6Hz), 4.20 -4.14 (m, 1H), 3.69 (s, 3H), 2.89 (s, 3H), 1.21 (d, 3H, J=6.8Hz), 1.12 (d, 3H, J=6.4Hz), the compound of ¹ HNMR and MS data showed consistency with its chemical structure.

Example 42: Synthesis and structure identification of compound WH-E21

In a 50 ml round bottom flask was added 10 ml of methanol followed by 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, 4-(1,1,2,2-tetrafluoroethoxy) -3,5-dichloroaniline and 2 mmoles of p-methoxy formaldehyde, 1.9 mmoles of isopropyl isonitrile, the reaction system was stirred at room temperature for 8 hours, and a small amount of white solid was precipitated in the reaction system after standing overnight , filter and wash the solid with methanol to obtain a crude product, yield: 22%, melting point: 141-143 degrees Celsius, HR MS (m/z): 609.0750 (M+H) ⁺ ; ¹ H NMR (solvent: CDCl ₃ , chemical shift ): δ7.30-6.78(m, 6H), 6.11(s, 1H), 6.13-5.87(t, 1H), 5.36(d, 1H, J=7.6Hz), 4.19-4.13(m, 1H), 3.77(s, 3H), 2.88(s, 3H), 1.20(d, 3H, J=6.4Hz), 1.114(d, 3H, J=6.4Hz), the ¹ H NMR and MS data of this compound show that it is related to chemical consistent structure.

Example 43: 4-methyl-1,2,3-thiadiazole containing 4-(1,1,2,2-tetrafluoroethoxy)-3,5-dichloroanilino of the present invention Bacteriostatic or fungicidal activity of ring derivative I

The name and code name of the common plant pathogenic fungus tested in the present invention include AS: tomato early blight fungus (Alternaria solani); BC: cucumber gray mold fungus (Botrytis cinerea); CA: peanut brown spot fungus (Cercospora arachidicola); GZ: wheat gibberella Gibberella zeae; PI: Phytophthora infestans (Mont.) deBary; PP: Physalospora piricola; PS: Rice sheath blight (Pellicularia sasakii); SS: Rapeseed sclerotia Sclerotinia sclerotiorum; RC: Rhizoctonia cerealis, these strains are well represented and can represent most of the pathogenic species that occur in the field in agricultural production. The results of the bacterial growth rate method are shown in Table 2, and Table 2 shows that at 50 micrograms per milliliter, most of the compounds synthesized by the present invention have various degrees of bactericidal activity, while the same kind of positive control medicament diflubenzurl has almost no bactericidal activity , especially prominent is the bactericidal activity of the synthetic compound WH-C12 of the present invention to AS; the bactericidal activity of WH-C15 to BC; the bactericidal activity of WH-C1, WH-C5, WH-C11, WH-C12 to PP; WH Bactericidal activity of -C15 against PS; The bactericidal activity of E18 and WH-E19 to SS; the bactericidal activity of WH-C12, WH-C14, WH-C15, and WH-E15 to RC were all higher than 60%, which was also higher than that of the positive control drug diflubenzuron under the same conditions. The activity of corresponding pathogenic fungi, therefore, this kind of compound shows better bactericidal activity, shows that this kind of compound also has better control effect on disease while controlling pests.

Example 44: 4-methyl-1,2,3-thiadiazole containing 4-(1,1,2,2-tetrafluoroethoxy)-3,5-dichloroanilino of the present invention Antiviral Activity of Cyclic Derivative I

Due to the large number of compounds, the determination of antiviral activity was carried out twice, and the results of the two determinations showed that the compound containing 4-(1,1,2,2-tetrafluoroethoxy)-3,5-bis The 4-methyl-1,2,3-thiadiazole heterocyclic derivatives of chloroanilino have better anti-plant virus activity and better induction of plant anti-plant virus activity, and the antiviral activity and induction of C series The results of the determination of the activity are shown in Table 3. Table 3 shows that the standard plant-induced disease resistance activator thiazil has good protection and inactivation of TMV activity, and can also induce tobacco resistance to TMV well. But the antiviral drug ribavirin has good direct antiviral activity, but almost no induction activity; The 4-methyl-1,2,3-thiadiazole heterocyclic derivatives part of the base has good direct anti-TMV activity, WH-C16 and WH-C20 have good protective activity, WH-C1, WH -C2, WH-C5, WH-C6, WH-C8, WH-C20 have significant passivation activity, WH-C1, WH-C2, WH-C3, WH-C8, WH-C10, WH-C12, WH -C14, WH-C16, WH-C17 have good therapeutic activity; WH-C1, WH-C4, WH-C10, WH-C13, WH-C17, WH-C18, WH-C19, WH-C21 have very good Good inducing activity; WH-C3, WH-C5, WH-C7, WH-C10, WH-C12, WH-C13, WH-C17, WH-C18 and WH-C19 have good semi-leaf blight activity, The activity of ribavirin is equivalent to or higher than that of the control drug ribavirin. The assay results of the antiviral activity and inductive activity of E series are shown in Table 4, and Table 4 shows that the protective activity of WH-E5 and WH-E8 is equivalent to or higher than that of the contrast agent; WH-E1, WH-E5, WH- The inactivating activity of E6, WH-E7, WH-E8, WH-E12, WH-E14, WH-E18 and WH-E20 was comparable to or higher than that of the control agent; WH-E12, WH-E13 and WH-E18 The therapeutic activity of WH-E10 and WH-E19 was comparable to or higher than that of the control drug; the induction activity of WH-E10 and WH-E19 was comparable to or higher than that of the control drug; WH-E3, WH-E4, WH-E6, WH-E7 and WH -E10 has very good half-leaf scorching activity, which is equivalent to or higher than that of ribavirin as the control agent. As a result of the two determinations, it was found that other compounds had different degrees of direct antiviral activity and inducing activity. The half-leaf method activity test results show that the antiviral activities of the C series and E series compounds of the present invention are equal to or higher than ribavirin at 500 μg/mL. The above-mentioned good activity or very good activity means that its activity is greater than or far greater than the activity of the positive control agent TDL, ribavirin or Ningnanmycin. Therefore, some compounds of the present invention have significant anti-plant virus and induce plant production. The effect of producing resistance to plant virus diseases.

It can be known from basic chemical principles that 4-methyl-1,2,3-thiadiazole containing 4-(1,1,2,2-tetrafluoroethoxy)-3,5-dichloroanilino The heterocyclic derivatives can be broken from the carbonyl after interacting with water molecules in plants to produce 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, which is also confirmed by relevant software predictions and experiments. The compound can be metabolized and degraded in plants to produce 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, and literature reports have confirmed that 4-methyl-1,2,3-thiadiazole-5-carboxylic acid has the ability to induce Plants develop resistance to plant pathogens and can be used for the prevention and treatment of plant diseases and plant virus diseases. Therefore, the compound of the present invention can be used for the preparation of anti-plant virus agents or inducing plant anti-plant virus agents.

Example 45: 4-methyl-1,2,3-thiadiazole containing 4-(1,1,2,2-tetrafluoroethoxy)-3,5-dichloroanilino of the present invention Insecticidal activity of ring derivative I

The new compounds WH-C3, WH-C15, and WH-C20 synthesized by the present invention have very good insecticidal activity to mosquito larvae, and their activity is comparable to that of the positive control drug hexaflumuron at a concentration of 2 μg/mL, both 100% was achieved (Table 5); trials with reduced concentration activity are ongoing. Under the concentration of 200 μg/mL, the new compounds synthesized by the present invention all have different degrees of insecticidal activity to Plutella xylostella, WH-C2, WH-C3, WH-C5, WH-C7, WH-C8, WH-C12, WH- The insecticidal activity of C17 and WH-C18 and WH-E5, WH-E8, WH-E9 and WH-E10 against Plutella xylostella was comparable to or higher than that of the positive control drug diflubenzuron Activity (Table 5);

Example 46: 4-methyl-1,2,3-thiadiazole containing 4-(1,1,2,2-tetrafluoroethoxy)-3,5-dichloroanilino of the present invention Combination of cyclic derivative I and antiviral agent in the prevention and treatment of agricultural and forestry and horticultural plant viral diseases

Containing 4-(1,1,2,2-tetrafluoroethoxy)-3,5-dichloroanilino 4-methyl-1,2,3-thiadiazole heterocyclic derivatives I and existing Anti-plant virus agents benzothiadiazole, thiazilamide, 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, 4-methyl-1,2,3-thiadiazole- Sodium 5-formate, ethyl 4-methyl-1,2,3-thiadiazole-5-carboxylate, ethyl 5-bromomethyl-1,2,3-thiadiazole-4-carboxylate, 5-iodo Methyl-1,2,3-thiadiazole-4-ethyl carboxylate, 4-methyl-5-bromomethyl-1,2,3-thiadiazole, 4-methyl-5-iodomethyl -1,2,3-thiadiazole, 5,5-dibromomethyl-1,2,3-thiadiazole-4-ethyl carboxylate, 4-bromomethyl-1,2,3-thiadiazole Azole-5-ethyl carboxylate, 4-iodomethyl-1,2,3-thiadiazole-5-ethyl carboxylate, 4-bromomethyl-5-methyl-1,2,3-thiadiazole , 4-iodomethyl-5-methyl-1,2,3-thiadiazole, 4,4-dibromomethyl-1,2,3-thiadiazole-5-ethyl carboxylate, DL-β -Any one or two of aminobutyric acid, ribavirin, antorfin, ningnanmycin, thiamid, thiamin, or salicylic acid, pyritomycin, dichloroisonicotinic acid, and allylisothiazole A combination of compounds; used to control agricultural pests such as East Asian migratory locust, cloud-spotted car locust, Chinese rice locust, Japanese yellow-spine locust, single-spined mole cricket, oriental mole cricket, rice thrips, tobacco thrips, greenhouse thrips, rice pipe thistle Horses, Thrips barley, Greenhouse Whitefly, Bemisia tabaci, Black-tailed Leafhopper, Daqing Leafhopper, Cotton Leafhopper, Spot-coated Waxhopper, Brown Planthopper, White-backed Planthopper, SBPH, Sugarcane Flathorned Fly Lice, cotton aphid, wheat two-pronged aphid, wheat long tube aphid, green peach aphid, sorghum aphid, radish aphid, cotton scale, mulberry shield scale, arrow point scale scale, pear round scale, white wax insect, red wax scale, Korean ball Scale, pear net bug, banana net bug, slender horned bug, tiny flower bug, needle bug, rice spider bug, rice brown bug, rice black bug, rice green bug, green mirid bug, alfalfa mirid bug, middle Black Lygus, Large Lacewing, Lacewing, Chinese Lacewing, Grain Moth, Clothes Moth, Yellow Cricket Moth, Brown Cricket Moth, Flat Cricket Moth, Wheat Moth, Cotton Red Bollworm, Sweet Potato Wheat Moth, Plutella xylostella, Peach Bollworm Pod borer, soybean borer, peach borer, apple top tip leaf roller, brown-banded leaf roller, pseudo small yellow leaf roller, rice borer, bean pod borer, corn borer, rice borer, rice borer, rice leaf roller, bar borer, cotton Leafroller, peach borer, armyworm, Spodoptera litura, rice borer, cotton small bridge builder, beet armyworm, large borer, cotton bollworm, tripod diamond, small cutworm, large cutworm, yellow cutworm, Stealing poisonous moth, gypsy moth, sweet potato hornworm, bean hornworm, straight-grained rice butterfly, hidden grain butterfly, citrus swallowtail, jade belt swallowtail, cabbage butterfly, ramie red nymph, ramie yellow nymph, bean parsley , Venus beetle, wrinkled sheath beetle, wheat ear beetle, ditch day lily worm, thin breast beetle, barley beetle, black skin beetle, citrus beetle, golden edge beetle, Tenebrio molitor, Tenebrio smut , red beetle, miscellaneous beetle, verdant beetle, dark beetle, North China giant beetle, mulberry beetle, star beetle, orange-brown beetle, pink-necked beetle, great ape leaf beetle, lesser ape Leafworm . Lemon-toothed wasp, Adenophora spp., mosquito, fly, horsefly, wheat red midge, wheat yellow midge, rice gall midge, citrus fruit fly, fruit fly, Liriomyza sativus, Liriomyza sativae , bean stalk blackminer, wheat stalk fly, seed fly, onion fly, radish fly, umbrella skirt chasing fly, corn borer fly, armyworm lacking barb fly and other pests; it can also cause plant virus diseases Resistance or inducing plants to produce resistance to viral diseases and fungal diseases, especially inducing tobacco resistance to TMV or for direct control of TMV activity, the plants used for induction include rice, wheat, barley, oats, corn, sorghum, sweet potato , potato, cassava, soybean, broad bean, pea, mung bean, adzuki bean, cotton, silkworm, peanut, rapeseed, sesame, sunflower, beet, sugar cane, coffee, cocoa, ginseng, fritillary, rubber, coconut, oil palm, sisal, Tobacco, melon, fruit, tea, wild vegetables, bamboo shoots, hops, pepper and other agricultural, horticultural, economical, forestry and other plants; the use of these compositions improves the immunity of the crops themselves, and is effective against pests, especially poisonous insects. During the prevention and treatment, plants are induced to prevent and control plant virus diseases; they can also produce direct control effects on virus diseases; therefore, these compositions can be used for the preparation and use of anti-plant virus agents and induced plant anti-plant virus agents. 4-methyl-1,2,3-thiadiazole heterocyclic derivative I containing 4-(1,1,2,2-tetrafluoroethoxy)-3,5-dichloroanilino of the present invention The total mass percentage in the composition is 1%-90%. The 4-(1,1,2,2-tetrafluoroethoxy)-3,5-dichloroanilino-containing 4 -The ratio of methyl-1,2,3-thiadiazole heterocyclic derivative I to commodity pesticide is mass percent 1%: 99% to 99%: 1%; the dosage form of composition processing is selected from wettable powder, slow release agent, powder, microcapsule suspension, dispersible concentrate, seed treatment emulsion, water emulsion, macrogranule, granule, microemulsion, oil suspension, oil, seeds coated with pesticides, suspoemulsion, water-soluble Any one of granules, soluble concentrates, and water-dispersible granules; these compositions all exhibit additive or synergistic effects, and while maintaining insecticidal activity, their antiviral activity is greater than that of any compound alone The effect of use; no composition with antagonistic effect is found, and the drug effect duration of the composition is long.

It can be known from basic chemical principles that 4-methyl-1,2,3-thiadiazole containing 4-(1,1,2,2-tetrafluoroethoxy)-3,5-dichloroanilino The heterocyclic derivative I can be broken from the carbonyl after interacting with water molecules in plants to produce 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, which is also confirmed by relevant software predictions and experiments The compound can be metabolized and degraded in plants to produce 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, and literature reports have confirmed that 4-methyl-1,2,3-thiadiazole-5-carboxylic acid has Inducing plants to produce resistance to plant pathogens can be used for the prevention and treatment of plant diseases and plant virus diseases. Therefore, these compositions can also be used for preparing anti-plant virus agents and inducing plants to resist plant virus agents.

The main crops to which these compositions are applicable include cereal crops (including rice, wheat, barley, oats, corn, millet, sorghum, etc.), potato crops (including sweet potatoes, potatoes, cassava, etc.), bean crops (including soybeans, broad beans, pea, mung bean, adzuki bean, etc.) and fiber crops (cotton, hemp, sericulture, etc.), oil crops (peanut, rape, sesame, soybean, sunflower, etc.), sugar crops (beet, sugar cane, etc.), beverage crops (tea, Coffee, cocoa, etc.), hobby crops (tobacco leaves, etc.), medicinal crops (ginseng, fritillary, etc.), tropical crops (rubber, coconut, oil palm, sisal, etc.) and other food crops and fruits, flowers, oil plants, sugar crops As well as economic crops such as cotton, hemp, tea, tobacco, and Chinese medicinal materials, as well as melons, fruits, tea, sericulture, vegetables (including various wild vegetables, etc.), bamboo shoots, flowers and ornamental plants, hops, medicinal materials, pepper, seedlings and Other horticultural crops and other horticultural crops such as tobacco (flue-cured tobacco, air-dried tobacco, sun-cured tobacco), vegetables, (tomatoes, peppers, radishes, cucumbers, cabbage, celery, mustard, beets, rapeseed, onions, garlic, etc.), melons (watermelon, Melon, cantaloupe, papaya, etc.), beans (soybean, broad bean, snow pea, etc.), potato, wheat, corn, rice, peanut, fruit tree, (apple, banana, citrus, peach tree, papaya), flowers (such as orchid ), bonsai, etc. Virus diseases include tobacco mosaic virus disease, various melon virus diseases, various solanaceous fruit virus diseases, bean virus diseases, cruciferous virus diseases, grain and oil crop virus diseases, cotton virus diseases and various Fruit tree virus diseases, etc. Among them, the serious ones are: tobacco virus disease, spicy and sweet pepper virus disease, tomato virus disease, Chinese cabbage virus disease, rice virus disease, including rice dwarf disease, yellow dwarf disease, stripe leaf blight, Tomato fern virus disease, capsicum mosaic virus disease and tobacco vein necrosis virus disease, corn dwarf mosaic disease, cauliflower mosaic virus, citrus virus disease, Jianlan mosaic virus, Jianlan ringspot virus, etc. Example 47: 4-methyl-1,2,3-thiadiazole containing 4-(1,1,2,2-tetrafluoroethoxy)-3,5-dichloroanilino of the present invention Combination of cyclic derivative I and fungicide for the prevention and control of agricultural and forestry and horticultural plant diseases

Bioassay results show that all 4-methyl-1,2,3-thiadiene containing 4-(1,1,2,2-tetrafluoroethoxy)-3,5-dichloroanilino groups of the present invention Azole heterocyclic derivatives I and existing fungicides such as benzothiadiazole, thiazilamide, thiamid, methylthiamid, 4-methyl-1,2,3-thiadiazole-5-carboxylic acid , 4-methyl-1,2,3-thiadiazole-5-sodium carboxylate, 4-methyl-1,2,3-thiadiazole-5-carboxylate ethyl ester, 5-bromomethyl-1,2 , 3-thiadiazole-4-carboxylic acid ethyl ester, 5-iodomethyl-1,2,3-thiadiazole-4-carboxylic acid ethyl ester, 4-methyl-5-bromomethyl-1,2, 3-thiadiazole, 4-methyl-5-iodomethyl-1,2,3-thiadiazole, 5,5-dibromomethyl-1,2,3-thiadiazole-4-carboxylic acid ethyl Esters, ethyl 4-bromomethyl-1,2,3-thiadiazole-5-carboxylate, ethyl 4-iodomethyl-1,2,3-thiadiazole-5-carboxylate, ethyl 4-bromomethyl Base-5-methyl-1,2,3-thiadiazole, 4-iodomethyl-5-methyl-1,2,3-thiadiazole, 4,4-dibromomethyl-1,2 , 3-thiadiazole-5-ethyl carboxylate, DL-β-aminobutyric acid, ribavirin, antorfin, Ningnanmycin, thiamide, methylthiamin or salicylic acid, cymoxanil, thiram Double, thiram zinc, mancozeb, ethyl phosphorus aluminum, thiophanate-methyl, chlorothalonil, dicortisone, procymidone, fenpropidin, thiophanate-methyl, thiophanate, mefenaxyl, water Salicylic acid, flumorph, dimethomorph, high-efficiency metalaxyl, high-efficiency benalaxyl, diclofenamide, sulfamethanil, sulfamethanil, thiafluzamide, flunamide, yekuphthalein, cyclic Propionamid, Cyflufenamide, Fenhexamid, Cyanoxamid, Sithiazil, Fubifen, Penthiopyrad, Mandipyramide, Benzamid, Mefuramide, Wilt Protozolin, Bactanil, Iprodione, Azoxystrobin, Kysstrobin, Fluoxastrobin, Kresoxim-methyl, Phenoxystrobin, Oryzastrobin, Picoxystrobin, Pyclostrobin, Trifloxystrobin Esters, Enoxastrobin, Enoxastrobin, Oxyconazole, Fuconazole, Cyproconazole, Difenoconazole, Diniconazole, Betadiniconazole, Epoconazole, Nibendazole, Fluoroquinol Azole, Flusilazole, Fenconazole, Hexaconazole, Imidazole, Conconazole, Meconazole, Mycloconazole, Penconazole, Propiconazole, Prothioconazole, Silicon Fluazole, Tebuconazole , Tetraflumezol, Triaconazole, Fenconazole, Bifentriazole, Thiabendazole, Maisuining, Imazalil, High-efficiency Imazalil, Prochloraz, Flubuconazole, Cyanazazole, Imidazole Cyclofenone, oximidazole, rice blastic ester, oxafluconone, pyridoxazole, hymexazol, oxadaxyl, ethaboxam, terbendazim, octhinone, thiocyanate, dodecamorph , fenfenmorph, tridemorph, seed dressing, fludioxonil, fluazinam, pyroxenil, cyclopyramide, boscalid, flubocalid, boscalid, azuridine Amine, fluoxamethanil, pyrimethanil, azoxystrobin, pyrimethanil, chloropyrimidinol, fluopyrimidinol, acetidine, dicyanoanthraquinone, ethoxyquin, hydroxyquinoline, propoxyquine phenoxyquinoline, Ditofencarb, Iprocarbam, Benthiocarbamide, Propamocarb, Sulfurcarb, Difenfo, Isofenzine, Pyrazophos, Tolclofos-Methyl, Methide Kasugamycin, polyantimycin Polyoxin, polyoxin, validamycin, jinggangmycin, streptomycin, metalaxyl, furaxyl, benalaxyl, furamide, rustamine, carbendazim, benomyl, methylthiobacterium Ling, triadimefon, pyrimethrimol sulfonate, pyrimethanol, pyrimethrimol, captafol, captan, folpet, vinclozolin, fluorochloride, sclerotin, 100 Junqing, Daobunling, Daobangjing, Yekuzol, Pentachloronitrobenzene, Mancozeb, Prozeb, Aluminum Triethylphosphonate, Sulfur, Bordeaux Mixture, Copper Sulfate, Copper Oxychloride, Oxidation Cuprous, cupric hydroxide, metrafenone, pentocuron, pyridoxalone, tetrachlorophthalide, pyroquinone, spirulina, tricyclazole, azinamide, dorbutin, biguanide octyl salt, biguanide Octylamine, Clonitramine, Bensulfastromine, Toluenesulfame, Indoxylate, Sodium Disulfone, Quintrazone, Allylbenzothiazole, Bronopol, Methyl Iodide, Vebam, Dicetone, Cotton Long, dichloroisopropyl ether, thiazolphos, thiamephos, fensofos, chrysanthemum, fenamiphos, phenamiphos, demiphos, chlorazophos, fenthion, killing line, aldimine Carbofuran, sulfuryl fluoride, dichloropropene, dichloroisonicotinic acid, allylisothiazole, etc., can be used as any one or combination of two of the fungicides; the present invention contains 4- The total amount of 4-methyl-1,2,3-thiadiazole heterocyclic derivatives I of (1,1,2,2-tetrafluoroethoxy)-3,5-dichloroanilino in the composition The mass percentage content is 1%-90%, the 4-methyl-1 containing 4-(1,1,2,2-tetrafluoroethoxy)-3,5-dichloroanilino of the present invention, The ratio of 2,3-thiadiazole heterocyclic derivatives I to commercial pesticides is 1% by mass: 99% to 99%: 1%; the control effect of the medicament is good, and these compositions have certain synergistic effects and additive effects. No antagonistic composition has been found; the above-mentioned composition can be used for the prevention and treatment of agricultural plant diseases and horticultural plant diseases, and the control objects include Cottonella, Aphanomyces, Pythium, Phytophthora, Refers to the diseases caused by more than 20 genera such as Phytophthora, Plasmodium, Pseudomonas, Peronospora, etc., such as rice seedling cotton rot, tomato root rot, potato late blight, tobacco black shank, millet Powdery mildew, grape downy mildew, lettuce downy mildew, cucumber downy mildew, cucumber anthracnose and other diseases of various food crops, economic crops, horticultural plants and forestry plants; the dosage form of the composition processing is selected from wettable powder , sustained release agent, powder, microcapsule suspension, dispersible concentrate, seed treatment emulsion, water emulsion, macrogranule, granule, microemulsion, oil suspension, oil, seeds coated with pesticides, suspoemulsion, Any of water-soluble granules, soluble concentrates, and water-dispersible granules.

Suitable crops for these compositions include cereals (including rice, wheat, barley, oats, corn, millet, sorghum, etc.), potato crops (including sweet potatoes, potatoes, cassava, etc.), beans (including soybeans, broad beans, peas, mung beans, etc.) , adzuki beans, etc.) and fibers (cotton, hemp, sericulture, etc.), oil crops (peanuts, rapeseed, sesame, soybeans, sunflowers, etc.), sugar crops (beets, sugar cane, etc.), beverages (tea, coffee, cocoa, etc.), hobbies (tobacco leaves, etc.), medicinal (ginseng, fritillary, etc.), tropical (rubber, coconut, oil palm, sisal, etc.) and other food crops and fruits, flowers, oil plants, sugar crops, cotton, hemp, tea, tobacco, traditional Chinese medicine Planting economic crops such as melons, fruits, tea, sericulture, vegetables (including various wild vegetables, etc.), bamboo shoots, flowers and ornamental plants, hops, medicinal materials, pepper, seedlings and other horticultural crops such as tobacco (flue-cured tobacco , drying tobacco, drying tobacco), vegetables, (tomatoes, peppers, radishes, cucumbers, cabbage, celery, mustard, beets, rapeseed, onions, garlic, etc.), melons (watermelon, melon, cantaloupe, papaya, etc.), beans (soybean, broad bean, snow pea, etc.), potato, wheat, corn, rice, peanut, fruit tree, (apple, banana, citrus, peach tree, papaya), flower (such as orchid), bonsai, etc.

Example 48: 4-methyl-1,2,3-thiadiazole containing 4-(1,1,2,2-tetrafluoroethoxy)-3,5-dichloroanilino of the present invention Application of Cyclic Derivative I and Insecticide Combination in Prevention and Control of Agriculture, Forestry and Horticultural Plant Pests

4-methyl-1,2,3-thiadiazole heterocyclic derivative I containing 4-(1,1,2,2-tetrafluoroethoxy)-3,5-dichloroanilino of the present invention The total mass percentage in the composition is 1%-90%. The 4-(1,1,2,2-tetrafluoroethoxy)-3,5-dichloroanilino-containing 4 - The ratio of methyl-1,2,3-thiadiazole heterocyclic derivative I to commercial pesticides is 1% by mass: 99% to 99%: 1%; it can be sprayed directly after watering, and its preparation contains agricultural Acceptable solvents and emulsifiers, co-solvents and synergists, etc., the formulation of the composition is selected from wettable powder, sustained release agent, powder, microcapsule suspension, dispersible concentrate, seed treatment emulsion, water emulsion , large granules, granules, microemulsions, oil suspensions, oils, seeds coated with pesticides, suspoemulsions, water-soluble granules, soluble concentrates, and water-dispersible granules; Pests mainly include spider mites, East Asian migratory locusts, cloud-spotted car locusts, Chinese rice locusts, Japanese yellow-ridged locusts, single-spined mole crickets, oriental mole crickets, rice thrips, tobacco thrips, greenhouse thrips, rice pipe thrips, and barley Tube thrips, greenhouse whitefly, whitefly, black-tailed leafhopper, green leafhopper, cotton leafhopper, spotted waxhopper, brown planthopper, white-backed planthopper, brown planthopper, sugarcane flathorn planthopper, cotton aphid , wheat two-fork aphid, wheat long tube aphid, green peach aphid, sorghum aphid, radish aphid, cotton scale, mulberry shield scale, arrow-pointed scale scale, pear round scale, white wax insect, red wax scale, Korean bulbous scale, pear Net bugs, banana net bugs, slender horned bugs, tiny flower bugs, needle bugs, rice spider bugs, rice brown bugs, rice black bugs, rice green bugs, green mirid bugs, alfalfa mirid bugs, middle black mirid bugs, Lacewing, Lacewing, Lacewing, Grain Moth, Clothes Moth, Yellow Prickly Moth, Brown Prickling Moth, Flat Prickly Moth, Wheat Moth, Cotton Red Bollworm, Sweet Potato Wheat Moth, Plutella xylostella, Peach Heartworm, Soybean Heartworm , peach small borer, apple top tip leaf roller, brown-banded long leaf roller, pseudo small yellow leaf roller, rice stem borer, pod borer, corn borer, rice stem borer, rice borer, rice leaf roller, bar borer, cotton leaf roller , peach borer, armyworm, litura, rice borer, cotton small bridge builder, beet armyworm, large borer, cotton bollworm, tripod diamond, small cutworm, large cutworm, yellow cutworm, poisonous moth, dancer Poison moth, sweet potato hornworm, bean hornworm, straight-grained rice butterfly, hidden-grained valley butterfly, citrus swallowtail, jade-belt swallowtail, cabbage butterfly, ramie red nymph, ramie yellow nymph, bean cypress, Venus carapace . Pirates, Miscellaneous Grain Pirates, Bronze Beetle, Dark Beetle, North China Beetle, Sang Beetle, Star Beetle, Orange Brown Beetle, Pink-necked Beetle, Great Ape Leaf Beetle, Lesser Ape Beetle, Yellow Shougua , yellow curly flea beetle, mung bean weevil, pea weevil, broad bean weevil, corn weevil, rice weevil, wheat sawfly, pear bee, yellow belt bee, armyworm white star bee, bollworm cocoon bee, cotton bollworm teeth Liriodendron chinensis, Adenophora spp., Mosquitoes, Flies, Gads, Red midges, Yellow midges, Rice gall midges, Bactrocera citrus, Fruitfly, Liriomyza sativus, Liriomyza sativae, Bean Liriomyza stalk , wheat stalk fly, seed fly, onion fly, radish fly, umbrella skirt fly, corn borer fly, armyworm lack of barb fly and other agricultural pests, forestry pests, horticultural pests and sanitary pests. The control methods also include Both treatment; 4-methyl-1,2,3-thiadiazole heterocyclic derivatization containing 4-(1,1,2,2-tetrafluoroethoxy)-3,5-dichloroanilino of the present invention The substance can be mixed with one or more of the insecticides in the following group: chlorpyrifos, diyamectin, acetamiprid, emamectin, mibamectin, abamectin, spinosad, Fenvalerate, Beta-Esfenvalerate, Cypermethrin, Beta-Cypermethrin, Cyhalothrin, Deltamethrin, Fenvalerate, Beta-Cyfluthrin, Cyfluthrin, Lambda-Cyhalothrin, Permethrin , permethrin, allethrin, kung fu thrin, bifenthrin, permethrin, ethofenproxil, bifenthrin, chlorfluamidin fenvalerate, imidacloprid, acetamiprid, nitenpyrid Amines, chlorothialine, thiacloprid, thiamethoxam, clothianidin, dinotefuran, canidin, dartnam, diflubenzuron, diflubenzuron, pyrifluron, diflubenuron, hexaflumuron, Flubenzuron, acetamiuron, lufenuron, chlorfenuron, flufenuron, Noviflumuron, flufenuron, Novifuron, chlorfluazuron, Bay sir 6874, fenfluzuron, Bistrifluron, furantenozide, tebufenozide, Chlorantraniliprozide, methoxyfenozide, cyclofenozide, dimethoate, omethoate, dichlorvos, acephate, triazophos, quinalphos, pyridazinphos, chlorazophos, leafhopper powder , Carbaryl, Pirimicarb, Meprocarb, Isoprocarb, Cartap, Zhongbucarb, Yefeisan, Carbaryl, Prosulfur Carbofuran, Carbosulfan, Cartap, Bromocarb Ester, Hexythiazox, Fenpyrafen, Pyridaben, Tetrafen, Propyridine, Diafenthiuron, Carbosulfan, Pymetrozine, Spirofen, Spiropeptid, Spirotetramat, Butyl Fipronil, triazoltin, buprofezin, fenamiphos, fipronil, monosultap, dimehypo, fibendiamide, chlorantraniliprole or tebufenpyrad, chlorfenapyr, pyrazinone, acetidine Facazole, tebufenpyrad, pyridoxone, pyriproxyfen, emamectin, etc., the combined agent has good control effect and stable drug effect.

Example 49: 4-methyl-1,2,3-thiadiazole containing 4-(1,1,2,2-tetrafluoroethoxy)-3,5-dichloroanilino of the present invention Processing technology and stability of compound preparation of cycloderivative I and commercial pesticide

4-methyl-1,2,3-thiadiazole heterocyclic derivative I containing 4-(1,1,2,2-tetrafluoroethoxy)-3,5-dichloroanilino of the present invention The processing technology of mixed formulations with commercial pesticides is shown in Table 6. It can be seen from Table 6 that most of the pesticides can be processed according to the stated method. The main components of the liquid formulations are active ingredients, co-solvents, surfactants, synergists, Freezing agents, stabilizers, thickeners or penetrating agents and other components, etc. The composition of solid preparations mainly includes active ingredients, surfactants, fillers and other agriculturally acceptable auxiliary components. Cold storage of processed preparations In the test, the liquid preparation was placed at 0±2 degrees Celsius for 1 week without precipitation, and the solid preparation was placed at 54±2 degrees Celsius for 2 weeks. The medicine did not agglomerate. There was no significant difference in the efficacy of the medicine before and after storage of all preparations, and the composition was effective. The decomposition rate of the components is less than 5%, and the stability is qualified.

The chemical structure of the new compound synthesized by the present invention of table 1

The bacteriostasis activity (/%) (concentration is 50 micrograms/ml) containing 4-methyl-1,2,3-thiadiazole derivatives synthesized by the present invention of table 2

compound F L D G AK I T N RC AS BC CA GZ PI PP PS SS RC WH-C1 33.33 18.18 14.29 0 0 64.10 14.08 45.45 41.94 WH-C2 4.76 18.18 21.43 0 23.81 46.15 14.08 72.73 41.94 WH-C3 14.29 0 0 0 0 33.33 7.04 18.18 48.39 WH-C4 9.52 0 0 0 0 33.33 14.08 54.55 32.26 WH-C5 33.33 27.27 0 0 14.29 71.79 14.08 36.36 48.39 WH-C6 4.76 4.55 0 0 0 20.51 42.25 72.73 0 WH-C7 33.33 36.36 0 0 0 20.51 42.25 54.55 22.58 WH-C8 33.33 27.27 14.29 0 0 38.46 4.23 45.45 32.26 WH-C9 20.00 38.46 26.32 21.88 7.41 40.00 3.95 58.06 45.00 WH-C10 0 0 14.29 0 19.05 38.46 42.25 36.36 22.58 WH-C11 47.62 0 21.43 23.81 23.81 61.54 14.08 45.45 9.68 WH-C12 61.90 27.27 42.86 0 23.81 71.79 21.13 0 64.52 WH-C13 47.62 27.27 0 0 9.52 28.21 0 45.45 41.94 WH-C14 33.33 59.09 0 0 0 20.51 42.25 63.64 70.97 WH-C15 45.00 73.08 47.37 40.63 33.33 47.50 63.16 70.97 100.00 WH-C16 14.29 4.55 0 0 0 53.85 14.08 36.36 29.03 WH-C17 33.33 4.55 0 0 0 33.33 42.25 63.64 32.26 WH-C18 0 4.55 0 0 0 7.69 14.08 27.27 16.13 WH-C19 42.86 4.55 21.43 0 0 58.97 42.25 54.55 0 WH-C20 23.81 13.64 0 0 23.81 28.21 0 27.27 16.13 WH-C21 33.33 0 0 0 0 33.33 0 27.27 22.58 WH-E1 0 55.17 0 7.69 14.81 21.05 8.45 65.12 31.58 WH-E2 5.26 17.24 0 0 3.70 18.42 4.23 37.21 23.68 WH-E3 5.26 41.38 0 0 14.81 18.42 0 60.47 31.58 WH-E4 5.26 44.83 0 0 11.11 31.58 4.23 20.93 18.42 WH-E5 5.26 37.93 0 0 3.70 18.42 0 39.53 18.42 WH-E6 5.26 37.93 0 0 33.33 23.68 4.23 48.84 31.58 WH-E7 15.79 34.48 0 11.54 11.11 0 4.23 32.56 5.26 WH-E8 21.05 17.24 0 7.69 3.70 15.79 4.23 39.53 26.32 WH-E9 5.26 31.03 0 0 29.63 31.58 0 16.28 26.32 WH-E10 5.26 27.59 0 0 3.70 5.26 4.23 27.91 18.42 WH-E11 ND ND ND ND ND ND ND ND ND WH-E12 9.09 21.88 0 0 17.24 38.46 32.35 66.67 21.62 WH-E13 15.79 34.48 0 19.23 22.22 2.63 4.23 60.47 21.05 WH-E14 5.26 55.17 21.43 0 22.22 18.42 35.21 55.81 57.89 WH-E15 5.26 55.17 14.29 0 3.70 31.58 0 53.49 73.68 WH-E16 26.32 44.83 0 7.69 11.11 10.53 4.23 62.79 15.79 WH-E17 5.26 44.83 0 19.23 3.70 31.58 14.08 27.91 26.32 WH-E18 26.32 10.34 0 7.69 3.70 18.42 0 44.19 15.79 WH-E19 26.32 51.72 0 0 33.33 18.42 4.23 65.12 23.68 WH-E20 4.55 28.13 5.56 3.03 24.14 38.46 5.88 66.67 43.24 WH-E21 5.26 31.03 0 0 11.11 21.05 0 0 18.42 diflubenzuron 5.26 21.88 0 4.00 3.45 21.05 14.08 18.42 3.70

The antiviral activity of the C series containing 4-methyl-1,2,3-thiadiazole derivatives synthesized by the present invention of table 3 (data is inhibitory rate/%)

*: 500 μg/ml corresponds to 100 μg/ml for inducing activity; 100 μg/ml corresponds to 50 μg/ml

Table 4 The antiviral activity of the synthetic 4-methyl-1,2,3-thiadiazole derivative E series of the present invention (data is inhibition rate/%)

*: 500 μg/ml corresponds to 100 μg/ml for inducing activity; 100 μg/ml corresponds to 50 μg/ml

The insecticidal activity (/%) containing 4-methyl-1,2,3-thiadiazole derivatives synthesized by the present invention of table 5

compound Concentration (mg/L) Mosquito larva mortality (%) Concentration (mg/L) Plutella xylostella mortality (%) WH-C1 2 20 200 7.89 WH-C2 2 20 200 22.86 WH-C3 2 100 200 21.62 WH-C4 2 40 200 7.69 WH-C5 2 20 200 17.50 WH-C6 2 0 200 5.41 WH-C7 2 10 200 21.05 WH-C8 2 0 200 23.68 WH-C9 2 10 200 ND WH-C10 2 10 200 5.26 WH-C11 2 0 200 7.89 WH-C12 2 20 200 15.00 WH-C13 2 30 200 ND WH-C14 2 10 200 ND WH-C15 2 100 200 ND WH-C16 2 20 200 2.63 WH-C17 2 20 200 15.79 WH-C18 2 40 200 22.92 WH-C19 200 10.81 WH-C20 2 100 200 7.90 WH-C21 2 20 200 20 WH-E1 2 30 200 ND WH-E2 ND ND 200 0 WH-E3 2 10 200 5.71 WH-E4 2 10 200 10.53 WH-E5 2 20 200 20.59 WH-E6 2 10 200 10.53 WH-E7 2 0 200 10.53 WH-E8 2 20 200 12.82 WH-E9 2 10 200 12.82 WH-E10 2 20 200 17.50 WH-E11 2 ND 200 ND WH-E12 2 30 200 ND WH-E13 2 20 200 9.09 WH-E14 2 10 200 ND WH-E15 2 30 200 ND WH-E16 2 30 200 8.11 WH-E17 2 20 200 ND WH-E18 2 0 200 10.53 WH-E19 2 10 200 10.53 WH-E20 2 30 200 ND WH-E21 2 10 200 ND Hexaflumuron 2 100 - - diflubenzuron 2 40 200 12.50

Table 6 Derivatization of 4-methyl-1,2,3-thiadiazole heterocycle containing 4-(1,1,2,2-tetrafluoroethoxy)-3,5-dichloroanilino of the present invention Material I is mixed with commodity pesticide and uses preparation processing method

Claims (6)

1. one kind contains 4-(1,1,2,2-tetrafluoro oxyethyl group)-3, the 4-methyl isophthalic acid of 5-dichlorobenzene amido, and 2,3-thiadiazoles Hete rocyclic derivatives is characterized in that: have suc as formula the general structure shown in the I:

Wherein: R ₁Be 4-(1,1,2,2-tetrafluoro oxyethyl group)-3,5-dichlorophenyl; R ₂For be selected from phenyl, Chloro-O-Phenyl, a chloro-phenyl-, rubigan, adjacent fluorophenyl, a fluorophenyl, to the group of fluorophenyl, o-trifluoromethyl phenyl, m-trifluoromethylphenyl, p-trifluoromethyl phenyl, ortho-nitrophenyl base, m-nitro base, p-nitrophenyl, o-methyl-phenyl-, an aminomethyl phenyl, p-methylphenyl, a hydroxy phenyl, p-hydroxybenzene, o-methoxyphenyl, m-methoxyphenyl, p-methoxyphenyl; R ₃For being selected from the group of cyclohexyl, sec.-propyl.

2. the described 4-(1,1,2,2-tetrafluoro oxyethyl group)-3 that contains of claim 1, the 4-methyl isophthalic acid of 5-dichlorobenzene amido, 2, the compound method of 3-thiadiazoles Hete rocyclic derivatives I, concrete synthetic route is following:

Wherein: R ₁Be 4-(1,1,2,2-tetrafluoro oxyethyl group)-3,5-dichlorophenyl; R ₂For be selected from phenyl, Chloro-O-Phenyl, a chloro-phenyl-, rubigan, adjacent fluorophenyl, a fluorophenyl, to the group of fluorophenyl, o-trifluoromethyl phenyl, m-trifluoromethylphenyl, p-trifluoromethyl phenyl, ortho-nitrophenyl base, m-nitro base, p-nitrophenyl, o-methyl-phenyl-, an aminomethyl phenyl, p-methylphenyl, a hydroxy phenyl, p-hydroxybenzene, o-methoxyphenyl, m-methoxyphenyl, p-methoxyphenyl; R ₃For being selected from the group of cyclohexyl, sec.-propyl.

3. the described 4-(1,1,2,2-tetrafluoro oxyethyl group)-3 that contains of claim 1, the 4-methyl isophthalic acid of 5-dichlorobenzene amido, 2,3-thiadiazoles Hete rocyclic derivatives I goes up the purposes of acceptable assistant in the preparation sterilant with agricultural, and said worm is selected from mosquito larvae and small cabbage moth.

4. the described 4-(1,1,2,2-tetrafluoro oxyethyl group)-3 that contains of claim 1, the 4-methyl isophthalic acid of 5-dichlorobenzene amido, 2,3-thiadiazoles Hete rocyclic derivatives I goes up the purposes of acceptable assistant in the preparation sterilant with agricultural.

5. the described 4-(1,1,2 that contains of claim 1; 2-tetrafluoro oxyethyl group)-3, the 4-methyl isophthalic acid of 5-dichlorobenzene amido, 2; 3-thiadiazoles Hete rocyclic derivatives I goes up the purposes of acceptable assistant in preparation Antiphytoviral medicament with agricultural, and said plant virus is a tobacco mosaic virus(TMV).

6. the described 4-(1,1,2,2-tetrafluoro oxyethyl group)-3 that contains of claim 1, the 4-methyl isophthalic acid of 5-dichlorobenzene amido, 2,3-thiadiazoles Hete rocyclic derivatives I goes up acceptable assistant is used for the plant activator of viral diseases of plants in preparation purposes with agricultural.