CN105541794A - Heptafluoroisopropyl-containing pyridyl pyrazole amide derivative and application thereof - Google Patents

Abstract

The present invention relates to the preparation and application of heptafluoroisopropyl-containing pyridylpyrazole amide derivatives represented by the general formula (I), which represent a broad-spectrum and high-efficiency insecticide and fungicide structure type. Pyridyl pyrazole amide derivatives containing heptafluoroisopropyl are used as new insecticides and fungicides to control oriental armyworm, diamondback moth, and beet armyworm; they are also very good for the control of cucumber brown spot disease , Cucumber bacterial spot, cucumber wilt, cucumber downy mildew, cucumber powdery mildew, tomato bacterial spot, rice sheath blight. For the meanings of R ₁ , R ₂ , and R ₃ in the formula, please refer to the description.

Description

Pyridylpyrazole amide derivatives containing heptafluoroisopropyl and application thereof

1. Technical field

The invention relates to pyridyl pyrazole amide derivatives containing heptafluoroisopropyl and their application as insecticides and fungicides, belonging to the technical field of pesticides.

2. Background technology

In recent years, breakthroughs have been made in the research and development of pesticides targeting ryanodine receptors in the field of agrochemicals. Nippon Pesticides, Bayer and DuPont respectively discovered two types of highly active insecticides-phthalamides and o-formylaminobenzamides. This is the first discovery of the synthesis of the target ryanodine receptors An insecticide that induces the activation of insect ryanodine receptors to release endogenous calcium ion pools, leading to insect death. Such insecticides exhibit the characteristics of high efficiency, broad spectrum, safety to non-target organisms, and no cross-resistance with traditional insecticides.

Chlorantraniliprole, chemical name 3-bromo-N-[4-chloro-2-methyl-6-[(methylcarbamoyl)benzene]-1-(3-chloropyridin-2-yl)- 1H-pyrazole-5-carboxamide, the trade name is Ryanxypyr. It is a new o-carboxamidobenzamide insecticide developed by DuPont of the United States. It is an insect ryanodine receptor inhibitor. Its novel mechanism of action can be used to control various Lepidoptera pests, and its control effect is significantly better than other commercial insecticides currently used in production. It is safe and can be used in vegetables, sugar beets, cotton and other crops to control various pests such as beet armyworm, cabbage armyworm, diamondback moth, cabbage butterfly, cotton bollworm, etc. It has a good control effect on larvae of all ages. It is currently a hot spot in the research of ryanodine receptor insecticides.

There are currently three ryanodine receptor-based insecticides that have been commercialized:

Major companies are also committed to the research of such compounds, such as the new structure created by Bayer Agroscience:

DuPont's new structure:

Syngenta's new structure:

3. Contents of the invention

The object of the present invention is to provide a class of pyridylpyrazole amide derivatives containing heptafluoroisopropyl and applications thereof, which have excellent insecticidal and bactericidal activities.

The present invention is the preparation and application of pyridyl pyrazole amide derivatives containing heptafluoroisopropyl group represented by general formula (I),

In the formula, R ₁ represents hydrogen, halogen, 1-6 carbon alkyl, one or more than one alkyl substituted by the same or different halogen atoms; R ₂ represents hydrogen, halogen, 1-6 carbon alkyl, one or more Alkyl groups substituted by the same or different halogen atoms; R ₃ represents substituted or unsubstituted alkyl groups, alkenyl groups, alkynyl groups, and cycloalkyl groups.

The pyridylpyrazole amide derivatives containing heptafluoroisopropyl described in the present invention can be prepared as follows: compound 1 is oxidized with potassium sulfate to obtain compound 2, and compound 2 is reacted with the corresponding halogenated hydrocarbon to obtain compound 3 , compound 3 is hydrolyzed to obtain acid 4, compound 4 and the corresponding aniline substituted with heptafluoroisopropyl group are prepared to obtain the target pyridylpyrazole amide derivatives containing heptafluoroisopropyl group of the general formula (I).

Compound 1 is commercially available or prepared according to known methods.

The invention can also be illustrated by the compounds listed in Table 1, but the invention is not limited.

The compound of the general formula (I) of the present invention has excellent insecticidal and bactericidal activity, and as an insecticide, it can be used to control Lepidoptera, Coleoptera, Homoptera, Diptera and Orthoptera pests ; As a fungicide, it can be used to control cucumber brown spot, cucumber bacterial angular spot, cucumber wilt, cucumber downy mildew, cucumber powdery mildew, tomato bacterial spot, rice sheath blight.

The compound of the general formula (I) of the present invention can be used directly, can also be used with an agriculturally acceptable carrier, and can also be used in combination with other types of insecticides and fungicides.

4. Specific implementation

Further illustrate the present invention below in conjunction with embodiment:

Embodiment one: the synthesis of intermediate 2

Dissolve compound 1 (37mmol) in 100mL acetonitrile, add sulfuric acid (74mmol) and stir at room temperature for 10min, add potassium persulfate (56mmol), heat up and reflux for 4h, cool to 55°C, filter, precipitate the filtrate under vacuum, add 100mL of water, and then Extracted with dichloromethane (3 × 150mL), the organic layers were combined, dried, the filtrate was concentrated, and the residue was subjected to silica gel column chromatography under reduced pressure, and the eluent was a mixed solvent of ethyl acetate and petroleum ether to obtain a white solid 2 ( 62.4%), mp136-138°C. ¹ HNMR (CDCl ₃ , 400M) δ: 9.35 (s, 1H, NH); 8.52 (d, J=4.4Hz, 1H, pyridyl-H); 7.90 (d, J= 8.0Hz, 1H, pyridyl-H); 7.43 (dd, J ₁ =4.4Hz, J ₂ =8.0Hz, 1H, pyridyl-H); 6.36 (s, 1H, pyrazolyl-H); 4.19 (q, 2H, J=7.2Hz, CH ₂ ); 1.19(t, 3H, J=7.2Hz, CH ₃ ).

Example 2: Synthesis of intermediate 3-methyl-1-(3-chloro-2-pyridyl)-1H-pyrazole-5-carboxylic acid ethyl ester

Dissolve compound 2 (7.5mmol) in 30mL DMF, add anhydrous potassium carbonate (11mmol), heat to 100°C, slowly add a DMF solution of iodomethane (9mmol) dropwise, react at 100°C for 3h, extract with ethyl acetate (3×50 mL), washed with water, dried the organic layer, and concentrated the filtrate to obtain ethyl 3-methyl-1-(3-chloro-2-pyridyl)-1H-pyrazole-5-carboxylate as an oily liquid. ¹ HNMR (CDCl ₃ , 400M) δ: 8.54 (d, J=4.6Hz, 1H, pyridyl-H); 8.21 (d, J=8.0Hz, 1H, pyridyl-H); 7.65 (dd, 1H, J ₁ = 4.6Hz, J2 = 8.0Hz, 1H, pyridyl _- H); 6.63 (s, 1H, pyrazolyl-H); 4.20 (q, J = 7.0Hz, 2H, _CH2 ); 3.80 (s, 3H, CH ₃ ); 1.07 (t, J=7.0Hz, 3H, CH ₃ ).

Example 3: Synthesis of intermediate 3-methyl-1-(3-chloro-2-pyridyl)-1H-pyrazole-5-carboxylic acid

In a 100mL round bottom flask, add ester (2.10g, 7.5mmol), 20mL of methanol, 5mL of water and NaOH (0.36g, 9mmol), the reaction mixture was stirred at room temperature for 6h, most of the solvent was removed under reduced pressure, and diluted with 50mL of water , extracted unreacted organic matter with ethyl acetate (10 mL), adjusted the aqueous layer to pH 1.5 with concentrated hydrochloric acid, and precipitated a solid, stirred at room temperature for 30 min, extracted with ethyl acetate (3×50 mL), washed with water, dried the organic layer, and concentrated the filtrate. 1.09 g of white solid 3-methyl-1-(3-chloro-2-pyridyl)-1H-pyrazole-5-carboxylic acid was obtained, yield 57.6%, mp 245-247°C. ¹ HNMR (DMSO-d ₆ , 400M) δ: 13.50 (s, 3H, CH ₃ ); 8.51 (d, J=4.6Hz, 1H, pyridyl-H); 8.18 (dd, J=8.0Hz, 1H, pyridyl-H); 7.61 (dd, J ₁ =4.6Hz, J ₂ =8.0Hz, 1H, pyridyl-H); 6.54(s, 1H, pyrazolyl-H); 3.85(s, 3H, CH ₃ ).

Example 4: Synthesis of intermediate 3-trifluoroethoxy-1-(3-chloro-2-pyridyl)-1H-pyrazole-5-carboxylic acid ethyl ester

Intermediate 2 (3.7mmol) was dissolved in 30mL DMF, anhydrous potassium carbonate (5.5mmol) was added, heated to 100°C, a DMF solution of 2,2,2-trifluoroiodoethane (4.4mmol) was slowly added dropwise, and After completion, reacted at 100°C for 3 h, extracted with ethyl acetate (3×50 mL), washed with water, dried the organic layer, concentrated the filtrate, and subjected the residue to silica gel column chromatography under reduced pressure. The eluent was a mixture of ethyl acetate and petroleum ether. Solvent, 1.28g white solid 3-trifluoroethoxy-1-(3-chloro-2-pyridyl)-1H-pyrazole-5-carboxylic acid ethyl ester, yield 99%, mp63-65°C. ¹ HNMR (CDCl ₃ , 400M) δ: 8.52 (dd, J ₁ =1.6Hz, J ₂ =4.8Hz, 1H, pyridyl-H); 7.91 (dd, J ₁ =1.6Hz, J ₂ =8.0Hz, 1H, pyridyl-H); 7.43 (dd, 1H, J ₁ =4.8Hz, J ₂ =8.0Hz, 1H, pyridyl-H); 6.54 (s, 1H, pyrazolyl-H); 4.66 (q, J = 16.4Hz, 2H, CH ₂ CF ₃ ); 4.20 (q, J=7.2Hz, 2H, CH ₂ ); 1.22 (t, J=7.2Hz, 3H, CH ₃ ).

Example 5: Synthesis of intermediate 3-trifluoroethoxy-1-(3-chloro-2-pyridyl)-1H-pyrazole-5-carboxylic acid

In a 100mL round bottom flask, add ester (3.7mmol), 20mL methanol, 5mL water and NaOH (4.5mmol), the reaction mixture was stirred at room temperature for 6h, most of the solvent was removed under reduced pressure, diluted with 50mL water, ethyl acetate ( 10 mL) to extract unreacted organic matter, the aqueous layer was adjusted to pH 1.5 with concentrated hydrochloric acid, a solid was precipitated, stirred at room temperature for 30 min, extracted with ethyl acetate (3×50 mL), washed with water, the organic layer was dried, and the filtrate was concentrated to obtain 0.84 g of a white solid 3-Trifluoroethoxy-1-(3-chloro-2-pyridyl)-1H-pyrazole-5-carboxylic acid, yield 71.3%, mp165-167°C. ¹ HNMR (CDCl ₃ , 300M)δ: 8.51 (dd, J ₁ =1.6Hz, J ₂ =4.8Hz, 1H, pyridyl-H); 7.92 (dd, J ₁ =1.6Hz, J ₂ =8.0Hz, 1H, pyridyl-H); 7.44 (dd, 1H, J=4.8Hz, 8.0Hz, pyridyl-H); 6.59(s, 1H, pyrazolyl-H); 4.65(q, J=16.4Hz, 2H, CH ₂ CF ₃ ).

Embodiment six: general formula (I) compound synthesis

Acid 4 (1.0 mmol) was dissolved in 20 mL of dichloromethane, oxalyl chloride (3 mmol) was added, the reaction mixture was reacted at room temperature for 3 h, and the solvent was distilled off under reduced pressure to obtain crude acid chloride. Under ice bath, acid chloride was dissolved in 10 mL of dichloromethane and slowly dropped into 20 mL of intermediate 5 (1.3 mmol) in dichloromethane solution, then triethylamine (1.5 mmol) was added dropwise as acid-binding agent, and stirred at room temperature for 4 h . After the reaction was completed and the solution was removed, dichloromethane (60mL) was added to the reaction flask, and then the organic layer was washed with saturated aqueous sodium bicarbonate (20mL), saturated aqueous sodium chloride (20mL) and water (50mL) respectively. Water Na ₂ SO ₄ dried, filtered, the filtrate was concentrated, and the residue was chromatographed on a silica gel column under reduced pressure. The eluent was a mixed solvent of ethyl acetate and petroleum ether to obtain the compound of general formula (I). The specific compound is shown in the table 1.

Embodiment six: Activity to Plutella xylostella larvae

Dissolve a certain amount of the compound to be tested in an appropriate amount of N,N-dimethylformamide, make a 400mgL ^-1 liquid medicine with water containing TW-20, and dilute it to a specific concentration as required, cut fresh cabbage leaves Form into pieces, dip the cabbage leaves in the liquid to be tested for 3-5 seconds, and shake off the remaining liquid. After the medicinal solution is dry, put it into a marked 10cm long straight test tube, insert the 3rd instar diamondback moth larvae, and cover the tube mouth with gauze. The test treatment was placed in the standard treatment room, and the result of 72h inspection was to lightly touch the insect body with a needle, and those who did not move were considered dead, and repeated three times at each concentration. Calculate and adjust for mortality. Table 2 is the test results of some compounds.

Embodiment 7: Control vegetable disease living micro-screening test

Select 2 cucumber seedlings at the cotyledon stage, use spore suspension spray inoculation for cucumber brown spot, powdery mildew, and downy mildew, use bacterial suspension spray for cucumber bacterial angular spot disease, and tomato bacterial spot disease, and use bacterial suspension spray for cucumber wilt disease. The radicle seed soaking inoculation method, the rice sheath blight adopts the mycelia spray inoculation method. Spray the test agent and the control agent evenly on the cucumber cotyledons in the morning on a sunny day, inoculate the pathogenic bacteria 2 hours later, and moisturize and cultivate. After the onset of the control is sufficient, the disease condition is investigated according to the grading standard, and the disease index and control effect are calculated. Table 3 is the test results of some compounds.

Table 1 list of pyridylpyrazole amide derivatives (I) containing heptafluoroisopropyl

^a ThevalueofHRMS[M+Na] ⁺ .

Part of the compound of table 2 is to Plutella xylostella activity test result test result

Table 3 Results of in vivo micro-screening test of some compounds for controlling vegetable diseases (500mgkg ^-1 )

Claims (4)

1. the pyridyl pyrazoles amide derivatives containing seven fluorine sec.-propyls, is characterized in that it has structure shown in following general formula (I):

In formula, R ₁represent the alkyl of hydrogen, halogen, 1-6 carbon alkyl, the replacement of one or more identical or different halogen atoms; R ₂represent the alkyl of hydrogen, halogen, 1-6 carbon alkyl, the replacement of one or more identical or different halogen atoms; R ₃represent substituted or unsubstituted alkyl, thiazolinyl, alkynyl, cycloalkyl.

2. the pyridyl pyrazoles amide derivatives containing seven fluorine sec.-propyls according to claim 1, is characterized in that.R ₁for hydrogen, methyl, ethyl, sec.-propyl; R ₂for hydrogen, methyl, ethyl, sec.-propyl; R ₃for methyl, ethylisopropyl base, allyl group, propargyl, trifluoroethyl.

3. the application containing the pyridyl pyrazoles amide derivatives of seven fluorine sec.-propyls according to claim 1, is characterized in that it is as sterilant, can be used for preventing and treating lepidopteran class, Coleoptera class, Homoptera class, Diptera class and Orthoptera class pest.

4. the application containing the pyridyl pyrazoles amide derivatives of seven fluorine sec.-propyls according to claim 1, it is characterized in that it is as sterilant, can be used for preventing and treating Cucumber Target Leaf Spot, cucumber bacterial angular leaf spot, cucumber fusarium axysporum, cucumber downy mildew, powdery mildew of cucumber, bacterial spot of tomato, rice sheath blight disease.