CN116947679B - Bisamide compound containing sevoflurane isopropyl, and preparation method and application thereof - Google Patents

Abstract

The present invention provides a compound of general formula (I-V), which is used for preparing a heptafluoroisopropyl-containing bisamide compound. The heptafluoroisopropyl bisamide compound has excellent insecticidal activity as verified by experiments, especially has excellent high insecticidal activity against resistant populations, has no cross-resistance with the existing insecticide chlorantraniliprole, has good insecticidal effect at low doses and good rapidity; in addition, the preparation method of the heptafluoroisopropyl bisamide compound is simple, efficient and easy to industrialize, and has broad application prospects in the prevention and control of insect pests in the fields of agriculture, forestry and horticulture.

Description

Bisamide compound containing sevoflurane isopropyl, and preparation method and application thereof

The divisional application is a divisional application of Chinese patent application with application date 2022-12-07, application number CN 2022115602361 and invention name of "a bisamide compound containing sevoflurane isopropyl and preparation method and application thereof".

The invention requests two homeland priorities, namely a diamide compound with a priority number of CN 2021115835066 and a seven-fluorine isopropyl group and a preparation method and application thereof, and a diamide compound with a priority number of CN 2022111613460 and a preparation method and application thereof, which are respectively the patent application of the invention.

Technical Field

The invention belongs to the field of pesticides, and relates to a bisamide compound containing sevoflurane isopropyl, and a preparation method and application thereof.

Technical Field

The neonicotinoid insecticide represented by imidacloprid is an ultra-efficient insecticide, the global market is stabilized at over 20 hundred million dollars at present, but a large number of frequent use causes serious resistance, and the 'king pesticide' chlorantraniliprole (structural formula: CK 01) in the androstane insecticide market for more than ten years also has serious resistance problem in most regions of the world at present, and the dosage must be increased to have the original effect, thus causing a certain problem on agricultural production, environment and ecology.

The damage caused by pests and the like is still very remarkable, and the pests have resistance to the existing pesticides and are not friendly to the environment, so that new pesticides with better activity, lower dosage and more friendly environment are always required to be developed. The investment for pesticide creation is continuously increased by domestic and overseas scientific research institutions and enterprises, and a plurality of novel pesticides with high activity, low dosage and environmental friendliness are also produced.

The metadiamide pesticide Broflanilide (structural formula: CK 02) developed by the joint cooperation of Sanjing chemical company and Pasteur company in Japan is marketed, and has the Chinese name of bromofluorobenzene bisamide, which is mainly used for fruits and vegetables, beans, cotton, corn, grains, flowers and non-crop, has very good effect of preventing and controlling pests such as lepidoptera, coleoptera, termite, ant, cockroach, fly and the like, and is shown in Chinese patent CN102119173B, an amide derivative, a pest control agent containing the amide derivative and a use method thereof. However, the research of a plurality of domestic enterprises and research institutions shows that Broflanilide has poor quick-acting property and poor insecticidal effect under low dosage, and structure optimization and improvement are carried out on the basis, and a series of novel pesticides with high activity, low dosage and environmental friendliness are also found. See Chinese patent CN 109497062B for a meta-diamide compound, a preparation method and application thereof, and a representative (structural formula: CK 03), chinese patent CN 110194726B for a benzamide compound and application thereof, and a representative (structural formula: CK 04). So that more medication choices are provided in the production of crops such as agriculture, gardening and the like.

The research shows that the insecticidal effect on certain resistant pests still needs to be improved at low doses of the CK02, CK03 and CK04 structural compounds, and the CK03 and CK04 structural compounds have low total preparation yield and high process cost, and are not beneficial to industrial production and large-scale application although quick-acting performance is improved. There is still a need in the art to actively develop new pesticides with high insecticidal activity, no cross resistance and industrialization prospect at low dosage to meet the demands of agriculture and forest industry.

Disclosure of Invention

Aiming at the defects of the prior art, the invention aims to provide a bisamide compound containing heptafluoroisopropyl as well as a preparation method and application thereof, and a novel pesticide compound with no cross resistance with the existing pesticide, which has higher insecticidal activity and good quick-acting performance at low dosage, is favorable for ecological and environmental protection, and meets the demands of agriculture, forest industry and gardening fields.

To achieve the purpose, the invention adopts the following technical scheme.

Firstly, the invention provides a bisamide compound containing sevoflurane isopropyl, which has a structure shown in the following structural general formula (I):

wherein m is independently represented as an integer of 1 to 3, n is independently represented as an integer of 0 to 5;

The R ¹ substituents may be located at any substitutable position on the phenyl ring, and R ¹ is independently selected from H, fluoro, chloro, bromo, iodo, trifluoromethyl, methoxy, trifluoromethoxy, methyl, ethyl, methylsulfonyl, cyano or nitro;

when m is 2 or 3, the R ¹ substituents may be the same or different;

R ² is independently selected from C1-C5 alkyl or benzyl with optional substituents.

Preferably, n is independently represented as 1 or 2.

The insecticidal composition has the structure shown in the general formula (I), has very good insecticidal activity at low dosage, even reaches 90% -100% of insecticidal activity, has no interactive resistance with chlorantraniliprole, reduces the dosage of medicaments in practical application, reduces medicament residues in application, and is more beneficial to ecology and environmental protection.

In the general formula (I), when m=1, the heptafluoroisopropyl-containing bisamide compound has a structure shown in the following general formula (II):

Wherein R ¹ is independently selected from H, fluoro, chloro, bromo, iodo, trifluoromethyl, methoxy, trifluoromethoxy, methyl, ethyl, methanesulfonyl, cyano, or nitro;

R ² is independently selected from C1-C5 alkyl or benzyl optionally substituted;

n is independently 1 or 2.

In the invention, as another preferable technical scheme, in the general formula (II), when the position of the R ¹ substituent is determined, the heptafluoroisopropyl-containing bisamide compound has a structure shown in the following general formula (III):

Wherein R ¹ is independently selected from H, fluoro, chloro, bromo, iodo, trifluoromethyl, methoxy, trifluoromethoxy, methyl, ethyl, methanesulfonyl, cyano, or nitro;

R ² is independently selected from methyl, ethyl, n-propyl, isopropyl, n-butyl or isobutyl;

n is independently 1 or 2.

In the present invention, as a particularly preferred embodiment, in the structure represented by the general formula III, wherein R ¹ is independently selected from H, fluoro, trifluoromethyl, trifluoromethoxy, cyano or nitro;

r ² is independently selected from methyl, ethyl or n-propyl;

n is independently 1 or 2.

Wherein, when m=1, representative compounds and CK02 materialization indexes are shown in the following table:

List one

The specific chemical structural formula and chemical name are represented as follows:

2-fluoro-3- [ (phenylcarbonyl) (2-methoxyethyl) amino ] -N- [ 2-bromo-4- (1, 2, 3-heptafluoropropane-2-yl) -6- (trifluoromethyl) phenyl ] benzamide

2-Fluoro-3- [ (phenylcarbonyl) (2-ethoxyethyl) amino ] -N- [ 2-bromo-4- (1, 2, 3-heptafluoropropane-2-yl) -6- (trifluoromethyl) phenyl ] benzamide

2-Fluoro-3- { [ (4-fluorophenyl) carbonyl ] (2-methoxyethyl) amino } -N- [ 2-bromo-4- (1, 2, 3-heptafluoropropane-2-yl) -6- (trifluoromethyl) phenyl ] benzamide

2-Fluoro-3- { [ (4-fluorophenyl) carbonyl ] (2-ethoxyethyl) amino } -N- [ 2-bromo-4- (1, 2, 3-heptafluoropropane-2-yl) -6- (trifluoromethyl) phenyl ] benzamide

2-Fluoro-3- { [ (4-trifluoromethylphenyl) carbonyl ] (2-methoxyethyl) amino } -N- [ 2-bromo-4- (1, 2, 3-heptafluoropropane-2-yl) -6- (trifluoromethyl) phenyl ] benzamide

2-Fluoro-3- { [ (4-trifluoromethylphenyl) carbonyl ] (2-ethoxyethyl) amino } -N- [ 2-bromo-4- (1, 2, 3-heptafluoropropane-2-yl) -6- (trifluoromethyl) phenyl ] benzamide

2-Fluoro-3- { [ (4-cyanophenyl) carbonyl ] (2-methoxyethyl) amino } -N- [ 2-bromo-4- (1, 2, 3-heptafluoropropane-2-yl) -6- (trifluoromethyl) phenyl ] benzamide

2-Fluoro-3- { [ (4-cyanophenyl) carbonyl ] (2-ethoxyethyl) amino } -N- [ 2-bromo-4- (1, 2, 3-heptafluoropropane-2-yl) -6- (trifluoromethyl) phenyl ] benzamide

2-Fluoro-3- { [ (4-trifluoromethoxyphenyl) carbonyl ] (2-methoxyethyl) amino } -N- [ 2-bromo-4- (1, 2, 3-heptafluoropropane-2-yl) -6- (trifluoromethyl) phenyl ] benzamide

2-Fluoro-3- { [ (4-trifluoromethoxyphenyl) carbonyl ] (2-ethoxyethyl) amino } -N- [ 2-bromo-4- (1, 2, 3-heptafluoropropane-2-yl) -6- (trifluoromethyl) phenyl ] benzamide

2-Fluoro-3- [ (phenylcarbonyl) (3-methoxypropyl) amino ] -N- [ 2-bromo-4- (1, 2, 3-heptafluoropropane-2-yl) -6- (trifluoromethyl) phenyl ] benzamide

2-Fluoro-3- [ (phenylcarbonyl) (3-ethoxypropyl) amino ] -N- [ 2-bromo-4- (1, 2, 3-heptafluoropropane-2-yl) -6- (trifluoromethyl) phenyl ] benzamide

2-Fluoro-3- [ (4-fluorophenylcarbonyl) (3-methoxypropyl) amino ] -N- [ 2-bromo-4- (1, 2, 3-heptafluoropropane-2-yl) -6- (trifluoromethyl) phenyl ] benzamide

2-Fluoro-3- [ (4-fluorophenylcarbonyl) (3-ethoxypropyl) amino ] -N- [ 2-bromo-4- (1, 2, 3-heptafluoropropane-2-yl) -6- (trifluoromethyl) phenyl ] benzamide

2-Fluoro-3- { [ (4-trifluoromethylphenyl) carbonyl ] (3-methoxypropyl) amino } -N- [ 2-bromo-4- (1, 2, 3-heptafluoropropane-2-yl) -6- (trifluoromethyl) phenyl ] benzamide

2-Fluoro-3- { [ (4-trifluoromethylphenyl) carbonyl ] (3-ethoxypropyl) amino } -N- [ 2-bromo-4- (1, 2, 3-heptafluoropropane-2-yl) -6- (trifluoromethyl) phenyl ] benzamide

The compounds of the general formula (I) according to the invention can be prepared by the following processes, where the radicals in the formulae are as defined above, unless otherwise indicated. The raw materials and reagents used in the present invention are generally commercially available in the form of industrial products unless otherwise specified. In order to realize the preparation method of the compound of the general formula (I), a synthetic route is designed, and the preparation method of the compound of the general formula (I) is realized through the following preparation method processes of the first step and the second step.

Step one, synthesizing an intermediate compound of the following general formula (I-V):

the preparation method is realized by the following two preparation methods:

the preparation method I-A is that the intermediate compound of the general formula (I-V) is synthesized by the steps of acyl chlorination reaction, amidation reaction, N-alkylation reaction, hydrolysis reaction and the like of the serial raw materials of the general formula (I-I). The preparation method has the following reaction formula:

Preparation method I-A

The intermediate compound of the general formula (I-V) can also be synthesized by adopting the preparation method I-B, namely, the steps of carrying out N-alkylation reaction on a 3-amino-2-fluorobenzoic acid methyl ester raw material, carrying out amidation reaction and hydrolysis reaction on the 3-amino-2-fluorobenzoic acid methyl ester raw material and a benzoyl chloride general formula (I-II) raw material. The preparation method has the following reaction formula:

Preparation method I-B

The benzoic acid general formula (I-I) series raw materials and the 3-amino-2-fluorobenzoic acid methyl ester raw materials related in the preparation method I-A, I-B are known compounds, are medical and pesticide intermediates, and can be directly purchased in the market. Chinese patent CN111320548a also discloses another method for the synthetic preparation of methyl 3-amino-2-fluorobenzoate. Other esters of methyl 3-amino-2-fluorobenzoate such as ethyl 3-amino-2-fluorobenzoate, n-butyl 3-amino-2-fluorobenzoate, isobutyl 3-amino-2-fluorobenzoate and the like are generally suitable for use in the preparation process of the present invention, and preferably the starting material of methyl 3-amino-2-fluorobenzoate is used.

The acylating agent is thionyl chloride, sulfuryl chloride, oxalyl chloride, methanesulfonyl chloride, benzoyl chloride, phosphorus trichloride, phosphorus pentachloride, phosphorus oxychloride or triphosgene, etc., preferably thionyl chloride, the molar amount is 1.0-10.0 times of that of the benzoic acid general formula (I-I) series raw material, the preferred economic amount is 1.0-3.0 times, the solvent adopted in the acylating chlorination reaction is dichloromethane, chloroform, dichloroethane, toluene or xylene, etc., the preferred solvent is dichloroethane or toluene, etc., the acylating chlorination reaction temperature is generally 20-150 ℃, the preferred reaction temperature is 40-100 ℃, and the acylating chlorination reaction time is generally 1-5 hours, preferably 2-3 hours.

The Friedel-crafts used in amidation reaction related in the preparation method I-A, I-B is triethylamine, pyridine, N-diisopropylethylamine, N-dimethylaniline, tetramethyl ethylenediamine, sodium bicarbonate, sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium methoxide, potassium methoxide, sodium tert-butoxide or potassium tert-butoxide and the like, preferably triethylamine or pyridine is adopted, the molar dosage is 1.0-5.0 times of that of the benzoyl chloride general formula (I-II) series raw materials, and the preferred economic dosage is 1.0-2.0 times; the amidation reaction is carried out by using dichloromethane, chloroform, dichloroethane, tetrahydrofuran, dioxane, dimethyl sulfoxide, acetonitrile, toluene, xylene, N-dimethylformamide, N-dimethylacetamide, N-methylpyrrolidone or 1, 3-dimethyl-2-imidazolidinone, etc., preferably using dichloroethane, toluene, acetonitrile, N-dimethylformamide or 1, 3-dimethyl-2-imidazolidinone, etc., in an amount of 1-20 times, preferably 2-5 times, the weight of the benzoyl chloride series raw material of the general formula (I-II), the amidation reaction temperature is generally-5-150 ℃, preferably 0-50 ℃, and the reaction time is generally 1-4 hours, preferably 2-3 hours.

The general formula of the alkylating agent used for the N-alkylation reaction involved in the preparation method I-A, I-B is:

wherein X is halogen, preferably bromine or iodine;

n is independently an integer from 0 to 5, preferably 1 or 2.

R ² is independently C1-C5 alkyl or benzyl optionally substituted, preferably methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, benzyl, p-chlorobenzyl, p-bromobenzyl, p-fluorobenzyl, etc.

The N-alkylating reagent adopted by the invention is generally a known compound, is a medical and pesticide intermediate, is conventionally such as bromomethyl ether, bromomethyl ethyl ether, 1-bromo-2-methoxyethane, 1-bromo-2-ethoxyethane, 1-bromo-3-methoxypropane, 1-bromo-3-ethoxypropane, 1-bromo-2-N-propoxyethane and the like, and can be directly purchased in the market or realized through synthesis. The synthesis of N-alkylating reagent is described in detail in reference, wang Yan et al, J.1-bromo-1-ethoxypropane, J.3.A.of Chinese medical industry, 2004,35 (4), 203-204; chen Fener et al, J.A.3.A.1-bromo-alkoxypropane synthesis method, J.A.3.A.of Chinese medical industry, 1995,26 (2), 88-89; U.S. Pat. No. 3,34, related examples. The molar amount of the N-alkylating agent is 1.0-5.0 times that of the raw material of the general formula (I-III) or 3-amino-2-fluorobenzoic acid methyl ester, and the preferable amount is 1.0-2.0 times; the N-alkylating reagent is added into the reaction system generally in a dropwise manner or in a one-time or multi-time manner, preferably in a dropwise manner; the solvent used in the N-alkylation reaction is N, N-dimethylformamide, N-dimethylacetamide, N-methylpyrrolidone, 1, 3-dimethyl-2-imidazolidinone, dimethylsulfoxide, acetonitrile, toluene, xylene, tetrahydrofuran, dioxane, acetone or the like, preferably N, N-dimethylformamide, N-dimethylacetamide or acetonitrile or the like is used in an amount of 1.0 to 20.0 times, preferably in an amount of 2 to 10 times, the amount of the raw material of the general formula (I-III) or the raw material of the 3-amino-2-fluorobenzoic acid methyl ester is preferably in an amount of 1.0 to 20.0 times, the alkali used in the N-alkylation reaction is pyridine, N-diisopropylethylamine, N-dimethylaniline, sodium bicarbonate, sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium methoxide, potassium methoxide, tertiary sodium butoxide, sodium hydride, sodium amide or lithium diisopropylamide or the like, preferably sodium carbonate, potassium carbonate or sodium hydride is used in an amount of the molar amount of the raw material of the general formula (I-III) or the raw material of 3-amino-2-fluorobenzoic acid methyl ester is preferably in an amount of 1.0 to 0.0 to 5 ℃ to 200.0 times, the temperature of the raw material of the N-2-fluorobenzoic acid methyl ester is preferably in an amount of 1 to 0, the reaction temperature is preferably 20 to 100℃and the N-alkylation reaction time is generally 2 to 12 hours, preferably 2 to 10 hours.

In the first step, the total yield of the preparation method I-A and the preparation method I-B is obviously higher than that of the preparation method I-B, and the preparation method I-A is preferably selected.

The synthesis of the compounds of the general formula (I) can also be achieved by the following two preparation methods.

The preparation method is that the intermediate compound of the general formula (I-V) is subjected to an acyl chlorination reaction and then is subjected to an amidation reaction and a bromination reaction with a raw material of 4- (1, 2, 3-heptafluoropropane-2-yl) -2- (trifluoromethyl) aniline to synthesize the compound of the general formula (I). The preparation method comprises the following steps:

Preparation method II-A

Another preparation method can also be adopted:

The intermediate compound of the general formula (I-V) is directly amidated with 2-bromo-4- (1, 2, 3-heptafluoropropane-2-yl) -6- (trifluoromethyl) aniline raw material to directly synthesize the compound of the general formula (I) after acyl chlorination reaction. The preparation method comprises the following steps:

preparation method II-B

The acylating agent is usually thionyl chloride, sulfuryl chloride, oxalyl chloride, methanesulfonyl chloride, benzoyl chloride, phosphorus trichloride, phosphorus pentachloride, phosphorus oxychloride or triphosgene, etc., preferably thionyl chloride, the molar amount is 1.0-10.0 times, preferably 1.0-3.0 times of the molar amount of the raw material of the general formula (I-V), the solvent used for the acyl chlorination is dichloromethane, chloroform, dichloroethane, acetonitrile, toluene or xylene, etc., preferably the solvent is dichloroethane, toluene, etc., the acyl chlorination temperature is generally 20-150 ℃, preferably the reaction temperature is 40-100 ℃, and the acyl chlorination time is generally 1-5 hours, preferably 2-3 hours.

This procedure gives the starting material 4- (1, 2, 3-heptafluoropropane-2-yl) -2- (trifluoromethyl) aniline and this fraction involved in process II-A a preparation method of raw material 2-bromo-4- (1, 2, 3-heptafluoropropane-2-yl) -6- (trifluoromethyl) aniline in preparation method II-B, the preparation process is detailed in examples 1,1-2 of Chinese patent CN102119143B, which is also widely reported in foreign journals and is not described in detail herein. They are generally used in molar amounts of from 1.0 to 2.0 times, preferably from 1.0 to 1.5 times, the starting materials of the general formulae (I-VII).

The amidation reaction solvent involved in the production method II-A and the production method II-B in this step is N, N-dimethylformamide, N-dimethylacetamide, N-methylpyrrolidone, 1, 3-dimethyl-2-imidazolidinone, dimethylsulfoxide, acetonitrile, dichloroethane, toluene, xylene, tetrahydrofuran, dioxane or acetone, etc., preferably N, N-dimethylformamide, N-methylpyrrolidone, 1, 3-dimethyl-2-imidazolidinone, acetonitrile or toluene, etc. The amount of the alkali used in the amidation reaction in the preparation method II-B in the step is 1.0 to 20.0 times, preferably 2 to 10 times, the amount of the alkali used in the amidation reaction in the preparation method II-B in the step is 1.0 to 5.0 times, preferably 1.0 to 1.5 times, the amount of the alkali used in the amidation reaction in the preparation method II-B in the general formula (I-VII) is preferably tetramethyl ethylenediamine, sodium methoxide, potassium methoxide, sodium hydride, lithium diisopropylamide and the like;

The amidation reaction temperatures involved in the preparation of process II-A and in the preparation of process II-B are from-20 to 200℃and preferably from 20 to 150℃and the reaction times are from 2 to 20 hours and preferably from 5 to 10 hours.

The bromination reaction involved in the preparation method II-A in this step is carried out by using N-bromosuccinimide, dibromohydantoin, phosphorus tribromide, phosphorus pentabromide, phosphorus tribromide or liquid bromine, etc., preferably N-bromosuccinimide or dibromohydantoin, etc. The molar amount of the brominating reagent is 1.0 to 5.0 times, preferably 1.0 to 1.5 times, the molar amount of the raw material of the general formula (I-VIII), the alkali for brominating reaction is sodium bicarbonate, sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium methoxide, potassium methoxide, sodium tert-butoxide, potassium tert-butoxide, sodium hydride, sodium amide, lithium diisopropylamide and the like, preferably sodium carbonate, potassium carbonate or sodium hydride, the molar amount of the alkali is 1.0 to 5.0 times, preferably 1.0 to 1.5 times, the molar amount of the raw material of the general formula (I-VIII) is preferably 1.0 to 5.0 times, the molar amount of the solvent for brominating reaction is N, N-dimethylformamide, N-dimethylacetamide, N-methylpyrrolidone, 1, 3-dimethyl-2-imidazolidinone, dimethyl sulfoxide, acetonitrile, toluene, xylene, tetrahydrofuran, dioxane or acetone and the like, preferably N, N-dimethylformamide, N-dimethylpyrrolidone, 1, 3-dimethylpyrrolidone, 1.2-dimethylpyrrolidone, 2-dimethylimidazolidinone and the like, the molar amount of the solvent for brominating reaction is preferably 1.0 to 5.0 times, the molar amount of the raw material of the general formula (I-VIII) is preferably 1.0 to 5 times, preferably 1.5 times, the reaction time is preferably 2 times, the reaction time is 20 times, when the raw material of the raw material is 100.0 to 100 DEG, and the raw material is preferably 2 times.

In the second step, the total yield of the preparation method II-A and the preparation method II-B is obviously higher than that of the preparation method II-B, and the preparation method II-A is preferably selected.

In the present invention, the operations of distillation, reduced pressure distillation, filtration, drying, extraction, delamination, etc., involved in the operation of the production process are conventional operations, and basic operations of general chemical professionals are not described in detail herein, and synthetic examples are described in detail.

On one hand, the compound with the general formula (I) containing the heptafluoroisopropyl, which is obtained through molecular structure optimization, has excellent insecticidal activity, particularly has excellent high insecticidal activity on resistant populations, has no cross resistance with the conventional pesticide chlorantraniliprole, has good insecticidal effect and good quick-acting property at low dosage, and on the other hand, the compound with the general formula (I) has the advantages of simple and efficient preparation method, easy industrial production and wide application prospect in the fields of agriculture, forestry and gardening for insect pest prevention.

In the present invention, the pests include lepidoptera, coleoptera, hemiptera, thysanoptera, diptera, orthoptera, homoptera, isoptera, hymenoptera, tetranychus pests and nematodes, mosquitoes, flies, ants, and the like.

The compound has wide application range, and the applied plants or ranges mainly comprise vegetables such as cucumber, luffa, watermelon, melon, pumpkin, melon, spinach, celery, cabbage, gourd, pepper, eggplant, tomato, shallot, ginger, garlic, leek, lettuce, beans, iridescent bean, broad bean, radish, carrot, potato and yam, cereals such as wheat, barley, corn, rice and sorghum, fruit trees such as apple, pear, banana, citrus, grape, litchi and mango, flowers, peony, china rose and crane, oil crops such as peanut, soybean, rape, sunflower and sesame, sugar crops such as beet and sugarcane, and other crops such as strawberry, potato, sweet potato, tobacco and tea. It can also be used in gardening, forestry, household sanitation, public sanitation area, etc. The above-listed plants or ranges have no limitation on the range of use of the sevoflurane-isopropyl-containing bisamides of the present invention.

In one aspect, the compounds of the invention may be used in formulations comprising an agropharmaceutically acceptable carrier, including a solid carrier or a liquid carrier. The compound of the formula (I) containing heptafluoroisopropyl as an active component is dissolved or dispersed in a carrier or prepared into a preparation. The preparation can be made into powder, wettable powder, soluble powder, granule, water dispersible granule, suspension, microemulsion, emulsion, water emulsion or emulsion, etc.

In another aspect, the use of the present invention also provides an insecticide composition. The compound of the general formula (I) containing the sevoflurane isopropyl has no cross resistance with the existing pesticide chlorantraniliprole, can be mixed with the existing pesticide, can improve the use effect of the existing pesticide due to the resistance problem, expands the insecticidal spectrum, and other mixed active ingredients can be one or more of common varieties such as chlorantraniliprole, abamectin, imidacloprid, pymetrozine, fipronil, dinotefuran, molluscacide amine, cartap, thiamethoxam and the like, preferably amide pesticide varieties are used, the pesticide composition comprises an active ingredient and a carrier acceptable in agropharmacy, the active ingredient is at least one active ingredient in the compound of the general formula (I) containing the sevoflurane isopropyl, and the mixing percentage ratio of other active ingredients is 0.1-99.9%.

Detailed Description

The technical solution of the present invention will be further described by the following specific embodiments, and it should be apparent to those skilled in the art that the examples are only for aiding in understanding the present invention and should not be construed as limiting the present invention in any way.

The raw materials described in the synthetic examples of the present invention are not specifically described, but are generally obtained by market purchase, and generally have a content specification of 95% or more, the content is not precisely corrected, the percentage concentration described in the synthetic examples is not specifically described, but generally refer to the weight percentage concentration, the HPLC content data is the area normalization content, the yield is the molar yield, and the yield data is also not precisely corrected.

Synthesis example 1 (preparation method of I-A and II-A)

Synthetic preparation of 2-fluoro-3- [ (phenylcarbonyl) (2-methoxyethyl) amino ] -N- [ 2-bromo-4- (1, 2, 3-heptafluoropropane-2-yl) -6- (trifluoromethyl) phenyl ] benzamide (structural formula SYN 001).

Step one:

100g of dichloroethane, 25g (0.20 mol) of benzoic acid, 72g (0.60 mol) of thionyl chloride and the like are put into a four-port glass reaction bottle of 250ml, reflux reaction is carried out for 3-5 hours under heating, the temperature is reduced to room temperature, the reaction solution is transferred into a 500ml rotary evaporator, the pressure is reduced to 80 ℃, benzoyl chloride oily liquid is obtained, the temperature is reduced to about 25 ℃, and 25g of new dichloroethane is added for dissolving for standby.

In another 250ml four-port glass reaction flask, 100g of dichloroethane, 35g (0.20 mol) of methyl 3-amino-2-fluorobenzoate, 24g (0.30 mol) of pyridine, cooling to 5-25 ℃ in an ice bath, dropwise adding the benzoyl chloride standby liquid within 1 hour, reacting for 1-2 hours at 5-25 ℃, adding 50ml of water, stirring for 0.5 hour, layering to obtain a solvent layer, transferring to a 500ml rotary evaporator, decompressing and desolventizing to 80 ℃ to obtain 53g of methyl 2-fluoro-3- [ (phenylcarbonyl) amino ] benzoate as a white solid, and carrying out HPLC (high performance liquid chromatography) with a normalized content of 94% (yield 91.2%) for standby, and directly using the mixture for the next reaction without further treatment. The reaction formula is as follows:

In another 250ml four-port glass reaction flask, 200g of N, N-dimethylformamide, 15g (0.10 mol) of potassium carbonate are put into the four-port glass reaction flask, 25g (0.086 mol) of methyl 2-fluoro-3- [ (phenylcarbonyl) amino ] benzoate obtained by the synthesis is put into the four-port glass reaction flask, the temperature is raised to 45-55 ℃, 15.8g (0.11 mol) of 1-bromo-2-methoxyethane is dripped in 1 hour, the temperature is kept for 5 hours, water is cooled to room temperature, the reaction solution is poured into 500ml of ice water for precipitation, 150g of dichloromethane is extracted and layered, the dichloromethane layer is obtained, the dichloromethane layer is transferred into a rotary evaporator for decompression and desolventization to 80 ℃ to obtain oily liquid, 50g of methanol is added, 60g (0.15 mol) of 10% liquid alkali is heated to 25-35 ℃, the temperature is kept for 2 hours, 50g of water is added, the pH is adjusted to 1-2% of 30% hydrochloric acid, 150g of dichloromethane is added for extraction and layering, the dichloromethane layer is transferred into the rotary evaporator for decompression and desolventization to 80 ℃ to obtain light brown liquid, the crystalline liquid (2.82% of phenylcarbonyl) after one-2.82% of fluorine is cooled down to 2% (2.82 mol). The reaction formula is as follows:

step two, synthesis of SYN001 Compound

Into a 250ml four-port glass reaction flask, 200g of dichloroethane, 25g (0.071 mol) of 2-fluoro-3- [ (2-methoxyethyl) (phenylcarbonyl) amino ] benzoic acid synthesized above, 24g (0.20 mol) of thionyl chloride, heating and refluxing for 3-5 hours, cooling to room temperature, transferring the reaction solution to a 500ml rotary evaporator, desolventizing under reduced pressure to 80 ℃ to obtain an acid chloride oily liquid, cooling to about 25 ℃, adding 150g of acetonitrile for dissolution, transferring to the reaction flask, and adding 27.8g (0.08 mol) of 4- (1, 2, 3-heptafluoropropane-2-yl) -2- (trifluoromethyl) aniline raw material, and heating and refluxing for 5-10 hours. Cooling to room temperature, pouring into 300ml ice water to precipitate, extracting 200g dichloroethane, washing with 50ml water for layering to obtain a dichloroethane layer, drying and filtering with anhydrous magnesium sulfate, decompressing and desolventizing to 80 ℃ to obtain oily intermediate of 2-fluoro-3- [ (phenylcarbonyl) (2-methoxyethyl) amino ] -N- [4- (1, 2, 3-heptafluoropropane-2-yl) -6- (trifluoromethyl) phenyl ] benzamide, adding 250g of N, N-dimethylformamide for dissolution, transferring the reaction solution into a 500ml reaction bottle, cooling to 0-25 ℃, adding 18g (0.1 mol) of N-bromosuccinimide, and reacting for 5-10 hours under heat preservation. Pouring into 500ml ice water to separate out, extracting 200g of dichloromethane, washing 50ml of water to separate the dichloromethane layer, decompressing and dissolving to 80 ℃ to obtain 54g of crude product of oily 2-fluoro-3- [ (phenylcarbonyl) (2-methoxyethyl) amino ] -N- [ 2-bromo-4- (1, 2, 3-heptafluoropropane-2-yl) -6- (trifluoromethyl) phenyl ] benzamide (namely a structural formula SYN 001), and obtaining the HPLC normalized content of 85%, wherein the three-step reaction yield is 91.4 percent based on 2-fluoro-3- [ (2-methoxyethyl) (phenylcarbonyl) amino ] benzoic acid. The reaction formula is as follows:

54g of crude compound is recrystallized by using 150g of normal hexane and 50g of ethyl acetate mixed solvent at 0-5 ℃ to obtain 40g of white crystal dry product, wherein the normalized content of HPLC is 96%, the melting point is 179.5-180.5, the crystallization yield is 83.6%, and the total yield after the step two is 76.5%.

The nuclear magnetism and mass spectrum data are as follows:

nuclear magnetic hydrogen spectra were measured using Bruker AV-400spectrometer (400 MHz), TMS as an internal standard, DMSO-d6 (same below) as the solvent, and UHR-TOF maXis (ESI) mass spectrometer as the high resolution mass spectrum (same below).

¹H-NMR(400MHz,DMSO-d6)δ(ppm):10.57(s,1H,CONH),8.39(s,1H),7.92(s,1H),7.61-7.51(m,3H),7.34-7.24(m,5H),4.32-3.70(m,2H),3.68-3.45(m,2H),3.19(s,3H).HRMS(ESI)calcd.for C₂₇H₁₈BrF₁₁N₂NaO₃[(M+Na)⁺]:729.0223[(M+Na)⁺],731.0202[(M+2+Na)⁺];Found:729.0213[(M+Na)⁺],731.0196[(M+2+Na)⁺].

Synthesis example 2 (preparation method of I-A and II-B)

Synthetic preparation of 2-fluoro-3- [ (phenylcarbonyl) (2-methoxyethyl) amino ] -N- [ 2-bromo-4- (1, 2, 3-heptafluoropropane-2-yl) -6- (trifluoromethyl) phenyl ] benzamide (structural formula SYN 001).

Step one 2-fluoro-3- [ (2-methoxyethyl) (phenylcarbonyl) amino ] benzoic acid (0.071 mol), the synthesis charge and the procedure were the same as in step one of synthesis example 1.

Step two, synthesis of SYN001 Compound

Into a 250ml four-port glass reaction flask, 200g of dichloroethane, 25g (0.071 mol) of 2-fluoro-3- [ (2-methoxyethyl) (phenylcarbonyl) amino ] benzoic acid obtained by the synthesis in the step one of example 1 above, 24g (0.20 mol) of thionyl chloride, heating and refluxing for 3-5 hours, cooling to room temperature, transferring the reaction solution to a 500ml rotary evaporator, desolventizing under reduced pressure to 80℃to obtain an acid chloride oily liquid, cooling to about 25℃and adding 150g of N, N-dimethylformamide for dissolution, transferring to the reaction flask and adding 35g (0.08 mol) of 2-bromo-4- (1, 2, 3-heptafluoropropane-2-yl) -6- (trifluoromethyl) aniline raw material, adding 5.8g (0.08 mol) of potassium methoxide, heating to 55-65 ℃ for reaction for 5-10 hours, cooling to room temperature, pouring into 500ml of ice water for precipitation, extracting 200g of dichloromethane, washing and layering with 50ml of water to obtain a dichloromethane layer, decompressing and desolventizing to 80 ℃ to obtain oily 2-fluoro-3- [ (phenylcarbonyl) (2-methoxyethyl) amino ] -N- [ 2-bromo-4- (1, 2, 3-heptafluoropropane-2-yl) -6- (trifluoromethyl) phenyl ] benzamide (namely 55g of crude compound with structural formula SYN 001) and HPLC normalized content of 56%, this step had a total of 61.3% yield of 2-fluoro-3- [ (2-methoxyethyl) (phenylcarbonyl) amino ] benzoic acid. The reaction formula is as follows:

55g of crude compound is recrystallized from 150g of normal hexane and 50g of ethyl acetate in a mixed solvent at 0-5 ℃ to obtain 15g of beige crystal dry product, wherein the content of HPLC normalized to 92%, the crystallization yield is 44.8%, and the total yield after the second crystallization is 27.5%.

Synthesis example 3 (preparation method of I-B and II-A)

Synthetic preparation of 2-fluoro-3- [ (phenylcarbonyl) (2-methoxyethyl) amino ] -N- [ 2-bromo-4- (1, 2, 3-heptafluoropropane-2-yl) -6- (trifluoromethyl) phenyl ] benzamide (structural formula SYN 001).

Step one:

100g of dichloroethane, 25g (0.20 mol) of benzoic acid, 72g (0.6 mol) of thionyl chloride and the like are put into a four-port glass reaction bottle of 250ml, reflux reaction is carried out for 3-5 hours under heating, the temperature is reduced to room temperature, the reaction solution is transferred into a 500ml rotary evaporator, the pressure is reduced to 80 ℃, benzoyl chloride oily liquid is obtained, the temperature is reduced to about 25 ℃, and 25g of new dichloroethane is added for dissolving for standby.

Into another 250ml four-port glass reaction bottle, 200g of N, N-dimethylformamide is added, 35g (0.20 mol) of 3-amino-2-fluorobenzoic acid methyl ester is added, the temperature is reduced by 10 to 25 ℃, under the protection of nitrogen, 8g (0.2 mol) of 60 percent sodium hydride is added in portions, the temperature is controlled by 15 to 25 ℃,30 g (0.21 mol) of 1-bromo-2-methoxyethane is dripped in 1 hour, and the temperature is raised by 45 to 55 ℃ for reaction for 5 hours. Cooling water to room temperature, pouring the reaction solution into 500ml ice water to separate out 150g dichloroethane, extracting, layering to obtain a dichloroethane layer, drying with anhydrous magnesium sulfate, filtering to obtain a dichloroethane layer, transferring to a 500ml four-port glass reaction bottle, adding 24g (0.30 mol) of pyridine, cooling to 5-25 ℃ in an ice bath, dripping the benzoyl chloride standby liquid in the previous step within 1 hour, reacting for 1-2 hours at 5-25 ℃, adding 50ml of water, stirring for 0.5 hour, layering to obtain a solvent layer, transferring to a 500ml rotary evaporator, decompressing and desolventizing to 80 ℃ to obtain an oily liquid, adding 100g of methanol, 12g (0.30 mol) of 10% caustic soda liquid, heating to 25-35 ℃, preserving the reaction for 2 hours, adding 100g of water, adjusting pH to 1-2 with 30% hydrochloric acid, adding 300g of dichloromethane, extracting, layering to obtain a dichloromethane layer, decompressing and desolventizing to 80 ℃ in the rotary evaporator to obtain an oily liquid 44g, cooling, and removing 80% of the oily liquid (80% of benzoic acid is calculated as 2-3-4% fluorine-ethyl phenylformic acid) in the following steps of a rotary evaporator, and directly treating the benzoic acid (the benzoic acid) for 2-fluorine-carbonyl) without using the following steps. The reaction formula is as follows:

step two, synthesis of SYN001 Compound

Into a 250ml four-port glass reaction flask, 200g of dichloroethane, 28g (0.071 mol) of 2-fluoro-3- [ (2-methoxyethyl) (phenylcarbonyl) amino ] benzoic acid synthesized above, 24g (0.20 mol) of thionyl chloride, heating and refluxing for 3-5 hours, cooling to room temperature, transferring the reaction solution to a 500ml rotary evaporator, decompressing and desolventizing to 80 ℃ to obtain an acid chloride oily liquid, cooling to about 25 ℃, adding 150g of acetonitrile for dissolution, transferring to the reaction flask, and adding 27.8g (0.08 mol) of 4- (1, 2, 3-heptafluoropropane-2-yl) -2- (trifluoromethyl) aniline raw material, and heating and refluxing for 5-10 hours. Cooling to room temperature, pouring into 300ml ice water to precipitate, extracting 200g dichloroethane, washing with 50ml water for layering to obtain a dichloroethane layer, drying and filtering with anhydrous magnesium sulfate, decompressing and desolventizing to 80 ℃ to obtain oily intermediate of 2-fluoro-3- [ (phenylcarbonyl) (2-methoxyethyl) amino ] -N- [4- (1, 2, 3-heptafluoropropane-2-yl) -6- (trifluoromethyl) phenyl ] benzamide, adding 250g of N, N-dimethylformamide for dissolution, transferring the reaction solution into a 500ml reaction bottle, cooling to 0-25 ℃, adding 18g (0.10 mol) of N-bromosuccinimide, and reacting for 5-10 hours under heat preservation. Pouring into 500ml ice water to separate out, extracting 200g of dichloromethane, washing 50ml of water to separate the dichloromethane layer, decompressing and dissolving to 80 ℃ to obtain 58g of crude product of 2-fluoro-3- [ (phenylcarbonyl) (2-methoxyethyl) amino ] -N- [ 2-bromo-4- (1, 2, 3-heptafluoropropane-2-yl) -6- (trifluoromethyl) phenyl ] benzamide (namely structural formula SYN 001), and obtaining the product with the HPLC normalized content of 78 percent, wherein the three-step reaction yield is 90.0 percent based on 2-fluoro-3- [ (2-methoxyethyl) (phenylcarbonyl) amino ] benzoic acid. The reaction formula is as follows:

58g of the crude compound with the HPLC normalization content of 78% is recrystallized by using 150g of normal hexane and 50g of ethyl acetate mixed solvent at 0-5 ℃ to obtain 35g of white crystal dry product, the HPLC normalization content of 96%, the melting point of 179.5-180.5, the single-step crystallization yield of 77.4% and the yield of 69.7% after the second crystallization. The total yield after crystallization in the step one and the step two is 38.6 percent.

Synthesis example 4 (preparation method of I-A and II-A)

Preparation of 2-fluoro-3- [ (phenylcarbonyl) (2-ethoxyethyl) amino ] -N- [ 2-bromo-4- (1, 2, 3-heptafluoropropane-2-yl) -6- (trifluoromethyl) phenyl ] benzamide. (structural formula SYN002 as follows)

Step one:

A similar procedure and feed ratio were followed in step one of Synthesis example 1, wherein 15.8g (0.11 mol) of 1-bromo-2-methoxyethane for N-alkylation was replaced with 17.5g (0.11 mol) of 1-bromo-2-ethoxyethane, with no change in the other conditions.

26G of cold-cured light brown crystals were obtained, the HPLC normalized content being 90%, as 2-fluoro-3- [ (2-ethoxyethyl) (phenylcarbonyl) amino ] benzoic acid (0.070 mol) for use without treatment, directly in the next reaction. The reaction formula is as follows:

Step two, synthesis of SYN002 Compound

The material obtained in step one, (0.070 mol) was used for the synthesis in step two, and the procedure was the same as in step two of synthesis example 1.

Finally, 54.3g of crude 2-fluoro-3- [ (phenylcarbonyl) (2-ethoxyethyl) amino ] -N- [ 2-bromo-4- (1, 2, 3-heptafluoropropane-2-yl) -6- (trifluoromethyl) phenyl ] benzamide (i.e. of formula SYN 002) are obtained as an oily crude product, HPLC-normalized content 86%, the three-step reaction yield of this step being 92.4% in terms of 2-fluoro-3- [ (2-ethoxyethyl) (phenylcarbonyl) amino ] benzoic acid. The reaction formula is as follows:

54.3g of crude compound is recrystallized from 150g of normal hexane and 50g of ethyl acetate in a mixed solvent at 0-5 ℃ to obtain 41g of white crystal, wherein the content of HPLC normalized is 96%, the melting point is 157.1-157.9, the crystallization yield is 84.2%, and the total yield after the crystallization in the second step is 77.8%.

The nuclear magnetism and mass spectrum data are as follows:

¹H-NMR(400MHz,DMSO-d6)δ(ppm):10.54(s,1H,CONH),8.39(s,1H),7.92(s,1H),7.63-7.30(m,3H),7.29-7.10(m,5H),4.08-3.45(m,4H),3.44-3.32(m,2H),1.01(t,J＝6.8Hz,3H).HRMS(ESI)calcd.for C₂₈H₂₀BrF₁₁N₂NaO₃[(M+Na)⁺]:743.0379[(M+Na)⁺],745.0359[(M+2+Na)⁺];Found:743.0370[(M+Na)⁺],745.0355[(M+2+Na)⁺].

Synthesis example 5

The procedure is analogous to procedure one of synthetic example 4.

The resulting cold-postcured light brown crystals 26g, HPLC normalized to 90%, were 2-fluoro-3- [ (2-ethoxyethyl) (phenylcarbonyl) amino ] benzoic acid (0.070 mol).

Then, 100g of normal hexane plus 20g of ethyl acetate are used for recrystallization at about 0-25 ℃ to obtain 20g of white crystal dry product. HPLC content 98%. Melting point of 129.5-130.2 ℃, and the structural formula is as follows:

The nuclear magnetism and mass spectrum data are as follows:

¹H-NMR(400MHz,DMSO-d6)δ(ppm):13.27(s,1H,CO2H),7.72-7.55(m,2H),7.35-7.05(m,6H),4.20-3.80(m,2H),3.65-3.45(m,2H),3.32-3.27(m,2H),0.94(t,J＝6.8Hz,3H,CH3).

HRMS(ESI)calcd.for C₁₈H₁₈FNNaO₄[(M+Na)⁺]:354.1118;Found:354.1115。

Synthesis example 6

Synthesis of 2-fluoro-3- [ (phenylcarbonyl) (3-methoxypropyl) amino ] -N- [ 2-bromo-4- (1, 2, 3-heptafluoropropane-2-yl) -6- (trifluoromethyl) phenyl ] benzamide has the following structural formula SYN011.

Step one the procedure and feed ratio were similar to those of step one of Synthesis example 1, except that 15.8g (0.11 mol) of N-alkylated 1-bromo-2-methoxyethane was replaced with 17.5g (0.11 mol) of 1-bromo-3-methoxypropane, and the other conditions were not changed. The yield and content data of the obtained 2-fluoro-3- [ (3-methoxypropyl) (phenylcarbonyl) amino ] benzoic acid are similar.

Step two, according to the similar operation and feeding proportion of the step two of the synthesis example 1, the structure is to obtain a white crystal dry product of the target compound SYN011, the HPLC normalized content is 96 percent, the melting point is 143.1-144.5 ℃, and the obtained yield data are similar.

The nuclear magnetism and mass spectrum data are as follows:

¹H-NMR(400MHz,DMSO-d6)δ(ppm):10.62(s,1H,CONH),8.39(s,1H),7.93(s,1H),7.63-7.30(m,3H),7.27-7.10(m,5H),3.88-3.45(m,2H),3.42-3.32(m,2H),3.16(s,3H,CH3O),1.90-1.60(m,2H).HRMS(ESI)calcd.for C₂₈H₂₀BrF₁₁N₂NaO₃[(M+Na)⁺]:743.0379[(M+Na)⁺],745.0359[(M+2+Na)⁺];Found:743.0359[(M+Na)⁺],745.0343[(M+2+Na)⁺].

Synthesis example 7

Synthesis of 2-fluoro-3- { [ (4-fluorophenyl) carbonyl ] (2-ethoxyethyl) amino } -N- [ 2-bromo-4- (1, 2, 3-heptafluoropropane-2-yl) -6- (trifluoromethyl) phenyl ] benzamide has the structural formula SYN004.

Step one, step two were conducted in a similar manner to the procedure one and step two in Synthesis example 1 and the feed ratio was set so that 25g (0.20 mol) of benzoic acid was replaced with 28.6g (0.20 mol) of p-fluorobenzoic acid.

N-alkylation 15.8g (0.11 mol) of 1-bromo-2-methoxyethane were replaced by 17.5g (0.11 mol) of 1-bromo-2-ethoxyethane, all other conditions being unchanged. The yield and content data of the obtained target compound are similar.

Melting point 168.2-169.2 ℃, and nuclear magnetism and mass spectrum data are as follows:

¹H-NMR(400MHz,DMSO-d6)δ(ppm):10.52(s,1H,CONH),8.38(s,1H),7.92(s,1H),7.67(dd,J＝7.6Hz,and 6.8Hz,1H),7.60-7.50(m,1H),7.48-7.20(m,3H),7.18-6.95(m,2H),4.20-3.72(m,2H),3.68-3.45(m,2H),3.42-3.32(m,2H),1.01(t,J＝6.8Hz,3H,CH3).

HRMS(ESI)calcd.For C₂₈H₁₉BrF₁₂N₂NaO₃[(M+Na)⁺]:761.0285[(M+Na)⁺],763.0265[(M+2+Na)⁺];Found:761.0263[(M+Na)⁺],763.0248[(M+2+Na)⁺].

Synthesis example 8

Synthesis of 2-fluoro-3- { [ (3, 5-dichloro-4-methylphenyl) carbonyl ] (2-ethoxyethyl) amino } -N- [ 2-bromo-4- (1, 2, 3-heptafluoropropane-2-yl) -6- (trifluoromethyl) phenyl ] benzamide. The structural formula is SYN021.

Step one, step two were conducted in a similar manner as step one and step two of the synthesis example 1 and the addition ratio was set up, wherein benzoyl chloride was replaced with 3, 5-dichloro-4-methylbenzoyl chloride, to obtain the title compound. The yield and content data of the obtained target compound are similar. The total yield calculated by 3, 5-dichloro-4-methylbenzoyl chloride is 63%, the melting point is 92.2-93.5 ℃, and the nuclear magnetism and mass spectrum data are as follows:

¹H-NMR(400MHz,DMSO-d6)δ(ppm):10.52(s,1H,CONH),8.36(s,1H),7.92(s,1H),7.74(s,1H),7.61(s,1H),7.50-7.00(m,3H),4.10-3.75(m,2H),3.72-3.50(m,2H),3.40-3.35(m,2H),2.47(s,3H),1.10-0.95(m,3H).

HRMS(ESI)calcd.for C₂₉H₂₀BrCl₂F₁₁N₂NaO₃[(M+Na)⁺]:824.9756[(M+Na)⁺],826.9736[(M+2+Na)⁺];Found:824.9444[(M+Na)⁺],826.9424[(M+2+Na)⁺].

Synthesis example 9

Synthesis of 2-fluoro-3- { [ (4-fluorophenyl) carbonyl ] (2-N-propoxyethyl) amino } -N- [ 2-bromo-4- (1, 2, 3-heptafluoropropane-2-yl) -6- (trifluoromethyl) phenyl ] benzamide has the following structural formula SYN024.

Step one, step two were conducted in a similar manner to the procedure one and step two in Synthesis example 1 and the feed ratio was set so that 25g (0.20 mol) of benzoic acid was replaced with 28.6g (0.20 mol) of p-fluorobenzoic acid.

N-alkylation 1-bromo-2-methoxyethane 15.8g (0.11 mol) of the starting material was replaced with 18.7g (0.11 mol) of 1-bromo-2-N-propoxyethane, with the other conditions and operations being similar. The yield and content data of the obtained target compound are similar. Melting point 156.5-156.8 deg.c.

Synthesis of comparative example 1

Synthesis of 2-fluoro-3- { [ (3, 5-dichloro-4-methylphenyl) carbonyl ] (methyl) amino } -N- [ 2-bromo-4- (1, 2, 3-heptafluoropropane-2-yl) -6- (trifluoromethyl) phenyl ] benzamide.

Following a procedure analogous to that of examples 1,1-3 to 1-7 of chinese CN 102119143B, wherein 1-7 steps were replaced with the same molar amount of 3, 5-dichloro-4-methylbenzoyl chloride, the title compound was obtained in an overall yield of 3.8% based on 3, 5-dichloro-4-methylbenzoyl chloride starting material, melting point 124.1-125.3 ℃, nuclear magnetism, mass spectrum data as follows:

¹H-NMR(400MHz,DMSO-d6)δ(ppm):10.65(s,1H,CONH),8.32(s,1H),7.88(s,1H),7.70(s,1H),7.60(s,1H),7.38-7.30(m,3H),3.32(s,3H),2.47(s,3H).

HRMS(ESI)calcd.for C₂₆H₁₄BrCl₂F₁₁N₂NaO₂[(M+Na)⁺]:766.9338[(M+Na)⁺],768.9317[(M+2+Na)⁺];Found:766.9321[(M+Na)⁺],768.9299[(M+2+Na)⁺].

The structural formula and the reaction formula are as follows:

The compounds in Table II were prepared or preparable by a similar method to those in step I and step II of Synthesis example 1, except for the compounds described above, and the nuclear magnetism and mass spectrum data of a part of the compounds synthesized by reference to Synthesis example 1 are shown in Table II below.

Watch II

Other compounds of formula (I) according to the invention can be synthesized by reference to the methods described above.

Formulation example 1

And (3) preparing a suspending agent sample, namely mixing active ingredients, auxiliary agents, water and the like according to the formula proportion (weight) of the raw materials in the following table III, performing high shearing, performing sand milling for three times by a sand mill, and detecting to be qualified to obtain the suspending agent sample, wherein the active ingredients can be selected from any one of the compounds in the general formula (I) or mixed with the existing pesticide varieties in the market.

Watch III

Formulation example 2

And (3) preparing an emulsifiable concentrate sample, namely heating and stirring auxiliary agents such as active ingredients, solvents, emulsifying agents and the like to be clear and transparent according to the formula proportion (weight) of raw materials in the fourth table, and detecting to be qualified to obtain the emulsifiable concentrate sample, wherein the active ingredients can be selected from one compound suitable for preparing emulsifiable concentrates in the compound of the general formula (I) or mixed with the existing pesticide varieties in the market.

Table four

Biological Activity test examples

The test of various pests with the partial compounds of the general formula (I) of the compounds obtained according to the invention

The preparation of the compound comprises weighing a certain mass of raw material with a balance (0.001 g), preparing a 1% mother solution with DMF, diluting with distilled water containing 0.1% Tween-80 to test concentration for standby, and weighing a certain mass of preparation sample with a balance (0.001 g) according to the active ingredient content of the preparation if the preparation is prepared, and diluting with distilled water to test concentration for standby.

Test example 1 Compounds for indoor biological Activity assay on Plutella xylostella

A sensitive population of plutella xylostella (Plutella xylostella) and a chlorantraniliprole resistant population, and breeding with radish seedlings indoors;

The testing method comprises the steps of adopting an immersion method to obtain a proper amount of radish leaves, immersing the radish leaves for 30s, naturally drying in the shade in a plastic culture dish filled with filter paper, inoculating 10 heads of 2-year-old plutella xylostella into each dish, and placing the plutella xylostella into a 22 ℃ and illumination (16/8 h) observation room. After 2 days, the insects are touched by a writing brush, no reaction is regarded as dead insects, the process is repeated for 3 times, and a blank control without adding a medicament is additionally arranged.

The test results show that the activity of SYN001 and other compounds SYN001, SYN003, SYN004, SYN006, SYN008, SYN011, SYN013 and SYN024 on the sensitive population of the plutella xylostella and the activity of the plutella xylostella on the chlorantraniliprole population reach 100% at the test concentration of 0.2mg/L, and the activity is equivalent to that of the comparison sample CK02 bromofluorobenzene bisamide. When the test concentration is 0.1mg/L, the activities of SYN001, SYN003, SYN004, SYN006, SYN008, SYN011, SYN013, SYN021 and SYN024 on the sensitive population of the plutella xylostella are all more than or equal to 90 percent, which is equivalent to that of a comparison sample CK02 bromofluorobenzamide, and the activities of SYN003, SYN004, SYN006, SYN008, SYN011, SYN013 and SYN024 on the population of the plutella xylostella anti-chlorantraniliprole are all 100 percent, which is equivalent to that of a comparison sample CK02 bromofluorobenzamide. At a low concentration of 0.05mg/L, SYN003, SYN004, SYN006, SYN008, SYN011, SYN013 and SYN024 have higher activity on the chlorantraniliprole population of plutella xylostella than the activity of the chlorantraniliprole of the comparison sample CK 02. Unexpectedly, the comparative sample CK05 was inactive against the diamondback moth anti-chlorantraniliprole population at the tested concentrations, indicating that the CK05 compound has cross-resistance to chlorantraniliprole.

The compounds SYN001, SYN003, SYN004, SYN006, SYN008, SYN011, SYN013, SYN021 and SYN024 have no cross resistance with chlorantraniliprole.

Table five results of determination of the Activity of the Compound of general formula (I) on Plutella xylostella

Test example 2 test of insecticidal quick-acting Properties of Compounds

According to the method of test example 1, compounds SYN001, SYN003, SYN006, SYN008, SYN0011 and CK02 are selected to conduct parallel measurement of insecticidal activity of the plutella xylostella sensitive population, dead numbers are investigated after 12 hours, 24 hours and 48 hours of the drug administration, mortality is calculated, and insecticidal quick-acting effects are compared, and test results are shown in a table six:

The test results show that the compounds SYN001, SYN003, SYN006, SYN008 and SYN0011 have different degrees of death after being applied for 12 hours, and the effect is faster than that of the comparison sample CK02 bromofluorobenzene bisamide.

The results of measuring the quick-acting activity of the compound of the general formula (I) on plutella xylostella in the six parts of the table

Test example 3 Compounds for indoor biological Activity assay on Chilo suppressalis

The activity of the chilo suppressalis is determined by soaking the wild rice stem slices in the water for 30s, naturally drying in the shade in plastic culture dishes filled with filter paper, and placing 10 heads of the chilo suppressalis at 3 years old in each dish, and observing the inside of a room under 26 ℃ and illumination (16/8 h). After 4 days, the insects are touched by a writing brush, no reaction is regarded as dead insects, the process is repeated for 3 times, and a blank control without adding a medicament is additionally arranged.

The test results are shown in Table seven:

the results show that SYN001, SYN003, SYN004, SYN006, SYN008, SYN011, SYN013 and SYN024 have better activity under the tested concentration, and are equivalent to the comparative sample CK 02. The comparative sample CK05 was not active against chilo suppressalis at the tested concentration.

Table seven part results of determination of Activity of Compounds of general formula (I) on Chilo suppressalis

Test example 4 indoor biological Activity assay of Compounds against Spodoptera frugiperda

The spodoptera frugiperda activity is determined by soaking appropriate amount of corn leaf for 30s, naturally drying in the shade in plastic culture dish with filter paper, collecting 10 heads of spodoptera frugiperda at 2 years old, and placing in 26 deg.C and illumination (16/8 hr) observation room. After 2 days, the insects are touched by a writing brush, no reaction is regarded as dead insects, the process is repeated for 3 times, and a blank control without adding a medicament is additionally arranged.

The test results are shown in Table eight:

the results show that SYN001, SYN003, SYN004, SYN006, SYN008, SYN011, SYN013 and SYN024 have better activity under the tested concentration, and are equivalent to the comparative sample CK 02. The control CK05 was not active against spodoptera frugiperda at the concentrations tested.

Table eight part determination of the Activity of the Compounds of formula (I) on Spodoptera frugiperda

In organic molecules, due to the electronegativity, volume size or spatial configuration of substituents, the conductivity or receptor binding variability of the whole molecule in organisms such as insects and plants can be large, the displayed biological activity can also be large, the conductivity and receptor binding suitability of the molecule are unpredictable, and a great deal of creative labor is required for knowing.

On one hand, the compound with the general formula (I) containing the heptafluoroisopropyl is obtained through molecular structure optimization, and experiments show that the compound has excellent insecticidal activity, particularly has excellent high insecticidal activity on resistant populations, has no cross resistance with the conventional insecticidal chlorantraniliprole, has good insecticidal effect and good quick-acting performance at low dosage, and on the other hand, the compound with the general formula (I) has the advantages of simple preparation method, high efficiency, easy industrial production and wide application prospect in the fields of agriculture, forestry and gardening for preventing and controlling insect pests.

The inventors state that the present application describes a bisamide compound containing a heptafluoroisopropyl group, and a preparation method and application thereof by the above-described representative examples, but the present application is not limited to the above-described examples, and does not mean that the present application can be realized by depending on the above-described examples. It should be apparent to those skilled in the art that any modification of the present application, equivalent substitution of raw materials for the product of the present application, addition of auxiliary components, selection of specific modes, etc., falls within the scope of the present application and the scope of disclosure.

Claims (2)

1. Compounds of general formula (I-V): wherein R ¹ is independently selected from H, fluorine, chlorine, bromine, iodine, trifluoromethyl, methoxy, trifluoromethoxy, methyl, ethyl, methanesulfonyl, cyano or nitro; ^R2 is independently selected from methyl, ethyl, n-propyl, isopropyl, n-butyl or isobutyl; n is independently represented by 1 or 2. 2. The compound of general formula (I-V) according to claim 1 is characterized in that the compound of general formula (I-V) is used in the field of synthetic insecticides.