CN108794461B

CN108794461B - Fluorine-containing phenyl oxadiazole pyrazole insecticidal bactericide

Info

Publication number: CN108794461B
Application number: CN201810754684.2A
Authority: CN
Inventors: 王明慧; 孙鉴昕; 许良忠; 胡娆; 崔焕奇
Original assignee: Qingdao University of Science and Technology
Current assignee: Qingdao University of Science and Technology
Priority date: 2018-07-11
Filing date: 2018-07-11
Publication date: 2021-03-09
Anticipated expiration: 2038-07-11
Also published as: CN108794461A

Abstract

The invention provides a fluorine-containing phenyl oxadiazole pyrazole insecticidal bactericide, which has a structure shown in a formula I:

Description

Fluorine-containing phenyl oxadiazole pyrazole insecticidal bactericide

The invention belongs to the field of pesticide and bactericide, and particularly relates to a fluorine-containing phenyl oxadiazole pyrazole insecticidal bactericide.

Background Art in 2013, Monsanta developed a New and highly effective Nematicide, thiophene and phenyl substituted oxadiazole compounds, Tioxazafen (Compound II), which had a completely New mechanism of action and exerted its potency by interfering with the activity of nematode ribosomes (Slomczynska U, South M S, Bunkers G J, et al.Tioxazafen: A New Broad-Spectrum Seed Treatment New [ M ], Discovery and Synthesis of Crop Protection Products, 2015.). In 1988 Idoux et al proposed a series of substituted alkoxyphenyl-containing oxadiazoles, such as 2- (2, 4-dichlorophenyl) -5- (4- (1,1,2, 2-tetrafluoroethoxy) phenyl) -1,3,4-oxadiazole (compound III) which had insecticidal activity with 100% Drosophila activity at 100mg/L [ Idoux J P, Gibbsrein K S, Gupton J T, et al. The literature [ Wang, Wen-yan, Nankai university. Synthesis of 1,3,4-thia (oxa) diazole-substitated Pyrazole Derivatives and therapeutic fungal Activities [ J ]. advanced chemical research (English edition), 2004,20(5):543 547] reports that Pyrazole-substituted oxadiazoles have a certain inhibitory effect on Phoma asparagi. According to the invention, an active group is used for substituting pyrazolyl to be introduced to the 5-position of 1,2, 4-oxadiazole and difluoroethoxybenzene to be introduced to the 3-position of 1,2, 4-oxadiazole through an active group splicing technology to obtain the compound with the structure shown in the formula I.

The invention aims to provide the fluorine-containing phenyl oxadiazole pyrazole agricultural insecticidal bactericide which is novel in structure, efficient, safe and low in prevention and control cost.

The technical scheme of the invention is as follows:

a fluorine-containing phenyl oxadiazole pyrazole compound has a structure shown as I:

the compounds of formula I can be prepared by the following reaction:

reacting the compound 4 (o-difluoroethoxybenzonitrile) with hydroxylamine hydrochloride to generate a compound 3, reacting the compound 3 with a compound 5 (1-methyl-3-ethyl-4-chloro-5-pyrazolecarbonyl chloride) to generate a compound 2, and refluxing the compound 2 in toluene to obtain the compound shown in the formula I. The specific preparation method is shown in the synthesis example of the specification.

The compound of the formula I has good insecticidal effect on asparagus caterpillars and diamond back moths and good inhibition effect on rice sheath blight bacteria, pepper colletotrichum gloeosporioides, wheat scab bacteria and Chinese rose downy mildew bacteria through insecticidal experiments, so the invention also comprises the application of the compound of the formula I in preventing and treating agricultural and forestry insect pests and bacterial diseases.

The invention has the advantages and positive effects that:

the compound is a pyrazole-substituted 1,2, 4-oxadiazole compound with a brand-new structure, and the structure of the compound contains oxadiazole, pyrazole and difluoroethoxyphenyl structures, and the compound of the invention contains oxadiazole, pyrazole and difluoroethoxyphenyl structurescontains-OCH₂CHF₂The group increases fat solubility and permeability, and remarkably improves the suction conduction effect, thereby improving the drug effect; the molecule contains oxadiazole and pyrazole structures simultaneously, so that the compound has insecticidal and bactericidal effects simultaneously, has dual-purpose efficacy of one medicine, introduces heterocyclic pharmacophores such as oxadiazole and pyrazole, increases action sites, is beneficial to increase of drug effect and broad-spectrum property, and has small influence on pest resistance. The compound has the advantages of easily obtained synthetic raw materials, simple synthetic process, no need of high temperature and high pressure and special equipment, less generation of three wastes in production, higher yield and low production cost. The compound of the invention is a nitrogen heterocyclic compound, has the characteristics of low toxicity to people, livestock and beneficial organisms, easy degradation and good environmental compatibility, and has the industrialization prospect and the commercialization potential as a new variety of creative insecticidal bactericides.

The invention also comprises the insecticidal and bactericidal composition with the compound shown in the formula I as an active component, and the composition also comprises an agriculturally acceptable carrier.

The compound of the invention can be used alone or in combination with other active compounds when preventing and controlling insect pests and bacterial pests, so as to be beneficial to improving the comprehensive prevention and control performance of the product.

The compound composition can be prepared into a reagent for application, and the compound of the invention is taken as an active component to be dispersed or dissolved in a carrier or a solvent, and is added with a proper surfactant to be prepared into a suspending agent, a microemulsion, missible oil, an aqueous emulsion and the like.

It should be understood that various changes and modifications may be made within the scope of the present invention as defined by the claims.

The specific implementation mode is as follows:

the following synthetic examples and results of biological tests are provided to further illustrate the invention, but are not meant to limit the invention.

Synthesis examples

Example 1 preparation of Compounds of formula I

(1) Synthesis of 2- (2, 2-difluoroethoxy) benzonitrile (Compound No. 4)

A250 mL three-necked flask was charged with 0.1mol (11.9g) of salicylanitrile, 0.105mol (14.49g) of potassium carbonate, and 100mL of DMF as a solvent. After stirring and warming to 80 ℃, 0.12mol (19.2g) of 2, 2-difluoroethanol methylsulfonate was slowly added dropwise to the flask via a 50mL dropping funnel, and the mixture was stirred for 4 hours. The reaction solution was poured into a 500mL flask, 100mL of 1% sodium hydroxide solution was added and washed, a small amount of unreacted salicylaldehyde was washed away, 100mL of ethyl acetate was added to extract the product, the organic phase was separated and retained, and then washed with 3 × 100mL of saturated brine, separated, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to obtain 17.1g of 2- (2, 2-difluoroethoxy) benzonitrile as a pale yellow oily liquid in 93.4% yield (based on the salicylaldehyde).

(2) Synthesis of Compound 3

A250 mL three-necked flask was charged with 100mL of ethanol, 13.8g (0.2mol) of hydroxylamine hydrochloride and 20g (0.2mol) of triethylamine, heated to 50-60 ℃ and reacted for 1 hour to liberate hydroxylamine hydrochloride. Adding 22g of compound 4 (o-difluoroethoxybenzonitrile) into a flask after 1h, heating and carrying out reflux reaction for 2h, detecting the disappearance of the compound 4 by TLC, removing ethanol by rotary evaporation, adding 150mL of water into the flask, dissolving triethylamine hydrochloride, carrying out suction filtration on residues to obtain a filter cake, namely a compound 3, and drying to obtain a white solid with the yield of 90%.

(2) Synthesis of Compound 2

10.8g (0.05mol) of Compound 3 was added to a 250mL round-bottomed flask, 100mL of ethyl acetate was added, 10.35g (0.05mol) of Compound 5 (1-methyl-3-ethyl-4-chloro-5-pyrazolecarbonyl chloride) was added dropwise at room temperature, reaction was carried out for 3 hours after completion of the addition, disappearance of Compound 3 was detected by TLC, ethyl acetate was distilled off under reduced pressure to give 2 as a pale yellow solid, and the yield was 91%.

(3) Synthesis of Compounds of formula I

To a 250mL round bottom flask was added 3.87g (0.01mol) of Compound 2, 80mL of toluene was added, refluxing was carried out for 3h, disappearance of Compound 2 was detected by TLC, and toluene was distilled off under reduced pressure to give a pale yellow solid of Compound I with a yield of 90.5%.

Nuclear magnetic and melting point data for compounds of formula I:¹H-NMR (500MHz, DMSO): delta/ppm is 1.21-1.24 (t, 3H), 2.63-2.68 (q, 2H), 4.22(s, 3H), 4.45-4.52 (m, 2H), 6.31-6.54 (m, 1H), 7.22-7.25 (m, 1H), 7.34-7.36 (d, 1H), 7.60-7.64 (m, 1H), 8.00-8.02 (m, 1H). Melting point: 137-139 ℃.

Biological activity assay

(1) Preparing a medicament:

dissolving the compound of the formula I in dimethyl sulfoxide, diluting with 1 ‰ tween 80 water solution to obtain 50ml of solution to be tested with required concentration, wherein the content of dimethyl sulfoxide in the total solution is not more than 10%.

(2) Determination of insecticidal Activity

The biological activity of the compounds synthesized herein was determined using the leaf-invasion method. Diamondback moth (Plutella xylostella Linnaeus) and Beet armyworm (Beet armyworm) were used as test subjects, and divided into two groups, and blank controls were set. Soaking cabbage leaves with consistent growth in the prepared medicament for 10s, taking out the liquid medicament by using tweezers, and spreading the liquid medicament on a clean flat plate in sequence. After air drying, the leaves are transferred to culture dishes which are well sorted and contain moisturizing filter paper, 30 heads of 2-year-old beet armyworms with similar growth conditions are planted in each culture dish, the culture dishes are placed in a constant-temperature incubator (25 +/-1 ℃) for breeding, the death condition of the beet armyworms is checked after 48 hours when the photoperiod L: D is 16:8 and the relative humidity is 60%, and the death number is recorded. The experiment was repeated 3 times, and the corrected mortality was calculated by taking the average, as shown in equation (1):

in the formula: p₁Mortality in percent (%); k-represents dead number of insects; n-represents the total number of insects treated.

The efficacy test of the diamondback moth is carried out by the same 2-year-old moth, and the experimental method is the same as the steps. The results of the test are given in Table 1, using Compound III as a control.

TABLE 1 biological Activity data of Compounds of formula I against beet armyworm and diamondback moth

(3) Measurement of fungicidal Activity

The bactericidal effect of the compounds was determined by the plate method. Four hyphae of rice sheath blight (Rhizoctonia solani), pepper anthracnose (Colletotrichum capsicii), wheat gibberellic disease (Gibberella zeae) and Chinese rose downy mildew are taken as test objects and divided into four groups, and blank controls are set. Sucking 1mL of liquid medicine, injecting into a sterile conical flask in which a sterilized culture medium is melted in advance, shaking up sufficiently, then pouring into 3 culture dishes with the diameter of 9cm in equal amount to prepare a medicine-containing flat plate with the concentration of 50 mug/L, setting 3 times of repeated experiments, and using the same treatment without medicine as a blank control. The above cultured pathogenic bacteria are sterilized by a sterilizing perforator with diameter of 5mm under aseptic condition, the bacterial cake is cut from the edge of bacterial colony, inoculated to the center of the drug-containing plate by an inoculator, the hypha face is upward, the cover of the culture dish is closed, and the culture dish is placed in a constant temperature incubator at (24 +/-1) DEG C for culture. After 72h, the diameter of the colonies was measured with a caliper, and the average diameter was measured once for each diameter by the cross method. And (3) according to the experimental result, calculating the hypha growth inhibition rate of different medicaments on the target bacteria to be tested according to the formulas (1) and (2).

D＝D₁-D₂························(1)

In the formula: d, colony growing diameter; d₁-colony diameter; d₂-the diameter of the cake.

In the formula: i-hypha growth inhibition rate; d₀-growing the diameter of the blank colony; d_tMedicament-treated colonies grow in diameter.

The results are shown in Table 2.

TABLE 2 biological Activity data of the Compounds against four pathogens

As can be seen from the data in Table 2, the compounds of formula I have bactericidal effects, especially on the peronospora rosea.

Claims

1. A fluorine-containing phenyl oxadiazole pyrazole compound has a structure shown in formula I:

2. the use of a fluorine-containing phenyl oxadiazole pyrazole compound for non-disease treatment according to claim 1, which is characterized in that the compound of formula I is used for preparing agricultural or forestry insecticides.

3. The use of the fluorine-containing phenyl oxadiazole pyrazole compound as claimed in claim 1 for non-disease treatment purposes, which is characterized in that the compound of formula I is used for preparing agricultural or forestry fungicides.

4. An insecticidal and fungicidal composition comprising the compound of formula I as claimed in claim 1 as an active ingredient and an agriculturally or forestry acceptable carrier.