WO2017148226A1

WO2017148226A1 - Fluorobenzoxazole compound and use thereof

Info

Publication number: WO2017148226A1
Application number: PCT/CN2017/071633
Authority: WO
Inventors: 许良忠; 吴华龙; 王明慧; 李焕鹏; 黄雪松; 杨曦
Original assignee: 浙江博仕达作物科技有限公司
Priority date: 2016-03-01
Filing date: 2017-01-19
Publication date: 2017-09-08
Also published as: CN105693648A

Abstract

Disclosed are a fluorobenzoxazole compound of the structure as shown in formula I and the use thereof, wherein the compound has an excellent inhibiting and killing effect towards pest mites and mite ova, can be used as an acaricide for preventing and treating agricultural pest mites, and at the same time has an excellent asparagus caterpillar killing activity.

Description

Flurobenzoxazole compound and use thereof

The invention claims priority from the Chinese invention patent application whose application date is March 1, 2016, and the application number is CN 201610114395.7.

TECHNICAL FIELD The present invention relates to the field of pesticide acaricides, and in particular to a fluorobenzoxazole compound and use thereof.

Background Art There are various acaricides for controlling cockroaches, such as acetylene, bromo oxime, avermectin, spironolactone, oxazolidine, hydrazine, and the like. Due to the long-term or frequent use of existing commercial acaricides, aphids have produced varying degrees of resistance and cross-resistance to existing insecticides. Therefore, the development of new or different activating agents with different mechanisms of action is an important means to control the resistance of cockroaches. CN1038809A discloses an oxazole compound of the formula (I) which has strong insecticidal and acaricidal activity against pests and mites which are harmful to agriculture and horticulture, and which is almost phytotoxic to crops. US5478855 discloses an oxazole compound of the formula III, which has excellent control effects on hawthorn leafhopper, citrus aphid, vegetable leafhopper, etc., and has the characteristics of super high efficiency, long-lasting effect, low toxicity and safety. . The oxazole compound disclosed in the above patent has certain similarities with the compound of the present invention, but in the prior art, such as the fluorobenzoxazole compound of the present invention (Formula I) and its insecticidal and acaricidal activity No reports have been reported.

SUMMARY OF THE INVENTION It is an object of the present invention to provide a more active insecticidal and acaricidal agent which is novel in structure and safe to use.

The technical solution of the present invention is as follows:

A fluorobenzoxazole compound having the structure shown in Formula I:

The compounds of formula I can be prepared by the following methods:

Using toluene and DMF (1:1) as a solvent, m-tert-butylphenol and difluoroethyl methanesulfonate were refluxed in the presence of K ₂ CO _{3 to} form compound IV, which was used. 2,6-Difluorobenzamide was reacted with chloroacetaldehyde dimethylacetal in the presence of concentrated H ₂ SO ₄ under ice-cooling to give compound V. Using dichloromethane as a solvent, the compound of formula V is reacted with compound IV in the presence of AlCl _{3 to} form intermediate VI; cyclization of intermediate VI in the presence of methanol as solvent, NaOH or KOH to form a compound of formula (Formula I), formula IV Specific preparation methods of the formula V, the formula VI and the compound of the invention (formula I) are shown in the synthesis examples of the invention.

Advantages and positive effects of the present invention:

Ethylazole (Compound III) is a representative acaricide in oxazoline acaricides. It is a brand new uniquely synthesized compound developed by Sumitomo Chemical Co., Ltd., which is a new compound with leaf mites, leaves and leaves. Xenopus laevis, cinnabar leafhopper, citrus red spider, etc. have excellent control effect and excellent ovicidal activity. Not only the acaricide is ultra-efficient, but also has the characteristics of long-lasting effect and low pollution. The leader in the agent market, but due to the large number of frequent use of the acaricide in recent years, the mites have caused serious resistance to them, and the control effect and duration of action have been significantly reduced. The present inventors have combined the years of research on the relationship between the efficacy of biologically active substances and the experience of bioresistant treatment to create a compound of the present invention (Formula I) by introducing a fluorine atom into the structure of the etoxazole. After the insecticidal, acaricidal (cough, scorpion egg) test, the compound of the present invention not only has an unexpected killing effect on the eggs (see Table 1), but also has good killing properties (see Table 2), and overcomes The disadvantage of acetoxime on the ineffectiveness of cockroach solves the shortcoming of the lack of quick-acting effect of acetoxime field control. Moreover, the compound of the present invention also has excellent insecticidal action (see Table 3). The comprehensive control performance is significantly better than that of etoxazole. The compound of the invention avoids the use of the highly toxic raw material diethyl sulfate in the synthesis process of oxazole, so that the production process is safer and more environmentally friendly; the introduction of fluorine atom is more beneficial to overcome or delay the generation of harmful drug resistance. Therefore, the compound of the present invention is a creative acaricide, and the commercialization thereof will be an ideal replacement product of an acaricide such as oxazole, and also an excellent insecticidal and acaricidal agent for the prevention and control of pests and cockroaches in China, and effectively promote the country. The development of the pesticide industry and the greening process of pesticides.

The present invention also encompasses acaricidal compositions of the compounds of formula I as active ingredients, which also include agriculturally or forestry acceptable carriers.

The compound of the present invention can be used alone or in combination with other active substances such as insecticides and acaricides in order to improve the comprehensive function of the product.

The composition of the present invention can be administered in the form of a preparation, and the compound of the formula I is dissolved or dispersed in a carrier or a solvent as an active ingredient, and an appropriate surfactant is added to prepare an emulsifiable concentrate, an aqueous emulsion, a microemulsion, a suspending agent and the like.

It is to be understood that various changes and modifications may be made within the scope of the appended claims.

detailed description

The following synthetic examples and bioassay results are used to further illustrate the invention, but are not intended to limit the invention.

Synthesis example

Example 1, Preparation of a compound of formula I

(1) Preparation of Compound IV

Procedure: 15.0 g (0.1 mol) of m-tert-butylphenol, powder K ₂ CO ₃ 16.6 g (0.12 mol), 50 mL each of toluene and DMF were added to a 250 mL four-necked flask, and difluoroethyl methanesulfonic acid was added with stirring. The ester was 20.8 g (0.13 mol), and the temperature was slowly refluxed for 4 h, and the reaction was completed by TLC. The mixture was washed with a slight temperature, and the filter cake was washed with a small portion of DMF. The solvent was removed by rotary evaporation. 50 mL of dichloromethane and water were added, and the mixture was separated, and the extract was washed twice with 50 mL of water. The organic phase was dried over anhydrous sodium sulfate and evaporated and evaporated, then,

(2) Preparation of Compound V

Procedure: 143 g (0.1 mol) of 2,6-difluorobenzamide and chloroacetaldehyde dimethylacetal 49.8 g (0.4 mol) were sequentially added to a 250 mL four-necked flask, vigorously stirred in an ice bath, and added dropwise within 1 h. 6 mL of concentrated sulfuric acid was stirred at room temperature for about 2 h, and the reaction was completed by TLC to 2,6-difluorobenzamide. The reaction solution was poured into a separatory funnel, and 150 mL of water and 150 mL of dichloromethane were added thereto, and the mixture was extracted, and the extract was washed twice with 80 mL of water. Dichloromethane and excess chloroacetaldehyde dimethylacetal were distilled off, and 80 mL of n-hexane was added thereto, and the mixture was stirred and cooled overnight. The crystals were precipitated, filtered and dried to give 18.3 g of white compound V, yield 73.5%.

(3) Preparation of Compound VI

Procedure: 14.9 g (0.06 mol) of compound V and 14.2 g (0.072 mol) of compound IV were dissolved in 80 mL of dichloromethane, and added dropwise to 14.2 g (0.108 mol) of aluminum trichloride in 80 mL of dichloromethane over 10 min. In an ice-cold solution. The temperature was slowly raised to reflux for about 2 h, TLC was traced to compound V and the basic reaction was completed. The reaction mixture was poured into ice water, and the dichloromethane layer was washed twice with 50 mL of water. The crystals were precipitated, filtered, washed with a small portion of ice cold methanol, and dried to give a white solid (21.89 g).

(3) Synthesis of Compound I

Procedure: 4.8 g of a 20% NaOH solution was slowly added dropwise to a solution of 8.3 g (0.02 mol) of Compound V dissolved in 60 mL of methanol, and the mixture was stirred at 70 ° C for about 1 h, and the basic reaction of Compound V was followed by TLC. The methanol and water were distilled off, 50 mL of water and benzene were added, and the mixture was separated. The organic phase was dried over anhydrous sodium sulfate. The mixture was evaporated to dryness under reduced pressure and evaporated to dryness. overnight. The crystals were precipitated, filtered and dried to give 6.95 g of White Compound I. Melting point: 82.5-85.2 °C.

The hydrogen nuclear magnetic data of the compound of formula I is as follows:

¹ H-NMR (500 MHz, DMSO): δ/ppm 1.257 (s, 9H), 4.085-4.118 (t, 1H), 4.378-4.436 (m, 2H), 4.78-4.838 (t, 1H), 5.525-5.563 (t, 1H), 6.274-6.499 (t, 1H), 7.025-7.663 (m, 6H)

Biometric example

Example 2 Compound I formula test for killing (egg) activity

The acaricidal egg activity was determined by the method of dipping and statistically correcting the mortality of the pest. The specific process is: diluting the test agent to the required concentration according to the active ingredients, and injecting 50 mL of the drug solution into the culture dish under aseptic conditions, and then immersing them in the cinnabar eggs respectively (the eggs are normally reared according to the indoor standardized method) The leaves were placed in a blank control with a plate containing 50 ml of sterilized water. Place the culture dish in a constant temperature incubator at 24 ± 1 °C. The mortality rate was investigated after 48 hours. The activity data of the eggs and the mites are shown in Tables 1 and 2, respectively.

Table 1 Test results of the compound of formula I

According to the test results of Table 1, the compound I of the present invention has excellent acaricidal activity, and the activity of the compound I of the present invention is significantly superior to the known commercial acaricide (the compound of the formula III) at the same dose.

Table 2 Test results of the compound of formula I

According to the test results of Table 2, the compound I of the present invention has good killing properties, and overcomes the disadvantages of the compound of the formula III being ineffective.

Example 2 The activity of the compound of formula I to kill beet armyworm

Determination of the activity of the compound of formula I against Spodoptera exigua: a leaf dip method proposed by the International Committee for the Resistance of Resistance (IRAC). Using the prepared test solution, the cabbage leaves were impregnated with straight ophthalmia tweezers, and the remaining solution was taken for 3-5 seconds. Each sample was 3 pieces per sample, and the order of the sample was placed on the treated paper in turn. After the drug solution was dried, it was placed in a straight tube of 10 cm long with a mark, and 30 heads of 2nd instar beet armyworm larvae were inserted, and the nozzle was covered with gauze. The test treatment was placed in a standard treatment room, and the results were examined at 48 hours to remove the needles and touch the worms, and those who did not move were killed. Calculate the mortality rate. (The test was repeated 3 times and averaged).

Table 3 Test results of the compound of formula I against beet armyworm

According to the test results of Table 3, the compound I of the present invention has excellent activity against Spodoptera exigua, and the activity of the compound I of the present invention is significantly superior to the known commercial acaricide (compound of the formula III) at the same concentration.

Claims

A fluorobenzoxazole compound having the structure shown in Formula I:
Use of a fluorobenzoxazole according to claim 1, characterized in that the compound of the formula I is useful as an acaricide for controlling agricultural pests.
A acaricidal composition comprising a compound of formula I as claimed in claim 1 as an active ingredient and an agricultural or forestry acceptable carrier.