Preparation method and application of benzodioxane compound

Abstract

The invention relates to the field of insecticides, in particular to a benzodioxane compound and / or salt thereof as well as a preparation method and application of the benzodioxane compound and / or salt thereof. The invention provides a benzodioxane compound which is novel in structure and good in comprehensive performance. The benzodioxane compound has the structure as shown in the formula I in the specification. The benzodioxane compound has an insecticidal function and can be used for preventing and treating main pests in agriculture, forestry and gardening. The benzodioxane compound provided by the invention is used as an active component as an insecticide, and has an excellent control effect on pests such as plutella xylostella and the like when the benzodioxane compound is used at a low concentration content. # imgabs0 #

Description

[Technical field]

[0001] The present invention relates to the field of pesticides, and in particular to a benzodioxetine heterocyclic compound and / or its salt, and a preparation method and application thereof. [Background technology]

[0002] In crop production such as agriculture and horticulture, the losses caused by pests are still very serious. In particular, as some pests develop resistance to existing pesticides, traditional chemical control methods face increasing challenges. The emergence of pest resistance not only leads to a decrease in drug efficacy, but also increases the economic burden on farmers and may aggravate environmental pollution. Therefore, the development of pesticides with new mechanisms of action, environmental friendliness, and less impact on natural enemies and beneficial insects has become an urgent need for the development of modern agricultural technology.

[0003] The Journal of organic chemistry, 2020, 85(20), 13069-13079. The following benzodioxetine heterocyclic compound (KC) is disclosed.

[0004]

[0005] This document does not disclose the use of the above compounds in agriculture. [Summary of the invention]

[0006] The purpose of the present invention is to provide a benzodioxetine heterocyclic compound with novel structure and good comprehensive performance, which can be used for the prevention and treatment of major pests in agriculture, forestry and gardening.

[0007] In order to achieve the above object, the first aspect of the present invention provides a benzodioxetane compound having a structure shown in formula (I):

[0008]

[0009] Wherein, in formula (I),

[0010] R 1 is fluorine, chlorine or hydrogen, R 2 is fluorine, chlorine or hydrogen, R 3 is methoxy, bromine or hydrogen, R 4 is methoxy, bromine or hydrogen, and n is 0, 1 or 2.

[0011] In some embodiments, R 1 is fluorine or hydrogen; R 2 is fluorine or hydrogen; R 3 is hydrogen; R 4 is hydrogen; n is 0, 1 or 2.

[0012] In some embodiments, the compound of formula I is selected from at least one of the compounds shown in Table 1.

[0013]

[0014] Table 1

[0015] Number <![CDATA[R 1 ]]> <![CDATA[R 2 ]]> <![CDATA[R 3 ]]> <![CDATA[R 4 ]]> n LC-MS I-1 F F OMe OMe 0 339.18 I-2 F F H OMe 0 310.33 I-3 F F Br OMe 0 385.77 / 387.45 I-4 F F OMe Br 0 385.90 / 387.95 I-5 F F H Br 0 355.63 / 357.47 I-6 F F Br Br 0 355.71 / 357.38 I-7 F F OMe H 0 309.36 I-8 F F H H 0 279.30 I-9 F F Br H 0 355.95 / 357.85 I-10 H H OMe OMe 0 303.30 I-11 H H H OMe 0 273.18 I-12 H H Br OMe 0 349.95 / 351.74 I-13 H H OMe Br 0 349.93 / 351.82 I-14 H H H Br 0 355.52 / 357.71 I-15 H H Br Br 0 399.85 / 397.91 I-16 H H OMe H 0 273.25 I-17 H H H H 0 243.36 I-18 H H Br H 0 319.95 / 321.74 I-19 F Cl OMe OMe 0 354.10 / 356.22 I-20 F F H H 0 279.30 I-21 F F Br Br 0 435.89 / 433.62 I-22 H H H H 1 257.36 I-23 H H H H 2 271.44

[0016] In some embodiments, the compound of formula I is selected from at least one of the compounds shown in Table 2.

[0017]

[0018] Table 2

[0019]

[0020]

[0021] The present invention provides the following compounds or agriculturally acceptable salts thereof,

[0022]

[0023] The second aspect of the present invention provides the use of the benzodioxetane compound described in the first aspect of the present invention in the preparation of an insecticide. The third aspect of the present invention provides an insecticide, the insecticide contains an active ingredient, and the active ingredient is selected from at least one of the benzodioxetane compounds described in the first aspect of the present invention.

[0024] The fourth aspect of the present invention provides the use of the insecticide described in the third aspect of the present invention in killing insects in agriculture, forestry and gardening. Compared with the prior art, the present invention has at least the following advantages:

[0025] The benzodioxetine heterocyclic compound provided by the present invention is used as an active ingredient as an insecticide and has an excellent control effect when used at a low concentration.

[0026] Other features and advantages of the present invention will be described in detail in the following detailed description. [Specific implementation method]

[0027] The endpoints and any values ​​of the ranges disclosed in this article are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of each range, the endpoint values ​​of each range and the individual point values, and the individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed in this article.

[0028] As mentioned above, the second aspect of the present invention provides the use of the benzodioxetine heterocyclic compound described in the first aspect of the present invention in the preparation of insecticides.

[0029] Preferably, the benzodioxetine compound is used as an active ingredient (ie, effective ingredient) in the insecticide.

[0030] In some embodiments of the present invention, preferably, the insect is selected from Plutella xylostella.

[0031] As mentioned above, the third aspect of the present invention provides an insecticide, which contains an active ingredient, and the active ingredient is selected from at least one of the benzodioxetine heterocyclic compounds described in the first aspect of the present invention.

[0032] In some embodiments of the present invention, preferably, based on the total weight of the pesticide, the content of the active ingredient is 1-99 weight%, for example, the content of the active ingredient is 1 weight%, 5 weight%, 10 weight%, 15 weight%, 20 weight%, 25 weight%, 30 weight%, 35 weight%, 40 weight%, 45 weight%, 50 weight%, 55 weight%, 60 weight%, 65 weight%, 70 weight%, 75 weight%, 80 weight%, 85 weight%, 90 weight%, 95 weight%, 99 weight% and any value in the range formed by any two of these point values. More preferably, based on the total weight of the pesticide, the content of the active ingredient is 5-60 weight%.

[0033] In some embodiments of the present invention, preferably, the insecticide further contains a carrier. Preferably, the carrier in the insecticide is a substance acceptable in agriculture, forestry and horticulture and helpful for the application of the active ingredient. Particularly preferably, the carrier is a liquid carrier and / or a solid carrier, wherein the solid carrier is preferably selected from at least one solid substance selected from clay, natural or synthetic silicates, silicon dioxide, resins, waxes, and solid fertilizers; the liquid carrier is preferably selected from liquid substances selected from water, alcohols, ketones, petroleum fractions, aromatic hydrocarbons, chlorinated hydrocarbons, and liquefied gas.

[0034] In some embodiments of the present invention, preferably, the insecticide may also contain surfactants, protective colloids, adhesives, thickeners, thixotropic agents, penetrants, chelating agents, colorants, polymers and other commonly used auxiliary components in the art. The present invention has no particular limitation on this, and those skilled in the art can select a reasonable composition and dosage according to actual needs.

[0035] In some embodiments of the present invention, preferably, the dosage forms of the insecticide are each independently selected from at least one of wettable powders, soluble powders, emulsifiable concentrates, aqueous suspensions, dispersible oil suspensions, aqueous emulsions, suspoemulsions, microemulsions, aqueous solutions, granules, microcapsules and water-dispersible granules, whereby the active ingredient is more easily soluble or dispersed so that it is easier to disperse when used as an active substance of the insecticide, thereby improving the application effect.

[0036] In some embodiments of the present invention, preferably, the present invention has no particular limitation on the preparation method of the pesticide, and those skilled in the art may refer to the methods in existing literature and standards in the field or adopt existing methods in the field to prepare the agent to obtain the desired composition and dosage form.

[0037] As mentioned above, the fourth aspect of the present invention provides the use of the insecticide described in the third aspect of the present invention in killing insects in agriculture, forestry and horticulture.

[0038] The present invention will be described in detail below by way of examples.

[0039] In the following examples, unless otherwise specified, all raw materials used are commercially available products.

[0040] In the following examples, unless otherwise specified, room temperature refers to 25±2°C.

[0041] [Example 1]

[0042] Preparation of Intermediate 1-Aminopyridine Iodide

[0043]

[0044] The specific preparation process is as follows:

[0045] Add raw material 2 (9.4 g, 0.083 mol) and 4M potassium hydroxide aqueous solution (62.5 ml, 0.25 mol) to a 500 ml three-necked flask, mix well under ice bath, add raw material 1 (20 g, 0.25 mol) dropwise, and react for 2 h. Then add 200 ml of ethanol and potassium iodide (13.8 g, 0.083 mol) aqueous solution in sequence, stir for 0.5 h, filter the system, spin dry the filtrate, and recrystallize with ethanol to obtain 12 g of white solid, which is directly used in the next step.

[0046] [Example 2]

[0047] Preparation of Compound I-8

[0048]

[0049] The specific preparation process is as follows:

[0050] (1) Raw material 4 (2 g, 0.01 mol), toluene (20 ml), thionyl chloride (1.79 g, 0.015 mol), and N,N-dimethylformamide (3 drops) were added to a 100 ml three-necked flask in sequence. The system was heated to 110°C and reacted for 5 h. TLC showed that the raw material had basically reacted. The system was spin-dried to obtain 2.2 g of a brown oil, which was directly used in the next step.

[0051] (2) Add intermediate 5 (2.2 g, crude product) and 1,2-dichloroethane (10 ml) to a 100 ml three-necked flask, and add triethylamine (2 g, 0.02 mol) and 1-aminopyridine iodide (2.2 g, 0.01 mol) to the system under a water bath. Stir overnight after the addition. TLC shows that the raw materials have basically reacted. Add water to the system to quench, extract with ethyl acetate, dry and desolventize, and obtain 1.3 g of brown solid by column chromatography. The purity is 97.34%, which is I-8. 1 H NMR (400MHz, Chloroform-d) δ8.85–8.79(m,2H),8.03–7.94(m,1H),7.80(p,J=4.1Hz,1H),7.73(t,J=7.0Hz,2H),7.12(d,J=4.8Hz,2H); MS(M+H + )=279.30.

[0052] [Example 3]

[0053] Preparation of Compound I-17

[0054]

[0055] The specific preparation process is as follows:

[0056] (1) Raw material 4 (1.66 g, 0.01 mol), toluene (15 ml), thionyl chloride (1.79 g, 0.015 mol), and N,N-dimethylformamide (3 drops) were added to a 100 ml three-necked flask in sequence. The system was heated to 110° C. and reacted for 5 h. TLC showed that the raw material had basically reacted. The system was spin-dried to obtain 1.74 g of a brown oil, which was directly used in the next step.

[0057] (2) Add intermediate 5 (1.74 g, crude product) and 1,2-dichloroethane (10 ml) to a 100 ml three-necked flask, add triethylamine (2 g, 0.02 mol) and 1-aminopyridine iodide (2.2 g, 0.01 mol) to the system under a water bath, stir overnight after the addition, and the raw materials are basically reacted by TLC. Add water to the system to quench, extract with ethyl acetate, dry and desolventize, and obtain 0.9 g of brown solid by column chromatography with a purity of 99.31%, i.e., I-17. 1H NMR(400MHz,Chloroform-d)δ8.81–8.74(m,2H),8.02–7.93(m,1H),7.71(t,J=7.1H z, 2H), 7.57 (dd, J=6.5, 2.9Hz, 1H), 6.89 (q, J=4.2, 3.6Hz, 2H), 6.08 (s, 2H); MS (M+H + )=243.36.

[0058] [Example 4]

[0059] Preparation of Compound I-22

[0060]

[0061] The specific preparation process is as follows:

[0062] (1) In a 100 ml three-necked flask, raw material 4 (1.8 g, 0.01 mol), toluene (20 ml), thionyl chloride (1.79 g, 0.015 mol), and N,N-dimethylformamide (3 drops) were added in sequence. The system was heated to 110°C and reacted for 5 h. TLC showed that the raw material had basically reacted. The system was spin-dried to obtain 1.81 g of a brown oil, which was directly used in the next step.

[0063] (2) Add intermediate 5 (1.81 g, crude product) and 1,2-dichloroethane (10 ml) to a 100 ml three-necked flask, and add triethylamine (2 g, 0.02 mol) and 1-aminopyridine iodide (2.2 g, 0.01 mol) to the system under a water bath. Stir overnight after the addition. TLC shows that the raw materials have basically reacted. Add water to the system to quench, extract with ethyl acetate, dry and desolventize, and obtain 1.79 g of brown solid by column chromatography with a purity of 98.89%, i.e., I-22. 1 H NMR(400MHz,Chloroform-d)δ8.84–8.78(m,2H),7.91(t,J=7.7Hz,1H),7.66(t,J=7.0Hz,2H),7.23(dd ,J=7.2,2.0Hz,1H),6.93–6.79(m,2H),4.32(dd,J=5.9,2.5Hz,2H),4.27(dd,J=5.4,2.8Hz,2H); MS(M+H + )=257.36.

[0064] [Example 5]

[0065] Preparation of Compound I-23

[0066]

[0067] (1) Raw material 4 (1.94 g, 0.01 mol), toluene (20 ml), thionyl chloride (1.79 g, 0.015 mol), and N,N-dimethylformamide (3 drops) were added to a 100 ml three-necked flask in sequence. The system was heated to 110°C and reacted for 5 h. TLC showed that the raw material had basically reacted. The system was spin-dried to obtain 2.1 g of a brown oil, which was directly used in the next step.

[0068] (2) Add intermediate 5 (2.1 g, crude product) and 1,2-dichloroethane (10 ml) to a 100 ml three-necked flask, and add triethylamine (2 g, 0.02 mol) and 1-aminopyridine iodide (2.2 g, 0.01 mol) to the system under a water bath. Stir overnight after the addition. TLC shows that the raw materials have basically reacted. Add water to the system to quench, extract with ethyl acetate, dry and desolventize, and obtain 2 g of brown solid by column chromatography. The purity is 98.95%, which is I-23. 1 H NMR(400MHz,Chloroform-d)δ8.82(d,J=6.2Hz,2H),7.95(t,J=7.8Hz,1H),7.80–7.66( m,4H),6.98(d,J=8.3Hz,1H),4.25(dt,J=9.0,5.6Hz,4H),2.21(p,J=5.6Hz,2H); MS(M+H + )=271.44.

[0069] [Example 6]

[0070] Preparation of Compound I-26

[0071]

[0072] (1) In a 100 ml three-necked flask, raw material 4 (2 g, 0.01 mol), toluene (20 ml), thionyl chloride (1.79 g,

[0074] 0.015 mol), N,N-dimethylformamide (3 drops), the system was heated to 110°C for 5 h, TLC showed that the raw material had basically reacted, the system was spin-dried to obtain 2.3 g of brown oil, which was directly used in the next step.

[0075] (2) Add intermediate 5 (2.3 g, crude product) and 1,2-dichloroethane (10 ml) to a 100 ml three-necked flask, and add triethylamine (2 g, 0.02 mol) and 1-aminopyridine iodide (2.2 g, 0.01 mol) to the system under a water bath. Stir overnight after the addition. TLC shows that the raw material has basically reacted. Add water to the system to quench, extract with ethyl acetate, dry and desolventize, and obtain 1.6 g of brown solid by column chromatography. The purity is 94.15%, which is I-26. 1H NMR(400MHz,Chloroform-d)δ8.83(d,J=6.2Hz,2H),8.03–7.95(m,2H),7.90(s,1H),7.73(t,J=7.0Hz,2H),7.08(d,J=8.3Hz,1H); MS(M+H + )=279.19.

[0076] [Example 7]

[0077] Preparation of Compound I-29

[0078]

[0079] (1) Raw material 4 (1.67 g, 0.01 mol), toluene (15 ml), thionyl chloride (1.79 g, 0.015 mol), and N,N-dimethylformamide (3 drops) were added to a 100 ml three-necked flask in sequence. The system was heated to 110°C and reacted for 5 h. TLC showed that the raw material had basically reacted. The system was spin-dried to obtain 1.8 g of a brown oil, which was directly used in the next step.

[0080] (2) Add intermediate 5 (1.8 g, crude product) and 1,2-dichloroethane (10 ml) to a 100 ml three-necked flask, and add triethylamine (2 g, 0.02 mol) and 1-aminopyridine iodide (2.2 g, 0.01 mol) to the system under a water bath. Stir overnight after the addition. TLC shows that the raw material has basically reacted. Add water to the system to quench, extract with ethyl acetate, dry and desolventize, and obtain 1.1 g of brown solid by column chromatography. The purity is 98.17%, which is I-29. 1 H NMR(400MHz,Chloroform-d)δ8.84(d,J=6.2Hz,2H),7.95(t,J=7.7Hz,1H),7.77(d,J =8.1Hz, 1H), 7.69 (dd, J = 15.5, 8.4Hz, 3H), 6.85 (d, J = 8.1Hz, 1H), 6.00 (s, 2H); MS (M+H) + )=243.15.

[0081]

Biological activity test

[0082] This test example tests the insecticidal activity of some of the compounds prepared in the present invention, specifically the insecticidal activity against Plutella xylostella. The specific test process is as follows:

[0083] (1) Dissolving the compound to be tested in acetone and diluting it to the required concentration with a 0.1% Tween 80 aqueous solution, as shown in Test Example 1, the acetone content does not exceed 5%, to prepare a drug;

[0084] (2) Use a brush to pick 10 2-year-old diamondback moth larvae and place them in a 9-cm diameter petri dish and starve them for 3-4 hours;

[0085] (3) Use a 3 cm diameter puncher to punch the purple cabbage into leaf discs of uniform size. Soak the leaf discs in the corresponding agent for 10 seconds, take them out to dry, and place them in a petri dish. Write the label information on the petri dish. Place the treated petri dish in an observation room (25°C) for observation. After 72 hours, check the number of live insects and calculate the mortality rate:

[0086] Mortality rate (%) = (number of worms inoculated - number of live worms) / number of worms inoculated * 100%.

[0087] [Test Example 1]

[0088] The compounds were diluted to a concentration of 100 mg / L and then tested according to the above process. In this test, compounds I-8, I-17, I-22, I-23, I-26, and I-29 showed 100% lethality to Plutella xylostella larvae.

[0089] According to the above test method, compounds I-8, I-17 and the compounds disclosed in The Journal of organic chemistry, 2020, 85 (20), 13069-13079 were selected for parallel tests on insecticide (Plutella xylostella). The test results are shown in Table 3 below:

[0090] Table 3

[0091]

[0092] It can be seen from the above test results that the benzodioxetine heterocyclic compounds provided by the present invention have good insecticidal effects, and the insecticidal activity is significantly higher than that of the control compounds.

[0093] The preferred embodiments of the present invention are described in detail above, but the present invention is not limited thereto. Within the technical concept of the present invention, the technical solution of the present invention can be subjected to a variety of simple modifications, including the combination of various technical features in any other suitable manner, and these simple modifications and combinations should also be regarded as the contents disclosed by the present invention and belong to the protection scope of the present invention.

Claims

1. A benzodioxetane compound as shown in formula I or an agriculturally acceptable salt thereof, characterized in that: In Formula I, R1 is methyl, ethyl, halogen or hydrogen; R2 is methyl, ethyl, halogen or hydrogen; R3 is halogen or hydrogen; R4 is halogen or hydrogen; n is 0, 1 or 2.

2. The benzodioxetine compound or its agriculturally acceptable salt according to claim 1, characterized in that: R1 is fluorine or hydrogen; R2 is fluorine or hydrogen; R3 is hydrogen; R4 is hydrogen; n is 0, 1 or 2.

3. The benzodioxetine compound or its agriculturally acceptable salt according to claim 2, characterized in that: Selected from the following structures, 4. Use of the benzodioxetine compound or its agriculturally acceptable salt according to any one of claims 1 to 3 in the preparation of pesticides.

5. An insecticidal composition, characterized in that: The insecticide composition comprises an active ingredient and at least one carrier, wherein the active ingredient is selected from at least one of the benzodioxetine compounds or agriculturally acceptable salts thereof according to any one of claims 1 to 3.

6. The insecticidal composition according to claim 5, characterized in that Based on the total weight of the insecticide composition, the weight percentage of the active ingredient is 1-99%, preferably 5-60%.

7. Use of the insecticidal composition according to any one of claims 5 to 6 in killing insects in agriculture, forestry and gardening.

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