ISOXAZOLINE COMPOUNDS, THEIR PREPARATION METHODS AND USE

Abstract

An isoxazoline compound, a preparation method therefor and an application thereof. The compound has a structured as represented by general formula I. Also provided is use of the compound represented by general formula I as an insecticide and acaricide as well as an animal parasite control agent.

##STR00001##

Claims

1. An isoxazoline compound as shown in Formula I: ##STR00046## In Formula I: R.sub.1 is selected from hydrogen, chlorine, or fluorine; R.sub.2 is selected from ethyl or 2,2,2-trifluoroethyl; R.sub.3 is selected from C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 haloalkyl, C.sub.3-C.sub.8 cycloalkyl, or C.sub.1-C.sub.6 alkoxy C.sub.1-C.sub.6 alkyl; or a stereoisomer of the compound of Formula I; or a salt of the compound of Formula I; or a salt of a stereoisomer of the compound of Formula I.

2. The isoxazoline compound according to claim 1, wherein in Formula I: R.sub.1 is selected from hydrogen, chlorine, or fluorine; R.sub.2 is selected from ethyl or 2,2,2-trifluoroethyl; R.sub.3 is selected from C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4 haloalkyl, C.sub.3-C.sub.4 cycloalkyl, or C.sub.1-C.sub.4 alkoxy C.sub.1-C.sub.3 alkyl.

3. The isoxazoline compound according to claim 2, wherein in Formula I: R.sub.1 is selected from hydrogen, chlorine, or fluorine; R.sub.2 is selected from ethyl or 2,2,2-trifluoroethyl; R.sub.3 is selected from C.sub.1-C.sub.4 alkyl, cyclopropyl, or C.sub.1-C.sub.4 alkoxy C.sub.1-C.sub.2 alkyl.

4. The isoxazoline compound according to claim 1, wherein the salt of the compound of Formula I includes: a salt formed by the reaction of the compound of Formula I with hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, propionic acid, butyric acid, valeric acid, trifluoroacetic acid, oxalic acid, malonic acid, methanesulfonic acid, 4-toluenesulfonic acid, malic acid, fumaric acid, lactic acid, maleic acid, salicylic acid, tartaric acid, or citric acid; and/or, the salt of the stereoisomer of the compound of Formula I includes a salt formed by the reaction of the stereoisomer of the compound of Formula I with hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, propionic acid, butyric acid, valeric acid, trifluoroacetic acid, oxalic acid, malonic acid, methanesulfonic acid, 4-toluenesulfonic acid, malic acid, fumaric acid, lactic acid, maleic acid, salicylic acid, tartaric acid, or citric acid.

5. The isoxazoline compound according to claim 1, wherein the isoxazoline compound is selected from the compounds in Table 1, which have the structure of Formula I with R.sub.1, R.sub.2, and R.sub.3 being those listed in Table 1: TABLE-US-00009 TABLE 1 Compound No. R.sub.1 R.sub.2 R.sub.3 1 H ethyl methyl 2 H ethyl ethyl 3 H ethyl n-propyl 4 H ethyl isopropyl 5 H ethyl n-butyl 6 H ethyl isobutyl 7 H ethyl tert-butyl 8 H ethyl cyclopropyl 9 H ethyl CH.sub.3OCH.sub.2— 10 H ethyl CH.sub.3CH.sub.2OCH.sub.2— 11 H ethyl CH.sub.3CH.sub.2CH.sub.2OCH.sub.2— 12 H ethyl (CH.sub.3).sub.2CHOCH.sub.2— 13 H ethyl CH.sub.3CH.sub.2CH.sub.2CH.sub.2OCH.sub.2— 14 H ethyl (CH.sub.3).sub.3COCH.sub.2— 15 H ethyl CH.sub.3OCH.sub.2CH.sub.2— 16 H ethyl CH.sub.3CH.sub.2OCH.sub.2CH.sub.2— 17 H ethyl CH.sub.3CH.sub.2CH.sub.2OCH.sub.2CH.sub.2— 18 H ethyl CH.sub.3CH.sub.2CH.sub.2CH.sub.2OCH.sub.2CH.sub.2— 19 F ethyl methyl 20 F ethyl ethyl 21 F ethyl n-propyl 22 F ethyl isopropyl 23 F ethyl n-butyl 24 F ethyl i sobutyl 25 F ethyl tert-butyl 26 F ethyl cyclopropyl 27 F ethyl CH.sub.3OCH.sub.2— 28 F ethyl CH.sub.3CH.sub.2OCH.sub.2— 29 F ethyl CH.sub.3CH.sub.2CH.sub.2OCH.sub.2— 30 F ethyl (CH.sub.3).sub.2CHOCH.sub.2— 31 F ethyl CH.sub.3CH.sub.2CH.sub.2CH.sub.2OCH.sub.2— 32 F ethyl (CH.sub.3).sub.3COCH.sub.2— 33 F ethyl CH.sub.3OCH.sub.2CH.sub.2— 34 F ethyl CH.sub.3CH.sub.2OCH.sub.2CH.sub.2— 35 F ethyl CH.sub.3CH.sub.2CH.sub.2OCH.sub.2CH.sub.2— 36 F ethyl CH.sub.3CH.sub.2CH.sub.2CH.sub.2OCH.sub.2CH.sub.2— 37 H 2,2,2-trifluoroethyl methyl 38 H 2,2,2-trifluoroethyl ethyl 39 H 2,2,2-trifluoroethyl n-propyl 40 H 2,2,2-trifluoroethyl isopropyl 41 H 2,2,2-trifluoroethyl n-butyl 42 H 2,2,2-trifluoroethyl isobutyl 43 H 2,2,2-trifluoroethyl tert-butyl 44 H 2,2,2-trifluoroethyl cyclopropyl 45 H 2,2,2-trifluoroethyl CH.sub.3OCH.sub.2— 46 H 2,2,2-trifluoroethyl CH.sub.3CH.sub.2OCH.sub.2— 47 H 2,2,2-trifluoroethyl CH.sub.3CH.sub.2CH.sub.2OCH.sub.2— 48 H 2,2,2-trifluoroethyl (CH.sub.3).sub.2CHOCH.sub.2— 49 H 2,2,2-trifluoroethyl CH.sub.3CH.sub.2CH.sub.2CH.sub.2OCH.sub.2— 50 H 2,2,2-trifluoroethyl (CH.sub.3).sub.3COCH.sub.2— 51 H 2,2,2-trifluoroethyl CH.sub.3OCH.sub.2CH.sub.2— 52 H 2,2,2-trifluoroethyl CH.sub.3CH.sub.2OCH.sub.2CH.sub.2— 53 H 2,2,2-trifluoroethyl CH.sub.3CH.sub.2CH.sub.2OCH.sub.2CH.sub.2— 54 H 2,2,2-trifluoroethyl CH.sub.3CH.sub.2CH.sub.2CH.sub.2OCH.sub.2CH.sub.2— 55 F 2,2,2-trifluoroethyl methyl 56 F 2,2,2-trifluoroethyl ethyl 57 F 2,2,2-trifluoroethyl n-propyl 58 F 2,2,2-trifluoroethyl isopropyl 59 F 2,2,2-trifluoroethyl n-butyl 60 F 2,2,2-trifluoroethyl isobutyl 61 F 2,2,2-trifluoroethyl tert-butyl 62 F 2,2,2-trifluoroethyl cyclopropyl 63 F 2,2,2-trifluoroethyl CH.sub.3OCH.sub.2— 64 F 2,2,2-trifluoroethyl CH.sub.3CH.sub.2OCH.sub.2— 65 F 2,2,2-trifluoroethyl CH.sub.3CH.sub.2CH.sub.2OCH.sub.2— 66 F 2,2,2-trifluoroethyl (CH.sub.3).sub.2CHOCH.sub.2— 67 F 2,2,2-trifluoroethyl CH.sub.3CH.sub.2CH.sub.2CH.sub.2OCH.sub.2— 68 F 2,2,2-trifluoroethyl (CH.sub.3).sub.3COCH.sub.2— 69 F 2,2,2-trifluoroethyl CH.sub.3OCH.sub.2CH.sub.2— 70 F 2,2,2-trifluoroethyl CH.sub.3CH.sub.2OCH.sub.2CH.sub.2— 71 F 2,2,2-trifluoroethyl CH.sub.3CH.sub.2CH.sub.2OCH.sub.2CH.sub.2— 72 F 2,2,2-trifluoroethyl CH.sub.3CH.sub.2CH.sub.2CH.sub.2OCH.sub.2CH.sub.2— 73 Cl ethyl methyl 74 Cl ethyl ethyl 75 Cl ethyl n-propyl 76 Cl ethyl isopropyl 77 Cl ethyl n-butyl 78 Cl ethyl isobutyl 79 Cl ethyl tert-butyl 80 Cl ethyl cyclopropyl 81 Cl ethyl CH.sub.3OCH.sub.2— 82 Cl ethyl CH.sub.3CH.sub.2OCH.sub.2— 83 Cl ethyl CH.sub.3CH.sub.2CH.sub.2OCH.sub.2— 84 Cl ethyl (CH.sub.3).sub.2CHOCH.sub.2— 85 Cl ethyl CH.sub.3CH.sub.2CH.sub.2CH.sub.2OCH.sub.2— 86 Cl ethyl (CH.sub.3).sub.3COCH.sub.2— 87 Cl ethyl CH.sub.3OCH.sub.2CH.sub.2— 88 Cl ethyl CH.sub.3CH.sub.2OCH.sub.2CH.sub.2— 89 Cl ethyl CH.sub.3CH.sub.2CH.sub.2OCH.sub.2CH.sub.2— 90 Cl ethyl CH.sub.3CH.sub.2CH.sub.2CH.sub.2OCH.sub.2CH.sub.2— 91 Cl 2,2,2-trifluoroethyl methyl 92 Cl 2,2,2-trifluoroethyl ethyl 93 Cl 2,2,2-trifluoroethyl n-propyl 94 Cl 2,2,2-trifluoroethyl isopropyl 95 Cl 2,2,2-trifluoroethyl n-butyl 96 Cl 2,2,2-trifluoroethyl isobutyl 97 Cl 2,2,2-trifluoroethyl tert-butyl 98 Cl 2,2,2-trifluoroethyl cyclopropyl 99 Cl 2,2,2-trifluoroethyl CH.sub.3OCH.sub.2— 100 Cl 2,2,2-trifluoroethyl CH.sub.3CH.sub.2OCH.sub.2— 101 Cl 2,2,2-trifluoroethyl CH.sub.3CH.sub.2CH.sub.2OCH.sub.2— 102 Cl 2,2,2-trifluoroethyl (CH.sub.3).sub.2CHOCH.sub.2— 103 Cl 2,2,2-trifluoroethyl CH.sub.3CH.sub.2CH.sub.2CH.sub.2OCH.sub.2— 104 Cl 2,2,2-trifluoroethyl (CH.sub.3).sub.3COCH.sub.2— 105 Cl 2,2,2-trifluoroethyl CH.sub.3OCH.sub.2CH.sub.2— 106 Cl 2,2,2-trifluoroethyl CH.sub.3CH.sub.2OCH.sub.2CH.sub.2— 107 Cl 2,2,2-trifluoroethyl CH.sub.3CH.sub.2CH.sub.2OCH.sub.2CH.sub.2— 108 Cl 2,2,2-trifluoroethyl CH.sub.3CH.sub.2CH.sub.2CH.sub.2OCH.sub.2CH.sub.2— or a stereoisomer ofany one of the compounds from Table 1; or a salt formed by the reaction of any one of the compounds from Table 1 with hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, propionic acid, butyric acid, valeric acid, trifluoroacetic acid, oxalic acid, malonic acid, methanesulfonic acid, 4- toluenesulfonic acid, malic acid, fumaric acid, lactic acid, maleic acid, salicylic acid, tartaric acid, or citric acid; or a salt formed by the reaction of a stereoisomer of any one of the compounds from Table 1 with hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, propionic acid, butyric acid, valeric acid, trifluoroacetic acid, oxalic acid, malonic acid, methanesulfonic acid, 4- toluenesulfonic acid, malic acid, fumaric acid, lactic acid, maleic acid, salicylic acid, tartaric acid, or citric acid.

6. The isoxazoline compound according to claim 5, wherein the isoxazoline compound is selected from the compounds in Table 2, which have the structure of Formula I with R.sub.1, R.sub.2, and R.sub.3 being those listed in Table 2: TABLE-US-00010 TABLE 2 Compound No. R.sub.1 R.sub.2 R.sub.3 1 H ethyl methyl 2 H ethyl ethyl 3 H ethyl n-propyl 4 H ethyl isopropyl 5 H ethyl n-butyl 6 H ethyl i sobutyl 7 H ethyl tert-butyl 8 H ethyl cyclopropyl 9 H ethyl CH.sub.3OCH.sub.2— 10 H ethyl CH.sub.3CH.sub.2OCH.sub.2— 11 H ethyl CH.sub.3CH.sub.2CH.sub.2OCH.sub.2— 12 H ethyl (CH.sub.3).sub.2CHOCH.sub.2— 19 F ethyl methyl 20 F ethyl ethyl 21 F ethyl n-propyl 22 F ethyl isopropyl 23 F ethyl n-butyl 24 F ethyl i sobutyl 25 F ethyl tert-butyl 26 F ethyl cyclopropyl 27 F ethyl CH.sub.3OCH.sub.2— 28 F ethyl CH.sub.3CH.sub.2OCH.sub.2— 29 F ethyl CH.sub.3CH.sub.2CH.sub.2OCH.sub.2— 30 F ethyl (CH.sub.3).sub.2CHOCH.sub.2— 37 H 2,2,2-trifluoroethyl methyl 38 H 2,2,2-trifluoroethyl ethyl 39 H 2,2,2-trifluoroethyl n-propyl 40 H 2,2,2-trifluoroethyl isopropyl 41 H 2,2,2-trifluoroethyl n-butyl 42 H 2,2,2-trifluoroethyl i sobutyl 43 H 2,2,2-trifluoroethyl tert-butyl 44 H 2,2,2-trifluoroethyl cyclopropyl 45 H 2,2,2-trifluoroethyl CH.sub.3OCH.sub.2— 46 H 2,2,2-trifluoroethyl CH.sub.3CH.sub.2OCH.sub.2— 47 H 2,2,2-trifluoroethyl CH.sub.3CH.sub.2CH.sub.2OCH.sub.2— 48 H 2,2,2-trifluoroethyl (CH.sub.3).sub.2CHOCH.sub.2— 55 F 2,2,2-trifluoroethyl methyl 56 F 2,2,2-trifluoroethyl ethyl 57 F 2,2,2-trifluoroethyl n-propyl 58 F 2,2,2-trifluoroethyl isopropyl 59 F 2,2,2-trifluoroethyl n-butyl 60 F 2,2,2-trifluoroethyl isobutyl 61 F 2,2,2-trifluoroethyl tert-butyl 62 F 2,2,2-trifluoroethyl cyclopropyl 63 F 2,2,2-trifluoroethyl CH.sub.3OCH.sub.2— 64 F 2,2,2-trifluoroethyl CH.sub.3CH.sub.2OCH.sub.2— 65 F 2,2,2-trifluoroethyl CH.sub.3CH.sub.2CH.sub.2OCH.sub.2— 66 F 2,2,2-trifluoroethyl (CH.sub.3).sub.2CHOCH.sub.2— 73 Cl ethyl methyl 74 Cl ethyl ethyl 75 Cl ethyl n-propyl 76 Cl ethyl isopropyl 77 Cl ethyl n-butyl 78 Cl ethyl isobutyl 79 Cl ethyl tert-butyl 80 Cl ethyl cyclopropyl 81 Cl ethyl CH.sub.3OCH.sub.2— 82 Cl ethyl CH.sub.3CH.sub.2OCH.sub.2— 83 Cl ethyl CH.sub.3CH.sub.2CH.sub.2OCH.sub.2— 84 Cl ethyl (CH.sub.3).sub.2CHOCH.sub.2— 91 Cl 2,2,2-trifluoroethyl methyl 92 Cl 2,2,2-trifluoroethyl ethyl 93 Cl 2,2,2-trifluoroethyl n-propyl 94 Cl 2,2,2-trifluoroethyl isopropyl 95 Cl 2,2,2-trifluoroethyl n-butyl 96 Cl 2,2,2-trifluoroethyl isobutyl 97 Cl 2,2,2-trifluoroethyl tert-butyl 98 Cl 2,2,2-trifluoroethyl cyclopropyl 99 Cl 2,2,2-trifluoroethyl CH.sub.3OCH.sub.2— 100 Cl 2,2,2-trifluoroethyl CH.sub.3CH.sub.2OCH.sub.2— 101 Cl 2,2,2-trifluoroethyl CH.sub.3CH.sub.2CH.sub.2OCH.sub.2— 102 Cl 2,2,2-trifluoroethyl (CH.sub.3).sub.2CHOCH.sub.2— or a stereoisomer of any one of the compounds from Table 2, or a salt formed by the reaction of any one of the compounds from Table 2 with hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, propionic acid, butyric acid, valeric acid, trifluoroacetic acid, oxalic acid, malonic acid, methanesulfonic acid, 4-toluenesulfonic acid, malic acid, fumaric acid, lactic acid, maleic acid, salicylic acid, tartaric acid, or citric acid, or a salt formed by the reaction of a stereoisomer of any one of the compounds from Table 2 with hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, propionic acid, butyric acid, valeric acid, trifluoroacetic acid, oxalic acid, malonic acid, methanesulfonic acid, 4-toluenesulfonic acid, malic acid, fumaric acid, lactic acid, maleic acid, salicylic acid, tartaric acid, or citric acid.

7. The isoxazoline compound according to claim 1, wherein the stereoisomer of the compound of Formula I is the compound as shown in Formula IA, ##STR00047##

8. The isoxazoline compound according to claim 7, wherein the compound as shown in Formula IA is selected from the compounds in Table 3, which have the structure as shown in Formula IA with R.sub.1, R.sub.2, and R.sub.3 being those listed in Table 3, TABLE-US-00011 TABLE 3 Compound No. R.sub.1 R.sub.2 R.sub.3 109 H ethyl methyl 110 H ethyl ethyl 111 H ethyl isopropyl 112 H ethyl cyclopropyl 113 H ethyl CH.sub.3OCH.sub.2— 114 H ethyl CH.sub.3CH.sub.2OCH.sub.2— 115 H ethyl CH.sub.3OCH.sub.2CH.sub.2— 116 H ethyl CH.sub.3CH.sub.2OCH.sub.2CH.sub.2— 117 F ethyl methyl 118 F ethyl ethyl 119 F ethyl isopropyl 120 F ethyl cyclopropyl 121 F ethyl CH.sub.3OCH.sub.2— 122 F ethyl CH.sub.3CH.sub.2OCH.sub.2— 123 F ethyl CH.sub.3OCH.sub.2CH.sub.2— 124 F ethyl CH.sub.3CH.sub.2OCH.sub.2CH.sub.2—

9. The compound according to claim 8, wherein the compound as shown in Formula IA is selected from the compounds in Table 4, which have the structure as shown in Formula IA with R.sub.1, R.sub.2, and R.sub.3 being those listed in Table 4, TABLE-US-00012 TABLE 4 Compound No. R.sub.1 R.sub.2 R.sub.3 109 H ethyl methyl 110 H ethyl ethyl 111 H ethyl isopropyl 112 H ethyl cyclopropyl 113 H ethyl CH.sub.3OCH.sub.2— 114 H ethyl CH.sub.3CH.sub.2OCH.sub.2— 117 F ethyl methyl 118 F ethyl ethyl 119 F ethyl isopropyl 120 F ethyl cyclopropyl 121 F ethyl CH.sub.3OCH.sub.2— 122 F ethyl CH.sub.3CH.sub.2OCH.sub.2—

10. A method for preparing the isoxazoline compound according to claim 1, wherein when the isoxazoline compound is the compound of Formula I, the method comprises the following steps, in which the meanings of R.sub.1, R.sub.2, and R.sub.3 in the reaction formula are the same as those in claim 1: ##STR00048## the compound of Formula II and the compound of Formula III are allowed to react in a solvent at a temperature from −10° C. to the boiling point of the solvent for 0.5-48 hours to prepare the compound of Formula I; the reaction can be carried out in the presence of alkali.

11. Use of the isoxazoline compound according to claim 1 in the preparation of insecticides and/or acaricides.

12. The use according to claim 11, wherein the insecticide and/or acaricide is used to control one or more of Leucania separata, Plutella xylostella, Chilo suppressalis, and Tetranychus cinnabarinus.

13. An insecticide formulation or acaricide formulation, wherein the insecticide formulation or acaricide formulation contains the isoxazoline compound according to claim 1 as an active ingredient, and also contains one or more adjuvants; optionally, the amount of the isoxazoline compound in the insecticide formulation or acaricide formulation is 0.1 to 99% by weight, and further optionally 0.5 to 90% by weight.

14. An insecticide composition or acaricide composition, comprising a mixture of the isoxazoline compound according to claim 1, and an additional active compound, in which the additional active compound is one or more of an insecticide, a poison bait, a disinfectant, an acaricide, a nematicide, a fungicide, a growth regulator, and an herbicide.

15. A method for controlling agricultural or forestry pests and/or mites, comprising applying an effective dose of material to the pests and/or mites to be controlled, or to their growth media, in which the material is one or more selected from the group consisting of: the isoxazoline compound according to claim 1; the insecticide formulation or acaricide formulation; the insecticide composition or acaricide composition.

16. Use of the isoxazoline compound according to claim 1 in the preparation of an animal parasite control agent.

17. The use according to claim 16, wherein the animal parasite control agent is used for controlling one or more of cat fleas and American dog ticks.

18. An animal parasite control agent, comprising the isoxazoline compound according to claim 1 as an active component, and one or more adjuvants; optionally, the amount of the isoxazoline compound in the animal parasite control agent is 1 to 80 wt %.

19. An animal parasite control composition, comprising a mixture of the isoxazoline compound according to claim 1 and an additional animal parasite control active compound, wherein the additional animal parasite control active compound is one or more of acaricides, insecticides, parasiticides, and antiplasmodium agents.

20. A method for controlling animal parasites, comprising the following steps: applying an effective dose of material to the animal parasites to be controlled, or to their growth media, wherein the material is one or more selected from the group consisting of: the isoxazoline compound according to claim 1; the animal parasite control agent; the animal parasite control composition.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0073] In order to make the purpose, technical solutions and advantages of the embodiments of the invention clearer, the technical solutions in the embodiments of the invention will be described clearly and completely, obviously, the described embodiments are some of the embodiments of the present invention, but not all of them. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative work are within the scope of the present invention.

[0074] In addition, in order to better explain the present invention, a lot of specific details are given in the following embodiments. It will be understood by those skilled in the art that the present invention may be practiced without certain specific details. In some embodiments, materials, elements, methods, means, etc., well known to those skilled in the art, are not described in detail so as to highlight the spirit of the present invention.

[0075] Throughout the specification and claims, the term “comprising” or variations thereof, such as “including” or “containing” and the like, will be understood to include the stated components and not to exclude other elements or other components, unless expressly indicated otherwise.

[0076] Unless otherwise indicated, all raw materials used are commercially available.

[0077] In the present invention, the terms used have the following meanings: In the definitions of compounds of the general formulae given above, the collective terms used generally represent the following substituents: Alkyl: linear or branched alkyl, such as methyl, ethyl, n-propyl, isopropyl, or various butyl, pentyl, or hexyl isomers.

[0078] Haloalkyl: linear or branched alkyl, in which part or all of hydrogen atoms can be substituted with halogen atoms, such as chloromethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, 2,2,2-trifluoroethyl, heptafluoroisopropyl, 1,1,2,2,2-pentafluoroethyl, etc.

[0079] Cycloalkyl: substituted or unsubstituted cyclic alkyl, such as cyclopropyl, cyclopentyl, or cyclohexyl; and the substituent can be, for example, methyl, halogen, cyano, etc.

[0080] Alkoxy alkyl: alkyl-O-alkyl-, for example, CH.sub.3O CH.sub.2-, CH.sub.3CH.sub.2OCH.sub.2-, CH.sub.3CH.sub.2CH.sub.2OCH.sub.2-, (CH.sub.3).sub.2CHOCH.sub.2-, CH.sub.3CH.sub.2CH.sub.2CH.sub.2OCH.sub.2-, (CH.sub.3).sub.3COCH.sub.2-, CH.sub.3O CH.sub.2CH.sub.2-, CH.sub.3CH.sub.2O CH.sub.2CH.sub.2-, CH.sub.3CH.sub.2CH.sub.2O CH.sub.2CH.sub.2-, or CH.sub.3CH.sub.2CH.sub.2CH.sub.2O CH.sub.2CH.sub.2-, etc.

[0081] Animal parasite control agent: refers to an active compound that can effectively reduce the incidence of various parasites in animals infected by the parasites. Control: means that active compounds can effectively kill parasites and inhibit their growth or reproduction.

[0082] Insecticide: a substance that has insecticidal efficacy on pests.

[0083] Acaricide: an agent used to control phytophagous mites.

Synthesis Examples

[0084] According to the above-mentioned synthetic route, the compounds shown in Formula I of the present invention can be prepared by using different raw materials, respectively, regarding which further detailed description is as follows.

Example 1: Preparation of Compound 109

[0085] ##STR00007##

[0086] 0.30 g (0.57 mmol) of 4-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole-3-yl) —N—((R)-2-ethyl-3-oxooxazolidin-4-yl)-2-methylbenzamide, 20 mL of toluene, 0.11 g (1.09 mmol) of triethylamine, and finally 66.35 mg (0.85 mmol) of acetyl chloride were added to a reaction bottle, followed by heating to reflux for reaction. After the reaction was complete, as detected by TLC, water was added to the reaction solution, which was then extracted with ethyl acetate, and the organic phase was dried over anhydrous magnesium sulfate, then filtered, concentrated, and purified by column chromatography to obtain 0.13 g of oily matter.

[0087] The NMR and MS data of Compound 109 were as follows: .sup.1H NMR (600 MHz, DMSO-d6) δ 7.83 (t, 1H), 7.71 (s, 1H), 7.67 (dt, 1H), 7.64 (d, 2H), 7.55 (d, 1H), 5.21 (t, 1H), 4.52-4.29 (m, 4H), 3.56-3.40 (m, 2H), 2.40 (s, 3H), 2.15 (s, 3H), 1.13 (t, 3H).

[0088] ESI-MS, m/Z: 594.23 [M+Na]+.

Example 2: Preparation of Compound 112

[0089] ##STR00008##

[0090] 0.50 g (0.95 mmol) of 4-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl) —N—((R)-2-ethyl-3-oxooxazolidin-4-yl)-2-methylbenzamide, 25 mL of toluene, 0.19 g (1.88 mmol) of triethylamine, and finally 0.15 g (1.44 mmol) of cyclopropanecarbonyl chloride were added to a reaction bottle, followed by heating to reflux for reaction. After the reaction was complete, as detected by TLC, water was added to the reaction solution, which was then extracted with ethyl acetate, and the organic phase was dried over anhydrous magnesium sulfate, then filtered, concentrated, and purified by column chromatography to obtain 0.29 g of yellow solid.

[0091] The NMR and MS data of Compound 112 were as follows: .sup.1H NMR (600 MHz, Chloroform-d) δ 7.63 (d, 1H), 7.60 (s, 1H), 7.56-7.49 (m, 3H), 7.44 (t, 1H), 5.56 (t, 1H), 4.56-4.42 (m, 2H), 4.08 (d, 1H), 3.75-3.56 (m, 3H), 2.52 (s, 3H), 1.40-1.15 (m, 4H), 1.11-0.94 (m, 2H), 0.60 (br s, 2H). ESI-MS, m/Z: 530.2 [M+H]+.

Example 3: Preparation of Compound 113

[0092] ##STR00009##

[0093] 1.00 g (1.89 mmol) of 4-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl) —N—((R)-2-ethyl-3-oxooxazolidin-4-yl)-2-methylbenzamide, 30 mL of toluene, 0.38 g (3.76 mmol) of triethylamine, and finally 0.31 g (2.87 mmol) of methoxyacetyl chloride were added to a reaction bottle, followed by heating to reflux for reaction. After the reaction was complete, as detected by TLC, water was added to the reaction solution, which was then extracted with ethyl acetate, and the organic phase was dried over anhydrous magnesium sulfate, then filtered, concentrated, and purified by column chromatography to obtain 0.53 g of oily matter.

[0094] The NMR and MS data of Compound 113 were as follows: .sup.1H NMR (600 MHz, DMSO-d6) δ 7.82 (t, 1H), 7.72 (t, 1H), 7.68-7.65 (m, 1H), 7.63 (d, 2H), 7.57 (dd, 1H), 5.08 (t, 1H), 4.49-4.28 (m, 4H), 4.15 (s, 2H), 3.57-3.36 (m, 2H), 3.22 (s, 3H), 2.39 (s, 3H), 1.12 (t, 3H). ESI-MS, m/Z: 624.25 [M+Na]+.

Example 4: Preparation of Compound 114

[0095] ##STR00010##

[0096] Compound 114 (oily matter) was prepared according to the synthesis method of Example 3. The NMR and MS data of Compound 114 were as follows: .sup.1H NMR (600 MHz, DMSO-d6) δ 7.83 (t, 1H), 7.72 (t, 1H), 7.69-7.66 (m, 1H), 7.64 (d, 2H), 7.57 (dd, 1H), 5.08 (t, 1H), 4.48-4.30 (m, 4H), 4.20 (s, 2H), 3.54-3.39 (m, 4H), 2.40 (s, 3H), 1.13 (t, 3H), 1.09 (t, 3H). ESI-MS, m/Z: 638.37 [M+Na]+.

Example 5: Preparation of Compound 120

[0097] ##STR00011##

[0098] Compound 120 (yellow solid) was prepared according to the synthesis method of Example 2. The NMR and MS data of Compound 120 were as follows: .sup.1H NMR (600 MHz, DMSO-d6) δ 7.82 (d, 2H), 7.69 (s, 1H), 7.66 (d, 1H), 7.56 (d, 1H), 5.54 (td, 1H), 4.58 (t, 1H), 4.46-4.30 (m, 3H), 3.57-3.44 (m, 2H), 2.43 (s, 3H), 1.42-1.35 (m, 1H), 1.15 (t, 3H), 0.87-0.78 (m, 2H), 0.77-0.58 (m, 2H). ESI-MS, m/Z: 616.30 [M+H]+.

Example 6: Preparation of Compound 121

[0099] ##STR00012##

[0100] Compound 121 (oily matter) was prepared according to the synthesis method of Example 3. The NMR and MS data of Compound 121 were as follows: .sup.1H NMR (600 MHz, DMSO-d6) δ 7.81 (d, 2H), 7.71 (t, 1H), 7.68-7.64 (m, 1H), 7.57 (dd, 1H), 5.08 (t, 1H), 4.48-4.29 (m, 4H), 4.15 (s, 2H), 3.53-3.40 (m, 2H), 3.22 (s, 3H), 2.39 (s, 3H), 1.13 (t, 3H). ESI-MS, m/Z: 642.13 [M+Na]+.

Example 7: Preparation of Compound 122

[0101] ##STR00013##

[0102] Compound 122 (oily matter) was prepared according to the synthesis method of Example 3. The NMR and MS data of Compound 122 were as follows: .sup.1H NMR (600 MHz, DMSO-d6) δ 7.82 (d, 2H), 7.73-7.64 (m, 2H), 7.58 (dd, 1H), 5.08 (t, 1H), 4.49-4.31 (m, 4H), 4.20 (s, 2H), 3.55-3.40 (m, 4H), 2.40 (s, 3H), 1.13 (t, 3H), 1.09 (t, 3H).

[0103] ESI-MS, m/Z: 656.34 [M+Na]+.

[0104] Other compounds as shown in Formula I of the present invention can be prepared according to the above examples.

[0105] Determination of Biological activity

Example 8: Determination of Biological Activities Against Leucania Separata, Plutella xylostella, and Chilo suppressalis

[0106] The compounds of the invention were determined for the insecticidal activities against several insects. The determination method was as follows: The compound to be determined was dissolved in a mixed solvent of acetone/methanol (1:1), followed by dilution with water containing 0.1% (wt) Tween 80 to a desired concentration.

[0107] The activities of the respective compounds against Leucania separata, Plutella xylostella, and Chilo suppressalis were determined by Airbrush spraying method. [0108] (1) Determination of the insecticidal activity against Leucania separata

[0109] The determination method was as follows: Corn leaves were cut into 2 cm long segments; the pressure of Airbrush spraying was 10 psi (about 0.7 kg/cm.sup.2); both sides of each leaf segment were sprayed with 0.5 mL of the compound solution to be tested. After drying in the shade, ten 3.sup.rd instar larvae were inoculated for each treatment, and each treatment was replicated 3 times. After treatment, they were cultured in an observation room at a temperature of 25° C. and a relative humidity of 60-70%, and the number of surviving insects was examined and the mortality was calculated three days after administration.

[0110] Some test results against Leucania separata were shown in Table 5:

TABLE-US-00005 TABLE 5 Insecticidal test results of the compounds of the invention against Leucania separata Compound Mortality (%, 3 days after administration) No. Formula 10 mg/L 5 mg/L 2.5 mg/L 1.25 mg/L 109 [00014] 100 83.33 63.33 26.67 112 [00015] 100 100 96.67 80 113 [00016] 100 100 100 100 114 [00017] 100 100 100 100 120 [00018] 100 100 100 100 121 [00019] 100 100 100 100 122 [00020] 100 100 100 100 Comparative compound [00021] 73.33 13.33 0 0

[0111] In the example of the present invention, compounds with better insecticidal, acaricidal, and parasiticidal efficacy were obtained by selecting the groups R.sub.1, R.sub.2, and R.sub.3 in the compound of formula I. As seen from the above table, when methoxy was selected as R.sub.3 (i.e., the comparative compound in the above table, which was prepared according to the preparation method of the invention), its activity against Leucania separataw was far less than that of the compound in the example of the present invention. [0112] (2) Determination of the insecticidal activity against Plutella xylostella

[0113] The determination method was as follows: Cabbage leaves were made into leaf discs with a diameter of 2 cm by using a hole puncher; the pressure of Airbrush spraying was 10 psi (about 0.7 kg/cm.sup.2); both sides of each leaf disc were sprayed with 0.5 mL of the compound solution to be tested. After drying in the shade, ten 3.sup.rd instar larvae were inoculated for each treatment, and each treatment was replicated 3 times. After treatment, they were cultured in an observation room at a temperature of 25° C. and a relative humidity of 60-70%, and the number of surviving insects was examined and the mortality was calculated three days after administration.

[0114] Some test results against Plutella xylostella were shown in Table 6:

TABLE-US-00006 TABLE 6 Insecticidal test results of the compounds of the invention against Plutella xylostella Compound Mortality (%, 3 days after administration) No. Formula 10 mg/L 5 mg/L 2.5 mg/L 109 [00022] 100 70 — 112 [00023] 100 70 — 113 [00024] 100 90 66.67 114 [00025] 100 86.67 60 120 [00026] 100 100 83.33 121 [00027] 100 100 86.67 122 [00028] 100 100 70 Comparative compound [00029] 76.67 30 0

[0115] In the example of the present invention, compounds with better insecticidal, acaricidal, and parasiticidal efficacy were obtained by selecting the groups R.sub.1, R.sub.2, and R.sub.3 in the compound of formula I. As seen from the above table, when methoxy was selected as R.sub.3 (i.e., the comparative compound in the above table, which was prepared according to the preparation method of the invention), its activity against Plutella xylostella was far less than that of the compound in the example of the present invention. [0116] (3) Determination of the insecticidal activity against Chilo suppressalis

[0117] The determination method was as follows: 1) Preparation of rice seedlings: rice plants were cultivated in a plastic cup with a diameter of 4.5 cm and a height of 4 cm in a thermostatic chamber (temperature 26-28° C., relative humidity 60-80%, illumination 16 hL: 8 hD), and when the rice plants were developed to have 4-5 leaves, strong seedlings with identical growth vigour were selected for chemical treatment, and each treatment was replicated 3 times. 2) Preparation of insects to be tested: Chilo suppressalis, 3rd instar larvae, continuous lab rearing. 3) Inoculation of insects by spraying rice plant stems: The whole rice seedlings were sprayed evenly by using the spraying method, with 15 mL of the compound solution for each treatment. Firstly, the blank control was treated, and then the above procedure was replicated according to the order of test concentration from low to high. After rice seedlings were spray-treated, they were placed in the shade to dry, and the stems about 5 cm from the stem bases were cut off to feed the insects to be tested. Glass culture dishes with a diameter of 90 mm were prepared; each dish was padded with a filter paper at the bottom and added with water to keep moisture; about 5 rice stems were put into each dish and inoculated with 10 larvae, and each culture dish was then sealed with a non-woven and cultured in a thermostatic chamber. The number of residual live insects was examined 3 days after administration.

[0118] Some test results against Chilo suppressalis were shown in Table 7:

TABLE-US-00007 TABLE 7 Insecticidal test results of the compounds of the invention against Chilo suppressalis Mortality (%, 3 days Compound after administration) No. Formula 10 mg/L 2.5 mg/L 0.625 mg/L 109 [00030] 100 100 80 112 [00031] 100 100 96.67 113 [00032] 100 100 86.67 114 [00033] 100 100 83.33 120 [00034] 100 100 96.67 121 [00035] 100 100 90 122 [00036] 100 100 93.33 Comparative compound [00037] 16.67 0 0

[0119] In the example of the present invention, compounds with better insecticidal, acaricidal, and parasiticidal efficacy were obtained by selecting the groups R.sub.1, R.sub.2, and R.sub.3 in the compound of formula I. As seen from the above table, when methoxy was selected as R.sub.3 (i.e., the comparative compound in the above table, which was prepared according to the preparation method of the invention), its activity against Chilo suppressalis was far less than that of the compound in the example of the present invention.

Example 9: Determination of Biological Activity Against Tetranychus cinnabarinus

[0120] The compounds of the invention were determined for the acaricidal activity in greenhouse. The determination method was as follows: The compound to be determined was dissolved in acetone or dimethyl sulfoxide according to its solubility, and 0.1% Tween 80 solution was used to formulate 50 mL of the solution to be tested at a desired concentration, and the content of acetone or dimethyl sulfoxide in the solution did not exceed 10%.

[0121] A bean seedling with two true leaves was taken for inoculating 30-40 adult mites of Tetranychus cinnabarinus. After examining the cardinal number, the whole seedling was treated by spraying with a hand-held sprayer, each treatment being replicated 3 times, and then placed in a standard observation room. The number of surviving mites was examined after 72 hours, and the mortality was calculated.

[0122] Some test results against Tetranychus cinnabarinus were shown in Table 8:

TABLE-US-00008 TABLE 8 The acaricidal test results of the compounds of the invention against Tetranychus cinnabarinus Mortality (%, 3 Compound days after treatment) No. Formula 5 mg/L 2.5 mg/L 1.25 mg/L 0.625 mg/L 109 [00038] 100 100 70 16.7 112 [00039] 100 100 100 96.7 113 [00040] 100 100 100 100 114 [00041] 100 100 100 100 120 [00042] 100 100 100 100 121 [00043] 100 100 100 100 122 [00044] 100 100 100 100 Comparative compound [00045] 100 73.3 20 —

[0123] In the example of the present invention, compounds with better insecticidal, acaricidal, and parasiticidal efficacy were obtained by selecting the groups R.sub.1, R.sub.2, and R.sub.3 in the compound of formula I. As seen from the above table, when methoxy was selected as R.sub.3 (i.e., the comparative compound in the above table, which was prepared according to the preparation method of the invention), its activity against Tetranychus cinnabarinus was far less than that of the compound in the example of the present invention.

Example 10: Insecticidal Test Against Cat Fleas

[0124] 4 mg of then mon to be tested was dissolved into 40 mL of acetone to obtain an acetone solution with a concentration of 100 ppm. 400 μL of the resultant solution was applied onto the bottom and side of a culture dish with an inner diameter of 5.3 cm, followed by standing until acetone was volatilized. A film of the compound of the invention was made on the inner wall of the culture dish. The inner wall of the used culture dish was 40 cm.sup.2 and was treated with a dose of 1 μg/cm.sup.2; and ten adult cat fleas (male and female mixed) were put into the culture dish, which then was covered and stored in a thermostatic chamber at 25° C. The number of dead insects was examined after 72 hours, and the mortality was calculated. The test was replicated 3 times. Test results: Compounds 109, 112, 113, 114, 120, 121, 122 showed more than 70% mortality of insects.

Example 11: Insecticidal Test Against American Dog Ticks

[0125] 4 mg of the compound to be tested was dissolved into 40 mL of acetone to obtain an acetone solution with a concentration of 100 ppm. 400 μL of the resultant solution was applied onto the bottom and side of each of two culture dishes with an inner diameter of 5.3 cm, followed by standing until acetone was volatilized. A film of the compound of the invention was made on the inner wall of each culture dish. The inner wall of the used culture dish was 40 cm.sup.2 and was treated with a dose of 1 μg/cm.sup.2. Ten level 1 nymph (male and female mixed) of American dog ticks were put into each of the two culture dishes, and then the two culture dishes were combined and sealed at the joint with a tape to prevent escape, and then stored in a thermostatic chamber at 25° C. The number of dead insects was examined after 24 hours, and the mortality was calculated. The test was replicated 3 times. Test results: Compounds 109, 112, 113, 114, 120, 121, 122 showed more than 70% mortality of insects.

INDUSTRIAL APPLICABILITY

[0126] The invention has disclosed an isoxazoline compound, the preparation method therefor, and the application thereof. The isoxazoline compound has unexpectedly excellent insecticidal and acaricidal efficacy, and also exhibits appropriate control efficacy on poisonous pests without phytotoxicity to cultivated crops and plants. In addition, the compounds of the present invention may be used to control, disinfect, and kill various pests, such as harmful piercing-sucking insects, chewing insects, and other plant parasitic pests, stored grain pests, sanitary pests, and the like.