ISOXAZOLINE COMPOUND WITH OPTICAL ACTIVITY AND USE

Abstract

An isoxazoline compound with optical activity is shown in the formula (I). The compound of the formula (I) has excellent herbicidal activity, can be used for weeding pre- and post-emergence, and can also be used for soil treatment. The compound of the formula (I) can effectively control various broad-leaved weeds, grass weeds and Cyperaceae weeds, and can control various resistant weeds, such as glyphosate-resistant weeds. The excellent weeding effect can be obtained at a low dose. The compound has good safety to crops such as corn, wheat, rice, soybean and sugar beet. The compound can be used as a selective herbicide in crop fields in agriculture, and can also be used as a non-selective herbicide in non-cultivated land, fallow land, woodland, orchards and ridges.

##STR00001##

Claims

1. An isoxazoline compound with optical activity, characterized in that the structure of the compound is shown in formula (I): ##STR00013## Wherein: * represents an asymmetric carbon atom with configuration S; R.sub.1 is selected from CH.sub.3 or NH.sub.2; R.sub.2 is selected from C.sub.1-C.sub.4 alkyl or C.sub.1-C.sub.4 haloalkyl; R.sub.3 and R.sub.4 are respectively selected from hydrogen, halogen, C.sub.1-C.sub.6 alkyl or C.sub.1-C.sub.6 alkoxy; R.sub.5 is selected from hydrogen, cyano, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 haloalkyl, C.sub.3-C.sub.6 cycloalkyl, phenyl, or phenyl substituted independently with 1-4 following substitutents: halogen, CN, NO.sub.2, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 haloalkyl, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 haloalkoxy, C.sub.1-C.sub.6 alkylthio or C.sub.1-C.sub.6 alkylsulfonyl; R.sub.6 is selected from C.sub.1-C.sub.6 alkyl CO.sub.2R.sub.7, CO.sub.2R.sub.7 or CONR.sub.8R.sub.9; R.sub.7 is selected from hydrogen, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 haloalkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.3-C.sub.6 alkenyl, C.sub.3-C.sub.6 alkynyl, C.sub.1-C.sub.6 alkoxy C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxycarbonyl C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.6 alkylcarbonyloxy C.sub.2-C.sub.4 alkyl, and benzyl, furylidene, thiazomethylene, tetrahydrofuranmethylene or pyridinemethylene which is unsubstituted or further substituted with 1-4 groups independently selected from the following: halogen, CN, NO.sub.2, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.1-C.sub.8 alkoxy, C.sub.1-C.sub.8 haloalkoxy, C.sub.1-C.sub.8 alkoxycarbonyl, C.sub.1-C.sub.8 alkylthio or C.sub.1-C.sub.8 alkylsulfonyl; R.sub.8 and R.sub.9 are respectively selected from hydrogen, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 haloalkyl or C.sub.1-C.sub.4 alkoxycarbonyl C.sub.1-C.sub.4 alkyl.

2. The compound according to claim 1, characterized in that in the formula (I): * represents an asymmetric carbon atom with configuration S; R.sub.1 is selected from CH.sub.3 or NH.sub.2; R.sub.2 is selected from methyl, isopropyl, tert-butyl, trifluoromethyl, trichloromethyl, difluoromethyl or heptafluoroisopropyl; R.sub.3 and R.sub.4 are respectively selected from hydrogen, fluorine, chlorine, bromine, methyl, ethyl, isopropyl, tert-butyl, methoxy, ethoxy or isopropoxy; R.sub.5 is selected from hydrogen, cyano, C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4 haloalkyl, C.sub.3-C.sub.6 cycloalkyl, phenyl, or phenyl substituted independently with 1-4 following substitutents: halogen, CN, NO.sub.2, C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4 haloalkyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.4 haloalkoxy, C.sub.1-C.sub.4 alkylthio or C.sub.1-C.sub.4 alkylsulfonyl; R.sub.6 is selected from C.sub.1-C.sub.4 alkyl CO.sub.2R.sub.7, CO.sub.2R.sub.7 or CONR.sub.8R.sub.9; R.sub.7 is selected from hydrogen, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 haloalkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.3-C.sub.6 alkenyl, C.sub.3-C.sub.6 alkynyl, C.sub.1-C.sub.4 alkoxy C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4 alkoxycarbonyl C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4 alkylcarbonyloxy C.sub.2-C.sub.4 alkyl, and benzyl, furylmethylene or tetrahydrofurylidene which is unsubstituted or further substituted with 1-4 groups independently selected from the following: halogen, CN, NO.sub.2, C.sub.1-C.sub.6 alkyl or C.sub.1-C.sub.6 haloalkyl; R.sub.8 and R.sub.9 are respectively selected from hydrogen, C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4 haloalkyl or C.sub.1-C.sub.4 alkoxycarbonyl C.sub.1-C.sub.4 alkyl.

3. The compound according to claim 2, characterized in that in the formula (I): * represents an asymmetric carbon atom with configuration S; R.sub.1 is selected from CH.sub.3 or NH.sub.2; R.sub.2 is selected from methyl, trifluoromethyl, trichloromethyl or difluoromethyl; R.sub.3 and R.sub.4 are respectively selected from hydrogen, fluorine, chlorine, bromine, methyl, methoxy, ethoxy or isopropoxy; R.sub.5 is selected from hydrogen, cyano, C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4 haloalkyl, C.sub.3-C.sub.6 cycloalkyl, phenyl, or phenyl substituted independently with 1-4 following substitutents: halogen, CN, NO.sub.2, C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4 haloalkyl, C.sub.1-C.sub.4 alkoxy or C.sub.1-C.sub.4 haloalkoxy; R.sub.6 is selected from C.sub.1-C.sub.4 alkyl CO.sub.2R.sub.7, CO.sub.2R.sub.7 or CONR.sub.8R.sub.9; R.sub.7 is selected from hydrogen, C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4 haloalkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.3-C.sub.6 alkenyl, C.sub.3-C.sub.6 alkynyl, C.sub.1-C.sub.4 alkoxy C.sub.1-C.sub.2 alkyl, C.sub.1-C.sub.4 alkoxycarbonyl C.sub.1-C.sub.2 alkyl, C.sub.1-C.sub.4 alkylcarbonyloxy C.sub.2-C.sub.4 alkyl, and benzyl, furylmethylene or tetrahydrofurylidene which is unsubstituted or further substituted with 1-3 groups independently selected from the following: halogen, CN, NO.sub.2, C.sub.1-C.sub.4 alkyl or C.sub.1-C.sub.4 haloalkyl; R.sub.8 and R.sub.9 are respectively selected from hydrogen, C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4 haloalkyl or C.sub.1-C.sub.4 alkoxycarbonyl C.sub.1-C.sub.2 alkyl.

4. The compound according to claim 3, characterized in that in the formula (I): * represents an asymmetric carbon atom with configuration S; R.sub.1 is selected from CH.sub.3 or NH.sub.2; R.sub.2 is selected from trifluoromethyl, trichloromethyl or difluoromethyl; R.sub.3 and R.sub.4 are respectively selected from hydrogen, fluorine, chlorine, bromine or isopropoxy; R.sub.5 is selected from hydrogen, cyano, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, trifluoromethyl, difluoromethyl, phenyl, or phenyl substituted independently with 1-4 following substitutents: halogen, CN, NO.sub.2, methyl, isopropyl, tert-butyl, trifluoromethyl, difluoromethyl, methoxy, ethoxy, isopropoxy, trifluoromethoxy, difluoromethoxy or trifluoroethoxy; R.sub.6 is selected from C.sub.1-C.sub.4 alkyl CO.sub.2R.sub.7, CO.sub.2R.sub.7 or CONR.sub.8R.sub.9; R.sub.7 is selected from hydrogen, C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4 haloalkyl, allyl, 2-methylallyl, 1,1-dimethylallyl, allyl carbinyl, propargyl, alkynyl butyl, cyclopropyl, cyclohexyl, C.sub.1-C.sub.3 alkoxy C.sub.1-C.sub.2 alkyl, C.sub.1-C.sub.4 alkoxycarbonyl C.sub.1-C.sub.2 alkyl, C.sub.1-C.sub.4 alkylcarbonyloxy C.sub.2-C.sub.3 alkyl, and benzyl, furylidene or tetrahydrofurylidene which is unsubstituted or further substituted with 1-3 groups independently selected from the following: halogen, CN, NO.sub.2 or C.sub.1-C.sub.4 alkyl; R.sub.8 and R.sub.9 are respectively selected from hydrogen, C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4 haloalkyl or C.sub.1-C.sub.4 alkoxycarbonyl C.sub.1-C.sub.2 alkyl.

5. The compound according to claim 4, characterized in that in the formula (I): * represents an asymmetric carbon atom with configuration S; R.sub.1 is selected from CH.sub.3 or NH.sub.2; R.sub.2 is selected from trifluoromethyl, trichloromethyl or difluoromethyl; R.sub.3 and R.sub.4 are respectively selected from hydrogen, fluorine, chlorine, bromine or isopropoxy; R.sub.5 is selected from hydrogen, cyano, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, trifluoromethyl, difluoromethyl, phenyl, or phenyl substituted independently with 1-4 following substitutents: halogen, CN, NO.sub.2, methyl, isopropyl, tert-butyl, trifluoromethyl, difluoromethyl, methoxy, ethoxy, isopropoxy, trifluoromethoxy, difluoromethoxy or trifluoroethoxy; R.sub.6 is selected from CH.sub.2CO.sub.2R.sub.7, CH.sub.2CH.sub.2CO.sub.2R.sub.7, CO.sub.2R.sub.7 or CONR.sub.8R.sub.9; R.sub.7 is selected from hydrogen, methyl, ethyl, n-propyl, n-butyl, isopropyl, isobutyl, tert-butyl, trifluoroethyl, trifluoromethyl, difluoroethyl, heptafluoroisopropyl, allyl, propargyl, 2-methylallyl, 1,1-dimethylallyl, allyl carbinyl, propargyl, alkynyl butyl, cyclopropyl, cyclohexyl, methoxyethyl, ethoxyethyl, isopropoxyethyl, CH.sub.3OCOCH.sub.2, CH.sub.3CH.sub.2OCOCH.sub.2, (CH.sub.3).sub.2CHOCOCH.sub.2, CH.sub.3OCOCH.sub.2CH.sub.2, CH.sub.3CH.sub.2OCOCH.sub.2CH.sub.2, (CH.sub.3).sub.2CHOCOCH.sub.2CH.sub.2, CH.sub.3OCOCH(CH.sub.3), CH.sub.3CH.sub.2OCOCH(CH.sub.3), benzyl, furylidene or tetrahydrofurylidene which is unsubstituted or further substituted with 1-2 groups independently selected from the following: fluorine, chlorine, bromine, CN, NO.sub.2, methyl, isopropyl or tert-butyl; R.sub.8 is selected from hydrogen, C.sub.1-C.sub.4 alkyl or C.sub.1-C.sub.4 haloalkyl; R.sub.9 is selected from hydrogen, C.sub.1-C.sub.4 alkyl or C.sub.1-C.sub.4 alkoxycarbonyl C.sub.1-C.sub.2 alkyl.

6. The compound according to claim 5, characterized in that in the formula (I): * represents an asymmetric carbon atom with configuration S; R.sub.1 is selected from CH.sub.3 or NH.sub.2; R.sub.2 is selected from trifluoromethyl or difluoromethyl; R.sub.3 and R.sub.4 are respectively selected from hydrogen, fluorine, chlorine, bromine or isopropoxy; R.sub.5 is selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl; R.sub.6 is selected from CH.sub.2CO.sub.2R.sub.7, CH.sub.2CH.sub.2CO.sub.2R.sub.7, CO.sub.2R.sub.7 or CONR.sub.8R.sub.9; R.sub.7 is selected from hydrogen, methyl, ethyl, n-propyl, n-butyl, isopropyl, isobutyl, tert-butyl, trifluoroethyl, trifluoromethyl, difluoroethyl, heptafluoroisopropyl, allyl, propargyl, 2-methylallyl, 1,1-dimethylallyl, allyl carbinyl, propargyl, alkynyl butyl, cyclopropyl, cyclohexyl, methoxyethyl, ethoxyethyl, isopropoxyethyl, CH.sub.3OCOCH.sub.2, CH.sub.3CH.sub.2OCOCH.sub.2, (CH.sub.3).sub.2CHOCOCH.sub.2, CH.sub.3OCOCH.sub.2CH.sub.2, CH.sub.3CH.sub.2OCOCH.sub.2CH.sub.2, (CH.sub.3).sub.2CHOCOCH.sub.2CH.sub.2, CH.sub.3OCOCH(CH.sub.3), CH.sub.3CH.sub.2OCOCH(CH.sub.3), furanmethylene or tetrahydrofurylidene, and benzyl which is unsubstituted or further substituted with 1-2 groups independently selected from the following: fluorine, chlorine, bromine, CN, NO.sub.2, methyl, isopropyl or tert-butyl; R.sub.8 is selected from hydrogen, methyl, ethyl, isopropyl, n-propyl, n-butyl, tert-butyl, trifluoroethyl, difluoroethyl, 1-chloroethyl, 1-chloropropyl or 2-chloropropyl; R.sub.9 is selected from hydrogen, methyl, ethyl, isopropyl, n-propyl, n-butyl, tert-butyl, CH.sub.3OCOCH.sub.2, CH.sub.3CH.sub.2OCOCH.sub.2, (CH.sub.3).sub.2CHOCOCH.sub.2, CH.sub.3OCOCH.sub.2CH.sub.2, CH.sub.3CH.sub.2OCOCH.sub.2CH.sub.2, (CH.sub.3).sub.2CHOCOCH.sub.2CH.sub.2, CH.sub.3OCOCH(CH.sub.3) or CH.sub.3CH.sub.2OCOCH(CH.sub.3).

7. The compound according to claim 6, characterized in that in the formula (I): * represents an asymmetric carbon atom with configuration S; R.sub.1 is selected from CH.sub.3 or NH.sub.2; R.sub.2 is selected from trifluoromethyl or difluoromethyl; R.sub.3 and R.sub.4 are respectively selected from hydrogen, fluorine, chlorine or isopropoxy; R.sub.5 is selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl; R.sub.6 is selected from CH.sub.2CO.sub.2R.sub.7, CH.sub.2CH.sub.2CO.sub.2R.sub.7 or CO.sub.2R.sub.7; R.sub.7 is selected from hydrogen, methyl, ethyl, n-propyl, n-butyl, isopropyl, isobutyl, tert-butyl, trifluoroethyl, trifluoromethyl, difluoroethyl, heptafluoroisopropyl, allyl, propargyl, 2-methylallyl, 1,1-dimethylallyl, allyl carbinyl, propargyl, alkynyl butyl, cyclopropyl, cyclohexyl, methoxyethyl, ethoxyethyl, isopropoxyethyl, CH.sub.3OCOCH.sub.2, CH.sub.3CH.sub.2OCOCH.sub.2, (CH.sub.3).sub.2CHOCOCH.sub.2, CH.sub.3OCOCH.sub.2CH.sub.2, CH.sub.3CH.sub.2OCOCH.sub.2CH.sub.2, (CH.sub.3).sub.2CHOCOCH.sub.2CH.sub.2, CH.sub.3OCOCH(CH.sub.3), CH.sub.3CH.sub.2OCOCH(CH.sub.3), furanmethylene or tetrahydrofurylidene, and benzyl which is unsubstituted or further substituted with 1-2 groups independently selected from the following: fluorine, chlorine, bromine, CN, NO.sub.2, methyl, isopropyl or tert-butyl.

8. A method of controlling, comprising weeds applying the compound having general formula (I) according to claim 1 to a subject in need of treatment.

9. A herbicidal composition, comprising the compound of the formula (I) of claim 1 as an active ingredient, wherein the weight percentage of the active ingredient in the composition is 0.1-99%.

10. A method of controlling weeds, comprising applying a herbicidal composition according to claim 9 to a subject in need of treatment.

Description

PREPARATION EXAMPLE

Example 1 the Preparation of Compound 3

[0086] ##STR00011##

1) Preparation of (S)-3-(5-amino-2-chloro-4-fluorophenyl)-5-methyl-4,5-dihydro-5-isoxazole carboxylic acid ethyl ester

[0087] 25 g of Amylose tris(3,5-dimethylphenylcarbamate) silica gel was loaded into a chromatographic column; 5 ml of dichloromethane solution containing 1 g of 3-(5-amino-2-chloro-4-fluorophenyl)-5-methyl-4,5-dihydro-5-isoxazole carboxylic acid ethyl ester (prepared according to the method in CN105753853) was adsorbed onto the chromatographic column; Biotage Purification Instrument(Isolera™) was used to separate and collect corresponding components to respectively obtain 0.47 g of optical isomer (R)-3-(5-amino-2-chloro-4-fluorophenyl)-5-methyl-4,5-dihydro-5-isoxazole carboxylic acid ethyl ester (with optical purity of 99.8% and melting point of 105-106° C.) and 0.46 g of (S)-3-(5-amino-2-chloro-4-fluorophenyl)-5-methyl-4,5-dihydro-5-isoxazole carboxylic acid ethyl ester (with optical purity of 99.4% and melting point of 104-105° C.).

[0088] Optical rotation (Shenguang WZZ-2S/2SS, sodium lamp wavelength: 589.44 nm, solvent: acetonitrile): S isomer [α].sup.26° C..sub.589.44 nm=150.65°, R isomer [α].sup.26° C..sub.589.44 nm=−111.66°.

2) Preparation of compound 3

[0089] 0.45 g (1.5 mmol) of (S)-3-(5-amino-2-chloro-4-fluorophenyl)-5-methyl-4,5-dihydro-5-isoxazole carboxylic acid ethyl ester and 0.46 g (1.8 mmol) of ethyl (Z)-3-(3,3-dimethylureido)-4,4,4-trifluorobut-2-enoate (prepared according to the method in CN108570041) were added to a reaction flask containing 20 ml of acetic acid in sequence, the mixture was then heated to reflux, and maintained at the temperature for 6 h; the mixture was concentrated under reduced pressure, followed by adjusting to a pH of 7 using sodium bicarbonate solution, extracted with ethyl acetate, and dried over anhydrous magnesium sulfate and concentrated under reduced pressure, then 0.45 g (3.24 mmol) of potassium carbonate and 50 ml of N,N-dimethylformamide were added in sequence to the residue, the mixture was cooled to 0° C., 0.51 g (3.6 mmol) of iodomethane was added dropwise to the mixture, and then the mixture was raised to room temperature and stirred for 6 h. After the TLC monitored that the reaction was finished, the reactants were poured into water and extracted with ethyl acetate, the organic phase was washed with a saturated brine solution, dried with anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified through silica column (ethyl acetate:petroleum ether=1:5, as an eluent) to obtain compound 3: 0.48 g of oil.

[0090] Optical rotation of compound 3 (Shenguang WZZ-2S/2SS, sodium lamp wavelength: 589.44 nm, solvent: acetonitrile): [α].sup.20° C..sub.589.44 nm=68.06°.

[0091] .sup.1H-NMR (300 MHz, CDCl.sub.3): δ 7.68 (d, J=9.0 Hz, 1H, Ph-H), 7.35 (d, J=9.0 Hz, 1H, Ph-H), 6.36 (s, 1H, Ar—H), 4.26 (q, J=7.1 Hz, 2H, OCH.sub.2), 4.00 (d, J=17.4 Hz, 1H, —CH.sub.2—), 3.56 (s, 3H, N—CH.sub.3), 3.39 (d, J=17.4 Hz, 1H, —CH.sub.2—), 1.71 (s, 3H, CH.sub.3), 1.32 (t, J=7.1 Hz, 3H, CH.sub.3).

Test of Biological Activity Example 2 Bioassay of Herbicidal Activity in Greenhouse

[0092] The test method of the herbicidal activity of the compound in the present invention is as follows:

[0093] Quantitative grass weed (Echinochloa crusgalli and Setaria viridis) and broad-leaved weed (Abutilon theophrasti and Zinnia elegans) seeds were sown in paper cups having a diameter of 7 cm and containing nutrient soil, after sowing, the seeds were covered with 1 cm of soil, the soil was pressed and watered, and then the seeds were cultivated in a greenhouse according to a conventional method. The grass weeds grew to 2-3 leaf stages, the broad-leaved weeds grew to 2-4 leaf stages, stem and leaves were sprayed. Before emergence, the soil was sprayed within 24 hours after sowing. According to the design dose of the test, spray treatment was carried out on a track-type crop sprayer (designed and produced by British Engineer Research Ltd.) (spray pressure is 1.95 kg/cm.sup.2, spray volume is 500 L/hm.sup.2 and track speed is 1.48 km/h). The test was repeated for three times. The test material was treated and then placed in an operation hall. The medicinal liquid was naturally dried in the shade, and then was placed in a greenhouse and managed according to the conventional method. The response of the weeds to the test compound was observed and recorded. After treatment, the control effects of the test compound on the weeds were visually inspected regularly.

[0094] The grading standards of the control effects: 0 represents no control effect and 100% represents that the weeds are completely killed or greatly controlled.

[0095] It is found through the herbicidal activity test that the post-emergence treatment of the compound 3 at a dose of 4-8 g a.i./hm.sup.2 has high herbicidal activity on Abutilon theophrasti, Zinnia elegans, Echinochloa crusgalli, Setaria viridi, and the activity is significantly better than that of the compound 6 in CN105753853 (Table 2-Table 3).

[0096] The specific structural formula of the compound 6 in CN105753853 is as follows:

##STR00012##

TABLE-US-00002 TABLE 2 Control Test Results of Grass Weed Dose Echinochloa Setaria g a.i./hm.sup.2 crusgalli viridis 3 4 90 75 8 98 85 CN105753853 4 45 25 Compound 6 8 50 55

TABLE-US-00003 TABLE 3 Control Test Results of Broad-Leaved Weed Dose Zinnia Abutilon g a.i./hm.sup.2 elegans theophrasti 3 4 100 90 CN105753853 4  90 60 Compound 6