Oxime ether compound and application thereof

Abstract

The present invention discloses an oxime ether compound with novel structure. The structure is shown in general formula I. The definition of each substituent in the formula is provided in the description. ##STR00001## The compound of general formula I has excellent microbicidal 1 activity, and has good control effects on plant bacterial diseases and fungal diseases. The present invention comprises an application of the compound of the general formula I as a microbicide in agriculture and other fields.

Claims

1. An oxime ether compound of formula I or a salt thereof: ##STR00074## wherein: X is sulfur or oxygen; Z is selected from hydrogen, and C.sub.1-C.sub.6 linear or branched alkyls that are unsubstituted or substituted with a substituent selected from halogen, cyano, trifluoromethyl, trifluoromethoxy, hydroxy, nitro, and amino; A is CN, (CO)OR.sup.1, (CO)NHR.sup.2, or (CO)NHNH.sub.2; R.sup.1 is C.sub.1-C.sub.8 alkyl; R.sup.2 is hydrogen or C.sub.1-C.sub.8 alkyl; W is selected from hydrogen, acetonitrile, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 haloalkenyl, C.sub.2-C.sub.8 alkynyl, C.sub.2-C.sub.8 haloalkynyl, C.sub.1-C.sub.8 alkoxy C.sub.1-C.sub.8alkyl, C(O)R.sup.3, C(O)CH.sub.2R.sup.3, C(O)CH.sub.2OR.sup.3, NO.sub.2, OR.sup.4, S(O).sub.2R.sup.5, N(R.sup.6)R.sup.7, and NC(R.sup.8)R.sup.9; Q is selected from hydrogen, acetonitrile, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 haloalkenyl, C.sub.2-C.sub.8 alkynyl, C.sub.2-C.sub.8 haloalkynyl, C.sub.1-C.sub.8 alkoxy C.sub.1-C.sub.8 alkyl, and C(O)R.sup.3, or, Q, N and W are connected to N to form a 3-6 membered saturated or unsaturated ring that contains 0-2 heteroatoms selected from NR.sup.10, O, S, and oxidized S optionally substituted by R.sup.11 or forms a fused ring with benzene ring; R.sup.3 is selected from hydrogen, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 haloalkenyl, C.sub.2-C.sub.8 alkynyl, C.sub.2-C.sub.8 haloalkynyl, C.sub.1-C.sub.8 alkoxy C.sub.1-C.sub.8 alkyl, N(R.sup.12)R.sup.13, optionally substituted aryl, and optionally substituted heteroaryl; R.sup.4 is selected from hydrogen, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, and C.sub.3-C.sub.6 cycloalkyl; R.sup.5 is selected from C.sub.1-C.sub.2 alkyl, C.sub.1-C.sub.2 haloalkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.4 alkyl substituted phenyl, and N(R.sup.12)R.sup.13; R.sup.6 is hydrogen or C.sub.1-C.sub.8 alkyl; R.sup.7 is hydrogen or C.sub.1-C.sub.8 alkyl; R.sup.8 is selected from hydrogen, C.sub.1-C.sub.8alkyl, C.sub.1-C.sub.8 haloalkyl, and phenyl that is unsubstituted or optionally substituted by hydrogen, halogen, cyano, nitro, C.sub.1-C.sub.4 alkyl, or C.sub.1-C.sub.4 haloalkyl; R.sup.9 is selected from C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, phenyl unsubstituted or optionally substituted by hydrogen, halogen, cyano, nitro, C.sub.1-C.sub.4 alkyl, or C.sub.1-C.sub.4 haloalkyl; R.sup.10 is selected from hydrogen, C.sub.1-C.sub.2 alkyl, C.sub.1-C.sub.2 haloalkyl, C.sub.1-C.sub.2 alkylcarbonyl, and C.sub.1-C.sub.2 alkoxycarbonyl; R.sup.11 is selected from H, halogen, CN, NO.sub.2, C.sub.1-C.sub.2 alkyl, C.sub.1-C.sub.2 haloalkyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.2 haloalkoxy, optionally substituted aryl, and S(O)nR.sup.14, wherein n is 0, 1 or 2; R.sup.12 is C.sub.1-C.sub.8 alkyl; R.sup.13 is C.sub.1-C.sub.8 alkyl; and R.sup.14 is hydrogen, C.sub.1-C.sub.2 alkyl, C.sub.1-C.sub.2 haloalkyl, C.sub.3-C.sub.6 cycloalkyl, and C.sub.1-C.sub.4 alkoxy.

2. The oxime ether compound or the salt thereof according to claim 1, wherein in formula I: X is sulfur or oxygen; Z is selected from hydrogen, and C.sub.1-C.sub.3 linear or branched alkyl that are unsubstituted or substituted by halogen, cyano, trifluoromethyl, trifluoromethoxy, hydroxy, nitro, or amino; A is CN, (CO)OR.sup.1, (CO)NHR.sup.2, or (CO)NHNH.sub.2; R.sup.1 is C.sub.1-C.sub.4 alkyl; R.sup.2 is hydrogen or C.sub.1-C.sub.4 alkyl; W is selected from hydrogen, acetonitrile, C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4 haloalkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.2-C.sub.4 alkenyl, C.sub.2-C.sub.4 haloalkenyl, C.sub.2-C.sub.4 alkynyl, C.sub.2-C.sub.4 haloalkynyl, C.sub.1-C.sub.4 alkoxy C.sub.1-C.sub.4 alkyl, C(O)R.sup.3, C(O)CH.sub.2R.sup.3, C(O)CH.sub.2OR.sup.3, NO.sub.2, OR.sup.4, S(O).sub.2R.sup.5, N(R.sup.6)R.sup.7, and NC(R.sup.8)R.sup.9; Q is selected from hydrogen, acetonitrile, C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4 haloalkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.2-C.sub.4 alkenyl, C.sub.2-C.sub.4 haloalkenyl, C.sub.2-C.sub.4 alkynyl, C.sub.2-C.sub.4 haloalkynyl, C.sub.1-C.sub.4 alkoxy C.sub.1-C.sub.4 alkyl, and C(O)R.sup.3, or, Q, N and W are connected to N to form a 3-6 membered saturated or unsaturated ring comprising 0-2 heteroatoms selected from NR.sup.10, O, S and oxidized S, and optionally substituted by R.sup.11 or forming a fused ring with benzene ring; R.sup.3 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.2-C.sub.4 alkenyl, C.sub.2-C.sub.4 haloalkenyl, C.sub.2-C.sub.4 alkynyl, C.sub.2-C.sub.4 haloalkynyl, C.sub.1-C.sub.4 alkoxy C.sub.1-C.sub.4 alkyl, N(R.sup.12)R.sup.13, unsubstituted or substituted phenyl, unsubstituted or substituted pyridyl, unsubstituted or substituted pyrazolyl, unsubstituted or substituted thiazolyl, unsubstituted or substituted isothiazolyl or unsubstituted or substituted thiadiazolyl, wherein the substituent is selected from hydrogen, halogen, cyano, nitro, hydroxyl, sulfhydryl, amino, aldehyde, C(O)NH.sub.2, C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4 haloalkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.3 alkoxy, C.sub.1-C.sub.3 haloalkoxy, C.sub.1-C.sub.3 alkylthio, C.sub.1-C.sub.3 haloalkylthio, C.sub.1-C.sub.3 alkylamino, C.sub.1-C.sub.3 dialkylamino, C.sub.3-C.sub.6 cycloalkylamino, C.sub.1-C.sub.3 alkoxycarbonyl, C.sub.1-C.sub.3 alkylsulfonyl, C.sub.1-C.sub.3 alkylaminocarbonyl, C.sub.1-C.sub.3 alkylaminosulfonyl, unsubstituted or substituted phenyl, and unsubstituted or substituted pyridyl, wherein the substituent for the substituted phenyl or substituted pyridyl is selected from hydrogen, halogen, cyano, nitro, C.sub.1-C.sub.4 alkyl, and C.sub.1-C.sub.4 haloalkyl; R.sup.4 is selected from hydrogen, C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4 haloalkyl, and C.sub.3-C.sub.6 cycloalkyl; R.sup.5 is selected from C.sub.1-C.sub.2 alkyl, C.sub.1-C.sub.2 haloalkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.4 alkyl substituted phenyl, and N(R.sup.12)R.sup.13; R.sup.6 is selected from hydrogen or C.sub.1-C.sub.4 alkyl; R.sup.7 is hydrogen or C.sub.1-C.sub.4 alkyl; R.sup.8 is selected from hydrogen, C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4 haloalkyl, and phenyl unsubstituted or optionally substituted with hydrogen, halogen, cyano, or nitro; R.sup.9 is selected from C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4 haloalkyl, and phenyl unsubstituted or optionally substituted with hydrogen, halogen, cyano, or nitro; R.sup.10 is selected from hydrogen, C.sub.1-C.sub.2 alkyl, C.sub.1-C.sub.2 haloalkyl, C.sub.1-C.sub.2 alkylcarbonyl, and C.sub.1-C.sub.2 alkoxycarbonyl; R.sup.11 is selected from H, halogen, CN, NO.sub.2, C.sub.1-C.sub.2 alkyl, C.sub.1-C.sub.2 haloalkyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.2 haloalkoxy, optionally substituted aryl, and S(O)nR.sup.14, wherein n is 0, 1 or 2; R.sup.12 is C.sub.1-C.sub.4 alkyl; R.sup.13 is C.sub.1-C.sub.4 alkyl; and R.sup.14 is hydrogen, C.sub.1-C.sub.2 alkyl, C.sub.1-C.sub.2 haloalkyl, C.sub.3-C.sub.6 cycloalkyl or C.sub.1-C.sub.4 alkoxy.

3. The oxime ether compound or the salt thereof according to claim 2, wherein in formula I: X is oxygen or sulfur; Z is hydrogen, methyl, or ethyl; A is CN, (CO)OR.sup.1, (CO)NHR.sup.2, or (CO)NHNH.sub.2; R.sup.1 is methyl or ethyl; R.sup.2 is hydrogen, methyl, or ethyl; W 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(O)R.sup.3, OR.sup.4, S(O).sub.2R.sup.5, N(R.sup.6)R.sup.7, and NC(R.sup.8)R.sup.9; Q 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, and C(O)R.sup.3, or, Q, N and W are connected to N to form a 3-6 membered saturated or unsaturated ring comprising 0-2 heteroatoms selected from NR.sup.10, O, S, and oxidized S; and optionally form a fused ring with the benzene ring; R.sup.3 is selected from C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4 haloalkyl, C.sub.3-C.sub.6 cycloalkyl, N(R.sup.12)R.sup.13, unsubstituted or substituted phenyl, unsubstituted or substituted pyridyl, unsubstituted or substituted pyrazolyl, unsubstituted or substituted thiazolyl, unsubstituted or substituted isothiazolyl, and unsubstituted or substituted thiadiazolyl, wherein the substituent is selected from of hydrogen, halogen, cyano, nitro, C(O)NH.sub.2, C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4 haloalkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.3 alkoxy, C.sub.1-C.sub.3 haloalkoxy, C.sub.1-C.sub.3 alkylthio, C.sub.1-C.sub.3 haloalkylthio, C.sub.1-C.sub.3 alkylamino, C.sub.1-C.sub.3 dialkylamino, C.sub.3-C.sub.6 cycloalkylamino, C.sub.1-C.sub.3 alkoxycarbonyl, C.sub.1-C.sub.3 alkylsulfonyl, C.sub.1-C.sub.3 alkylaminocarbonyl, C.sub.1-C.sub.3 alkylaminosulfonyl, unsubstituted or substituted phenyl, and unsubstituted or substituted pyridyl, wherein the substituent is selected from hydrogen, halogen, cyano, nitro, C.sub.1-C.sub.4 alkyl, and C.sub.1-C.sub.4 haloalkyl; R.sup.4 is hydrogen, C.sub.1-C.sub.4 alkyl, or C.sub.1-C.sub.4 haloalkyl; R.sup.5 is C.sub.1-C.sub.2 alkyl, C.sub.1-C.sub.2 haloalkyl, methyl substituted phenyl, or N(R.sup.11)R.sup.12; R.sup.6 is hydrogen, methyl, or ethyl; R.sup.7 is hydrogen, methyl, or ethyl; R.sup.8 is selected from methyl, ethyl, trifluoromethyl, and phenyl that is unsubstituted or optionally substituted by hydrogen, halogen, cyano, or nitro; R.sup.9 is selected from methyl, ethyl, trifluoromethyl, and phenyl unsubstituted or optionally substituted by hydrogen, halogen, cyano, or nitro; R.sup.12 is methyl or ethyl; and R.sup.13 is methyl or ethyl.

4. The oxime ether compound or the salt thereof according to claim 3, wherein in the general formula I: X is oxygen or sulfur; Z is hydrogen; A is CN, (CO)OR.sup.1, or (CO)NH.sub.2; R.sup.1 is methyl or ethyl; W 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(O)R.sup.3, S(O).sub.2R.sup.5, N(R.sup.6)R.sup.7, and NC(R.sup.8)R.sup.9; Q 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, and C(O)R.sup.3; R.sup.3 is selected from C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4 haloalkyl, C.sub.3-C.sub.6 cycloalkyl, N(R.sup.12)R.sup.13, unsubstituted or substituted phenyl, unsubstituted or substituted pyridyl, unsubstituted or substituted pyrazolyl, unsubstituted or substituted thiazolyl, unsubstituted or substituted isothiazolyl, and unsubstituted or substituted thiadiazolyl, wherein the substituent is selected from hydrogen, halogen, cyano, nitro, 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, and C.sub.1-C.sub.4 haloalkylthio; R.sup.5 is C.sub.1-C.sub.2 alkyl, C.sub.1-C.sub.2 haloalkyl, p-methylphenyl, or N(R.sup.12)R.sup.13; R.sup.6 is hydrogen, methyl, or ethyl; R.sup.7 is hydrogen, methyl, or ethyl; R.sup.8 is selected from methyl, ethyl, trifluoromethyl, and phenyl unsubstituted or optionally substituted by hydrogen, halogen, cyano, or nitro; R.sup.9 is selected from methyl, ethyl, trifluoromethyl, and phenyl unsubstituted or optionally substituted by hydrogen, halogen, cyano, or nitro; R.sup.12 is methyl or ethyl; and R.sup.13 is methyl or ethyl.

5. The oxime ether compound or the salt thereof according to claim 4, wherein in formula I: X is sulfur; Z is hydrogen; A is CN or (CO)NH.sub.2; W is hydrogen, C.sub.1-C.sub.4 alkyl, C.sub.3-C.sub.6 cycloalkyl, C(O)R.sup.3, or NC(R.sup.8)R.sup.9; Q is hydrogen, C.sub.1-C.sub.4 alkyl, C.sub.3-C.sub.6 cycloalkyl, or C(O)R.sup.3; R.sup.3 is selected from C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4 haloalkyl, C.sub.3-C.sub.6 cycloalkyl, unsubstituted or substituted phenyl, unsubstituted or substituted pyridyl, unsubstituted or substituted pyrazolyl, unsubstituted or substituted thiazolyl, unsubstituted or substituted isothiazolyl and unsubstituted or substituted thiadiazolyl, wherein the substituent is selected from hydrogen, halogen, cyano, nitro, 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, and C.sub.1-C.sub.4 haloalkylthio; R.sup.8 is selected from methyl, ethyl, trifluoromethyl, and phenyl unsubstituted or optionally substituted by hydrogen, halogen, cyano, or nitro; and R.sup.9 is selected from methyl, ethyl, trifluoromethyl, and phenyl unsubstituted or optionally substituted by hydrogen, halogen, cyano, or nitro.

6. The oxime ether compound or the salt thereof according to claim 5, wherein in formula I: X is sulfur; Z is hydrogen; A is CN or (CO)NH.sub.2; W is hydrogen, C.sub.1-C.sub.4 alkyl, or C(O)R.sup.3; Q is hydrogen, C.sub.1-C.sub.4 alkyl, or C(O)R.sup.3; R.sup.3 is selected from C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4 haloalkyl, C.sub.3-C.sub.6 cycloalkyl, group K.sup.1 to group K.sup.10, unsubstituted or substituted phenyl, and unsubstituted or substituted pyridyl, wherein the substituent is selected from halogen, cyano, nitro, 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, and C.sub.1-C.sub.4 haloalkylthio; group K.sup.1 to group K.sup.10 are ##STR00075## ##STR00076## wherein the salt is formed by reacting the compound of formula I and an acid selected from hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, propionic acid, butyric acid, pentanoic acid, trifluoroacetic acid, oxalic acid, malonic acid, methanesulfonic acid, 4-toluenesulfonic acid, malic acid, fumaric acid, lactic acid, maleic acid, salicylic acid, tartaric acid, and citric acid.

7. A method for controlling fungi and bacteria, comprising applying the oxime ether compound or the salt thereof according to claim 1 to a subject in need thereof.

8. A fungicidal and bactericidal composition, comprising the oxime ether compound or the salt thereof according to claim 1 as an active ingredient, wherein a weight percentage of the active ingredient in the composition is 0.1-99%.

9. A method for controlling plant diseases caused by bacteria or fungi, comprising applying an effective amount of the composition of claim 8 to a crop or a growth medium or site of the crop.

Description

DETAILED DESCRIPTION

(1) The following specific embodiments are used to further illustrate the present invention, but are not intended to limit the present invention.

Synthesis Embodiments

Embodiment 1

Preparation of Compound 34

(2) ##STR00063##

(3) ((2-aminothiazole-4-yl)methoxy)iminoimide dicyanide (0.5 g, 2.41 mmol), triethylamine (0.37 g, 3.66 mmol), DMAP (0.3 g, 2.46 mmol) and 20 ml of dichloromethane were added to a 50 ml reaction flask; then stirring was started; then 2.4-dichlorobenzoyl chloride (0.5 g, 2.39 mmol) was dissolved in 10 ml of dichloromethane; an acid chloride solution was added dropwise to the reaction flask under ice bath conditions; after dropping, the reaction was continued while stirring at room temperature; TLC (ethyl acetate:petroleum ether=1:5) monitoring was conducted; after the reaction was completed, the solvent was evaporated under reduced pressure; and the residue was purified by column chromatography (ethyl acetate:petroleum ether=1:5 as eluent; 100-140-mesh silica gel produced by Qingdao Marine Biological Chemical Plant Branch) to obtain 0.42 g of yellow solid, with a yield of 46%.

Embodiment 2

Preparation of Compound 47

Preparation of Intermediate 4-(chloromethyl)thiazole-2-amino hydrochloride

(4) ##STR00064##

(5) Thiourea (6.49 g, 85.26 mmol) and 40 ml of methanol were added to a 100 ml reaction flask; then 1,3-dichloroacetone (10.83 g, 85.26 mmol) was dissolved in 30 ml of acetone; under ice bath conditions, the 1,3-dichloroacetone solution was slowly added dropwise to the thiourea solution; after dropping, an ice bath was removed and stirring was continued; the solution was stirred overnight at room temperature, and spin-dried to remove the solvent; then 20 ml of acetone was added to the residue, and stirred vigorously until solid was precipitated; and then the solid was subjected to suction filtration and air drying to obtain 13.5 g of white solid, with a yield of 86%.

(6) ##STR00065##

(7) 4-(chloromethyl)thiazole-2-amino hydrochloride (0.5 g, 2.7 mmol), sodium malononitrile oxime ether (0.32 g, 2.7 mmol), triethylamine (0.28 g, 2.77 mmol) and 15 ml of acetonitrile were added to a 50 ml reaction flask; the temperature was raised to 60 C. to conduct the reaction while stirring; TLC (ethyl acetate:petroleum ether=1:1) monitoring was conducted; after the reaction was completed, the solvent was evaporated under reduced pressure; and the residue was purified by column chromatography (ethyl acetate:petroleum ether=1:2 as an eluent; 100-140-mesh silica gel produced by Qingdao Marine Biological Chemical Plant Branch) to obtain 0.21 g of yellow solid, with a yield of 37%.

Embodiment 3

Preparation of Compound 97

(8) ##STR00066##

(9) ((2-aminothiazole-4-yl)methoxy)iminoimide dicyanide (0.27 g, 1.30 mmol), triethylamine (0.19 g, 1.88 mmol), DMAP (0.16 g, 1.31 mmol) and 20 ml of dichloromethane were added to a 50 ml reaction flask; then stirring was started; then 4-tert-butylbenzoyl chloride (0.25 g, 1.27 mmol) was dissolved in 10 ml of dichloromethane; an acid chloride solution was added dropwise to the reaction flask under ice bath conditions; after dropping, the reaction was continued while stirring at room temperature; TLC (ethyl acetate:petroleum ether=1:5) monitoring was conducted; after the reaction was completed, the solvent was evaporated under reduced pressure; and the residue was purified by column chromatography (ethyl acetate:petroleum ether=1:5 as eluent; 100-140-mesh silica gel produced by Qingdao Marine Biological Chemical Plant Branch) to obtain 0.22 g of black oil, with a yield of 47%.

Embodiment 4

Preparation of Compound 179

(10) ##STR00067##

(11) 4-(chloromethyl)thiazole-2-amino hydrochloride (0.45 g, 2.43 mmol), cyanoacetamidoxime ether (0.28 g, 2.48 mmol), potassium carbonate (1.01 g, 7.29 mmol) and 25 ml of acetonitrile were added to a 50 ml reaction flask; stirring was conducted at 65 C. for reaction for 8 hours; after cooling, the reaction solution was filtered with diatomite to obtain a clear solution; then, the solvent was removed under reduced pressure; and the residue was washed with dichloromethane to obtain 0.22 g of yellow solid, with a yield of 40%.

Embodiment 5

Preparation of Compound 361

(12) ##STR00068##

(13) 4-fluoroacetophenone (2 g, 14.48 mmol), thiosemicarbazide (1.32 g, 14.48 mmol), 0.2 ml of acetic acid and 35 ml of ethanol were added to a 50 ml reaction flask, and heated to reflux and react for 8 hours; and after the reaction solution was cooled, white solid was precipitated, and then filtered to obtain 2.2 g of target object, with a yield of 72%.

(14) ##STR00069##

(15) The condensation product (1.2 g, 5.68 mmol) and 1,3-dichloroacetone (0.72 g, 5.68 mmol) obtained in the previous step were added to a single-neck flask; then 50 ml of ethanol was added, and heated to 60 C. to react for 8 hours; TLC (ethyl acetate:petroleum ether=1:5) monitoring was conducted; after the reaction was completed, the solvent was evaporated under reduced pressure; and the residue was purified by column chromatography (ethyl acetate:petroleum ether=1:5 as an eluent; 100-140-mesh silica gel produced by Qingdao Marine Biological Chemical Plant Branch) to obtain 0.66 g of black oil, with a yield of 41%.

(16) ##STR00070##

(17) The chloride (0.4 g, 1.41 mmol) obtained in the previous step, sodium malononitrile oxime ether (0.17 g, 1.41 mmol) and 15 ml of acetonitrile were added to a 50 ml reaction flask, and heated to 60 C. to react while stirring; TLC (ethyl acetate:petroleum ether=1:3) monitoring was conducted; after the reaction was completed, the solvent was evaporated off under reduced pressure; and the residue was purified by column chromatography (ethyl acetate:petroleum ether=1:3 as an eluent; 100-140-mesh silica gel produced by Qingdao Marine Biological Chemical Plant Branch) to obtain 0.18 g of black oil, with a yield of 37%.

Embodiment 6

Preparation of Compound 363

(18) ##STR00071##

(19) ((2-aminothiazole-4-yl)methoxy)iminoimide dicyanide (0.21 g, 1.01 mmol), triethylamine (0.16 g, 1.58 mmol), DMAP (0.13 g, 1.06 mmol) and 20 ml of dichloromethane were added to a 50 ml reaction flask; then stirring was started; then methyl 4-formate benzoyl chloride (0.20 g, 1.01 mmol) was dissolved in 10 ml of dichloromethane; an acid chloride solution was added dropwise to the reaction flask under ice bath conditions; after dropping, the reaction was continued while stirring at room temperature; TLC (ethyl acetate:petroleum ether=1:5) monitoring was conducted; after the reaction was completed, the solvent was evaporated under reduced pressure; and the residue was purified by column chromatography (ethyl acetate:petroleum ether=1:5 as eluent; 100-140-mesh silica gel produced by Qingdao Marine Biological Chemical Plant Branch) to obtain 0.18 g of yellow solid, with a yield of 48%.

Embodiment 7

Preparation of Compound 364

(20) ##STR00072##

(21) 4-(chloromethyl)thiazole-2-amino hydrochloride (0.4 g, 2.16 mmol), triethylamine (0.54 g, 5.34 mmol), DMAP (0.26 g, 2.13 mmol) mol) and 20 ml of dichloromethane were added to a 50 ml reaction flask, and then stirring was started. O-ethoxybenzoyl chloride (0.39 g, 2.11 mmol) was dissolved in 10 ml of dichloromethane; then acid chloride was added dropwise to the reaction flask under ice bath conditions; after dropping, the reaction was continued while stirring at room temperature; TLC (ethyl acetate:petroleum ether=1:5) monitoring was conducted; after the reaction was completed, the solvent was removed under reduced pressure; and the residue was purified by column chromatography (ethyl acetate:petroleum ether=1:5 as an eluent; 100-140-mesh silica gel produced by Qingdao Marine Biological Chemical Plant Branch) to obtain 0.46 g of white solid, with a yield of 73%.

(22) ##STR00073##

(23) N-(4-(chloromethyl)thiazole-2-yl)-2-ethoxybenzamide (0.45 g, 1.52 mmol), sodium malononitrile oxime ether (0.18 g, 1.54 mmol) and 15 ml of acetonitrile were added to a 50 ml reaction flask, and heated to 60 C. to react while stirring; TLC (ethyl acetate:petroleum ether=1:3) monitoring was conducted; after the reaction was completed, the acetonitrile was evaporated off under reduced pressure; and the residue was purified by column chromatography (ethyl acetate:petroleum ether=1:3 as an eluent; 100-140-mesh silica gel produced by Qingdao Marine Biological Chemical Plant Branch) to obtain 0.25 g of yellow solid, with a yield of 46%.

(24) According to the description of the above embodiments and the synthetic route of the general formula I in the summary of the present invention, other compounds shown by the general formula I can be obtained by replacing the raw materials.

Determination of Biological Activity

Embodiment 8

Determination of Control Effect on Plant Bacterial Diseases

(25) The compounds of the present invention are used to determine the control effect on various plant bacterial diseases. For different bacterial diseases, the test procedures are as follows:

(26) Melon bacterial fruit blotch: the compound to be tested is dissolved with a small amount of N,N dimethylformamide and diluted with water to the required concentration. The pathogenic bacteria cultured to a stable growth stage is evenly mixed with a quantitative compound solution; the germinated melon seeds are soaked in the mixed solution of a bacteria solution and the compound for half an hour; then, the seeds are sown in an earthworm soil culture cup and put into a greenhouse for moisturizing cultivation for two weeks generally; and the control effect is investigated after full onset of diseases through control.

(27) Soft rot of Chinese cabbage: 2 cm of square Chinese cabbage leaf is cut and placed in a glass petri dish lined with double-layer filter paper. A compound dissolved in N,N dimethylformamide and diluted with water to a required concentration is sprayed onto the surface of the Chinese cabbage leaf. After the medicinal liquid on the surface of the Chinese cabbage leaf is dried in a fume hood, the surface of the Chinese cabbage leaf is acupunctured by using an inoculating needle to cause a wound. 5 ml of soft rot bacteria of Chinese cabbage cultured to a stable growth period is added to the wound for inoculation. Finally, the test materials are placed in an incubator and cultured for 48 hours in the dark; and the control effect is investigated after full onset of diseases through control.

(28) Test results are as follows:

(29) At 400 mg/L, compounds 4, 5, 6, 20, 22, 23, 34, 36, 45, 47, 65, 74, 86, 87, 95, 97, 99, 104, 117, 118, 119, 123, 134, 179, 228, 253, 361, 366 and 367 have 100% control effects on soft rot of Chinese cabbage.

(30) At 400 mg/L, compounds 4, 5, 6, 20, 22, 23, 34, 36, 45, 47, 65, 74, 86, 87, 95, 97, 99, 104, 117, 118, 119, 123, 134, 179, 228, 253, 361, 366 and 367 have 100% control effects on melon bacterial fruit blotch.

Embodiment 9

Determination of Control Effect on Plant Fungal Diseases

(31) An in vivo pot determination method was adopted, i.e., a sample of the compound to be tested was dissolved with a small amount of solvent (the type of the solvent may be, for example, acetone, methanol and DMF, and selected according to the capability to dissolve the sample; the volume ratio of the amount of the solvent to the amount of sprayed solution is equal to or less than 0.05), diluted with water containing 0.1% Tween 80 and formulated into a required concentration of solution to be tested. Foliar spray treatment was carried out with the compounds of the present invention at the designed concentrations. A blank control with clear water spray was set and repeated for three times. Disease inoculation was carried out on the second day after the treatment. After inoculation, the plants were placed in a phytotron for moisturizing cultivation (temperature: 25 C. on day, 20 C. at night, relative humidity 95-99%). After culturing the test material for 24 hours, the plants were transferred to a greenhouse for cultivation, and the plants that did not require moisturizing cultivation were directly inoculated and cultivated in the greenhouse. After the control was fully diseased (generally one week), the control effects of the compounds were evaluated. For the result survey, A Manual of Assessment Keys for Plant Diseases compiled by American Phytopathological Society can be referred to, which uses 100-0 for representation. 100 level represents no disease and 0 level represents the most severe disease degree.

(32) Control effects on soybean rust:

(33) For part of the test compounds, when the concentration of the following compounds is 400 ppm, compounds 10, 16, 19, 20, 22, 23, 34, 36, 47, 57, 65, 86, 87, 95, 98, 100, 117, 179, 363, 364 and 365 have better control effects on soybean rust, and the control effects are 80%.

(34) According to the above method, compounds 10, 23, 47, 179 and 365 are selected for parallel comparison with the known compound CK1 in control of soybean rust. Test results are shown in Table 3.

(35) TABLE-US-00003 TABLE 3 Control Effects on Soybean Rust (%) Compound 200 ppm 100 ppm 10 100 100 23 100 100 47 100 85 179 100 80 365 100 100 CK1 0 0
Control effects on cucumber downy mildew:

(36) For part of the test compounds, when the concentration of the following compounds is 400 ppm, compounds 10, 16, 19, 20, 22, 23, 36, 45, 47, 57, 65, 86, 87, 95, 97, 98, 100, 117, 123, 134, 179 and 365 have better control effects on cucumber downy mildew, and the control effects are 80%.

(37) According to the above method, compounds 20, 45, 97 and 117 are selected for parallel comparison with the known compounds CK1, CK2 and CK3 in control of cucumber downy mildew. Test results are shown in Table 4.

(38) TABLE-US-00004 TABLE 4 Control Effects on Cucumber Downy Mildew (%) Compound 400 ppm 20 100 45 100 97 100 117 100 CK1 0 CK2 0 CK3 0

Embodiment 10

Field Trial

(39) Compounds 47 and 97 were selected from the above compounds for field trial to control bacterial spot of cucumber (Pseudomonas syringae pv. lachrymans). The treatment dose of the test drug was 400 mg/L, and the treatment dose of a control drug CK2 was 700 mg/L. The test drug and the control drug were arranged in random blocks; the plot area was 15 m.sup.2; and repetition was conducted for 3 times. The drug delivery mode was the whole plant spray. Drug delivery was conducted for three times, with an interval of 7 days, and control effect investigation was carried out 7 days after the last drug delivery. During investigation, 5 points in each plot were sampled; all leaves were investigated; and disease indexes and control effects were calculated according to the percentage level of diseased spot area of each leaf in the whole leaf area. Results are shown in Table 5.

(40) TABLE-US-00005 TABLE 5 Active Ingredient Dose Control Compound (mg/L) Effect (%) 47 400 77.00 97 400 79.84 CK2 700 76.89