• 专利附录
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    • 专利摘要:
    malononitrile oxime ether compound and use thereof. disclosed is a malononitrile oxime ether compound having a novel structure as shown in general formula i. the respective substituents in general formula i are as defined in the specification. The compound of general formula I exhibits excellent microbicidal activity and can effectively prevent and treat plant diseases caused by bacteria and fungi. there is also provided a use of the compound of general formula I as a microbicide in agricultural and other fields.
    公开号:BR112018012717B1
    申请号:R112018012717-5
    申请日:2016-12-22
    公开日:2022-01-11
    发明作者:Xueming CHENG；Lixin Zhang；Liang Chen；Qin Sun；Junli Liu；Zhinian Li；Jie Zhao；Jingbo Xu；Hongfei Wu
    申请人:Shenyang Sinochem Agrochemicals R&D Co., Ltd.；
    IPC主号:
    专利说明:

    FIELD OF THE INVENTION
    [0001] The invention relates to fungicide and bactericide in agriculture, specifically to a class of malononitrile oxime ether compounds and their use. BACKGROUND OF THE INVENTION
    [0002] Oxime ether derivatives refer to a class of compounds with broad spectrum biological activity, which are widely used for insecticide, herbicide and fungicide in pesticide. Since the first commercial oxime ether fungicide (cymoxanil) was developed by DuPont in 1974, new commercial pesticides are constantly being developed, such as pyrifenox, kresoxim-methyl, orisastrobim, etc. Because of its characteristics of high efficiency, low toxicity and low residue, oxime ethers always have solid research concentration point in many famous companies.
    [0003] Neither the preparation of the malononitrile oxime ether compounds represented by the structure of formula I, nor their fungicidal and bactericidal activities are described in the prior art. SUMMARY OF THE INVENTION
    [0004] The purpose of the present disclosure is to provide a type of novel malononitrile oxime ether compounds, which can be used to control disease in agricultural or other fields.
    [0005] To achieve the above-mentioned purpose, the detailed descriptions of the invention are as follows:
    [0006] The present disclosure provides one type of malononitrile oxime ether compounds as represented by the structure of formula I: CN
    wherein: L represents a divalent group selected from the list consisting of -(CR1R2)n- -(CR1R2)m-CH2-(C=O)-CH2-(CR1R2)p- 1 2 1 2 12 -(CR R )m-(CR =CR)-(CR R)p- -(CR1R2)m-(C=O)-O-CH2-(CR1R2)p- - (CR1R2)m-(C=C) - (CR1R2 )p- -(CR1R2)mO-(C=O)-CH2-(CR1R2)p- -(CR1R2)mO-CH2-(CR1R2)p-(CR1R2)m-(C=O)-NH-CH2 -(CR1R2)p- -(CR1R2)m-NH-CH2-(CR1R2)p- -(CR1R2)m-NH-(C=O)-CH2-(CR1R2)p- or -(CR1R2)mS-CH2 -(CR1R2)p-; n represents 1, 2, 3 or 4; m and p independently represent 0, 1, 2 or 3; R1and R2are independently selected from the list consisting of hydrogen, halogen, cyano, [C1-C4] alkyl, [C1-C4] haloalkyl, [C3-C5] cycloalkyl, [C2-C4] alkenyl, [C2-haloalkenyl] C2-C4], [C2-C4] alkynyl, [C2-C4] haloalkynyl, [C1-C4] alkoxy, [C1-C4] haloalkoxy, [C1-C4] alkoxy-[C1-]alkyl C4], [C1-C4]alkoxy-[C1-C4]alkoxy and [C1-C4]alkoxy-[C1-C4]alkyl; W is selected from unsubstituted or substituted aryl and unsubstituted or substituted aromatic heterocycle; And when L is -(CR1R2)n-, R1and R2are selected from hydrogen and n is 1, W is not benzene;
    [0007] Preferred compounds of general formula I in the present disclosure are: L represents a divalent group selected from the list consisting of -(CR1R2)n-(CR1R2)m-CH2-(C=O)-CH2-(CR1R2 )p- 1 2 1 2 12 - (CR R)m-(CR =CR)-(CR R)p--(CR1R2)m-(C=O)-O-CH2-(CR1R2)p- - ( CR1R2)m-(C=C)-(CR1R2)p- - (CR1R2)mO-(C=O)-CH2-(CR1R2)p- - (CR1R2)mO-CH2-(CR1R2)p- - (CR1R2 )m-(C=O)-NH-CH2-(CR1R2)p--(CR1R2)m-NH-CH2-(CR1R2)p--(CR1R2)m-NH-(C=O)-CH2-( CR1R2)p-, -(CR1R2)mS-CH2-(CR1R2)p-; n represents 1, 2, 3 or 4; m and p independently represent 0, 1, 2 or 3; R1and R2are selected from hydrogen; W is selected from the list consisting of W1a W84:


    X 12345678 9 , X, X, X, X, X, X, X and X are independently selected from the list consisting of hydrogen, halogen, cyano, nitro, -SF5, [C1-C8] alkyl, [C1] haloalkyl -C8], [C3-C6] cycloalkyl, [C2-C8] alkenyl, [C2-C8] haloalkenyl, [C2-C8] alkynyl, [C2-C8] haloalkynyl, [C1-C8] alkoxy ]-[C13 3 4 5 35 C8]-alkyl, -OR, -C(=O)OR, -N(R)S(=O)2R, -S(=O)2NR R, -N(R4) C(=O)OR3, -CR4=NOR3, -CH2ON=C(CN)2, -C(=O)SR3, - 3 3 4 5 4 35 456 C(=S)OR, -C(=S) SR, -CR=NR, -CR=N-NRR, -OSiRRR, - 4 3 34 34 34 OC(=O)R, -OC(=O)OR, -OC(=O)NR R, -OC( =S)NR R, -NRR, -N 4 35 4 35 45 34 (R)C(=O)NR R , -N(R)C(=S)NR R , -N=CR R , -N= C-NR R , -N 4 5 36 4 3 4 35 4 (R)C(=NR)NR R , -N(R)OR , -N(R)NR R , -N=NR , -N(R4 )S(=O)R5, -N(R4)S(=O)2OR3, -N(R4)S(=O)OR3, -N 4 35 4 35 4 5 3 (R)S(=O)NR R, -N(R)S(=O)2NR R, NR C(=O)R, -SR, -S 4 4 3 34 3 (=O)2R, -S(=O)R, -S( =O)OR, -S(=O)NR R, -S(=O)2OR, -S(=O)NR3R4, -SiR3R4R5, unsubstituted or substituted phenyl, unsubstituted pyridyl, or s substituted, unsubstituted or substituted pyrazolyl, unsubstituted or substituted thiazolyl, unsubstituted or substituted isothiazolyl, and unsubstituted or substituted thiadiazolyl, wherein the substituent group is selected from the list consisting of halogen, cyano, nitro, [C1-C8]alkyl ], [C1-C8] haloalkyl, [C1-C8] alkoxy, [C1-C8] haloalkoxy, [C1-C8] alkylthio or [C1-C8] haloalkylthio; Z is selected from the list consisting of hydrogen, [C1-C8] alkyl, [C1-C8] haloalkyl, [C3-C6] cycloalkyl, [C2-C8] alkenyl, [C2-C8] haloalkenyl, [C2-C8] alkynyl, [C2-C8] haloalkynyl, aryl, [C1-C8] alkyl, [C1-C8]-alkyl [C1-C8] alkoxy, -C(=O) R3e -C(=O)OR3; K is selected from the list consisting of oxygen, sulfur, NR3, N-OR4, and N-NR3R4; R3 is selected from the list consisting of hydrogen, [C1-C8] alkyl, [C1-C8] haloalkyl, [C3-C6] cycloalkyl, [C1-C8] alkoxycarbonyl, [C2-C8] alkenyl, [C2-C8] haloalkenyl, [C2-C8] alkynyl, [C2-C8] haloalkynyl, unsubstituted or substituted phenyl, unsubstituted or substituted pyridyl, unsubstituted or substituted pyrazolyl, unsubstituted or substituted thiazolyl, unsubstituted isothiazolyl substituted or substituted and unsubstituted or substituted thiadiazolyl, wherein the substituent group is selected from the list consisting of halogen, cyano, nitro, hydroxyl, mercapto, amino, CONH2, COOH, CHO, [C1-C4] alkyl, [C1-C4], [C3-C6] cycloalkyl, [C1-C3] alkoxy], [C1-C3] haloalkoxy, [C1-C3] alkylthio, [C1-C3] haloalkylthio, [C1] alkylamino -C3], [C1-C3] dialkylamino, [C3-C6]cycloalkylamino, [C1-C3]alkoxycarbonyl, [C1-C3]alkylsulfonyl, [C1-C3]alkylaminocarbonyl, and [C1-C3]alkylaminosulfonyl ]; R4, R5, and R6 are independently selected from the list consisting of hydrogen, [C1-C8] alkyl, [C1-C8] haloalkyl, [C3-C6] cycloalkyl, [C1-C8] alkoxy, [C1- C8], [C1-C8] alkoxycarbonyl, [C2-C8] alkenyl, [C2-C8] haloalkenyl, [C2-C8] alkynyl, [C2-C8] haloalkynyl, unsubstituted or substituted phenyl, pyridyl unsubstituted or substituted, unsubstituted or substituted pyrazolyl, unsubstituted or substituted thiazolyl, unsubstituted or substituted isothiazolyl, and unsubstituted or substituted thiadiazolyl, wherein the substituent group is selected from the list consisting of halogen, cyano, nitro, hydroxyl, mercapto , amino, CONH2, COOH, CHO, [C1-C4] alkyl, [C1-C4] haloalkyl, [C3-C6] cycloalkyl, [C1-C3] alkoxy, [C1-C3] haloalkoxy, alkylthio of [C1-C3], haloalkylthio of [C1-C3], alkylamino of [C1-C3], dialkylamino of [C1-C3], cycloalkylamino of [C3-C6], [C1-C3]alkoxycarbonyl, [C1-C3]alkylsulfonyl C1- C3], [C1-C3] alkylaminocarbonyl and [C1-C3] alkylaminosulfonyl; Q is selected from the list consisting of 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 group is selected in the list consisting of halogen, cyano, nitro, hydroxyl, mercapto, amino, CONH2, COOH, CHO, [C1-C4] alkyl, [C1-C4] haloalkyl, [C3-C6] cycloalkyl, [C3]alkoxy C1-C3], [C1-C3] haloalkoxy, [C1-C3] alkylthio, [C1-C3] haloalkylthio, [C1-C3] alkylamino, [C1-C3] dialkylamino, [C3-C6]cycloalkylamino , [C1-C3]alkoxycarbonyl, [C1-C3]alkylsulfonyl, [C1-C3]alkylaminocarbonyl and [C1-C3]alkylaminosulfonyl; T is selected from the list consisting of cyano, [C1-C8] alkyl, [C1-C8] haloalkyl, [C3-C6] cycloalkyl, [C2-C8] alkenyl, [C2-C8] haloalkenyl, [C2-C8]alkynyl, [C2-C8]haloalkynyl, unsubstituted or substituted phenyl, unsubstituted or substituted pyridyl, unsubstituted or substituted pyrazolyl, unsubstituted or substituted thiazolyl, unsubstituted or substituted isothiazolyl, and unsubstituted or thiadiazolyl substituted, wherein the substituent group is selected from the list consisting of halogen, cyano, nitro, hydroxyl, mercapto, amino, CONH2, COOH, CHO, alkyl of [C1-C4], haloalkyl of [C1-C4], cycloalkyl of [C3-C6], [C1-C3] alkoxy, [C1-C3] haloalkoxy, [C1-3] alkylthio, [C1-C3] haloalkylthio, [C1-C3] alkylamino, [C1-C3] dialkylamino ], [C3-C6]cycloalkylamino, [C1-C3]alkoxycarbonyl, [C1-C3]alkylsulfonyl, [C1-C3]alkylaminocarbonyl, and [C1-C3]alkylaminosulfonyl. When L is -(CR1R2)n-, R1and R2are selected from hydrogen and n is 1, W is not benzene;
    [0008] Additional preferred compounds of general formula I in the present disclosure are:
    [0009] Additional preferred compounds of general formula I in the present disclosure are: L is selected from the list consisting of - 1 2 12 12 12 (CR R)n-, -(CR R)m-NH-(C=O )-CH2-(CR R)p-, -(CR R)mO-CH2-1 2 12 12 (CRR)p-, -(CR R)mS-CH2-(CR R)p-; n represents 1, 2, 3 or 4; m and p independently represent 0, 1, 2 or 3; R1and R2are selected from hydrogen; W is selected from the list consisting of W1, W2, 3 4 12 16 18 21 23 48 49 67 68 69 70 71 W, W, W , W , W , W , W , W , W , W , W , W , W, W, 72 73 74 75 76 77 78 79 80 81 82 83 84 W, W, W, W, W, W, W, W, W, W, W, We W; 12345678 9 X, X, X, X, X, X, X, X and X are independently selected from the list consisting of hydrogen, halogen, cyano, nitro, [C1-C3] alkyl, [C1-C3] haloalkyl , [C1-C3]-alkyl [C1-C3] alkyl, 3 3 4 5 35 4 3 -OR , -C(=O)OR , -N(R)S(=O)2R , -S( =O)2NR R , -N(R)C(=O)OR , -CR4=NOR3, -CH2ON=C(CN)2, NR4C(=O)R5, unsubstituted or substituted phenyl and unsubstituted or substituted pyridyl , wherein the substituent group is selected from the list consisting of halogen, cyano, nitro, [C1-C3] alkyl, [C1-C3] haloalkyl, [C1-C3] alkoxy, [C1-C3] haloalkoxy , [C1-C3] alkylthio and [C1-C3] haloalkylthio; Z is selected from the list consisting of hydrogen, [C1-C3] alkyl, [C1-C3] haloalkyl, phenylmethyl, -C(=O)R3, and -C(=O)OR3; K is selected from the list consisting of oxygen and sulfur; R3 is selected from the list consisting of hydrogen, [C1-C3] alkyl, [C1-C3] haloalkyl, [C1-C8] alkoxycarbonyl, unsubstituted or substituted phenyl, and unsubstituted or substituted pyridi, wherein the substituent group is selected from the list consisting of halogen, cyano, nitro, [C1-C3] alkyl, [C1-C3] haloalkyl, [C1-C3] alkoxy, [C1-C3] haloalkoxy, [C1- C3] and haloalkylthio of [C1-C3]; R4and R5 are independently selected from the list consisting of hydrogen, [C1-C3] alkyl, [C1-C3] haloalkyl, [C1-C3] alkoxy, [C1-C3] haloalkoxy, [C1-C3] alkoxycarbonyl , unsubstituted or substituted phenyl, and unsubstituted or substituted pyridyl, wherein the substituent group is selected from the list consisting of halogen, cyano, nitro, [C1-C3] alkyl, [C1-C3] haloalkyl, [C1-C3] alkoxy C1-C3], [C1-C3] haloalkoxy, [C1-C3] alkylthio and [C1-C3] haloalkylthio; Q is selected from the list consisting of Q1-10, unsubstituted or substituted phenyl, and unsubstituted or substituted pyridyl, wherein the substituent group is selected from the list consisting of halogen, cyano, nitro, hydroxyl, mercapto, amino, CONH2, COOH, CHO, [C1-C3] alkyl, [C1-C3] haloalkyl, [C3-C6] cycloalkyl, [C1-C3] alkoxy, [C1-C3] haloalkoxy, [C1-C3] alkylthio ], [C1-C3] haloalkylthio, [C1-C3] alkylamino, [C1-C3] dialkylamino, [C3-C6]cycloalkylamino, [C1-C3]alkoxycarbonyl, [C1-C3]alkylsulfonyl [C1-C3]alkylaminocarbonyl and [C1-C3]alkylaminosulfonyl;
    T is selected from the list consisting of cyano, [C1-C3] alkyl, [C1-C3] haloalkyl, [C3-C6] cycloalkyl, unsubstituted or substituted phenyl, and unsubstituted or substituted pyridyl, wherein the group substituent is selected from the list consisting of halogen, cyano, nitro, [C1-C3] alkyl, [C1-C3] haloalkyl, [C3-C6] cycloalkyl, [C1-C3] alkoxy, [C1] haloalkoxy -C3], [C1-C3] alkylthio, [C1-C3] haloalkylthio, [C1-C3] alkylamino, [C1-C3] dialkylamino, [C3-C6]cycloalkylamino, [C1-C3]alkoxycarbonyl ], [C1-C3]alkylsulfonyl, [C1-C3]alkylaminocarbonyl, and [C1-C3]alkylaminosulfonyl. When L is -(CR1R2)n-, R1and R2are selected from hydrogen and n is 1, W is not benzene;
    [0010] Additional preferred compounds of general formula I in the present disclosure are: L is selected from the list consisting of - 1 2 12 12 12 (CR R)n-, -(CR R)m-NH-(C=O )-CH2-(CR R)p-, -(CR R)mO-CH2-1 2 12 12 (CRR)p-, -(CR R)mS-CH2-(CR R)p-; n represents 1 or 2; m and p independently represent 0, 1 or 2; R1and R2are selected from hydrogen; W is selected from the list consisting of W1, W2, 3 4 12 16 18 21 23 48 49 67 68 69 70 71 W, W, W , W , W , W , W , W , W , W , W , W , W, W, 72 73 74 75 76 77 78 79 80 81 82 83 84 W, W, W, W, W, W, W, W, W, W, W, We W; 12345678 9 X, X, X, X, X, X, X, X and X are independently selected from the list consisting of hydrogen, halogen, cyano, nitro, [C1-C3] alkyl, [C1-C3] haloalkyl , [C1-C3]-alkyl [C1-C3] alkyl, 3 3 4 5 35 4 3 -OR , -C(=O)OR , -N(R)S(=O)2R , -S( =O)2NR R , -N(R)C(=O)OR , -CR4=NOR3, -CH2ON=C(CN)2, NR4C(=O)R5, unsubstituted or substituted phenyl and unsubstituted or substituted pyridyl , wherein the substituent group is selected from the list consisting of halogen, cyano, nitro, [C1-C3] alkyl, [C1-C3] haloalkyl, [C1-C3] alkoxy, [C1-C3] haloalkoxy , [C1-C3] alkylthio and [C1-C3] haloalkylthio; Z is selected from the list consisting of hydrogen, [C1-C3] alkyl, [C1-C3] haloalkyl, phenylmethyl, -C(=O)R3, and -C(=O)OR3; K is selected from the list consisting of oxygen or sulfur; R3 is selected from the list consisting of hydrogen, [C1-C3] alkyl, [C1-C3] haloalkyl, [C1-C3] alkoxycarbonyl, unsubstituted or substituted phenyl, and unsubstituted or substituted pyridi, wherein the substituent group is selected from the list consisting of halogen, cyano, nitro, [C1-C3] alkyl, [C1-C3] haloalkyl, [C1-C3] alkoxy, [C1-C3] haloalkoxy, [C1- C3] and haloalkylthio of [C1-C3]; R4and R5 are independently selected from the list consisting of hydrogen, [C1-C3] alkyl, [C1-C3] haloalkyl, [C1-C3] alkoxy, [C1-C3] haloalkoxy, [C1-C3] alkoxycarbonyl , unsubstituted or substituted phenyl, and unsubstituted or substituted pyridyl, wherein the substituent group is selected from the list consisting of halogen, cyano, nitro, [C1-C3] alkyl, [C1-C3] haloalkyl, [C1-C3] alkoxy C1-C3], [C1-C3] haloalkoxy, [C1-C3] alkylthio and [C1-C3] haloalkylthio; Q is selected from the list consisting of Q1-10, unsubstituted or substituted phenyl, and unsubstituted or substituted pyridyl, wherein the substituent group is selected from the list consisting of halogen, cyano, nitro, hydroxyl, mercapto, amino, CONH2, COOH, CHO, [C1-C3] alkyl, [C1-C3] haloalkyl, [C3-C6] cycloalkyl, [C1-C3] alkoxy, [C1-C3] haloalkoxy, [C1-C3] alkylthio ], [C1-C3] haloalkylthio, [C1-C3] alkylamino, [C1-C3] dialkylamino, [C3-C6]cycloalkylamino, [C1-C3]alkoxycarbonyl, [C1-C3]alkylsulfonyl [C1-C3]alkylaminocarbonyl and [C1-C3]alkylaminosulfonyl; T is selected from the list consisting of cyano, [C1-C3] alkyl, [C1-C3] haloalkyl, [C3-C6] cycloalkyl, unsubstituted or substituted phenyl, and unsubstituted or substituted pyridyl, wherein the group substituent is selected from the list consisting of halogen, cyano, nitro, [C1-C3] alkyl, [C1-C3] haloalkyl, [C3-C6] cycloalkyl, [C1-C3] alkoxy, [C1] haloalkoxy -C3], [C1-C3] alkylthio, [C1-C3] haloalkylthio, [C1-C3] alkylamino, [C1-C3] dialkylamino, [C3-C6]cycloalkylamino, [C1-C3]alkoxycarbonyl ], [C1-C3]alkylsulfonyl, [C1-C3]alkylaminocarbonyl, and [C1-C3]alkylaminosulfonyl. When L is -(CR1R2)n-, R1and R2are selected from hydrogen and n is 1, W is not benzene;
    [0011] Additional preferred compounds of general formula I in the present disclosure are: L is selected from the list consisting of - 1 2 12 12 12 (CR R)n-, -(CR R)m-NH-(C=O )-CH2-(CR R)p-, -(CR R)mO-CH2- 1 2 12 12 (CR R)p-, -(CR R)mS-CH2-(CR R)p-; n represents 1 or 2; m represents 0 or 1; p represents 0, 1 or 2; R1and R2are selected from hydrogen; W is selected from the list consisting of W1, W2, 3 4 12 16 18 21 23 48 49 67 68 69 70 71 W, W, W , W , W , W , W , W , W , W , W , W , W, W, 72 73 74 75 76 77 78 79 80 81 82 83 84 W, W, W, W, W, W, W, W, W, W, W, We W; 12345678 9 X, X, X, X, X, X, X, X and X are independently selected from the list consisting of hydrogen, halogen, cyano, nitro, [C1-C3] alkyl, [C1-C3] haloalkyl , [C1-C3]-alkyl [C1-C3] alkyl, 3 3 4 5 35 4 3 -OR , -C(=O)OR , -N(R)S(=O)2R , -S( =O)2NR R , -N(R)C(=O)OR , -CR4=NOR3, -CH2ON=C(CN)2, NR4C(=O)R5, unsubstituted or substituted phenyl and unsubstituted or substituted pyridyl , wherein the substituent group is selected from the list consisting of halogen, cyano, nitro, [C1-C3] alkyl, [C1-C3] haloalkyl, [C1-C3] alkoxy, and [C1-C3] haloalkoxy ; Z is selected from the list consisting of hydrogen, methyl, phenylmethyl, -C(=O)R3, and -C(=O)OR3; K is selected from oxygen; R3 is selected from the list consisting of hydrogen, [C1-C3] alkyl, [C1-C3] haloalkyl, [C1-C3] alkoxycarbonyl, unsubstituted or substituted phenyl, and unsubstituted or substituted pyridi, wherein the substituent group is selected from the list consisting of halogen, cyano, nitro, [C1-C3] alkyl, [C1-C3] haloalkyl, [C1-C3] alkoxy, [C1-C3] haloalkoxy, [C1- C3] and haloalkylthio of [C1-C3]; R4and R5 are independently selected from the list consisting of hydrogen, [C1-C3] alkyl, [C1-C3] haloalkyl, [C1-C3] alkoxy, [C1-C3] haloalkoxy, [C1-C3] alkoxycarbonyl , unsubstituted or substituted phenyl, and unsubstituted or substituted pyridyl, wherein the substituent group is selected from the list consisting of halogen, cyano, nitro, [C1-C3] alkyl, [C1-C3] haloalkyl, [C1-C3] alkoxy C1-C3], [C1-C3] haloalkoxy, [C1-C3] alkylthio and [C1-C3] haloalkylthio; Q is selected from the list consisting of Q1-10, unsubstituted or substituted phenyl, and unsubstituted or substituted pyridyl, wherein the substituent group is selected from the list consisting of halogen, cyano, nitro, hydroxyl, mercapto, amino, CONH2, COOH, CHO, [C1-C3] alkyl, [C1-C3] haloalkyl, [C3-C6] cycloalkyl, [C1-C3] alkoxy, [C1-C3] haloalkoxy, [C1-C3] alkylthio ], [C1-C3] haloalkylthio, [C1-C3] alkylamino, [C1-C3] dialkylamino, [C3-C6]cycloalkylamino, [C1-C3]alkoxycarbonyl, [C1-C3]alkylsulfonyl [C1-C3]alkylaminocarbonyl and [C1-C3]alkylaminosulfonyl; T is selected from the list consisting of cyano, [C1-C3] alkyl, [C1-C3] haloalkyl, [C3-C6] cycloalkyl, unsubstituted or substituted phenyl, or unsubstituted or substituted pyridyl, wherein the substituent group is selected from the list consisting of halogen, cyano, nitro, [C1-C3] alkyl, [C1-C3] haloalkyl, [C3-C6] cycloalkyl, [C1-C3] alkoxy, [C1-C3] haloalkoxy C3], [C1-C3] alkylthio and [C1-C3] haloalkylthio. When L is -(CR1R2)n-, R1and R2are selected from hydrogen and n is 1, W is not benzene;
    [0012] Additional preferred compounds of general formula I in the present disclosure are: L is selected from the list consisting of - 1 2 12 12 12 (CR R)n-, -(CR R)m-NH-(C=O )-CH2-(CR R)p-, -(CR R)mO-CH2-1 2 12 12 (CRR)p-, -(CR R)mS-CH2-(CR R)p-; n represents 1 or 2; m represents 0; p represents 0 or 1; R1and R2are selected from hydrogen; W is selected from the list consisting of W1, W2, 3 4 12 16 18 21 23 48 49 67 68 69 70 71 W, W, W , W , W , W , W , W , W , W , W , W , W, W, W72, W74, W79, W80, W81, W82, and W83; X 12345678 9 , X, X, X, X, X, X, X and X are independently selected from the list consisting of hydrogen, fluorine, chlorine, bromine, cyano, nitro, methyl, ethyl, isopropyl, chloromethyl, bromomethyl, difluoromethyl , trifluoromethyl, heptafluoroisopropyl, -OR3, -C(=O)OR3, -N4 5 34 4 3 4 3 (R)S(=O)2R, -S(=O)2NR R, -N(R)C( =O)OR, -CR =NOR, -CH2ON=C(CN)2, NR4C(=O)R5, unsubstituted or substituted phenyl, and unsubstituted or substituted pyridyl, where the substituent group is selected from the list consisting of halogen, cyano, nitro, trifluoromethyl, heptafluoropropyl, heptafluoroisopropyl, methoxy and trifluoromethoxy; Z is selected from the list consisting of hydrogen, methyl and phenylmethyl; K is selected from oxygen; R3 is selected from the list consisting of hydrogen, methyl, ethyl, propyl, isopropyl, cyclopropyl, difluoromethyl, trifluoromethyl, heptafluoropropyl, heptafluoroisopropyl, methoxycarbonyl, unsubstituted or substituted phenyl, and unsubstituted or substituted pyridi, wherein the substituent group is selected from the list consisting of halogen, cyano, nitro and trifluoromethyl; R4and R5are independently selected from the list consisting of hydrogen, methyl, ethyl, propyl, isopropyl, cyclopropyl, difluoromethyl, trifluoromethyl, heptafluoropropyl, heptafluoroisopropyl, methoxy, trifluoromethoxy, methoxycarbonyl, unsubstituted or substituted phenyl and unsubstituted or substituted pyridyl, wherein the substituent group is selected from the list consisting of halogen, cyano, nitro, methyl, ethyl, propyl, chloromethyl, bromomethyl, trifluoromethyl, heptafluoroisopropyl, methoxy and trifluoromethoxy; Q is selected from the list consisting of Q1-10, unsubstituted or substituted phenyl and unsubstituted or substituted pyridyl, wherein the substituent group is selected from the list consisting of halogen, cyano, nitro, hydroxyl, mercapto, amino, haloalkyl of [C1-C3], [C1-C3] alkoxy, [C1-C3] haloalkoxy, [C1-C3] alkylthio and [C1-C3] haloalkylthio; T is selected from the list consisting of cyano, [C1-C3] alkyl, [C1-C3] haloalkyl, [C3-C6] cycloalkyl, unsubstituted or substituted phenyl, and unsubstituted or substituted pyridyl, wherein the group substituent is selected from the list consisting of halogen, cyano, nitro, [C1-C3] alkyl, [C1-C3] haloalkyl, [C3-C6] cycloalkyl, [C1-C3] alkoxy, [C1] haloalkoxy -C3], [C1-C3] alkylthio and [C1-C3] haloalkylthio. When L is -(CR1R2)n-, R1and R2are selected from hydrogen and n is 1, W is not benzene;
    [0013] Additional preferred compounds of general formula I in the present disclosure are: L is selected from the list consisting of -CH2-, -CH2-CH2-, -NH-(C=O)-CH2- and -O-CH2 -CH2-; W is selected from the list consisting of W1, W2, 3 4 12 16 18 21 23 48 49 67 68 69 70 71 W, W, W , W , W , W , W , W , W , W , W , W , W, W, 72 74 79 80 81 82 83 W, W, W, W, W, We W; X 12345678 9 , X, X, X, X, X, X, X and X are independently selected from the list consisting of hydrogen, fluorine, chlorine, bromine, cyano, nitro, methyl, ethyl, isopropyl, chloromethyl, bromomethyl, difluoromethyl , trifluoromethyl, heptafluoroisopropyl, -OR3, -C(=O)OR3, -N4 5 34 4 3 4 3 (R)S(=O)2R, -S(=O)2NR R, -N(R)C( =O)OR, -CR =NOR, -CH2ON=C(CN)2, NR4C(=O)R5, unsubstituted or substituted phenyl, and unsubstituted or substituted pyridyl, where the substituent group is selected from the list consisting of halogen, cyano, nitro, trifluoromethyl, heptafluoropropyl, heptafluoroisopropyl, methoxy and trifluoromethoxy; Z is selected from the list consisting of hydrogen, methyl and phenylmethyl; K is selected from oxygen; R3 is selected from the list consisting of hydrogen, methyl, ethyl, propyl, isopropyl, cyclopropyl, difluoromethyl, trifluoromethyl, heptafluoropropyl, heptafluoroisopropyl, methoxycarbonyl, unsubstituted or substituted phenyl, and unsubstituted or substituted pyridi, wherein the substituent group is selected from the list consisting of halogen, cyano, nitro and trifluoromethyl; R4and R5are independently selected from the list consisting of hydrogen, methyl, ethyl, propyl, isopropyl, cyclopropyl, difluoromethyl, trifluoromethyl, heptafluoropropyl, heptafluoroisopropyl, methoxy, trifluoromethoxy, methoxycarbonyl, unsubstituted or substituted phenyl and unsubstituted or substituted pyridyl, wherein the substituent group is selected from the list consisting of halogen, cyano, nitro, methyl, ethyl, propyl, chloromethyl, bromomethyl, trifluoromethyl, heptafluoroisopropyl, methoxy and trifluoromethoxy; Q is selected from the list consisting of Q1-10, unsubstituted or substituted phenyl, and unsubstituted or substituted pyridyl, wherein the substituent group is selected from the list consisting of halogen, cyano, nitro, hydroxyl, mercapto, amino, chloromethyl, bromomethyl, difluoromethyl, trifluoromethyl, heptafluoroisopropyl, methoxy, ethoxy, propoxy, isopropoxy, trifluoromethoxy, methylthio, ethylthio, trifluoromethylthio and trifluorethylthio; T is selected from the list consisting of cyano, methyl, ethyl, propyl, isopropyl, cyclopropyl, trifluorethyl, difluorethyl, cyclopropyl, cyclobutanyl, cyclopentyl, cyclohexyl, unsubstituted or substituted phenyl, and unsubstituted or substituted pyridyl, wherein the group substituent is selected from the list consisting of halogen, cyano, nitro, methyl, ethyl, propyl, isopropyl, chloromethyl, bromomethyl, trifluoromethyl, heptafluoroisopropyl, cyclopropyl, cyclobutanyl, cyclopentyl, cyclohexyl, methoxy, ethoxy, propoxy, isopropoxy, trifluoromethoxy, methylthio, ethylthio, trifluoromethylthio and trifluorethylthio; When L is -(CR1R2)n-, R1and R2are selected from hydrogen and n is 1, W is not benzene;
    [0014] The most preferred compounds of general formula I in the present disclosure are: L is selected from the list consisting of -CH2-, -CH2-CH2-, -NH-(C=O)-CH2- and -O-CH2 -CH2-; W is selected from the list consisting of W1, W2, W3, and W4; X 12345678 9 , X, X, X, X, X, X, X and X are independently selected from the list consisting of hydrogen, fluorine, chlorine, bromine, cyano, nitro, methyl, ethyl, isopropyl, chloromethyl, bromomethyl, difluoromethyl , trifluoromethyl, heptafluoroisopropyl, -OR3, -C(=O)OR3, -N4 5 34 4 3 4 3 (R)S(=O)2R, -S(=O)2NR R, -N(R)C( =O)OR, -CR =NOR, -CH2ON=C(CN)2, NR4C(=O)R5, unsubstituted or substituted phenyl, and unsubstituted or substituted pyridyl, where the substituent group is selected from the list consisting of halogen, cyano, nitro, trifluoromethyl, heptafluoropropyl, heptafluoroisopropyl, methoxy and trifluoromethoxy; R3 is selected from the list consisting of hydrogen, methyl, ethyl, propyl, isopropyl, cyclopropyl, difluoromethyl, trifluoromethyl, heptafluoropropyl, heptafluoroisopropyl, methoxycarbonyl, unsubstituted or substituted phenyl, and unsubstituted or substituted pyridi, wherein the substituent group is selected from the list consisting of halogen, cyano, nitro and trifluoromethyl; R4and R5are independently selected from the list consisting of hydrogen, methyl, ethyl, propyl, isopropyl, cyclopropyl, difluoromethyl, trifluoromethyl, heptafluoropropyl, heptafluoroisopropyl, methoxy, trifluoromethoxy, methoxycarbonyl, unsubstituted or substituted phenyl and unsubstituted or substituted pyridyl, wherein the substituent group is selected from the list consisting of halogen, cyano, nitro, methyl, ethyl, propyl, chloromethyl, bromomethyl, trifluoromethyl, heptafluoroisopropyl, methoxy and trifluoromethoxy; when L represents -CH2-, W is not benzene.
    [0015] Or the most preferred compounds of general formula I in the present description are: L is selected from the list consisting of -CH2-, -CH2-CH2-, -NH-(C=O)-CH2- and -O- CH2-CH2-; W is selected from the list consisting of W12, W16, 18 23 49 67 68 69 82 W, W, W, W, W, We W; X 12345678 9 , X, X, X, X, X, X, X and X are independently selected from the list consisting of hydrogen, fluorine, chlorine, bromine, cyano, nitro, methyl, ethyl, isopropyl, chloromethyl, bromomethyl, difluoromethyl , trifluoromethyl, heptafluoroisopropyl, -OR3, -C(=O)OR3, -N4 5 34 4 3 4 3 (R)S(=O)2R, -S(=O)2NR R, -N(R)C( =O)OR, -CR =NOR, -CH2ON=C(CN)2, NR4C(=O)R5, unsubstituted or substituted phenyl, and unsubstituted or substituted pyridyl, where the substituent group is selected from the list consisting of halogen, cyano, nitro, trifluoromethyl, heptafluoropropyl, heptafluoroisopropyl, methoxy and trifluoromethoxy; Z is selected from the list consisting of hydrogen, methyl and phenylmethyl; K is selected from oxygen; R3 is selected from the list consisting of hydrogen, methyl, ethyl, propyl, isopropyl, cyclopropyl, difluoromethyl, trifluoromethyl, heptafluoropropyl, heptafluoroisopropyl, methoxycarbonyl, unsubstituted or substituted phenyl, and unsubstituted or substituted pyridi, wherein the substituent group is selected from the list consisting of halogen, cyano, nitro and trifluoromethyl; R4and R5are independently selected from the list consisting of hydrogen, methyl, ethyl, propyl, isopropyl, cyclopropyl, difluoromethyl, trifluoromethyl, heptafluoropropyl, heptafluoroisopropyl, methoxy, trifluoromethoxy, methoxycarbonyl, unsubstituted or substituted phenyl and unsubstituted or substituted pyridyl, wherein the substituent group is selected from the list consisting of halogen, cyano, nitro, methyl, ethyl, propyl, chloromethyl, bromomethyl, trifluoromethyl, heptafluoroisopropyl, methoxy and trifluoromethoxy;
    [0016] The most preferred compounds of general formula I in the present disclosure are: L is selected from the list consisting of -CH2-, -CH2-CH2-, -NH-(C=O)-CH2- and -O-CH2 -CH2-;; W is selected from the list consisting of W21, W48, 70 71 72 74 79 80 81 83 W, W, W, W, W, W, We W; X 12345678 9 , X, X, X, X, X, X, X and X are independently selected from the list consisting of hydrogen, fluorine, chlorine, bromine, cyano, nitro, methyl, ethyl, isopropyl, chloromethyl, bromomethyl, difluoromethyl , trifluoromethyl, heptafluoroisopropyl, methoxy and trifluoromethoxy; Z is selected from the list consisting of hydrogen or methyl K is selected from oxygen; Q is selected from the list consisting of Q1-10, unsubstituted or substituted phenyl, and unsubstituted or substituted pyridyl, wherein the substituent group is selected from the list consisting of halogen, cyano, nitro, hydroxyl, mercapto, amino, chloromethyl, bromomethyl, difluoromethyl, trifluoromethyl, heptafluoroisopropyl, methoxy, ethoxy, propoxy, isopropoxy, trifluoromethoxy, methylthio, ethylthio, trifluoromethylthio and trifluorethylthio; T is selected from the list consisting of cyano, methyl, ethyl, propyl, isopropyl, cyclopropyl, trifluorethyl, difluorethyl, cyclopropyl, cyclobutanyl, cyclopentyl, cyclohexyl, unsubstituted or substituted phenyl, and unsubstituted or substituted pyridyl, wherein the group substituent is selected from the list consisting of halogen, cyano, nitro, methyl, ethyl, propyl, isopropyl, chloromethyl, bromomethyl, trifluoromethyl, heptafluoroisopropyl, cyclopropyl, cyclobutanyl, cyclopentyl, cyclohexyl, methoxy, ethoxy, propoxy, isopropoxy, trifluoromethoxy, methylthio, ethylthio, trifluoromethylthio and trifluorethylthio.
    [0017] The terms used above to define compounds of general formula are as follows:
    [0018] Unsubstituted means all substituents are hydrogen.
    [0019] The "halogen" or "halo" is fluorine, chlorine, bromine or iodine.
    [0020] The "alkyl" means a straight chain or branched alkyl, such as methyl, ethyl, n-propyl, isopropyl, butyl, butyl isomers, pentyl, pentyl isomers, hexyl and hexyl isomers.
    [0021] The "haloalkyl" means a straight chain or branched alkyl, in which the hydrogen atoms may be substituted in whole or in part with halogen, such as chloromethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, heptafluoroisopropyl, etc.
    [0022] The "cycloalkyl" is a cyclic substituted or unsubstituted alkyl, such as cyclopropyl, cyclopentyl or cyclohexyl, the substitute(s) is(are) methyl, halogen, etc.
    [0023] "Alkenyl" refers to straight-chain or branched alkenyl, such as ethenyl, 1-propenyl, 2-propenyl, and isomer other than butenyl, pentenyl, and hexenyl. Alkenyl also includes polyene, such as propa-1,2-dienyl and hexa-2,4-dienyl.
    [0024] "Haloalkenyl" means a straight-chain or branched alkenyl in which the hydrogen atoms may be wholly or in part substituted with halogen.
    [0025] "Alkynyl" refers to straight-chain or branched alkynyl, such as ethynyl, 1-propynyl, 2-propynyl, and isomer other than butynyl, pentynyl, and hexynyl. Alkynyl also includes groups that include more than one triple bond, such as hexa-2,5-dinyl.
    [0026] "Haloalkynyl" means a straight-chain or branched alkynyl in which the hydrogen atoms may be wholly or in part substituted with halogen.
    [0027] The "alkoxy" refers to straight or branched chain alkyl, which is linked to the structure by an oxygen atom, such as methoxy, ethoxy, tert-butoxy, etc.
    [0028] "Haloalkoxy" refers to straight-chain or branched alkoxy, in which the hydrogen atoms may be substituted in whole or in part with halogen, such as chloromethoxy, dichloromethoxy, trichloromethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, chlorofluoromethoxy, trifluorethoxy, etc.
    [0029] "Alkylthio" refers to straight-chain or branched alkyl, which is attached to the structure by a sulfur atom, such as methylthio, ethylthio, etc.
    [0030] "Haloalkylthio" refers to straight-chain or branched alkylthio, in which the hydrogen atoms may be substituted in whole or in part with halogen, such as difluoromethylthio, trifluorethylthio, etc.
    [0031] "Alkylamino" refers to straight-chain or branched alkyl which is attached to the backbone by a nitrogen atom, such as methylamino, ethylamino, n-propylamino, isopropylamino, ethylthio, or isomer other than butylamino.
    [0032] "Dialkylamino" refers to two identical or different straight-chain or branched-chain alkyls which are linked to the backbone by a CH3 —N nitrogen atom, such as -N(CH3)2-
    , , etc.
    [0033] The "cycloalkylamino" refers to cycloalkyl-NH-, such as cyclopropylamino.
    [0034] "Alkylaminocarbonyl" refers to alkyl-NH-CO-, such as CH3NHCO-.
    [0035] "Alkylaminosulfonyl" refers to alkyl-NH-S(O)2-, such as CH3NHS(O)2-.
    [0036] "Alkoxyalkyl" refers to alkyl-O-alkyl, such as CH3OCH2-.
    [0037] "Haloalkoxyalkyl" refers to alkoxyalkyl, in which the hydrogen atoms may be substituted in whole or in part with halogen, such as ClCH2-O-CH2-, Cl2CH-O-CH2-, Cl3C-O-CH2 -, FCH2-O-CH2-, F2CH-O-CH2-, F3C-O-CH2-, FC1CH-O-CH2-, CF3-CH2-O-CH2-, etc.
    [0038] The "alkoxyalkoxy" refers to alkyl-O-alkyl-O-, such as CH3OCH2O-.
    [0039] "Alkoxycarbonyl" refers to alkyl-O-CO-, such as CH3OCO-.
    [0040] "Alkylsulfonyl" refers to alkyl-S(O)2-, such as methylsulfonyl.
    [0041] "Aryl" means monocyclic aromatic groups having 6 to 20 carbon atoms or polycyclic aromatic groups having 6 to 20 carbon atoms, such as phenyl, naphthyl.
    [0042] "Arylalkyl" refers to aryl-alkyl, such as PhCH2-.
    [0043] "Heteroaryl" means monocyclic heteroaromatic groups having 6 to 20 carbon atoms, 1 to 4 heteroatoms selected from N, S, O or polycyclic heteroaromatic groups having 6 to 20 carbon atoms, 1 to 4 heteroatoms selected from from N, S, O, such as pyrrolyl, furyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyridazinonyl, indolyl, benzofuranyl, benzoxazolyl, benzothienyl, benzothiazolyl, benzisoxazolyl, benzisothiazolyl, benzimidazolyl, benzopyrazolyl, quinoxalinyl, etc.
    [0044] The specific compounds in Table 1 are used to illustrate the present invention, but not to limit it. Table 1 CN wx ,ox IN cN I








    [0045] 1H NMR data (300 MHz, CDCl .3) and physical properties of some representative compounds are as follows: Table 2






    [0046] The compounds of formula I in the present disclosure can be prepared by the following methods, unless otherwise specified, the substituents in the reaction schemes are the same as the definitions above:

    [0047] Intermediates II and III are reacted in an appropriate solvent to produce compounds of general formula I at a certain temperature from -10°C to boiling point, for 30 minutes to 48 hours. The suitable solvent is selected from dichloromethane, chloroform, tetrachloride, hexane, benzene, toluene, methanol, ethanol, ethyl acetate, acetonitrile, dioxane, tetrahydrofuran, N,N-dimethylformamide, dimethyl sulfoxide and the like.
    [0048] In the above preparation method: LG represents a leaving group, suitable leaving groups can be selected from the list consisting of a halogen atom or other usual nucleofuge groups such as triflate, mesylate or tosylate. M stands for cation, such as Na+, K+, CS+, Ag+, NH4+, etc.
    [0049] Intermediate II is commercially available or can be prepared according to the following methods described in the European Journal of Inorganic Chemistry, 2014(5), 888-895, 2014, or in the Asian Journal of Chemistry, 20(2), 1425-1430, 2008, etc. (The definition of each substituent is as defined above, unless otherwise noted).

    [0050] Intermediate III can be prepared according to the methods described in CN103804321, WO2008139481, US20130096098, Journal of the Chemical Society of Pakistan, 33(3), 324-332, 2011, etc.
    [0051] The compounds of formula I according to the invention can be used to control fungal diseases caused by oomycetes, basidiomycetes, ascomycetes, deuteromycetes, etc. The active compounds show good activity at low dosages against cucumber powdery mildew, cucumber gray mold, cucumber anthracnose, cucumber downy mildew, tomato blight, tomato late blight, pepper blight, grape powdery mildew, grape white rot, apple ring rot, apple alternaria blight, rice sheath blight, rice blast, wheat blight, wheat leaf blight, wheat mildew, sclerotium sclerotia, bipolar corn blight, etc.
    [0052] The compounds of formula I according to the invention show good bactericidal activity and can be used to control various bacterial plant diseases, such as bacterial wilt, bacterial blight, canker, soft rot, bacterial angular leaf spot, bacterial leaf spot, bacterial leaf blight, wildfire, bacterial scab, etc.
    [0053] The present invention also includes fungicidal/bactericidal compositions containing the compounds having the general formula I as the active ingredient, and the weight percentage of the active ingredient in the composition is 0.1-99%. The fungicidal/bactericidal compositions also include the carrier being agriculturally acceptable.
    [0054] According to the invention, there is also provided a method of preparing the composition defined above: compounds having formula I are mixed with carrier(s). The composition according to the invention may contain a single compound of the present invention or a mixture of several compounds of the present invention.
    [0055] A carrier in a composition according to the present invention is any material that satisfies the following conditions: the carrier with the active ingredient is formulated to facilitate the site to be treated, which may, for example, be a plant, a seed or the soil, or to facilitate storage, transport or handling. A carrier can be a solid or a liquid, including a material that is normally a gas but has a solid compressed to form a liquid. They are generally used in the formulation of insecticidal and bactericidal compositions. Carriers commonly used in formulating insecticidal and fungicidal compositions can be used.
    [0056] Suitable solid carriers include natural or synthetic clays or natural or synthetic silicates, such as diatomite, talc, attapulgite, aluminum silicate (kaolin), montmorillonite, mica; calcium carbonate; calcium sulfate; ammonium sulfate; synthetic monox, synthetic calcium silicate or synthetic aluminum silicate; an element, such as carbon, sulfur; natural or synthetic resins, such as benzofuran resins, polyvinyl chloride, styrene polymers or copolymers; solid polychlorophenol; the asphalt; wax, such as beeswax, paraffin.
    [0057] Suitable liquid carriers include water; alcohol, such as isopropanol, ethanol; the ketone, such as acetone, methyl ethyl ketone, methyl isopropyl ketone, cyclohexyl ketone; the ether; aromatic hydrocarbons such as benzene, toluene, xylene; the petroleum fraction, such as kerosene, mineral oil; chlorinated hydrocarbons, such as carbon tetrachloride, perchlorethylene, trichlorethylene. Mixtures of different liquids are often suitable. DETAILED DESCRIPTION OF THE INVENTION
    [0058] The following examples are illustrative of, but not limited to, the present invention. EXAMPLE OF PREPARATION Example 1: The preparation of compound 4

    [0059] To a solution of malononitrile oxime ether sodium salt (0.22 g, 1.86 mmol) dissolved in 15 mL of acetonitrile in a 50 mL reaction flask was added p-chlorobenzyl chloride ( 0.3 g, 1.86 mmol). The reaction was stirred at room temperature, and monitored by Thin Layer Chromatography (ethyl acetate: petroleum ether = 1: 8) until the reaction was complete, excess acetonitrile was evaporated under reduced pressure, the residue was purified by chromatography. on silica gel column (eluent: ethyl acetate: petroleum ether = 1:10; silica gel: 100-140 mesh, Qingdao Marine Chemical Co., Ltd.) to obtain the title compound 4 (0.21 g) as a yellow oil in 51% yield. Example 2: The preparation of compound 25

    [0060] To a solution of malononitrile oxime ether sodium salt (0.12 g, 0.98 mmol) dissolved in 15 mL of acetonitrile in a 50 mL reaction flask was added 1-(bromomethyl)- 4-(trifluoromethoxy)benzene (0.25 g, 0.98 mmol). The reaction was stirred at room temperature, and monitored by Thin Layer Chromatography (ethyl acetate: petroleum ether = 1: 8) until the reaction was complete, excess acetonitrile was evaporated under reduced pressure, the residue was purified by chromatography. column over silica gel (eluent: ethyl acetate: petroleum ether = 1:10; silica gel: 100-140 mesh, Qingdao Marine Chemical Co., Ltd.) to obtain the title compound 25 (0.16 g). ) as a white solid in 61% yield. Example 3: The preparation of compound 37

    [0061] To a solution of malononitrile oxime ether sodium salt (0.18 g, 1.53 mmol) dissolved in 15 mL of acetonitrile in a 50 mL reaction flask was added 4-(bromomethyl)benzonitrile (0.3 g, 1.53 mmol). The reaction was stirred at room temperature, and monitored by Thin Layer Chromatography (ethyl acetate: petroleum ether = 1: 8) until the reaction was complete, excess acetonitrile was evaporated under reduced pressure, the residue was purified by chromatography. column over silica gel (eluent: ethyl acetate: petroleum ether = 1:10; silica gel: 100-140 mesh, Qingdao Marine Chemical Co., Ltd.) to obtain the title compound 37 (0.18 g). ) as a white solid in 56% yield. Example 4: The preparation of compound 53

    [0062] To a solution of malononitrile oxime ether sodium salt (0.25 g, 2.16 mmol) dissolved in 15 mL of acetonitrile in a 50 mL reaction flask was added 2-chloro-5- (chloromethyl)pyridine (0.35 g, 2.16 mmol). The reaction was stirred at room temperature, and monitored by Thin Layer Chromatography (ethyl acetate: petroleum ether = 1: 8) until the reaction was complete, excess acetonitrile was evaporated under reduced pressure, the residue was purified by chromatography. column over silica gel (eluent: ethyl acetate: petroleum ether = 1:10; silica gel: 100-140 mesh, Qingdao Marine Chemical Co., Ltd.) to obtain the title compound 53 (0.21 g). ) as a yellow solid in 44% yield. Example 5: The preparation of compound 59

    [0063] To a solution of malononitrile oxime ether sodium salt (0.18 g, 1.53 mmol) dissolved in 15 mL of acetonitrile in a 50 mL reaction flask was added 1,2-dichloro- 4-(chloromethyl)benzene (0.3 g, 1.53 mmol). The reaction was stirred at room temperature, and monitored by Thin Layer Chromatography (ethyl acetate: petroleum ether = 1: 8) until the reaction was complete, excess acetonitrile was evaporated under reduced pressure, the residue was purified by chromatography. on silica gel column (eluent: ethyl acetate: petroleum ether = 1:10; silica gel: 100-140 mesh, Qingdao Marine Chemical Co., Ltd.) to obtain the title compound 59 (0.22 g). ) as a yellow solid in 56% yield.Example 6: The preparation of compound 96 NNA NBS Z= NC CN
    NC
    [0064] A mixture of 2-methyl-1,1'-biphenyl (0.8 g, 4.76 mmol), NBS (0.85 g, 4.76 mmol), AIBN (0.02 g) and tetrachloromethane (25 mL) was refluxed and monitored by Thin Layer Chromatography until the reaction was complete. Excess tetrachloromethane was evaporated under reduced pressure, the residue was purified by silica gel column chromatography (eluent: ethyl acetate: petroleum ether = 1:10; silica gel: 100-140 mesh, Qingdao Marine Chemical Co. , Ltd.) to obtain 2-(bromomethyl)-1,1'-biphenyl (0.81 g) in 69% yield.
    [0065] To a solution of malononitrile oxime ether sodium salt (0.24 g, 2.02 mmol) dissolved in 15 mL of acetonitrile in a 50 mL reaction flask was added 2-(bromomethyl)- 1,1'-biphenyl (0.5 g, 2.02 mmol). The reaction was stirred at room temperature, and monitored by Thin Layer Chromatography (ethyl acetate: petroleum ether = 1: 8) until the reaction was complete, excess acetonitrile was evaporated under reduced pressure, the residue was purified by chromatography. column over silica gel (eluent: ethyl acetate: petroleum ether = 1:10; silica gel: 100-140 mesh, Qingdao Marine Chemical Co., Ltd.) to obtain the title compound 96 (0.31 g). ) as a yellow oil in 59% yield. Example 7: The preparation of compound 102

    [0066] To a solution of (2-methyl-[1,1'-biphenyl]-3-yl)methanol (1 g, 5.04 mmol) dissolved in 25 mL of acetonitrile in a 50 mL reaction flask added thionyl chloride (10 ml) is slowly added. The reaction was stirred overnight, and monitored by Thin Layer Chromatography until the reaction was complete, then poured into water (100 mL). The water layer was extracted with ethyl acetate (2 x 50 mL), the organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: ethyl acetate: petroleum ether = 1:10; silica gel: 100-140 mesh, Qingdao Marine Chemical Co., Ltd.) to obtain the 3-( chloromethyl)-2-methyl-1,1'-biphenyl (0.95 g) in 87% yield.
    [0067] To a solution of malononitrile oxime ether sodium salt (0.27 g, 2.31 mmol) dissolved in 15 mL of acetonitrile in a 50 mL reaction flask was added 3-(chloromethyl)- 2-methyl-1,1'-biphenyl (0.5 g, 2.31 mmol). The reaction was stirred at room temperature and monitored by Thin Layer Chromatography (ethyl acetate: petroleum ether = 1: 5) until the reaction was complete, excess acetonitrile was evaporated under reduced pressure, the residue was purified by chromatography on silica gel column (eluent: ethyl acetate: petroleum ether = 1:5, silica gel: 100-140 mesh, Qingdao Marine Chemical Co., Ltd.) to obtain the title compound 102 (0.31 g) as a yellow solid in 60% yield. Example 8: The preparation of compound 114

    [0068] A mixture of phenyl(o-tolyl)methanone (0.8 g, 4.08 mmol), NBS (0.73 g, 4.76 mmol), AIBN (0.01 g) and tetrachloromethane (25 mL ) was refluxed and monitored by Thin Layer Chromatography until the reaction was complete. Excess tetrachloromethane was evaporated under reduced pressure, the residue was purified by silica gel column chromatography (eluent: ethyl acetate: petroleum ether = 1:10; silica gel: 100-140 mesh, Qingdao Marine Chemical Co. , Ltd.) to obtain (2-(bromomethyl)phenyl)(phenyl)methanone (0.95 g) in 85% yield.
    [0069] To a solution of malononitrile oxime ether sodium salt (0.26 g, 2.18 mmol) dissolved in 15 mL of acetonitrile in a 50 mL reaction flask was added (2-(bromomethyl) phenyl(phenyl) methanone (0.6 g, 2.18 mmol) The reaction was stirred at room temperature and monitored by Thin Layer Chromatography (ethyl acetate: petroleum ether = 1: 3) until the reaction was complete, excess acetonitrile was evaporated under reduced pressure, the residue was purified by silica gel column chromatography (eluent: ethyl acetate: petroleum ether = 1:5, silica gel: 100-140 mesh, Qingdao Marine Chemical Co. , Ltd.) to obtain the title compound 114 (0.42 g) as a yellow solid in 67% yield.Example 9: The preparation of compound 115

    [0070] A mixture of benzothioamide (1.5 g, 10.93 mmol), 1,3-dichloropropan-2-one (0.64 g, 10.93 mmol) and ethanol (50 mL) was refluxed in a 100 mL reaction flask and monitored by Thin Layer Chromatography until the reaction was complete. Excess ethanol was evaporated under reduced pressure, the residue was purified by silica gel column chromatography (eluent: ethyl acetate: petroleum ether = 1:10; silica gel: 100-140 mesh, Qingdao Marine Chemical Co. , Ltd.) to obtain 4-(chloromethyl)-2-phenylthiazole (1.9 g) in 83% yield.
    [0071] To a solution of malononitrile oxime ether sodium salt (0.28 g, 2.38 mmol) dissolved in 25 mL of acetonitrile in a 50 mL reaction flask was added 4-(chloromethyl)- 2-phenylthiazole (0.5 g, 2.38 mmol). The reaction was stirred at room temperature and monitored by Thin Layer Chromatography (ethyl acetate: petroleum ether = 1: 5) until the reaction was complete, excess acetonitrile was evaporated under reduced pressure, the residue was purified by chromatography on silica gel column (eluent: ethyl acetate: petroleum ether = 1:5, silica gel: 100-140 mesh, Qingdao Marine Chemical Co., Ltd.) to obtain the title compound 115 (0.35 g) as a yellow solid in 55% yield. Example 10: The preparation of compound 119

    [0072] A mixture of 2-methylbenzo[d]thiazole (0.8 g, 5.36 mmol), NBS (0.95 g, 5.36 mmol), AIBN (0.01 g) and tetrachloromethane (25 mL ) was refluxed and monitored by Thin Layer Chromatography until the reaction was complete. Excess tetrachloromethane was evaporated under reduced pressure, the residue was purified by silica gel column chromatography (eluent: ethyl acetate: petroleum ether = 1:10; silica gel: 100-140 mesh, Qingdao Marine Chemical Co. , Ltd.) to obtain 2-(bromomethyl)benzo[d]thiazole (0.75 g) in 61% yield.
    [0073] To a solution of malononitrile oxime ether sodium salt (0.26 g, 2.19 mmol) dissolved in 15 mL of acetonitrile in a 50 mL reaction flask was added 2-(bromomethyl)benzoic acid. [d]thiazole (0.5 g, 2.19 mmol). The reaction was stirred at room temperature and monitored by Thin Layer Chromatography (ethyl acetate: petroleum ether = 1: 5) until the reaction was complete, excess acetonitrile was evaporated under reduced pressure, the residue was purified by chromatography on silica gel column (eluent: ethyl acetate: petroleum ether = 1:5, silica gel: 100-140 mesh, Qingdao Marine Chemical Co., Ltd.) to obtain the title compound 119 (0.31 g) as a red solid in 58% yield. Example 11: The preparation of compound 142

    [0074] 3-(Difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (2 g, 11.36 mmol) was dissolved in 20 mL of sulfuryl dichloride, and then heated to reflux for 3 h, excess sulfuryl dichloride was evaporated under reduced pressure to obtain 3-(difluoromethyl)-1-methyl-1H-pyrazol-4-carbonyl chloride, and then the carbonyl chloride was dissolved in 30 mL of dichloromethane for the next reaction. To a cooled solution of (3-aminophenyl)methanol (1.4 g, 11.36 mmol) dissolved in 20 mL of dichloromethane and 5 mL of triethylamine was slowly added the carbonyl chloride solution at 0-5°C. After the reaction was stirred for 6 hours at room temperature, Thin Layer Chromatography analysis showed complete conversion to the product, excess solvent was evaporated under reduced pressure, the residue was purified by silica gel column chromatography (eluent: ethyl acetate: petroleum ether = 1: 3; silica gel: 100-140 mesh, Qingdao Marine Chemical Co., Ltd.) to obtain 3-(difluoromethyl)-N-(3-(hydroxymethyl)phenyl)- 1-Methyl-1H-pyrazole-4-carboxamide (2.32 g) as a white solid in 73% yield. 1H NMR (300 MHz, CDCl 3 ) δ (ppm): 4.11 (s, 3H), 4.73 (s, 2H), 7.16-7.81 (m, 6H).

    [0075] To a solution of 3-(difluoromethyl)-N-(3-(hydroxymethyl)phenyl)-1-methyl-1H-pyrazole-4-carboxamide (1 g, 3.56 mmol) dissolved in 25 mL of acetonitrile to a 50 mL reaction flask, thionyl chloride (10 mL) was slowly added. The reaction was stirred overnight, and monitored by Thin Layer Chromatography until the reaction was complete, then poured into water (100 mL). The water phase was extracted with ethyl acetate (2 x 50 ml), the organic phase was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure, the residue was purified by column chromatography on silica gel (eluent: ethyl acetate: petroleum ether = 1:3; silica gel: 100-140 mesh, Qingdao Marine Chemical Co., Ltd.) to obtain N-(3-(chloromethyl)phenyl)-3 -(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide (0.83 g) in 78% yield.
    [0076] To a solution of malononitrile oxime ether sodium salt (0.20 g, 1.67 mmol) dissolved in 15 mL of acetonitrile in a 50 mL reaction flask was added N-(3-( chloromethyl)phenyl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide (0.5 g, 1.67 mmol). The reaction was stirred at room temperature and monitored by Thin Layer Chromatography (ethyl acetate: petroleum ether = 1: 2) until the reaction was complete, excess acetonitrile was evaporated under reduced pressure, the residue was purified by chromatography on silica gel column (eluent: ethyl acetate: petroleum ether = 1:3; silica gel: 100-140 mesh, Qingdao Marine Chemical Co., Ltd.) to obtain the title compound 142 (0.21 g) as a yellow solid in 35% yield. Example 12: The preparation of compound 167

    [0077] To 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (1.5 g, 8.52 mmol) was added dropwise 20 mL of sulfuryl dichloride and, in then heated at reflux for 3 h, excess sulfuryl dichloride was evaporated under reduced pressure to obtain 3-(difluoromethyl)-1-methyl-1H-pyrazol-4-carbonyl chloride and then the carbonyl chloride was dissolved in 30 ml of dichloromethane for the next reaction. To a cooled solution of (3-(aminomethyl)phenyl)methanol (1.17 g, 8.52 mmol) dissolved in 20 mL of dichloromethane and 5 mL of triethylamine was added the carbonyl chloride solution dropwise. at 0-5°C. After the reaction was stirred for 6 h at room temperature, analysis by Thin Layer Chromatography showed complete conversion to the product, the excess solvent was evaporated under reduced pressure, the residue was purified by silica gel column chromatography (eluent: ethyl acetate: petroleum ether = 1: 3; silica gel: 100-140 mesh, Qingdao Marine Chemical Co., Ltd.) to obtain 3-(difluoromethyl)-N-(3-(hydroxymethyl)benzyl)- 1-Methyl-1H-pyrazole-4-carboxamide (1.8 g) as a white solid in 72% yield.
    0 0
    [0078] To a solution of 3-(difluoromethyl)-N-(3-(hydroxymethyl)benzyl)-1-methyl-1H-pyrazole-4-carboxamide (0.5 g, 1.69 mmol) dissolved in 25 mL of acetonitrile in a 50 mL reaction flask was slowly added thionyl chloride (8 mL). The reaction was stirred overnight, and monitored by Thin Layer Chromatography until the reaction was complete, then poured into water (100 mL). The water phase was extracted with ethyl acetate (2 x 50 ml), the organic phase was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure, the residue was purified by column chromatography on silica gel (eluent: ethyl acetate: petroleum ether = 1:3; silica gel: 100-140 mesh, Qingdao Marine Chemical Co., Ltd.) to obtain N-(3-(chloromethyl)benzyl)-3 -(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide (0.39 g) in 73% yield.
    [0079] To a solution of malononitrile oxime ether sodium salt (0.1 g, 0.85 mmol) dissolved in 15 mL of acetonitrile in a 50 mL reaction flask was added N-(3-( chloromethyl)benzyl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide (0.25 g, 0.8 mmol). The reaction was stirred at room temperature and monitored by Thin Layer Chromatography (ethyl acetate: petroleum ether = 1: 2) until the reaction was complete, excess acetonitrile was evaporated under reduced pressure, the residue was purified by chromatography on column over silica gel (eluent: ethyl acetate: petroleum ether = 1:3; silica gel: 100-140 mesh, Qingdao Marine Chemical Co., Ltd.) to obtain the title compound 167 (0.15 g) as a yellow oil in 51% yield. Example 13: The preparation of compound 185 o soci2 9

    [0080] 4-Methylbenzoic acid (1.5 g, 11.02 mmol) was dissolved in 20 mL of sulfuryl dichloride, and then heated at reflux for 3 h, excess sulfuryl dichloride was evaporated under reduced pressure to obtain the 4-methylbenzoyl chloride, and then the carbonyl chloride was dissolved in 30 ml of dichloromethane for the next reaction. To a cooled solution of N-methylaniline (1.18 g, 11.02 mmol) dissolved in 20 mL of dichloromethane and 5 mL of triethylamine was slowly added the carbonyl chloride solution at 0-5°C. After the reaction was stirred for 4 h at room temperature, analysis by Thin Layer Chromatography showed complete conversion to the product, excess solvent was evaporated under reduced pressure, the residue was purified by silica gel column chromatography (eluent: ethyl acetate: petroleum ether = 1:3; silica gel: 100-140 mesh, Qingdao Marine Chemical Co., Ltd.) to obtain N,4-dimethyl-N-phenylbenzamide (1.8 g) as a white solid in 73% yield. 1H NMR (300 MHz, CDCl 3 ) δ (ppm): 2.25 (s, 3H), 3.49 (s, 3H), 6.94-7.05 (m, 4H), 7.147.26 (m, 5H).

    [0081] A mixture of N,4-dimethyl-N-phenylbenzamide (0.8 g, 3.55 mmol), NBS (0.64 g, 3.56 mmol), AIBN (0.01 g) and tetrachloromethane ( 25 mL) was refluxed and monitored by Thin Layer Chromatography until the reaction was complete. Excess tetrachloromethane was evaporated under reduced pressure, the residue was purified by silica gel column chromatography (eluent: ethyl acetate: petroleum ether = 1:5, silica gel: 100-140 mesh, Qingdao Marine Chemical Co. , Ltd.) to obtain 4-(bromomethyl)-N-methyl-N-phenylbenzamide (0.79 g) in 73% yield.
    [0082] To a solution of malononitrile oxime ether sodium salt (0.16 g, 1.37 mmol) dissolved in 15 mL of acetonitrile in a 50 mL reaction flask was added 4-(bromomethyl)- N-methyl-N-phenylbenzamide (0.4 g, 1.32 mmol). The reaction was stirred at room temperature and monitored by Thin Layer Chromatography (ethyl acetate: petroleum ether = 1: 3) until the reaction was complete, excess acetonitrile was evaporated under reduced pressure, the residue was purified by chromatography on column over silica gel (eluent: ethyl acetate: petroleum ether = 1:3; silica gel: 100-140 mesh, Qingdao Marine Chemical Co., Ltd.) to obtain the title compound 185 (0.25 g) as a yellow solid in 60% yield. Example 14: The preparation of compound 202

    [0083] To a cooled solution of 6-methoxybenzo[d]thiazol-2-amine (2.0 g, 1110 mmol) dissolved in 30 mL of dichloromethane and 5 mL of triethylamine was slowly added to the chloroacetyl chloride solution. (2.0 g, 11.10 mmol) in dichloromethane (10 mL) at 0-5°C. After the reaction was stirred for 4 h at room temperature, analysis by Thin Layer Chromatography showed complete conversion to the product, excess solvent was evaporated under reduced pressure, the residue was purified by silica gel column chromatography (eluent: ethyl acetate: petroleum ether = 1: 2; silica gel: 100-140 mesh, Qingdao Marine Chemical Co., Ltd.) to obtain 2-chloro-N-(6-methoxybenzo[d]thiazol-2- yl)acetamide (2.42 g) in 85% yield.
    [0084] To a solution of malononitrile oxime ether sodium salt (0.92 g, 7.79 mmol) dissolved in 25 mL of acetonitrile in a 50 mL reaction flask was added 2-chloro-N- (6-methoxybenzo[d]thiazol-2-yl)acetamide (2.0 g, 7.79 mmol). The reaction was stirred at room temperature, and monitored by Thin Layer Chromatography (ethyl acetate: petroleum ether = 1: 1) until the reaction was complete, excess acetonitrile was evaporated under reduced pressure, the residue was purified by chromatography. on silica gel column (eluent: ethyl acetate: petroleum ether = 1:1; silica gel: 100-140 mesh, Qingdao Marine Chemical Co., Ltd.) to obtain the title compound 202 (1.14 g ) as a yellow solid in 46% yield. Example 15: The preparation of compound 203

    [0085] To a solution of quinolin-6-ylmethanol (1g, 6.28 mmol) dissolved in 25 mL of acetonitrile in a 50 mL reaction flask was slowly added thionyl chloride (5 mL). The reaction was stirred overnight, and monitored by Thin Layer Chromatography until the reaction was complete, then poured into water (100 mL). The water phase was extracted with ethyl acetate (2 × 50 mL), the organic phase was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure, the residue was purified by column chromatography on silica gel (eluent: ethyl acetate: petroleum ether = 1:10; silica gel: 100-140 mesh, Qingdao Marine Chemical Co., Ltd.) to obtain 6-(chloromethyl)quinoline (0.75 g) with a yield of 67%. Example 15: The preparation of compound 203
    N-quinolin-6-ylmethanol g, 6.28 mmol) dissolved in 25 mL of acetonitrile in a 50 mL reaction flask was slowly added to thionyl chloride (5 mL). The reaction was stirred overnight, and monitored by Thin Layer Chromatography until the reaction was complete, then poured into water (100 mL). The water phase was extracted with ethyl acetate (2 x 50 ml), the organic phase was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure, the residue was purified by column chromatography on silica gel (eluent: ethyl acetate: petroleum ether = 1:10; silica gel: 100-140 mesh, Qingdao Marine Chemical Co., Ltd.) to obtain 6-(chloromethyl)quinoline (0.75 g) with a yield of 67%.
    [0086] To a solution of malononitrile oxime ether sodium salt (0.33 g, 2.81 mmol) dissolved in 15 mL of acetonitrile in a 50 mL reaction flask was added 6-(chloromethyl)quinoline (0.5 g, 2.81 mmol). The reaction was stirred at room temperature and monitored by Thin Layer Chromatography (ethyl acetate: petroleum ether = 1: 3) until the reaction was complete, excess acetonitrile was evaporated under reduced pressure, the residue was purified by chromatography on silica gel column (eluent: ethyl acetate: petroleum ether = 1:3; silica gel: 100-140 mesh, Qingdao Marine Chemical Co., Ltd.) to obtain the title compound 203 (0.35 g) as a brown oil with a yield of 53%. Example 16: The preparation of compound 210 CN

    [0087] To a solution of malononitrile oxime sodium ether salt (0.29 g, 2.48 mmol) dissolved in 25 mL of acetonitrile in a 50 mL reaction flask was added 1-(2-chloroethoxy) )-4-nitrobenzene (0.5 g, 2.48 mmol). The reaction was stirred at 80°C, and monitored by Thin Layer Chromatography (ethyl acetate: petroleum ether = 1: 5) until the reaction was complete, excess acetonitrile was evaporated under reduced pressure, the residue was purified by silica gel column chromatography (eluent: ethyl acetate: petroleum ether = 1:5, silica gel: 100-140 mesh, Qingdao Marine Chemical Co., Ltd.) to obtain the title compound 210 (0.26 g) as a white solid in 40% yield. Example 17: The preparation of compound 222

    [0088] To a cooled solution of 1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid (1 g, 5.15 mmol) dissolved in 25 mL of tetrahydrofuran and triethylamine (0.63 g, 6 .18 mmol) into a 50 mL reaction flask, ethyl chloroformate (0.67 g, 6.18 mmol) was slowly added. After the reaction was stirred at room temperature, Thin Layer Chromatography analysis showed complete conversion to the product. Sodium borohydride (1.95 g, 51.52 mmol) was added and then methanol (10 mL) was added slowly at 0°C. The mixture was stirred at 0-5°C for 30 min, the reaction was stirred overnight, and monitored by Thin Layer Chromatography until the reaction was complete, then poured into water (100 mL). The water phase was extracted with ethyl acetate (2 x 50 mL), the organic phase was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure, the residue was purified by column chromatography on silica gel (eluent: ethyl acetate: petroleum ether = 1:3; silica gel: 100-140 mesh, Qingdao Marine Chemical Co., Ltd.) to obtain N-(3-(chloromethyl)phenyl)-3 -(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide (0.53 g) in 57% yield.

    [0089] To a solution of N-(3-(chloromethylphenyl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide (0.3 g, 1.67 mmol) dissolved in 25 mL of acetonitrile In a 50 mL reaction flask, thionyl chloride (5 mL) was slowly added.The reaction was stirred overnight, and monitored by Thin Layer Chromatography until the reaction was complete, then poured into water (100 mL The water phase was extracted with ethyl acetate (2 x 50 ml), the organic phase was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure, the residue was purified by chromatography on silica gel column to obtain 4-(chloromethyl)-1-methyl-3-(trifluoromethyl)-1H-pyrazole (0.25 g) in 76% yield.
    [0090] To a solution of malononitrile oxime ether sodium salt (0.13 g, 1.11 mmol) dissolved in 15 mL of acetonitrile in a 50 mL reaction flask was added 4-(chloromethyl)- 1-methyl-3-(trifluoromethyl)-1H-pyrazole (0.2 g, 1.11 mmol). The reaction was stirred at room temperature and monitored by Thin Layer Chromatography (ethyl acetate: petroleum ether = 1: 2) until the reaction was complete, excess acetonitrile was evaporated under reduced pressure, the residue was purified by chromatography on silica gel column (eluent: ethyl acetate: petroleum ether = 1:3; silica gel: 100-140 mesh, Qingdao Marine Chemical Co., Ltd.) to obtain the title compound 222 (0.13 g) as a yellow oil in 46% yield. Example 18: The preparation of compound 230

    [0091] To a cooled solution of (3-chloro-5-(trifluoromethyl)pyridin-2-yl)methanamine (0.45 g, 2.12 mmol) dissolved in 30 mL of dichloromethane and 5 mL of triethylamine in a flask of 100 mL reaction mixture was slowly added to a solution of 4-(chloromethyl)benzoyl chloride (0.4 g, 2.12 mmol) in dichloromethane (10 mL). After the reaction was stirred at room temperature, Thin Layer Chromatography analysis showed complete conversion to the product, the reaction mixture was concentrated under reduced pressure, the residue was purified by silica gel column chromatography (eluent: ethyl acetate : petroleum ether = 1: 2; silica gel: 100-140 mesh, Qingdao Marine Chemical Co., Ltd.) to obtain N-((3-chloro-5-(trifluoromethyl)pyridin-2-yl)methyl )-4-(chloromethyl)benzamide (0.52 g) in 68% yield.

    [0092] To a solution of malononitrile oxime ether sodium salt (0.1 g, 0.85 mmol) dissolved in 25 mL of acetonitrile in a 50 mL reaction flask was added N-((3- chloro-5-(trifluoromethyl)pyridin-2-yl)methyl)-4-(chloromethyl)benzamide (0.3 g, 0.83 mmol). The reaction was stirred at room temperature and monitored by Thin Layer Chromatography (ethyl acetate: petroleum ether = 1: 5) until the reaction was complete, excess acetonitrile was evaporated under reduced pressure, the residue was purified by chromatography on column over silica gel (eluent: ethyl acetate: petroleum ether = 1:5; silica gel: 100-140 mesh, Qingdao Marine Chemical Co., Ltd.) to obtain the title compound 230 (0.19 g) as a yellow solid in 55% yield. BIOLOGICAL TEST Example 19: Blast and gray mold test on rice
    [0093] Method of determining fungicidal activity in vitro: High Through Put is used in the test, the compound is dissolved in a suitable solvent (the solvent is selected from acetone, methanol, DMF and so on on, according to its ability to dissolve in the sample.) to become a test solution whose concentration is projected. In a no-animalculum condition, the test solution and the pathogen suspension are added to the cells in the 96-cell culture dish, which are then placed in the constant temperature box. 24 hours later, the germination or growth of pathogens can be investigated by observation and the in vitro activity of the compound is evaluated based on germination or growth of the control treatment.
    [0094] The in vitro activities (inhibition rate) of some compounds are as follows:
    [0095] At the dosage of 25 mg/L, the inhibition rate of compounds 5, 7, 23, 57, 59, 65, 69, 85, 91, 93, 99, 102, 106, 107, 112, 113, 114 I , 230, 231, 232, 233 was 100% against rice blast.
    [0096] At the dosage of 25 mg/L, the rate of inhibition of compounds 4, 7, 22, 36, 53, 59, 60, 69, 86, 96, 99, 102, 105, 107, 109, 112, 113 I , 231, 232, was 100% against gray mold. Example 20: The method of determining protective activity in vivo
    [0097] The method is as follows: The compound is dissolved in a suitable solvent to obtain the mother liquor. The solvent is selected from acetone, methanol, DMF and so on, according to its ability to dissolve in the sample. The volume ratio of solvent and test solution (v/v) is equal to or less than 5%. The stock solution is diluted with water containing 0.1% tween-80 to obtain the test solution, whose concentration is designed. The plants are sprayed onto the leaves with the active compound preparation according to the invention and the spray application is repeated 3 times. The plants, used as controls, are treated with an aqueous solution that does not contain the active material. Plants are inoculated one day after treating the plants with the compounds of this invention. The plants are stored in a humidity chamber (25°C (day), 20°C (night), 95-99% humidity) and then transferred to the greenhouse after 24 hours. Compound activity is obtained through observation after 7 days, according to A Manual of Assessment Keys for Plant Diseases, published by the American Phytopathological Society. 0% means an efficacy that matches that of the control, while an efficacy of 100% means that no disease is observed.
    [0098] At the dosage of 400 ppm, compounds 86, 91, 94, 103, 109, 110, 114, 115, 142, 187, 188, 189, 233 showed more than 80% control against corn rust Example 21: Determination of bacterial disease control in plants
    [0099] The compounds of the present invention were tested for the control of various bacterial diseases in plants. The test procedure is as follows:
    [0100] Bacterial watery spot on melon: The test compound is dissolved in a small amount of DMF and diluted with water to the desired concentration. Pathogenic bacteria in the stable growth phase are mixed with the test solution. After the melon seeds (acceleration germination) are soaked in the solution containing the pathogenic bacteria and compost for 0.5 hour, the seeds are sown in a cup of earthworm soil and then transferred to a greenhouse to allow the disease develops. After 2 weeks, compost activity is assessed based on germination or growth of the control treatment.
    [0101] Swiss chard soft rot: Swiss chard leaves are cut into a 2 cm square and placed on double filter paper in a petri dish. The test compound is dissolved in DMF and diluted with water to the desired concentration. The test solution is sprayed onto the chard leaf surface and dried in a fume hood. The surface of the Swiss chard leaf is pierced using an inoculation needle. A spore suspension (5 μl) of chard soft rot bacteria in the stable growth phase is inoculated on the leaf break, disease development is allowed to progress in a growth chamber under dark condition for 48 hours. Compost activity is evaluated based on germination or growth of the control treatment.
    [0102] Bacterial leaf spot on cucumber, bacterial leaf spot on tomato, bacterial leaf spot on rice, bacterial leaf spot on rice: The test compound is dissolved in DMF and diluted with water to the desired concentration. The test solution is sprayed onto the host plant by a special plant sprayer. After air drying in a cool place, the plant is inoculated with the pathogen in the stable growth phase, and then transferred to a greenhouse and incubated for 10 days under a common humid atmosphere. The classification is performed, in comparison with the control plants.
    [0103] The test results are as follows:
    [0104] At the dosage of 800 mg/L, compounds 9, 59, 83 and 115 showed 100% control against bacterial water spot of melon.
    [0105] At the dosage of 600 mg/L, compounds 9, 19, 34, 37, 59, 83 and 115 showed 100% control against bacterial leaf spot of cucumber, bacterial leaf spot of rice and bacterial leaf blight of rice. rice.
    [0106] At the dosage of 400 mg/L, compounds 9, 19, 34, 36, 37, 59, 83 and 115 showed 100% control against Swiss chard soft rot and tomato bacterial leaf spot. Example 22: Field trial
    [0107] Compounds 59 and 115 were selected from the compounds mentioned above for the field trial, to control bacterial leaf spot of rice (Xanthomonas oryzae pv. Oryzicola), at a dose of 400 g ai/hm2. The control (thiazole zinc and kocide 3000, commercially available) was set at one dose (400 g ai/hm2). The plot size was 15 m2 and treatments were randomly assigned to plots. Spray applications on leaves and trunks were made at 7-day intervals and each application was repeated 3 times. One week after 3 spray applications, five random spots from each plot were investigated to calculate the effectiveness of the test compounds in controlling the disease, in accordance with the pesticide guidelines for the field efficacy trials. Table 3. Results of field trials for test compounds against bacterial leaf spot of rice
    权利要求:
    Claims (6)
    [0001]
    1. A malononitrile oxime ether compound characterized by having the formula (I)
    [0002]
    A compound according to claim 1, characterized in that in the general formula I: substituted and unsubstituted or substituted pyridyl, wherein the substituent group is selected from the group consisting of halogen, cyano, [C1-C3]haloalkyl; when W is selected from W, X1, X2, X3, X4 and X5 are not simultaneously selected from hydrogen; Z is selected from the group consisting of hydrogen and [C1-C3] alkyl; K is selected from oxygen; R3 is selected from the group consisting of [C1-C3]alkyl, [C1-C3]haloalkyl, unsubstituted or substituted phenyl and unsubstituted or substituted pyridyl, wherein the substituent group is selected from the group consisting of halogen and haloalkyl [C1C3]; Q is selected from the group consisting of Q1, Q2, unsubstituted or substituted phenyl and unsubstituted or substituted pyridyl, wherein the substituent group is selected from the group consisting of halogen and [C1-C3]alkyl; T be selected from the group consisting of unsubstituted or substituted phenyl and unsubstituted or substituted pyridyl, wherein the substituent group is selected from the group consisting of halogen, cyano, [C1-C3]alkyl, [C1]haloalkyl -C3] and haloalkoxy [C1C3].
    [0003]
    Compound according to claim 2, characterized in that in the general formula I: W is selected from the group consisting of W , W2, W3, W4, W16, W49, W59, W69, W70, W71, W72, W79 , W80 and W81; X1, X2, X3, X4, X5, X6, X7, X8 and X9 are independently selected from the group consisting of hydrogen, halogen, cyano, nitro, alkyl [C1C3], haloalkyl [C1-C3], -OR3, unsubstituted or substituted phenyl and unsubstituted or substituted pyridyl, wherein the substituent group is selected from the group consisting of halogen, cyano and [C1-C3]haloalkyl; when W is selected from W1, X1, X2, X3, X4 and X5 are not simultaneously selected from hydrogen; Z is selected from hydrogen; K is selected from oxygen; R3 will be selected from the group consisting of [C1-C3] alkyl and [C1-C3] haloalkyl; Q is selected from the group consisting of Q1, Q2, unsubstituted or substituted phenyl and unsubstituted or substituted pyridyl, wherein the substituent group is selected from the group consisting of halogen and [C1-C3]alkyl; T be selected from the group consisting of unsubstituted or substituted phenyl and unsubstituted or substituted pyridyl, wherein the substituent group is selected from the group consisting of halogen, [C1-C3] alkyl, [C1-C3] haloalkyl ] and haloalkoxy [C1-C3].
    [0004]
    Compound according to claim 3, characterized in that in the general formula I: R1 and R2 are selected from hydrogen; W is selected from the group consisting of W1, W2, W3, W4, W16, W49 and W69; X1, X2, X3, X4, X5, X6, X7, X8 and X9 are independently selected from the group consisting of hydrogen, fluorine, chlorine, bromine, cyano, nitro, methyl, ethyl, isopropyl, chloromethyl, bromomethyl, difluoromethyl, trifluoromethyl, -OR3 and unsubstituted or substituted phenyl, wherein the substituent group is selected from the group consisting of halogen and cyano; when W is selected from W1, X1, X2, X3, X4 and X5 are not simultaneously selected from hydrogen; R3 will be selected from the group consisting of methyl and trifluoromethyl.
    [0005]
    5. A fungicidal and bactericidal composition, characterized in that it comprises the compound of general formula I, as defined in claim 1, as an active ingredient and an agriculturally acceptable carrier, wherein the percentage by weight of the active ingredient(s) ) in the composition is from 0.1 to 99%.
    [0006]
    A method for controlling plant diseases characterized in that an effective amount of a composition as defined in claim 5 is applied to plants or soil where plants grow or are capable of growing.
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    法律状态:
    2020-06-09| B06U| Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette]|
    2021-06-29| B06A| Patent application procedure suspended [chapter 6.1 patent gazette]|
    2021-10-19| B09A| Decision: intention to grant [chapter 9.1 patent gazette]|
    2022-01-11| B16A| Patent or certificate of addition of invention granted [chapter 16.1 patent gazette]|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 22/12/2016, OBSERVADAS AS CONDICOES LEGAIS. |
    优先权:
    申请号 | 申请日 | 专利标题
    CN201510998120|2015-12-25|
    CN201510998120.X|2015-12-25|
    PCT/CN2016/111411|WO2017107939A1|2015-12-25|2016-12-22|Malononitrile oxime ether compound and use thereof|
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