CN111480649B

CN111480649B - Application of malononitrile compound as bactericide

Info

Publication number: CN111480649B
Application number: CN202010062715.5A
Authority: CN
Inventors: 张立新; 张静; 张力群; 康卓
Original assignee: Shenyang University of Chemical Technology
Current assignee: Shenyang University of Chemical Technology
Priority date: 2019-01-29
Filing date: 2020-01-20
Publication date: 2021-11-23
Anticipated expiration: 2040-01-20
Also published as: CN113875757B; CN113875757A; WO2020156298A1; CN111480649A

Abstract

The invention discloses an application of a malononitrile compound shown as a general formula I as a bactericide. The definition of each substituent group in the formula is shown in the specification.

Description

Application of malononitrile compound as bactericide

Technical Field

The invention belongs to the field of agricultural bactericides, and particularly relates to an application of a malononitrile compound as a bactericide.

Background

Bacterial diseases become the second most common diseases next to fungal diseases in agricultural production in China, according to incomplete statistics, the bacterial diseases of China currently occur in an area of 1.2 hundred million acres, and the bacterial disease control market capacity exceeds 20 hundred million yuan. In the current agricultural production, the medicaments for preventing and treating bacterial diseases mainly comprise copper preparations (including organic or inorganic copper preparations) with large use amount and antibiotic products; wherein, the copper preparation has low control effect and a large amount of heavy metals are sprayed into the environment to pollute soil, water and food, thus causing the safety worry of the environment and the food; on the other hand, the use of a large amount of antibiotics may cause human pathogenic bacteria to develop resistance to medical antibiotics. Other varieties which can be used for agricultural bacterial treatment are only a few, and are limited by resistance and prevention effect in actual production, so that the popularization area is small. Therefore, the development of novel, highly effective, low-toxicity, environmentally friendly bacterial disease control agents is very necessary and urgent.

In the prior art, the application of the malononitrile compound as a bactericide is not reported.

Disclosure of Invention

The invention aims to provide application of a malononitrile compound shown as a general formula I as a bactericide in the fields of agriculture, forestry or sanitation.

The technical scheme of the invention is as follows:

the application of a malononitrile compound as a bactericide is disclosed, wherein the structure of the malononitrile compound is shown as a general formula I:

in the formula:

n is selected from 0, 1, 2 or 3;

w is selected from W₁-W₁₀One of the groups shown:

X₁、X₂、X₃、X₄、X₅each independently selected from hydrogen, halogen, cyano, nitro, hydroxy, mercapto, amino, carboxyl, C₁-C₆Alkyl, halo C₁-C₆Alkyl radical, C₁-C₆Alkoxy, halo C₁-C₆Alkoxy radical, C₁-C₆Alkylthio, halo C₁-C₆Alkylthio radical, C₁-C₆Alkylamino radical, C₁-C₆Dialkylamino radical, C₁-C₆Alkylcarbonyl group, C₁-C₆Alkoxycarbonyl, -NHCH = C (CN)₂or-CH₂NHCH=C(CN)₂；

Y₁、Y₂、Y₃、Y₄Each independently selected from hydrogen, halogen, cyano, C₁-C₆Alkyl, halo C₁-C₆Alkyl radical, C₁-C₆Alkoxy, halo C₁-C₆Alkoxy radical, C₁-C₆Alkylthio or halogeno C₁-C₆An alkylthio group;

Z₁、Z₂、Z₃、Z₄、Z₅、Z₆、Z₇each independently selected from hydrogen, halogen or C₁-C₆An alkyl group;

R₁selected from hydrogen, hydroxy, mercapto, amino, cyano, C₁-C₆Alkyl radical, C₁-C₆Alkoxy, halo C₁-C₆Alkoxy radical, C₁-C₆Alkylthio, halo C₁-C₆Alkylthio radical, C₁-C₆Alkylamino or C₁-C₆A dialkylamino group;

R₂selected from hydrogen, C₁-C₆Alkyl, halo C₁-C₆Alkyl, cyano C₁-C₆Alkyl radical, C₁-C₆Alkylcarbonyl group, C₃-C₆Cycloalkyl carbonyl or C₁-C₆An alkoxycarbonyl group;

or a salt of a compound of formula I.

Preferred compounds for use as bactericides of the compounds of the formula I are:

n is selected from 0 or 1;

w is selected from W₁-W₁₀One of the groups shown:

X₁、X₂、X₃、X₄、X₅each independently selected from hydrogen, halogen, cyano, nitro, hydroxy, mercapto, amino, carboxyl, C₁-C₄Alkyl, halo C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halo C₁-C₄Alkoxy radical, C₁-C₄Alkylthio, halo C₁-C₄Alkylthio radical, C₁-C₄Alkylamino radical, C₁-C₄Dialkylamino radical, C₁-C₄Alkylcarbonyl group, C₁-C₄Alkoxycarbonyl, -NHCH = C (CN)₂or-CH₂NHCH=C(CN)₂；

Y₁、Y₂、Y₃、Y₄Each independently selected from hydrogen, halogen, cyano, C₁-C₄Alkyl, halo C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halo C₁-C₄Alkoxy radical, C₁-C₄Alkylthio or halogeno C₁-C₄An alkylthio group;

Z₁、Z₂、Z₃、Z₄、Z₅、Z₆、Z₇each independently selected from hydrogen, halogen or C₁-C₄An alkyl group;

R₁selected from hydrogen, hydroxy, mercapto, amino, cyano, C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halo C₁-C₄Alkoxy radical, C₁-C₄Alkylthio, halo C₁-C₄Alkylthio radical, C₁-C₄Alkylamino or C₁-C₄A dialkylamino group;

R₂selected from hydrogen, C₁-C₄Alkyl, halo C₁-C₄Alkyl, cyano C₁-C₄Alkyl radical, C₁-C₄Alkylcarbonyl group, C₃-C₆Cycloalkyl carbonyl or C₁-C₄An alkoxycarbonyl group;

or salts of the compounds of the general formula I with hydrochloric acid, hydrobromic acid, sulphuric acid, phosphoric acid, formic acid, acetic acid, propionic acid, butyric acid, valeric acid, trifluoroacetic acid, oxalic acid, malonic acid, methanesulphonic acid, 4-toluenesulphonic acid, malic acid, fumaric acid, lactic acid, maleic acid, salicylic acid, tartaric acid or citric acid.

Further preferred compounds for use as bactericides are the compounds of the formula I:

n is selected from 0 or 1;

w is selected from W₁-W₁₀One of the groups shown:

X₁、X₂、X₃、X₄、X₅each independently selected from the group consisting of hydrogen, fluoro, chloro, bromo, cyano, nitro, hydroxy, mercapto, amino, carboxy, methyl, ethyl, N-propyl, isopropyl, N-butyl, isobutyl, sec-butyl, tert-butyl, chloromethyl, dichloromethyl, trichloromethyl, monobromomethyl, dibromomethyl, tribromomethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, 2, 2, 2-trifluoroethyl, heptafluoroisopropyl, methoxy, ethoxy, N-propoxy, isopropoxy, difluoromethoxy, trifluoromethoxy, methylthio, ethylthio, trifluoromethylthio, 2, 2, 2-trifluoroethylthio, methylamino, ethylamino, N-dimethylamino, -NHCH = C (CN)₂or-CH₂NHCH=C(CN)₂；

Y₁、Y₂、Y₃、Y₄Each independently selected from hydrogen, fluoro, chloro, bromo, cyano, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, monochloromethyl, dichloromethyl, trichloromethyl, monobromomethyl, dibromomethyl, tribromomethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, 2, 2, 2-trifluoroethyl, heptafluoroisopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, difluoromethoxy, trifluoromethoxy, methylthio, ethylthio, trifluoromethylthio or 2, 2, 2-trifluoroethylthio;

Z₁、Z₂、Z₃、Z₄、Z₅、Z₆、Z₇each independently selected from hydrogen, fluoro, chloro, bromo, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl;

R₁selected from hydrogen, hydroxy, mercapto, amino, cyano, methyl, ethyl, n-propyl, n-butyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, methylthio, ethylthio, n-propylthio, n-butylthio, methylamino, ethylamino, n-propylamino or n-butylamino;

R₂selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butylButyl, tert-butyl, cyanomethyl, 2, 2, 2-trifluoroethyl, acetyl, n-propionyl, cyclopropylformyl, methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl or n-butoxycarbonyl;

Further preferred compounds for use as bactericides for compounds of the general formula I are:

n is selected from 0 or 1;

w is selected from W₁-W₁₀One of the groups shown:

X₁、X₂、X₃、X₄、X₅each independently selected from hydrogen, fluoro, chloro, bromo, cyano, nitro, hydroxy, mercapto, amino, carboxy, methyl, ethyl, N-propyl, isopropyl, N-butyl, isobutyl, sec-butyl, tert-butyl, trifluoromethyl, methoxy, ethoxy, trifluoromethoxy, methylthio, methylamino, N-dimethylamino, -NHCH = C (CN)₂or-CH₂NHCH=C(CN)₂；

Y₁、Y₂、Y₃、Y₄Selected from hydrogen;

Z₁、Z₂、Z₃、Z₄、Z₅、Z₆、Z₇selected from hydrogen;

R₁selected from hydrogen, amino, methyl, methoxy, ethoxy, methylthio, ethylthio, methylamino or ethylamino;

R₂selected from hydrogen, methyl, ethyl, 2, 2, 2-trifluoroethyl, cyanomethyl, acetyl, n-propionyl, cyclopropylformyl, methoxycarbonyl or ethoxycarbonyl;

In the definitions of the compounds of the general formula given above, the terms used in the collection generally represent the following substituents:

halogen: refers to fluorine, chlorine, bromine or iodine.

Alkyl groups: straight-chain or branched alkyl radicals, such as methyl, ethyl, n-propyl, isopropyl or the different butyl, pentyl or hexyl isomers, etc.

Halogenated alkyl groups: straight-chain or branched alkyl groups, the hydrogen atoms on which may be partially or totally substituted by halogen, such as, for example, chloromethyl, dichloromethyl, trichloromethyl, monobromomethyl, dibromomethyl, tribromomethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, 2, 2, 2-trifluoroethyl, heptafluoroisopropyl, and the like.

Cyanoalkyl group: straight-chain or branched alkyl groups in which the hydrogen atoms may be partially or completely replaced by cyano groups,

for example cyanomethyl (CNCH)₂-), cyanoethyl (CNCH)₂CH₂-)、CNCH₂CH₂CH₂-、CNCH₂CH₂CH₂CH₂-and the like.

Alkoxy groups: straight or branched chain alkyl groups bonded to the structure via an oxygen atom, such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, and the like.

Haloalkoxy groups: straight-chain or branched alkoxy groups in which the hydrogen atoms may be partially or completely replaced by halogen, for example chloromethoxy, dichloromethoxy, trichloromethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, chlorofluoromethoxy, 2, 2, 2-trifluoroethoxy and the like.

Alkylthio group: straight or branched chain alkyl groups attached to the structure via a sulfur atom, such as methylthio, ethylthio, and the like.

Haloalkylthio: straight-chain or branched alkylthio groups in which the hydrogen atoms may be partially or fully substituted by halogen, such as difluoromethylthio, trifluoromethylthio, 2, 2, 2-trifluoroethylthio and the like.

Alkylamino group: straight or branched chain alkyl groups attached to the structure via a nitrogen atom, such as methylamino, ethylamino, n-propylamino, isopropylamino or the isomeric butylamines.

Dialkylamino group: two identical or different straight-chain or branched alkyl groups are bonded to the structure via a nitrogen atom, such as N, N-dimethylamino, N-methyl-N-ethylamino, etc.

An alkylcarbonyl group: the alkyl group is bonded to the structure via a carbonyl group, such as acetyl (CH3CO-), propionyl (CH3CH2CO-), and the like.

Cycloalkyl carbonyl group: the cycloalkyl group is attached to the structure via a carbonyl group, such as cyclopropylformyl.

Alkoxycarbonyl group: alkyl-O-CO-, e.g. methoxycarbonyl (CH)₃OCO-), ethoxycarbonyl (CH)₃CH₂OCO-), n-propoxycarbonyl (CH)₃CH₂CH₂OCO-), n-butoxycarbonyl (CH)₃CH₂CH₂CH₂OCO-), etc.

Some of the compounds of general formula I of the present invention are shown in tables 1 to 218, but the present invention is by no means limited to these compounds.

In the general formula I, when W = W₁And when n =1, the compound of formula I is represented by formula I-W₁-1 represents (for ease of description, W)₁Substituent X of₁、X₂、X₃、X₄、X₅Represented by R, the same applies below).

Table 1: general formula I-W₁In-1, when R is₁=R₂When the substituent is H, R is different substituent groups shown in Table 1, and represents the compound number of 1.1-1.360.

TABLE 1

Table 2: general formula I-W₁In-1, when R is₁=CH₃And R is₂When the substituent R is in accordance with table 1, the representative compound number is 2.1 to 2.360, which in turn corresponds to 1.1 to 1.360 of table 1.

Table 3: general formula I-W₁In-1, when R is₁=CH₂CH₃And R is₂When the substituent R is in accordance with table 1, the representative compound numbers are 3.1 to 3.360, which in turn correspond to 1.1 to 1.360 of table 1.

Table 4: general formula I-W₁In-1, when R is₁=SCH₃And R is₂When the substituent R is in accordance with table 1, the representative compound numbers are 4.1 to 4.360, which in turn correspond to 1.1 to 1.360 of table 1.

Table 5: general formula I-W₁In-1, when R is₁=SCH₂CH₃And R is₂When the substituent R is in accordance with table 1, the representative compound numbers are 5.1 to 5.360, which in turn correspond to 1.1 to 1.360 of table 1.

Table 6: general formula I-W₁In-1, when R is₁=NH₂And R is₂When the substituent R is in accordance with table 1, the representative compound numbers are 6.1 to 6.360, which in turn correspond to 1.1 to 1.360 of table 1.

Table 7: general formula I-W₁In-1, when R is₁=NHCH₃And R is₂When the substituent R is in accordance with table 1, the representative compound numbers are 7.1 to 7.360, which in turn correspond to 1.1 to 1.360 of table 1.

Table 8: general formula I-W₁In-1, when R is₁=NHCH₂CH₃And R is₂When the substituent R is in accordance with table 1, the representative compound numbers are 8.1 to 8.360, which in turn correspond to 1.1 to 1.360 of table 1.

Table 9: general formula I-W₁In-1, when R is₁=N(CH₃)₂And R is₂When the substituent R is in accordance with table 1, the representative compound numbers are 9.1 to 9.360, which in turn correspond to 1.1 to 1.360 of table 1.

Table 10: general formula I-W₁In-1, when R is₁=OCH₃And R is₂When the substituent R is in accordance with table 1, the representative compound numbers are 10.1 to 10.360, which in turn correspond to 1.1 to 1.360 of table 1.

Table 11: general formula I-W₁In-1, when R is₁=OCH₂CH₃And R is₂When the substituent R is in accordance with table 1, the representative compound numbers are 11.1 to 11.360, which in turn correspond to 1.1 to 1.360 of table 1.

Table 12: general formula I-W₁In-1, when R is₁= H and R₂=CH₃When R is in accordance with Table 1, the compound numbers are 12.1-12.360, which in turn correspond to 1.1-1.360 of Table 1.

Table 13: general formula I-W₁In-1, when R is₁=CH₃And R is₂=CH₃When R is in accordance with Table 1, the compound numbers 13.1-13.360 are shown, which in turn correspond to 1.1-1.360 of Table 1.

Table 14: general formula I-W₁In-1, when R is₁=CH₂CH₃And R is₂=CH₃When R is in accordance with Table 1, the compound is numbered from 14.1 to 14.360, which in turn correspond to 1.1 to 1.360 of Table 1.

Table 15: general formula I-W₁In-1, when R is₁=SCH₃And R is₂=CH₃When R is in accordance with Table 1, the compound is numbered from 15.1 to 15.360, which in turn correspond to 1.1 to 1.360 of Table 1.

Table 16: general formula I-W₁In-1, when R is₁=SCH₂CH₃And R is₂=CH₃When R is in accordance with Table 1, the compound is numbered from 16.1 to 16.360, which in turn correspond to 1.1 to 1.360 of Table 1.

Table 17: general formula I-W₁In-1, when R is₁=NH₂And R is₂=CH₃When R is in accordance with Table 1, the compound is shown as 17.1-17.360, which in turn corresponds to 1.1-1.360 of Table 1.

Table 18: general formula I-W₁In-1, when R is₁=NHCH₃And R is₂=CH₃When R is in accordance with Table 1, the compound is numbered from 18.1 to 18.360, which in turn correspond to 1.1 to 1.360 of Table 1.

Table 19: general formula I-W₁In-1, when R is₁=NHCH₂CH₃And R is₂=CH₃When R is in accordance with Table 1, the compound numbers 19.1-19.360, which correspond to 1.1-1.360 of Table 1.

Table 20: general formula I-W₁In-1, when R is₁=N(CH₃)₂And R is₂=CH₃When R is in accordance with Table 1, the compound is numbered from 20.1 to 20.360, which in turn correspond to 1.1 to 1.360 of Table 1.

Table 21: general formula I-W₁In-1, when R is₁=OCH₃And R is₂=CH₃When R is in accordance with Table 1, the compound numbers 21.1-21.360 are shown, which in turn correspond to 1.1-1.360 of Table 1.

Table 22: general formula I-W₁In-1, when R is₁=OCH₂CH₃And R is₂=CH₃When R is the same as in Table 1, the substituent represents the compound numberIs 22.1-22.360, which in turn corresponds to 1.1-1.360 of Table 1.

Table 23: general formula I-W₁In-1, when R is₁= H and R₂=CH₂CH₃When R is in accordance with Table 1, the compound numbers 23.1-23.360 are shown, which in turn correspond to 1.1-1.360 of Table 1.

Table 24: general formula I-W₁In-1, when R is₁=CH₃And R is₂=CH₂CH₃When R is in accordance with Table 1, the compound is numbered from 24.1 to 24.360, which in turn correspond to 1.1 to 1.360 of Table 1.

Table 25: general formula I-W₁In-1, when R is₁=CH₂CH₃And R is₂=CH₂CH₃When R is in accordance with Table 1, the compound is numbered from 25.1 to 25.360, which in turn correspond to 1.1 to 1.360 of Table 1.

Table 26: general formula I-W₁In-1, when R is₁=SCH₃And R is₂=CH₂CH₃When R is in accordance with Table 1, the compound is numbered from 26.1 to 26.360, which in turn correspond to 1.1 to 1.360 of Table 1.

Table 27: general formula I-W₁In-1, when R is₁=SCH₂CH₃And R is₂=CH₂CH₃When R is in accordance with Table 1, the compound is numbered 27.1-27.360, which in turn corresponds to 1.1-1.360 of Table 1.

Table 28: general formula I-W₁In-1, when R is₁=NH₂And R is₂=CH₂CH₃When R is in accordance with Table 1, the compound is numbered from 28.1 to 28.360, which in turn correspond to 1.1 to 1.360 of Table 1.

Table 29: general formula I-W₁In-1, when R is₁=NHCH₃And R is₂=CH₂CH₃When R is in accordance with Table 1, the compound numbers 29.1-29.360 are shown, which in turn correspond to 1.1-1.360 of Table 1.

Table 30: general formula I-W₁In-1, when R is₁=NHCH₂CH₃And R is₂=CH₂CH₃When the substituent R is in accordance with Table 1, the number of the compound represented by the formula is 30.1 to 30.360, which in turn corresponds to 1.1-1.360 of table 1.

Table 31: general formula I-W₁In-1, when R is₁=N(CH₃)₂And R is₂=CH₂CH₃When R is in accordance with Table 1, the compound numbers 31.1-31.360 are shown, which in turn correspond to 1.1-1.360 of Table 1.

Table 32: general formula I-W₁In-1, when R is₁=OCH₃And R is₂=CH₂CH₃When R is in accordance with Table 1, the compound is numbered from 32.1 to 32.360, which in turn correspond to 1.1 to 1.360 of Table 1.

Table 33: general formula I-W₁In-1, when R is₁=OCH₂CH₃And R is₂=CH₂CH₃When R is in accordance with Table 1, the compound numbers 33.1-33.360 are represented, which in turn correspond to 1.1-1.360 of Table 1.

Table 34: general formula I-W₁In-1, when R is₁= H and R₂=CH₂CN, the substituent R is consistent with the compound shown in the table 1, represents the compound number of 34.1-34.360, and sequentially corresponds to 1.1-1.360 of the compound shown in the table 1.

Table 35: general formula I-W₁In-1, when R is₁=CH₃And R is₂=CH₂CN, the substituent R is consistent with the compound shown in the table 1, represents the compound number of 35.1-35.360, and sequentially corresponds to 1.1-1.360 of the compound shown in the table 1.

Table 36: general formula I-W₁In-1, when R is₁=CH₂CH₃And R is₂=CH₂CN, the substituent R is consistent with the compound shown in the table 1, represents the compound number of 36.1-36.360, and sequentially corresponds to 1.1-1.360 of the compound shown in the table 1.

Table 37: general formula I-W₁In-1, when R is₁=SCH₃And R is₂=CH₂CN, the substituent R is consistent with the compound shown in the table 1, represents the compound number of 37.1-37.360, and sequentially corresponds to 1.1-1.360 of the compound shown in the table 1.

Table 38: general formula I-W₁In-1, when R is₁=SCH₂CH₃And R is₂=CH₂CN, the substituent R is consistent with the compound shown in the table 1, represents the compound number of 38.1-38.360, and sequentially corresponds to 1.1-1.360 of the compound shown in the table 1.

Table 39: general formula I-W₁In-1, when R is₁=NH₂And R is₂=CH₂CN, the substituent R is identical to that in Table 1, represents the compound number of 39.1-39.360, which in turn corresponds to 1.1-1.360 of Table 1.

Table 40: general formula I-W₁In-1, when R is₁=NHCH₃And R is₂=CH₂CN, the substituent R is consistent with the compound shown in the table 1, represents the compound number of 40.1-40.360, and sequentially corresponds to 1.1-1.360 of the compound shown in the table 1.

Table 41: general formula I-W₁In-1, when R is₁=NHCH₂CH₃And R is₂=CH₂CN, the substituent R is consistent with the compound shown in the table 1, represents the compound number of 41.1-41.360, and sequentially corresponds to 1.1-1.360 of the compound shown in the table 1.

Table 42: general formula I-W₁In-1, when R is₁=N(CH₃)₂And R is₂=CH₂CN, the substituent R is consistent with the compound shown in the table 1, represents the compound number of 42.1-42.360, and sequentially corresponds to 1.1-1.360 of the compound shown in the table 1.

Table 43: general formula I-W₁In-1, when R is₁=OCH₃And R is₂=CH₂CN, the substituent R is consistent with the compound shown in the table 1, represents the compound number of 43.1-43.360, and sequentially corresponds to 1.1-1.360 of the compound shown in the table 1.

Table 44: general formula I-W₁In-1, when R is₁=OCH₂CH₃And R is₂=CH₂CN, the substituent R is consistent with the compound shown in the table 1, represents the compound number of 44.1-44.360, and sequentially corresponds to 1.1-1.360 of the compound shown in the table 1.

Table 45: general formula I-W₁In-1, when R is₁= H and R₂In the case of acetyl group, the substituent R corresponds to table 1, and represents a compound number of 45.1 to 45.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 46: general formula I-W₁In-1, when R is₁=CH₃And R is₂Where the substituent R is in accordance with table 1 when acetyl, the representative compound number is 46.1 to 46.360, which in turn corresponds to 1.1 to 1.360 of table 1.

Table 47: general formula I-W₁In-1, when R is₁=CH₂CH₃And R is₂When the acetyl group is not substitutedThe substituents R correspond to those in Table 1 and represent compounds having the numbers 47.1 to 47.360, which in turn correspond to those in Table 1 from 1.1 to 1.360.

Table 48: general formula I-W₁In-1, when R is₁=SCH₃And R is₂Where the substituent R is in accordance with table 1 when acetyl, the representative compound number is 48.1 to 48.360, which in turn corresponds to 1.1 to 1.360 of table 1.

Table 49: general formula I-W₁In-1, when R is₁=SCH₂CH₃And R is₂Where the substituent R is in accordance with table 1 when acetyl, the representative compound number is 49.1 to 49.360, which in turn corresponds to 1.1 to 1.360 of table 1.

Table 50: general formula I-W₁In-1, when R is₁=NH₂And R is₂Where the substituent R is in accordance with table 1 when acetyl, the representative compound number is 50.1 to 50.360, which in turn corresponds to 1.1 to 1.360 of table 1.

Table 51: general formula I-W₁In-1, when R is₁=NHCH₃And R is₂In the case of acetyl group, the substituent R corresponds to table 1, and represents a compound number of 51.1 to 51.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 52: general formula I-W₁In-1, when R is₁=NHCH₂CH₃And R is₂Where the substituent R is in accordance with table 1 when acetyl, the representative compound number is 52.1 to 52.360, which in turn corresponds to 1.1 to 1.360 of table 1.

Table 53: general formula I-W₁In-1, when R is₁=N(CH₃)₂And R is₂In the case of acetyl group, the substituent R corresponds to table 1, and represents a compound number of 53.1 to 53.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 54: general formula I-W₁In-1, when R is₁=OCH₃And R is₂Where the substituent R is in accordance with table 1 when acetyl, the representative compound number is 54.1 to 54.360, which in turn corresponds to 1.1 to 1.360 of table 1.

Table 55: general formula I-W₁In-1, when R is₁=OCH₂CH₃And R is₂Where the substituent R is in accordance with table 1 when acetyl, the representative compound number is 55.1 to 55.360, which in turn corresponds to 1.1 to 1.360 of table 1.

Table 56: general formula I-W₁In-1, when R is₁= H and R₂In the case of n-propionyl group, the substituent R corresponds to table 1, and represents a compound number of 56.1 to 56.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 57: general formula I-W₁In-1, when R is₁=CH₃And R is₂In the case of n-propionyl group, the substituent R corresponds to table 1, and represents a compound number of 57.1 to 57.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 58: general formula I-W₁In-1, when R is₁=CH₂CH₃And R is₂In the case of n-propionyl group, the substituent R corresponds to table 1, and represents a compound number of 58.1 to 58.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 59: general formula I-W₁In-1, when R is₁=SCH₃And R is₂In the case of n-propionyl group, the substituent R corresponds to table 1, and represents the compound number of 59.1 to 59.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 60: general formula I-W₁In-1, when R is₁=SCH₂CH₃And R is₂In the case of n-propionyl group, the substituent R corresponds to table 1, and represents a compound number of 60.1 to 60.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 61: general formula I-W₁In-1, when R is₁=NH₂And R is₂In the case of n-propionyl group, the substituent R corresponds to table 1, and represents a compound number of 61.1 to 61.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 62: general formula I-W₁In-1, when R is₁=NHCH₃And R is₂In the case of n-propionyl group, the substituent R corresponds to table 1, and represents a compound number of 62.1 to 62.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 63: general formula I-W₁In-1, when R is₁=NHCH₂CH₃And R is₂In the case of n-propionyl group, the substituent R corresponds to table 1, and represents a compound number of 63.1 to 63.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 64: general formula I-W₁In-1, when R is₁=N(CH₃)₂And R is₂Where n-propionyl is present, the substituents R are as defined in Table 1,the representative compounds are numbered from 64.1 to 64.360 and correspond in sequence to 1.1 to 1.360 of Table 1.

Table 65: general formula I-W₁In-1, when R is₁=OCH₃And R is₂In the case of n-propionyl group, the substituent R corresponds to table 1, and the representative compound number is 65.1 to 65.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 66: general formula I-W₁In-1, when R is₁=OCH₂CH₃And R is₂In the case of n-propionyl group, the substituent R corresponds to table 1, and represents the compound number of 66.1 to 66.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 67: general formula I-W₁In-1, when R is₁= H and R₂In the case of a cyclopropylformyl group, the substituent R corresponds to table 1, and represents a compound having a number of 67.1 to 67.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 68: general formula I-W₁In-1, when R is₁=CH₃And R is₂In the case of a cyclopropylformyl group, the substituent R corresponds to table 1, and represents a compound number of 68.1 to 68.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 69: general formula I-W₁In-1, when R is₁=CH₂CH₃And R is₂In the case of a cyclopropylformyl group, the substituent R corresponds to table 1, and represents a compound number of 69.1 to 69.360, which in turn corresponds to 1.1 to 1.360 of table 1.

Table 70: general formula I-W₁In-1, when R is₁=SCH₃And R is₂In the case of a cyclopropylformyl group, the substituent R corresponds to table 1, and represents a compound number of 70.1 to 70.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 71: general formula I-W₁In-1, when R is₁=SCH₂CH₃And R is₂In the case of a cyclopropylformyl group, the substituent R corresponds to table 1, and represents a compound number of 71.1 to 71.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 72: general formula I-W₁In-1, when R is₁=NH₂And R is₂In the case of a cyclopropylformyl group, the substituent R corresponds to table 1, and represents a compound number of 72.1 to 72.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 73: general formula I-W₁In-1, when R is₁=NHCH₃And R is₂In the case of a cyclopropylformyl group, the substituent R corresponds to table 1, and represents a compound number of 73.1 to 73.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 74: general formula I-W₁In-1, when R is₁=NHCH₂CH₃And R is₂In the case of a cyclopropylformyl group, the substituent R corresponds to table 1, and represents the compound number 74.1 to 74.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 75: general formula I-W₁In-1, when R is₁=N(CH₃)₂And R is₂In the case of a cyclopropylformyl group, the substituent R corresponds to table 1, and represents a compound having a number of 75.1 to 75.360, which in turn corresponds to 1.1 to 1.360 of table 1.

Table 76: general formula I-W₁In-1, when R is₁=OCH₃And R is₂In the case of a cyclopropylformyl group, the substituent R corresponds to table 1, and represents a compound number of 76.1 to 76.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 77: general formula I-W₁In-1, when R is₁=OCH₂CH₃And R is₂In the case of a cyclopropylformyl group, the substituent R corresponds to table 1, and represents a compound number of 77.1 to 77.360, which in turn corresponds to 1.1 to 1.360 of table 1.

Table 78: general formula I-W₁In-1, when R is₁= H and R₂In the case of a methoxycarbonyl group, the substituent R corresponds to table 1, and represents a compound number of 78.1 to 78.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 79: general formula I-W₁In-1, when R is₁=CH₃And R is₂In the case of a methoxycarbonyl group, the substituent R corresponds to table 1, and represents a compound number of 79.1 to 79.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 80: general formula I-W₁In-1, when R is₁=CH₂CH₃And R is₂In the case of a methoxycarbonyl group, the substituent R corresponds to table 1, and represents a compound number of 80.1 to 80.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 81: general formula I-W₁In-1, when R is₁=SCH₃And R is₂= nailIn the case of oxycarbonyl, the substituent R corresponds to Table 1 and represents the compound numbers 81.1 to 81.360, which in turn correspond to 1.1 to 1.360 of Table 1.

Table 82: general formula I-W₁In-1, when R is₁=SCH₂CH₃And R is₂In the case of a methoxycarbonyl group, the substituent R corresponds to table 1, and represents a compound number of 82.1 to 82.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 83: general formula I-W₁In-1, when R is₁=NH₂And R is₂In the case of a methoxycarbonyl group, the substituent R corresponds to table 1, and represents a compound number of 83.1 to 83.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 84: general formula I-W₁In-1, when R is₁=NHCH₃And R is₂In the case of a methoxycarbonyl group, the substituent R corresponds to table 1, and represents a compound number of 84.1 to 84.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 85: general formula I-W₁In-1, when R is₁=NHCH₂CH₃And R is₂In the case of a methoxycarbonyl group, the substituent R corresponds to table 1, and represents a compound number of 85.1 to 85.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 86: general formula I-W₁In-1, when R is₁=N(CH₃)₂And R is₂In the case of a methoxycarbonyl group, the substituent R corresponds to table 1, and represents a compound number of 86.1 to 86.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 87: general formula I-W₁In-1, when R is₁=OCH₃And R is₂In the case of a methoxycarbonyl group, the substituent R corresponds to table 1, and represents a compound number of 87.1 to 87.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 88: general formula I-W₁In-1, when R is₁=OCH₂CH₃And R is₂In the case of a methoxycarbonyl group, the substituent R corresponds to table 1, and represents a compound number of 88.1 to 88.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 89: general formula I-W₁In-1, when R is₁= H and R₂In the case of an ethoxycarbonyl group, the substituent R corresponds to that in Table 1, and the representative compound number is 89.1 to 89.360, which correspond to that in Table 11.1-1.360。

Table 90: general formula I-W₁In-1, when R is₁=CH₃And R is₂In the case of an ethoxycarbonyl group, the substituent R corresponds to table 1, and represents a compound number of 90.1 to 90.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 91: general formula I-W₁In-1, when R is₁=CH₂CH₃And R is₂In the case of an ethoxycarbonyl group, the substituent R corresponds to table 1, and represents a compound number of 91.1 to 91.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 92: general formula I-W₁In-1, when R is₁=SCH₃And R is₂In the case of an ethoxycarbonyl group, the substituent R corresponds to table 1, and represents a compound number of 92.1 to 92.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 93: general formula I-W₁In-1, when R is₁=SCH₂CH₃And R is₂In the case of an ethoxycarbonyl group, the substituent R corresponds to table 1, and represents a compound number of 93.1 to 93.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 94: general formula I-W₁In-1, when R is₁=NH₂And R is₂In the case of an ethoxycarbonyl group, the substituent R corresponds to table 1, and represents a compound number of 94.1 to 94.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 95: general formula I-W₁In-1, when R is₁=NHCH₃And R is₂In the case of an ethoxycarbonyl group, the substituent R corresponds to table 1, and represents a compound number of 95.1 to 95.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 96: general formula I-W₁In-1, when R is₁=NHCH₂CH₃And R is₂In the case of an ethoxycarbonyl group, the substituent R corresponds to table 1, and represents a compound number of 96.1 to 96.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 97: general formula I-W₁In-1, when R is₁=N(CH₃)₂And R is₂In the case of an ethoxycarbonyl group, the substituent R corresponds to table 1, and represents a compound number of 97.1 to 97.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 98: general formula I-W₁In-1, when R is₁=OCH₃And R is₂In the case of an ethoxycarbonyl group, the substituent R corresponds to table 1, and represents a compound number of 98.1 to 98.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 99: general formula I-W₁In-1, when R is₁=OCH₂CH₃And R is₂In the case of an ethoxycarbonyl group, the substituent R corresponds to table 1, and represents a compound number of 99.1 to 99.360, which in turn corresponds to 1.1 to 1.360 in table 1.

In the general formula I, when W = W₁And when n =0, the compound of formula I is represented by formula I-W₁-0 represents.

Table 100: general formula I-W₁In-0, when R is₁= H and R₂When the substituent R is in accordance with table 1, the representative compound numbers are 100.1 to 100.360, which in turn correspond to 1.1 to 1.360 of table 1.

Table 101: general formula I-W₁In-0, when R is₁=CH₃And R is₂When the substituent R is in accordance with table 1, the representative compound numbers are 101.1 to 101.360, which in turn correspond to 1.1 to 1.360 of table 1.

Table 102: general formula I-W₁In-0, when R is₁=CH₂CH₃And R is₂When the substituent R is in accordance with table 1, the representative compound numbers are 102.1 to 102.360, which in turn correspond to 1.1 to 1.360 of table 1.

Table 103: general formula I-W₁In-0, when R is₁=SCH₃And R is₂When the substituent R is in accordance with table 1, the representative compound numbers are 103.1 to 103.360, which in turn correspond to 1.1 to 1.360 of table 1.

Table 104: general formula I-W₁In-0, when R is₁=SCH₂CH₃And R is₂When the substituent R is in accordance with table 1, the representative compound numbers are 104.1 to 104.360, which in turn correspond to 1.1 to 1.360 in table 1.

Table 105: general formula I-W₁In-0, when R is₁=NH₂And R is₂When = H, the substituent R is as in Table 1 and represents a compoundThe materials are numbered 105.1-105.360, which are sequentially corresponding to 1.1-1.360 of Table 1.

Table 106: general formula I-W₁In-0, when R is₁=NHCH₃And R is₂When the substituent R is in accordance with table 1, the representative compound numbers are 106.1 to 106.360, which in turn correspond to 1.1 to 1.360 in table 1.

Table 107: general formula I-W₁In-0, when R is₁=NHCH₂CH₃And R is₂When the substituent R is in accordance with table 1, the representative compound numbers are 107.1 to 107.360, which in turn correspond to 1.1 to 1.360 of table 1.

Table 108: general formula I-W₁In-0, when R is₁=N(CH₃)₂And R is₂When the substituent R is in accordance with table 1, the representative compound numbers are 108.1 to 108.360, which in turn correspond to 1.1 to 1.360 in table 1.

Table 109: general formula I-W₁In-0, when R is₁=OCH₃And R is₂When the substituent R is in accordance with table 1, the representative compound numbers are 109.1 to 109.360, which in turn correspond to 1.1 to 1.360 of table 1.

Table 110: general formula I-W₁In-0, when R is₁=OCH₂CH₃And R is₂When the substituent R is in accordance with table 1, the representative compound numbers are 110.1 to 110.360, which in turn correspond to 1.1 to 1.360 of table 1.

Table 111: general formula I-W₁In-0, when R is₁= H and R₂=CH₃When R is in accordance with Table 1, the compound numbers 111.1-111.360 are shown, which in turn correspond to 1.1-1.360 of Table 1.

Table 112: general formula I-W₁In-0, when R is₁=CH₃And R is₂=CH₃When R is in accordance with Table 1, the compound is numbered from 112.1 to 112.360, which in turn correspond to 1.1 to 1.360 of Table 1.

Table 113: general formula I-W₁In-0, when R is₁=CH₂CH₃And R is₂=CH₃When R is in accordance with Table 1, the compound is numbered from 113.1 to 113.360, which in turn correspond to 1.1 to 1.360 of Table 1.

Table 114: general formula I-W₁In-0, when R is₁=SCH₃And R is₂=CH₃When R is in accordance with Table 1, the compound is numbered from 114.1 to 114.360, which in turn correspond to 1.1 to 1.360 of Table 1.

Table 115: general formula I-W₁In-0, when R is₁=SCH₂CH₃And R is₂=CH₃When R is in accordance with Table 1, the compound numbers 115.1-115.360 are shown, which in turn correspond to 1.1-1.360 of Table 1.

Table 116: general formula I-W₁In-0, when R is₁=NH₂And R is₂=CH₃When R is in accordance with Table 1, the compound is numbered 116.1-116.360, which in turn corresponds to 1.1-1.360 of Table 1.

Table 117: general formula I-W₁In-0, when R is₁=NHCH₃And R is₂=CH₃When R is in accordance with Table 1, the compound numbers 117.1-117.360 are shown, which in turn correspond to 1.1-1.360 of Table 1.

Table 118: general formula I-W₁In-0, when R is₁=NHCH₂CH₃And R is₂=CH₃When R is in accordance with Table 1, the compound is numbered 118.1-118.360, which in turn corresponds to 1.1-1.360 of Table 1.

Table 119: general formula I-W₁In-0, when R is₁=N(CH₃)₂And R is₂=CH₃When R is in accordance with Table 1, the compound is numbered 119 to 119.360, which in turn correspond to 1.1 to 1.360 of Table 1.

Table 120: general formula I-W₁In-0, when R is₁=OCH₃And R is₂=CH₃When R is in accordance with Table 1, the compound is numbered from 120.1 to 120.360, which in turn correspond to 1.1 to 1.360 of Table 1.

Table 121: general formula I-W₁In-0, when R is₁=OCH₂CH₃And R is₂=CH₃When R is in accordance with Table 1, the compound is numbered 121.1-121.360, which in turn corresponds to 1.1-1.360 of Table 1.

Table 122: general formula I-W₁In-0, when R is₁= H and R₂=CH₂CH₃When R is in accordance with Table 1Representative compounds are numbered 122.1-122.360, which in turn correspond to 1.1-1.360 of Table 1.

Table 123: general formula I-W₁In-0, when R is₁=CH₃And R is₂=CH₂CH₃When R is in accordance with Table 1, the compound is numbered from 123.1 to 123.360, which in turn correspond to 1.1 to 1.360 of Table 1.

Table 124: general formula I-W₁In-0, when R is₁=CH₂CH₃And R is₂=CH₂CH₃When R is in accordance with Table 1, the compound numbers 124.1-124.360 are indicated, which in turn correspond to 1.1-1.360 of Table 1.

Table 125: general formula I-W₁In-0, when R is₁=SCH₃And R is₂=CH₂CH₃When R is in accordance with Table 1, the compound numbers 125.1-125.360 are represented, which in turn correspond to 1.1-1.360 of Table 1.

Table 126: general formula I-W₁In-0, when R is₁=SCH₂CH₃And R is₂=CH₂CH₃When R is in accordance with Table 1, the compound numbers 126.1-126.360 are shown, which in turn correspond to 1.1-1.360 of Table 1.

Table 127: general formula I-W₁In-0, when R is₁=NH₂And R is₂=CH₂CH₃When R is in accordance with Table 1, the compound numbers 127.1-127.360 are represented, which in turn correspond to 1.1-1.360 of Table 1.

Table 128: general formula I-W₁In-0, when R is₁=NHCH₃And R is₂=CH₂CH₃When R is in accordance with Table 1, the compound is numbered 128.1-128.360, which in turn corresponds to 1.1-1.360 of Table 1.

Table 129: general formula I-W₁In-0, when R is₁=NHCH₂CH₃And R is₂=CH₂CH₃When R is in accordance with Table 1, the compound is numbered 129.1 to 129.360, which in turn correspond to 1.1 to 1.360 of Table 1.

Table 130: general formula I-W₁In-0, when R is₁=N(CH₃)₂And R is₂=CH₂CH₃When R is in accordance with Table 1, the compound numbers 130.1-130.360 are shown, which in turn correspond to 1.1-1.360 of Table 1.

Table 131: general formula I-W₁In-0, when R is₁=OCH₃And R is₂=CH₂CH₃When R is in accordance with Table 1, the compound numbers 131.1-131.360 are shown, which in turn correspond to 1.1-1.360 of Table 1.

Table 132: general formula I-W₁In-0, when R is₁=OCH₂CH₃And R is₂=CH₂CH₃When R is in accordance with Table 1, the compound is numbered 132.1-132.360, which in turn corresponds to 1.1-1.360 of Table 1.

Table 133: general formula I-W₁In-0, when R is₁= H and R₂=CH₂CN, the substituent R is consistent with the compound shown in the table 1, represents the compound number of 133.1-133.360, and sequentially corresponds to 1.1-1.360 of the compound shown in the table 1.

Table 134: general formula I-W₁In-0, when R is₁=CH₃And R is₂=CH₂CN, the substituent R is consistent with the compound shown in the table 1, represents the compound number of 134.1-134.360, and sequentially corresponds to 1.1-1.360 of the compound shown in the table 1.

Table 135: general formula I-W₁In-0, when R is₁=CH₂CH₃And R is₂=CH₂CN, the substituent R is consistent with the compound shown in the table 1, represents the compound number of 135.1-135.360, and sequentially corresponds to 1.1-1.360 of the compound shown in the table 1.

Table 136: general formula I-W₁In-0, when R is₁=SCH₃And R is₂=CH₂CN, the substituent R is consistent with the compound shown in the table 1, represents the compound number of 136.1-136.360, and sequentially corresponds to 1.1-1.360 of the compound shown in the table 1.

Table 137: general formula I-W₁In-0, when R is₁=SCH₂CH₃And R is₂=CH₂CN, the substituent R is consistent with the compound shown in the table 1, represents the compound number of 137.1-137.360, and sequentially corresponds to 1.1-1.360 of the compound shown in the table 1.

Table 138: general formula I-W₁In-0, when R is₁=NH₂And R is₂=CH₂CN, the substituent R is in accordance with Table 1 and represents the compound number138.1-138.360, which in turn correspond to 1.1-1.360 of Table 1.

Table 139: general formula I-W₁In-0, when R is₁=NHCH₃And R is₂=CH₂CN, the substituent R is consistent with the compound shown in the table 1, represents the compound with the number of 139.1-139.360, and sequentially corresponds to 1.1-1.360 of the compound shown in the table 1.

Table 140: general formula I-W₁In-0, when R is₁=NHCH₂CH₃And R is₂=CH₂CN, the substituent R is consistent with the compound shown in the table 1, represents the compound number of 140.1-140.360, and sequentially corresponds to 1.1-1.360 of the compound shown in the table 1.

Table 141: general formula I-W₁In-0, when R is₁=N(CH₃)₂And R is₂=CH₂CN, the substituent R is consistent with the compound shown in the table 1, represents the compound number of 141.1-141.360, and sequentially corresponds to 1.1-1.360 of the compound shown in the table 1.

Table 142: general formula I-W₁In-0, when R is₁=OCH₃And R is₂=CH₂CN, the substituent R is consistent with the compound shown in the table 1, represents the compound number of 142.1-142.360, and sequentially corresponds to 1.1-1.360 of the compound shown in the table 1.

Table 143: general formula I-W₁In-0, when R is₁=OCH₂CH₃And R is₂=CH₂CN, the substituent R is consistent with the compound shown in the table 1, represents the compound number of 143.1-143.360, and sequentially corresponds to 1.1-1.360 of the compound shown in the table 1.

Table 144: general formula I-W₁In-0, when R is₁= H and R₂In the case of acetyl group, the substituent R corresponds to table 1, and represents a compound number of 144.1 to 144.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 145: general formula I-W₁In-0, when R is₁=CH₃And R is₂In the case of acetyl group, the substituent R corresponds to table 1, and represents a compound number of 145.1 to 145.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 146: general formula I-W₁In-0, when R is₁=CH₂CH₃And R is₂In the case of acetyl group, the substituent R corresponds to table 1, and represents the compound number of 146.1 to 146.360, which in turn corresponds to 1.1 to 1.360 in table 1.

TABLE 147: general formula I-W₁In-0, when R is₁=SCH₃And R is₂In the case of acetyl group, the substituent R corresponds to table 1, and represents a compound number of 147.1 to 147.360, which in turn corresponds to 1.1 to 1.360 of table 1.

Table 148: general formula I-W₁In-0, when R is₁=SCH₂CH₃And R is₂Where the substituent R is in accordance with table 1 when acetyl, the representative compound numbers are 148.1 to 148.360, which in turn correspond to 1.1 to 1.360 of table 1.

Table 149: general formula I-W₁In-0, when R is₁=NH₂And R is₂In the case of acetyl group, the substituent R corresponds to table 1, and represents a compound number of 149.1 to 149.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 150: general formula I-W₁In-0, when R is₁=NHCH₃And R is₂Where the substituent R is in accordance with table 1 when acetyl, the representative compound number is 150.1 to 150.360, which in turn corresponds to 1.1 to 1.360 of table 1.

Table 151: general formula I-W₁In-0, when R is₁=NHCH₂CH₃And R is₂In the case of acetyl group, the substituent R corresponds to table 1, and represents a compound number of 151.1 to 151.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 152: general formula I-W₁In-0, when R is₁=N(CH₃)₂And R is₂Where the substituent R is in accordance with table 1 when acetyl, the representative compound number is 152.1 to 152.360, which in turn corresponds to 1.1 to 1.360 of table 1.

Table 153: general formula I-W₁In-0, when R is₁=OCH₃And R is₂Where the substituent R is in accordance with table 1 when acetyl, the representative compound numbers are 153.1 to 153.360, which in turn correspond to 1.1 to 1.360 of table 1.

Table 154: general formula I-W₁In-0, when R is₁=OCH₂CH₃And R is₂Where the substituent R is in accordance with table 1, the representative compound numbers are 154.1 to 154.360, which in turn correspond to 1.1 to 1.360 of table 1.

Table 155: general formula I-W₁In-0, when R is₁= H and R₂Where n-propionyl is present, the substituents R are as defined in Table 1,the representative compounds are numbered 155.1-155.360, which in turn correspond to 1.1-1.360 of Table 1.

Table 156: general formula I-W₁In-0, when R is₁=CH₃And R is₂In the case of n-propionyl group, the substituent R corresponds to table 1, and represents a compound number of 156.1 to 156.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 157: general formula I-W₁In-0, when R is₁=CH₂CH₃And R is₂In the case of n-propionyl group, the substituent R corresponds to table 1, and represents the compound number 157.1 to 157.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 158: general formula I-W₁In-0, when R is₁=SCH₃And R is₂In the case of n-propionyl group, the substituent R corresponds to table 1, and represents a compound number of 158.1 to 158.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 159: general formula I-W₁In-0, when R is₁=SCH₂CH₃And R is₂In the case of n-propionyl group, the substituent R corresponds to table 1, and represents the compound number of 159.1 to 159.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 160: general formula I-W₁In-0, when R is₁=NH₂And R is₂In the case of n-propionyl group, the substituent R corresponds to table 1, and represents a compound number of 160.1 to 160.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 161: general formula I-W₁In-0, when R is₁=NHCH₃And R is₂In the case of n-propionyl group, the substituent R corresponds to table 1, and represents a compound number of 161.1 to 161.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 162: in the general formula I-W1-0, when R is₁=NHCH₂CH₃And R is₂In the case of n-propionyl group, the substituent R corresponds to table 1, and represents the compound number 162.1 to 162.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 163: general formula I-W₁In-0, when R is₁=N(CH₃)₂And R is₂In the case of n-propionyl group, the substituent R corresponds to table 1, and the representative compound number is 163.1 to 163.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 164: general formula I-W₁In-0, when R is₁=OCH₃And R is₂In the case of n-propionyl group, the substituent R corresponds to table 1, and represents a compound number of 164.1 to 164.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 165: general formula I-W₁In-0, when R is₁=OCH₂CH₃And R is₂In the case of n-propionyl group, the substituent R corresponds to table 1, and represents a compound number of 165.1 to 165.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 166: general formula I-W₁In-0, when R is₁= H and R₂In the case of a cyclopropylformyl group, the substituent R corresponds to table 1, and represents a compound number of 166.1 to 166.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 167: general formula I-W₁In-0, when R is₁=CH₃And R is₂In the case of a cyclopropylformyl group, the substituent R corresponds to table 1, and represents the compound number 167.1 to 167.360, which in turn corresponds to 1.1 to 1.360 of table 1.

Table 168: general formula I-W₁In-0, when R is₁=CH₂CH₃And R is₂In the case of a cyclopropylformyl group, the substituent R corresponds to table 1, and represents a compound having a number of 168.1 to 168.360, which in turn corresponds to 1.1 to 1.360 of table 1.

Table 169: general formula I-W₁In-0, when R is₁=SCH₃And R is₂In the case of a cyclopropylformyl group, the substituent R corresponds to table 1, and represents the compound number 169.1 to 169.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 170: general formula I-W₁In-0, when R is₁=SCH₂CH₃And R is₂In the case of a cyclopropylformyl group, the substituent R corresponds to table 1, and represents a compound number of 170.1 to 170.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 171: general formula I-W₁In-0, when R is₁=NH₂And R is₂In the case of a cyclopropylformyl group, the substituent R corresponds to table 1, and represents a compound number of 171.1 to 171.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 172: general formula I-W₁In-0, when R is₁=NHCH₃And R is₂In the case of a cyclopropylformyl group, the substituent R corresponds to table 1, and represents a compound number of 172.1 to 172.360, which in turn corresponds to 1.1 to 1.360 of table 1.

Table 173: general formula I-W₁In-0, when R is₁=NHCH₂CH₃And R is₂In the case of a cyclopropylformyl group, the substituent R corresponds to table 1 and represents a compound number of 173.1 to 173.360, which in turn corresponds to 1.1 to 1.360 of table 1.

Table 174: general formula I-W₁In-0, when R is₁=N(CH₃)₂And R is₂In the case of a cyclopropylformyl group, the substituent R corresponds to table 1, and represents a compound having a number of 174.1 to 174.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 175: general formula I-W₁In-0, when R is₁=OCH₃And R is₂In the case of a cyclopropylformyl group, the substituent R corresponds to table 1 and represents a compound number of 175.1 to 175.360, which in turn corresponds to 1.1 to 1.360 of table 1.

Table 176: general formula I-W₁In-0, when R is₁=OCH₂CH₃And R is₂In the case of a cyclopropylformyl group, the substituent R corresponds to table 1, and represents a compound having a number of 176.1 to 176.360, which in turn corresponds to 1.1 to 1.360 of table 1.

Table 177: general formula I-W₁In-0, when R is₁= H and R₂In the case of a methoxycarbonyl group, the substituent R corresponds to table 1, and represents a compound number of 177.1 to 177.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 178: general formula I-W₁In-0, when R is₁=CH₃And R is₂In the case of a methoxycarbonyl group, the substituent R corresponds to table 1, and represents a compound number of 178.1 to 178.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 179: general formula I-W₁In-0, when R is₁=CH₂CH₃And R is₂In the case of a methoxycarbonyl group, the substituent R corresponds to table 1, and represents a compound number of 179.1 to 179.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 180: general formula I-W₁In-0, when R is₁=SCH₃And R is₂In the case of a methoxycarbonyl group, the substituent R is as defined in Table 1 and representsThe compounds are numbered 180.1-180.360, which in turn correspond to 1.1-1.360 of Table 1.

Table 181: general formula I-W₁In-0, when R is₁=SCH₂CH₃And R is₂In the case of a methoxycarbonyl group, the substituent R corresponds to table 1, and represents a compound number of 181.1 to 181.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 182: general formula I-W₁In-0, when R is₁=NH₂And R is₂In the case of a methoxycarbonyl group, the substituent R corresponds to table 1, and represents a compound number of 182.1 to 182.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 183: general formula I-W₁In-0, when R is₁=NHCH₃And R is₂In the case of a methoxycarbonyl group, the substituent R corresponds to table 1, and represents a compound number of 183.1 to 183.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 184: general formula I-W₁In-0, when R is₁=NHCH₂CH₃And R is₂In the case of a methoxycarbonyl group, the substituent R corresponds to table 1, and represents a compound number of 184.1 to 184.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 185: general formula I-W₁In-0, when R is₁=N(CH₃)₂And R is₂In the case of a methoxycarbonyl group, the substituent R corresponds to table 1, and represents a compound number of 185.1 to 185.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 186: general formula I-W₁In-0, when R is₁=OCH₃And R is₂In the case of a methoxycarbonyl group, the substituent R corresponds to table 1, and represents a compound number of 186.1 to 186.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 187: general formula I-W₁In-0, when R is₁=OCH₂CH₃And R is₂In the case of a methoxycarbonyl group, the substituent R corresponds to table 1, and represents a compound number of 187.1 to 187.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 188: general formula I-W₁In-0, when R is₁= H and R₂In the case of an ethoxycarbonyl group, the substituent R corresponds to table 1, and represents a compound number of 188.1 to 188.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 189: general formula I-W₁In-0, when R is₁=CH₃And R is₂In the case of an ethoxycarbonyl group, the substituent R corresponds to table 1, and represents a compound number of 189.1 to 189.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 190: general formula I-W₁In-0, when R is₁=CH₂CH₃And R is₂In the case of an ethoxycarbonyl group, the substituent R corresponds to table 1, and represents a compound number of 190.1 to 190.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 191: general formula I-W₁In-0, when R is₁=SCH₃And R is₂In the case of an ethoxycarbonyl group, the substituent R corresponds to table 1, and represents a compound number of 191.1 to 191.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 192: general formula I-W₁In-0, when R is₁=SCH₂CH₃And R is₂In the case of an ethoxycarbonyl group, the substituent R corresponds to table 1, and the representative compound numbers are 192.1 to 192.360, which in turn correspond to 1.1 to 1.360 in table 1.

Table 193: general formula I-W₁In-0, when R is₁=NH₂And R is₂In the case of an ethoxycarbonyl group, the substituent R corresponds to table 1, and the representative compound number is 193.1 to 193.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 194: general formula I-W₁In-0, when R is₁=NHCH₃And R is₂In the case of an ethoxycarbonyl group, the substituent R corresponds to table 1, and represents a compound number of 194.1 to 194.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 195: general formula I-W₁In-0, when R is₁=NHCH₂CH₃And R is₂In the case of an ethoxycarbonyl group, the substituent R corresponds to table 1, and represents a compound number of 195.1 to 195.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 196: general formula I-W₁In-0, when R is₁=N(CH₃)₂And R is₂In the case of an ethoxycarbonyl group, the substituent R corresponds to table 1, and represents a compound number of 196.1 to 196.360, which in turn corresponds to 1.1 to 1.360 in table 1.

TABLE 197: general formula I-W₁In-0, whenR₁=OCH₃And R is₂In the case of an ethoxycarbonyl group, the substituent R corresponds to table 1, and represents a compound number of 197.1 to 197.360, which in turn corresponds to 1.1 to 1.360 in table 1.

Table 198: general formula I-W₁In-0, when R is₁=OCH₂CH₃And R is₂In the case of an ethoxycarbonyl group, the substituent R corresponds to table 1, and represents a compound number of 198.1 to 198.360, which in turn corresponds to 1.1 to 1.360 in table 1.

In the general formula I, when W = W₉，Z₁=Z₂=Z₃=Z₄=Z₅=Z₆=Z₇= H and n =0, the compound of formula I is represented by formula I-W₉And (4) showing.

Table 199: general formula I-W₉In when R is₂When H, R₁For the various substituents, see Table 199, representative compounds are numbered 199.1-199.9.

Watch 199

Table 200: general formula I-W₉In when R is₂=CH₃When R is₁For various substituents consistent with Table 199, the compounds are numbered 200.1-200.9, which in turn correspond to tables 199.1-199.9 of Table 199.

Table 201: general formula I-W₉In when R is₂=CH₂CH₃When R is₁For various substituents consistent with Table 199, the compounds are numbered 201.1-201.9, which in turn correspond to tables 199.1-199.9 of Table 199.

Table 202: general formula I-W₉In when R is₂When the radical is acetyl, R₁Corresponding to Table 199 for the various substituents, represent compounds having numbers 202.1-202.9, which in turn correspond to tables 199.1-199.9 of Table 199.

Table 203: general formula I-W₉In when R is₂In case of = methoxycarbonyl group, R₁For various substituents consistent with Table 199, the compounds are numbered 203.1-203.9, which in turn correspond to 199.1-199.9 of Table 199.

Table 204: general formula I-W₉In when R is₂In case of = ethoxycarbonyl group, R₁Corresponding to Table 199 for the various substituents, represent compounds having numbers 204.1-204.9, which in turn correspond to tables 199.1-199.9 of Table 199.

In the general formula I, when W = W₁₀，Z₁=Z₂=Z₃=Z₄=Z₅=Z₆=Z₇= H and n =0, the compound of formula I is represented by formula I-W₁₀And (4) showing.

Table 205: general formula I-W₁₀In when R is₂When H, R₁For various substituents consistent with Table 199, the compounds are numbered 205.1-205.9, which in turn correspond to tables 199.1-199.9 of Table 199.

Table 206: general formula I-W₁₀In when R is₂=CH₃When R is₁For various substituents consistent with Table 199, compounds are identified as compounds having numbers 206.1-206.9, which in turn correspond to 199.1-199.9 of Table 199.

Table 207: general formula I-W₁₀In when R is₂=CH₂CH₃When R is₁For various substituents consistent with Table 199, the compounds are numbered 207.1-207.9, which in turn correspond to tables 199.1-199.9 of Table 199.

Table 208: general formula I-W₁₀In when R is₂When the radical is acetyl, R₁Corresponding to Table 199 for the various substituents, represent compounds numbered 208.1-208.9, which in turn correspond to tables 199.1-199.9 of Table 199.

Table 209: general formula I-W₁₀In when R is₂In case of = methoxycarbonyl group, R₁For various substituents consistent with Table 199, compounds are identified as compounds having numbers 209.1-209.9, which in turn correspond to tables 199.1-199.9 of Table 199.

Table 210: general formula I-W₁₀In when R is₂In case of = ethoxycarbonyl group, R₁For various substituents consistent with Table 199, the compounds are numbered 210.1-210.9, which in turn correspond to tables 199.1-199.9 of Table 199.

In the general formula I, when W = W₂，Y₁=Y₂=Y₃=Y₄= H and n =1, the compound of formula I is represented by formula I-W₂And (4) showing.

Table 211: general formula I-W₂In when R is₂When H, R₁For various substituents consistent with Table 199, the compounds are numbered 211.1-211.9, which in turn correspond to 199.1-199.9 of Table 199.

In the general formula I, when W = W₃，Y₁=Y₂=Y₃=Y₄= H and n =1, the compound of formula I is represented by formula I-W₃And (4) showing.

Table 212: general formula I-W₃In when R is₂When H, R₁For various substituents consistent with Table 199, the compounds are identified by numbers 212.1-212.9, which in turn correspond to 199.1-199.9 of Table 199.

In the general formula I, when W = W₄，Y₁=Y₂=Y₃=Y₄= H and n =1, the compound of formula I is represented by formula I-W₄And (4) showing.

Table 213: general formula I-W₄In when R is₂When H, R₁For various substituents consistent with Table 199, compounds are identified as numbers 213.1-213.9, which in turn correspond to 199.1-199.9 of Table 199.

In the general formula I, when W = W₅，Y₁=Y₂=Y₃= H and n =1, the compound of formula I is represented by formula I-W₅And (4) showing.

Table 214: general formula I-W₅In when R is₂When H, R₁For various substituents consistent with Table 199, compounds are identified by numbers 214.1-214.9, which in turn correspond to 199.1-199.9 of Table 199.

In the general formula I, when W = W₆，Y₁=Y₂=Y₃= H and n =1, the compound of formula I is represented by formula I-W₆And (4) showing.

Table 215: general formula I-W₆In when R is₂When H, R₁For various substituents consistent with Table 199, the representative compounds are numbered 215.1-215.9, which in turn correspond to tables 199.1-199.9 of Table 199.

In the general formula I, when W = W₇，Y₁=Y₂=Y₃= H and n =1, the compound of formula I is represented by formula I-W₇And (4) showing.

Table 216: general formula I-W₇In when R is₂When H, R₁For various substituents consistent with Table 199, the compounds are identified by numbers 216.1-216.9, which in turn correspond to 199.1-199.9 of Table 199.

In the general formula I, when W = W₈，Y₁=Y₂=Y₃= H and n =1, the compound of formula I is represented by formula I-W₈And (4) showing.

Table 217: general formula I-W₈In when R is₂When H, R₁For various substituents consistent with Table 199, compounds are identified by numbers 217.1-217.9, which in turn correspond to 199.1-199.9 of Table 199.

Table 218: the following compounds are used as the active ingredients of the compound,

watch 218

The physicochemical properties of some of the compounds of the invention are shown in table 219, and the nuclear magnetic and mass spectra data are shown in table 220:

table 219

Note: in Table 219, "-" indicates no cas number.

Watch 220

The compounds of the general formula I according to the invention can be prepared by the following process (where the radicals are as defined above unless otherwise stated):

the method comprises the following steps: when R is₁Is hydrogen or C₁-C₆When alkyl, the compounds of formula I may be prepared as follows (wherein Alkoxyl represents C)₁-C₆Alkoxy groups such as methoxy, ethoxy, and the like):

reacting the compound of the general formula II-1 with the compound of the general formula III-1 in a suitable solvent at a temperature of between-10 ℃ and the boiling point of the solvent for 0.5 to 48 hours to obtain the compound of the general formula I-1; the reaction may be carried out in the presence of a base.

Reacting the compound of the general formula I-1 with an alkylating reagent (such as methyl iodide, ethyl iodide, propyl iodide, dimethyl sulfate, diethyl sulfate, 2, 2, 2-trifluoroiodoethane, chloroacetonitrile, bromoacetonitrile and the like) or an acylating reagent (such as acetyl chloride, n-propionyl chloride, acetic anhydride, cyclopropylcarbonyl chloride, methyl chloroformate, ethyl chloroformate and the like) in a suitable solvent at a temperature of from-10 ℃ to the boiling point of the solvent for 0.5 to 48 hours to obtain a compound of the general formula I-2; the reaction may be carried out in the presence of a base.

In the above reaction, suitable solvents may be the same or different and may be alcohols (e.g., methanol, ethanol, etc.), aromatic hydrocarbons (e.g., benzene, toluene, xylene, etc.), ketones (e.g., acetone, methyl ethyl ketone, methyl isobutyl ketone, etc.), halogenated hydrocarbons (e.g., chloroform, methylene chloride, etc.), esters (e.g., methyl acetate, ethyl acetate, etc.), ethers (e.g., tetrahydrofuran, dioxane, diethyl ether, 1, 2-dimethoxyethane, etc.), polar solvents (e.g., water, acetonitrile, dioxane, N-dimethylformamide, N-methylpyrrolidone, dimethyl sulfoxide, etc.), or a mixed solvent of the above solvents. The bases may be the same or different and may be organic bases such as trimethylamine, triethylamine, pyridine, DBU, 4-dimethylaminopyridine and the like (e.g., trimethylamine, triethylamine, pyridine, DBU, 4-dimethylaminopyridine and the like), alkali metal hydrides (e.g., sodium hydride, potassium hydride and the like), alkali metal hydroxides (e.g., sodium hydroxide, potassium hydroxide and the like), alkaline earth metal hydroxides (e.g., calcium hydroxide and the like), alkali metal carbonates (e.g., sodium carbonate, potassium carbonate and the like), alkali metal bicarbonates (e.g., sodium bicarbonate and the like), metal alkoxides (e.g., sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium tert-butoxide and the like).

The method 2 comprises the following steps: when R is₁Is C₁-C₆Alkylthio or halogeno C₁-C₆When alkylthio, the compounds of the general formula I can be prepared by the following process (wherein A represents C₁-C₆Alkyl or halo C₁-C₆Alkyl):

reacting the compound of the general formula II-2 with the compound of the general formula III-1 in a suitable solvent at a temperature of between-10 ℃ and the boiling point of the solvent for 0.5 to 48 hours to obtain a compound of the general formula I-3; in the reaction, the compound of the general formula II-2 to the compound of the general formula III-1 is more than or equal to 1: 1 (molar ratio); the reaction may be carried out in the presence of a base.

The method for preparing the compound of the general formula I-4 from the compound of the general formula I-3 is the same as the method for preparing the compound of the general formula I-2 from the compound of the general formula I-1.

The method 3 comprises the following steps: when R is₁Is hydroxy, mercapto, amino or C₁-C₆When alkylamino, the compounds of formula I can be prepared as follows:

the compound of the general formula I-5 can be prepared by reacting the compound of the general formula I-3 with a nucleophilic reagent in a proper solvent for 0.5 to 48 hours at the temperature of between 10 ℃ below zero and the boiling point of the solvent; the compound of the general formula I-6 can be prepared by reacting the compound of the general formula I-4 with a nucleophilic reagent in a suitable solvent at a temperature of between-10 ℃ and the boiling point of the solvent for 0.5 to 48 hours.

In the above reaction, the nucleophilic reagent is sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium hydrosulfide, sodium amide, ammonia water, C₁-C₆Alkyl ammonia (such as methylamine, ethylamine, etc.) or its hydrochloride (such as methylamine hydrochloride, ethylamine hydrochloride, etc.).

In the above reaction, when the nucleophilic reagent is C₁-C₆In the case of an alkyl amine hydrochloride, the reaction requires an appropriate base to participate in the reaction to neutralize the hydrochloride, and the appropriate base is preferably trimethylamine, triethylamine, pyridine, potassium carbonate, sodium carbonate, potassium bicarbonate, sodium bicarbonate or the like.

In the above reaction, suitable solvents may be the same or different and may be alcohols (e.g., methanol, ethanol, etc.), aromatic hydrocarbons (e.g., benzene, toluene, xylene, etc.), ketones (e.g., acetone, methyl ethyl ketone, methyl isobutyl ketone, etc.), halogenated hydrocarbons (e.g., chloroform, methylene chloride, etc.), esters (e.g., methyl acetate, ethyl acetate, etc.), ethers (e.g., tetrahydrofuran, dioxane, diethyl ether, 1, 2-dimethoxyethane, etc.), polar solvents (e.g., water, acetonitrile, dioxane, N-dimethylformamide, N-methylpyrrolidone, dimethyl sulfoxide, etc.), or a mixed solvent of the above solvents.

The method 4 comprises the following steps: when R is₁Is cyano, C₁-C₆Alkoxy, halo C₁-C₆Alkoxy or C₁-C₆In the case of dialkylamino, the compounds of the formula I can be prepared by the following process:

the compound of the general formula I-3 and a nucleophilic reagent react in a proper solvent for 0.5 to 48 hours at the temperature of between 10 ℃ below zero and the boiling point of the solvent to prepare a compound of the general formula I-7; the compound of the general formula I-8 can be prepared by reacting the compound of the general formula I-4 with a nucleophilic reagent in a suitable solvent at a temperature of between-10 ℃ and the boiling point of the solvent for 0.5 to 48 hours.

In the above reaction, the nucleophilic reagent is sodium cyanide, potassium cyanide, C₁-C₆Alkali metal salts of alkanols (e.g. sodium methoxide, potassium methoxide, sodium ethoxide, potassium ethoxide, etc.), halogen C₁-C₆Alkali metal salts of alkanols (e.g., sodium 2, 2, 2-trifluoroethoxide or potassium 2, 2, 2-trifluoroethoxide, etc.), C₁-C₆Dialkylamino (e.g., N-dimethylamino, N-methyl-N-ethylamino, etc.) or a hydrochloride thereof (e.g., N-dimethylamino hydrochloride, N-methyl-N-ethylamino hydrochloride, etc.).

In the above reaction, when the nucleophilic reagent is C₁-C₆In the case of the dialkylamine hydrochloride, the reaction requires an appropriate base to participate in the reaction to neutralize the hydrochloride, and the appropriate base is preferably trimethylamine, triethylamine, pyridine, potassium carbonate, sodium carbonate, potassium hydrogencarbonate, sodium hydrogencarbonate, or the like.

The process for preparing the compound of the formula I-8 from the compound of the formula I-7 is the same as the process for preparing the compound of the formula I-2 from the compound of the formula I-1.

The method 5 comprises the following steps: when R is₂Is C₁-C₆Alkyl, halo C₁-C₆Alkyl or cyano C₁-C₆When alkyl, the compounds of formula I can be prepared as follows:

(1) when R is₁Is hydrogen or C₁-C₆When the alkyl is substituted:

the compound of the general formula I-9 can be prepared by reacting the compound of the general formula II-1 with the compound of the general formula III-2.

The method for preparing the compound of the general formula I-9 from the compound of the general formula II-1 is the same as the method for preparing the compound of the general formula I-1 from the compound of the general formula II-1.

(2) When R is₁Not being hydrogen or C₁-C₆When it is alkyl (wherein K represents hydroxy, mercapto, amino, cyano, or C)₁-C₆Alkoxy, halo C₁-C₆Alkoxy radical, C₁-C₆Alkylamino or C₁-C₆Dialkylamino group):

the compound of the general formula I-10 can be prepared by reacting the compound of the general formula II-2 with the compound of the general formula III-2.

The method for preparing the compound of the general formula I-10 from the compound of the general formula II-2 is the same as the method for preparing the compound of the general formula I-3 from the compound of the general formula II-2.

The compound of the general formula I-10 can react with a nucleophilic reagent to prepare the compound of the general formula I-11.

The preparation of compounds of formula I-11 from compounds of formula I-10 is the same as the preparation of compounds of formula I-6 from compounds of formula I-4 or compounds of formula I-8 from compounds of formula I-4.

The compounds of the formula II-1 can be prepared commercially or by known methods (for example as described in US2503524, RSC Advances, 6(29), 24491-.

The compounds of formula II-2 can be prepared commercially or by known methods (e.g.as described in Organic Process Research & Development, 15(3), 556-.

The compounds of the formula III-1, the compounds of the formula III-2 and other starting materials and reagents can be purchased or prepared in the self-production by conventional methods.

The compound shown in the general formula I can be used for controlling various plant bacterial diseases, such as fruit blotch (such as muskmelon fruit blotch) and leaf blotch (such as tomato bacterial leaf blotch), bacterial wilt (such as tomato bacterial leaf blotch and potato bacterial wilt), bacterial blight, canker (such as citrus canker and kiwi canker), soft rot (such as Chinese cabbage soft rot), bacterial angular leaf spot (such as cucumber bacterial angular leaf spot), bacterial streak (such as rice bacterial streak), leaf blight, bacterial leaf blight (such as rice bacterial leaf blight), wildfire, bacterial scab and the like.

Detailed Description

The following specific examples are intended to further illustrate the invention, but the invention is by no means limited to these examples. (all materials are commercially available unless otherwise noted)

Synthetic examples

The compounds of formula I of the present invention can be prepared according to the synthetic routes described above, using different starting compounds, and are further described in detail below:

example 1: preparation of Compound 1.116

A 50 ml reaction flask was charged with 3, 4-dichlorobenzylamine (0.30 g, 1.71 mmol), ethoxymethylenemalononitrile (0.22 g, 1.80 mmol), and 20 ml of ethanol, stirred at room temperature, and after completion of the reaction monitored by TLC, most of the ethanol was evaporated under reduced pressure, cooled, and filtered to obtain 0.42 g of a white solid.

Example 2: preparation of Compound 1.360

Benzylamine (2.00 g, 18.68 mmol), ethoxymethylenemalononitrile (2.28 g, 18.67 mmol) and 50 ml ethanol were added to a 100 ml reaction flask, and the reaction was refluxed at 80 ℃, followed by TLC monitoring, most of the ethanol was distilled off under reduced pressure, cooled, and filtered to obtain 3.08 g of a yellow solid.

Example 3: preparation of Compound 2.116

In a 100 ml reaction flask were charged 3, 4-dichlorobenzylamine (1.00 g, 5.71 mmol), 2- (1-ethoxyethylene) malononitrile (0.78 g, 5.73 mmol), and 50 ml of ethanol, and the mixture was refluxed at 80 ℃, followed by TLC to remove most of the ethanol under reduced pressure, followed by cooling and filtration to obtain 1.36 g of a white solid.

Example 4: preparation of Compound 2.360

Benzylamine (1.00 g, 9.34 mmol), 2- (1-ethoxyethylene) malononitrile (1.27 g, 9.33 mmol) and 50 ml ethanol were added to a 100 ml reaction flask, and the mixture was refluxed at 80 ℃, and after completion of the reaction monitored by TLC, most of ethanol was distilled off under reduced pressure, cooled, and filtered to obtain 1.66 g of a white solid.

Example 5: preparation of Compound 4.19

A 50 ml reaction flask was charged with 2-methylbenzylamine (0.50 g, 4.13 mmol), 2- (bis (methylthio) methylene) malononitrile (0.71 g, 4.18 mmol) and 25 ml of methanol, refluxed at 65 ℃, after completion of the reaction monitored by TLC, most of the methanol was distilled off under reduced pressure, cooled, and filtered to obtain 0.90 g of a white solid.

The starting 2- (bis (methylthio) methylene) malononitrile can be prepared by known methods, for example, as described in Organic Process Research & Development, 15(3), 556-564; 2011.

Example 6: preparation of Compound 4.360

Benzylamine (1.00 g, 9.34 mmol), 2- (bis (methylthio) methylene) malononitrile (1.59 g, 9.35 mmol) and 50 ml methanol were charged into a 100 ml reaction flask, and the mixture was refluxed at 65 ℃, and after completion of the reaction monitored by TLC, most of the methanol was distilled off under reduced pressure, cooled, and filtered to obtain 2.14 g of a white solid.

Example 7: preparation of Compound 6.19

Compound 4.19 (0.50 g, 2.06 mmol), ammonia (0.72 g, 20.55 mmol) and 100 ml ethanol were weighed into a 250 ml reaction flask, refluxed at 80 ℃, monitored by TLC, desolventized under reduced pressure, and subjected to column chromatography to obtain 0.40 g white solid.

Example 8: preparation of Compound 6.360

Compound 4.360 (0.15 g, 4.37 mmol), ammonia (0.23 g, 6.56 mmol) and 50 ml ethanol were weighed into a 100 ml reaction flask, refluxed at 80 ℃, monitored by TLC, desolventized under reduced pressure, and subjected to column chromatography to obtain 0.13 g of a white solid.

Example 9: preparation of Compound 7.19

Compound 4.19 (0.50 g, 2.06 mmol), methylamine hydrochloride (0.69 g, 10.22 mmol), triethylamine 5 ml and 40 ml ethanol were weighed and placed in a 100 ml reaction flask, reflux reaction was carried out at 80 ℃, and after completion of the reaction monitored by TLC, precipitation under reduced pressure and column chromatography gave 0.47 g of white solid.

Example 10: preparation of Compound 7.360

Compound 4.360 (0.12 g, 0.52 mmol), methylamine hydrochloride (0.18 g, 2.67 mmol), triethylamine 5 ml and 20 ml ethanol were weighed and placed in a 50 ml reaction flask, reflux reaction was carried out at 80 ℃, and after completion of the reaction monitored by TLC, precipitation under reduced pressure and column chromatography gave 0.11 g of white solid.

Example 11: preparation of Compound 10.19

Compound 4.19 (0.50 g, 2.06 mmol), sodium methoxide (0.56 g, 10.37 mmol), triethylamine 5 ml and 25 ml ethanol were weighed and placed in a 50 ml reaction flask for reflux reaction at 80 ℃, after the reaction was monitored by TLC, the solution was desolventized under reduced pressure and subjected to column chromatography to obtain 0.47 g of white solid.

Example 12: preparation of Compound 10.360

Compound 4.360 (0.15 g, 0.65 mmol), sodium methoxide (0.18 g, 3.33 mmol), triethylamine 5 ml and 25 ml ethanol were weighed and placed in a 50 ml reaction flask for reflux reaction at 80 ℃, and after completion of the reaction monitored by TLC, the solution was desolventized under reduced pressure and subjected to column chromatography to obtain 0.14 g of white solid.

Example 13: preparation of Compound 12.116

A50 ml reaction flask was charged with N-methylbenzylamine (1.00 g, 8.26 mmol), ethoxymethylenemalononitrile (1.01 g, 8.28 mmol) and 30 ml of ethanol, refluxed at 80 ℃ for reaction, and after completion of the reaction monitored by TLC, most of the ethanol was distilled off under reduced pressure, cooled, and filtered to obtain 1.75 g of a white solid.

Example 14: preparation of Compound 15.360

A 100 ml reaction flask was charged with N-methylbenzylamine (1.00 g, 8.26 mmol), 2- (bis (methylthio) methylene) malononitrile (1.50 g, 8.82 mmol) and 40 ml of methanol, refluxed at 65 ℃, after completion of the reaction monitored by TLC, most of the methanol was distilled off under reduced pressure, cooled, and filtered to obtain 1.61 g of a white solid.

Example 15: preparation of Compound 34.116

Compound 1.116 (0.29 g, 1.16 mmol), bromoacetonitrile (0.14 g, 1.18 mmol), sodium hydride (0.04 g, 1.00 mmol) and 25 ml tetrahydrofuran were weighed and placed in a 50 ml single-neck flask, and the reaction was stirred at normal temperature, followed by TLC monitoring, desolventization under reduced pressure and column chromatography to obtain 0.13 g of a white solid.

Example 16: preparation of Compound 67.116

Compound 1.116 (0.38 g, 1.51 mmol), cyclopropylcarbonyl chloride (0.16 g, 1.54 mmol) and 30 ml of toluene were weighed into a 50 ml single-neck flask, and the reaction was refluxed at 110 ℃, followed by TLC monitoring, desolvation under reduced pressure and column chromatography to give 0.17 g of a yellow solid.

Example 17: preparation of Compound 89.116

Compound 1.116 (0.45 g, 1.79 mmol), ethyl chloroformate (0.20 g, 1.89 mmol), sodium hydride (0.068 g, 1.70 mmol) and 25 ml of tetrahydrofuran were weighed and placed in a 50 ml single-neck flask, and the reaction was stirred at normal temperature, followed by TLC monitoring, and then, after completion of the reaction, desolvation under reduced pressure and column chromatography, 0.18 g of a yellow solid was obtained.

Example 18: preparation of Compound 100.7

A50 ml reaction flask was charged with 4-fluoroaniline (1.00 g, 9.00 mmol), ethoxymethylenemalononitrile (1.10 g, 9.01 mmol) and 30 ml of ethanol, refluxed at 80 ℃ for reaction, and after completion of the reaction monitored by TLC, most of the ethanol was distilled off under reduced pressure, cooled, and filtered to obtain 1.18 g of a white solid.

Example 19: preparation of Compound 103.360

Aniline (3.00 g, 32.24 mmol), 2- (bis (methylthio) methylene) malononitrile (5.48 g, 32.24 mmol) and 50 ml of methanol were added to a 100 ml reaction flask, and the mixture was refluxed at 65 ℃, and after completion of the reaction monitored by TLC, most of the methanol was distilled off under reduced pressure, cooled and filtered to obtain 4.85 g of a white solid.

Example 20: preparation of Compound 105.360

Compound 100.360 (1.00 g, 2.06 mmol), ammonia water (1.53 g, 43.66 mmol) and 30 ml ethanol were weighed into a 50 ml reaction flask, and reflux reaction was carried out at 80 ℃, and after completion of the reaction monitored by TLC, precipitation under reduced pressure and column chromatography gave 0.10 g of a white solid.

Example 21: preparation of Compound 199.4

1-naphthylamine (2.00 g, 13.97 mmol), 2- (bis (methylthio) methylene) malononitrile (0.84 g, 14.71 mmol), sodium hydride (0.84 g, 21.00 mmol) and 30 ml of tetrahydrofuran were weighed and placed in a 50 ml single-neck flask, and a reflux reaction was carried out at 65 ℃, after completion of the reaction monitored by TLC, most of the tetrahydrofuran was distilled off under reduced pressure, cooled and filtered to obtain 3.00 g of a white solid.

Example 22: preparation of Compound 211.1

2-aminomethylpyridine (0.30 g, 2.78 mmol), ethoxymethylenemalononitrile (0.34 g, 2.78 mmol) and 30 ml of ethanol were weighed and placed in a 50 ml single-neck flask, reflux reaction was carried out at 80 ℃, most of ethanol was distilled off under reduced pressure after the completion of the reaction monitored by TLC, and the mixture was cooled and filtered to obtain 0.51 g of a brown solid.

Example 23: preparation of Compound 214.1

A50 ml reaction flask was charged with 2-thienylmethylamine (0.50 g, 4.42 mmol), ethoxymethylenemalononitrile (0.54 g, 4.42 mmol) and 25 ml of ethanol, refluxed at 80 ℃ for reaction, and after completion of the reaction monitored by TLC, most of the ethanol was distilled off under reduced pressure, cooled, and filtered to obtain 0.84 g of a white solid.

Example 24: preparation of Compound 218.1

A 50 ml reaction flask was charged with 3, 4-dichlorophenethylamine (1.00 g, 5.29 mmol), ethoxymethylenemalononitrile (0.65 g, 5.32 mmol) and 30 ml of ethanol, refluxed at 80 ℃, after completion of the reaction monitored by TLC, most of the ethanol was distilled off under reduced pressure, cooled, and filtered to give 1.12 g of a yellow solid.

Example 25: preparation of Compound 218.2

A50 ml reaction flask was charged with 3-phenylpropan-1-amine (1.00 g, 7.40 mmol), ethoxymethylenemalononitrile (0.91 g, 7.45 mmol) and 30 ml of ethanol, refluxed at 80 ℃ for reaction, monitored by TLC after the reaction was completed, most of the ethanol was distilled off under reduced pressure, cooled, and filtered to obtain 1.17 g of a yellow solid.

Other compounds of formula I of the present invention may be prepared by reference to the above examples.

Biological activity assay

Example 26: measurement of controlling Effect on plant bacterial diseases

The compound of the invention is used for carrying out prevention and treatment determination on various plant bacterial diseases, and aiming at different bacterial diseases, the test procedures are as follows:

and (3) dissolving the compound to be tested in a small amount of N, N dimethylformamide, and diluting the solution to the required concentration by using water. Uniformly mixing pathogenic bacteria cultured to a stable growth period with a quantitative compound solution, soaking the melon seeds subjected to germination acceleration in a mixed solution of a bacterial liquid and a compound for half an hour, sowing the seeds in an earthworm soil culture cup, putting the earthworm soil culture cup into a greenhouse for wet culture, culturing for two weeks generally, and performing control effect investigation after full control disease attack.

Cutting 2 cm square leaf of Chinese cabbage, and placing into a glass culture dish filled with double-layer filter paper. The method comprises the steps of dissolving N, N-dimethylformamide, spraying a compound diluted by water to a required concentration on the surface of a Chinese cabbage leaf, airing the liquid medicine on the surface of the Chinese cabbage leaf in a fume hood, carrying out needle-punching on the surface of the Chinese cabbage leaf by using an inoculating needle to cause a wound, taking 5 microliters of Chinese cabbage soft rot bacteria cultured to a stable growth period, adding the Chinese cabbage soft rot bacteria into the wound, and inoculating. And finally, placing the test material into an incubator to be cultured for 48 hours in a dark place, and carrying out control effect investigation after the control is fully developed.

Dissolving the compound to be detected in a small amount of N, N dimethylformamide, and diluting the solution to the required concentration by using water. Spraying the compound on the surface of a plant test material, air-drying the surface liquid medicine in a shade, spraying and inoculating the pathogenic bacteria liquid which is cultured to a stable growth period on the surface of the plant test material, and then putting the plant test material into a greenhouse for moisture preservation and culture. Usually, the culture is carried out for about ten days, and after the control is fully ill, the control effect investigation is carried out.

The test results were as follows:

at 600 mg/L, compounds 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 1.19, 1.22, 1.25, 1.36, 1.40, 1.43, 1.45, 1.102, 1.107, 1.116, 1.173, 1.360, 2.8, 2.19, 2.36, 2.116, 2.360, 4.7, 4.8, 4.19, 4.22, 4.36, 4.45, 4.116, 4.173, 4.360, 6.19, 6.36, 6.45, 6.360, 7.19, 7.36, 7.360, 10.19, 10.36, 10.360, 12.116, 15.360, 34.116, 67.116, 89.116, 100.6, 100.7, 100.8, 100.17, 2, 100.22, 56, 8653, 100.107, 8653, 8672, 100.360, 36218, 36212, 36218, 100.360, 36218, 100.360, 36218, 1.72, 1.36, 1.7.7.7.7.7.7, 100.360, 1.7.7.7.7.7.7.7.7.7.7.7.7.7.7.7.7.7.7.7.7.7.7.7.7.7.7.7.7.7.7.7.7.7.7.7.7.7.7.7.7.7.7.7.7.7.7.7.7.7.7.7.36, 3, 100.360, 36218, 1.7.7.7.7.7.7.7.7.36, 36218, 1.7.7.7.36, 36218, 1.36, 1.7.7.7.7.7.7.7.7.7.7.36, 36218, 100.360, 1.36, 36218, 1.7, 1.36, 36218, 1.36, 36218, 100.360, 1.36, 36218, 1.36, 36218, 1.36, 36218, 1.36, 36218, 1.36, 1.

At 400 mg/L, the compound 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 1.19, 1.22, 1.25, 1.36, 1.40, 1.43, 1.45, 1.102, 1.107, 1.116, 1.173, 1.360, 2.8, 2.19, 2.36, 2.116, 2.360, 4.7, 4.8, 4.19, 4.22, 4.36, 4.45, 4.116, 4.173, 4.360, 6.19, 6.36, 6.45, 6.360, 7.19, 7.36, 7.360, 10.19, 10.36, 10.360, 12.116, 15.360, 34.116, 67.116, 89.116, 100.6, 100.7, 100.8, 100.17, 2, 100.22, 56, 8653, 100.107, 100.360, 36218, 100.360, 36218, 100.360, 3619, 100.360, 3619, 100.360, f bacterial leaf spot, 3619, and the leaf spot, 3619, 100.360, 3619, 100.360, 3619, 100.360, 3619, 100.360, 366, 100.360, 3619, 100.360, 3619, 100.360, f bacterial leaf spot, 3619, 100.360, 3619, f bacterial leaf spot, 3619, 100.360, f bacterial leaf spot, f bacterial leaf blight and 3619, f.

At 400 mg/L, the compound 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 1.19, 1.22, 1.25, 1.36, 1.40, 1.43, 1.45, 1.102, 1.107, 1.116, 1.173, 1.360, 2.8, 2.19, 2.36, 2.116, 2.360, 4.7, 4.8, 4.19, 4.22, 4.36, 4.45, 4.116, 4.173, 4.360, 6.19, 6.36, 6.45, 6.360, 7.19, 7.36, 7.360, 10.19, 10.36, 10.360, 12.116, 15.360, 34.116, 67.116, 89.116, 100.6, 100.7, 100.8, 100.17, 2, 100.22, 56, 8643, 8653, 8672, 100.360, 36218, 100.360, 36218 and 3, 100.360 percent of bacterial leaf blight and 3.

Claims

1. Use of a malononitrile-based compound for controlling bacterial diseases in plants, wherein the malononitrile-based compound is selected from the group consisting of:

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2. use of malononitrile based compound according to claim 1 for controlling bacterial diseases in plants, characterized in that: the plant bacterial diseases are fruit blotch, leaf spot, bacterial wilt, bacterial blight, ulcer disease, soft rot, bacterial angular leaf spot, bacterial streak, bacterial leaf blight, wildfire disease or bacterial scab.

3. Use of malononitrile based compound according to claim 2 for controlling bacterial diseases in plants, wherein the fruit blotch is melon fruit blotch.

4. Use of malononitrile-based compound according to claim 2 for controlling bacterial diseases in plants, wherein the leaf spot is tomato bacterial leaf spot.

5. The use of malononitrile-based compound according to claim 2 for controlling bacterial diseases in plants, wherein the bacterial wilt is tomato bacterial wilt or potato bacterial wilt.

6. Use of malononitrile-based compound according to claim 2 for controlling bacterial diseases in plants, wherein the canker is citrus canker or kiwi canker.

7. The use of malononitrile based compound according to claim 2 for controlling bacterial diseases in plants, wherein the soft rot is Chinese cabbage soft rot.

8. Use of malononitrile-based compound according to claim 2 for controlling plant bacterial diseases, wherein the bacterial angular leaf spot is cucumber bacterial angular leaf spot.

9. Use of malononitrile-based compound according to claim 2 for controlling bacterial diseases in plants, wherein the bacterial leaf streak is rice bacterial leaf streak.

10. The use of malononitrile-based compound according to claim 2 for controlling bacterial diseases in plants, wherein the bacterial blight is rice bacterial blight.