CN113754639B - Pyridylether compound containing pyrimidinamine and preparation and application thereof - Google Patents

Pyridylether compound containing pyrimidinamine and preparation and application thereof Download PDF

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CN113754639B
CN113754639B CN202010492284.6A CN202010492284A CN113754639B CN 113754639 B CN113754639 B CN 113754639B CN 202010492284 A CN202010492284 A CN 202010492284A CN 113754639 B CN113754639 B CN 113754639B
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chloro
amine
oxy
propan
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CN113754639A (en
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柳爱平
刘卫东
欧晓明
李建明
刘民华
刘兴平
任叶果
胡礼
黄至畅
李立中
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Hunan Research Institute of Chemical Industry
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/54—1,3-Diazines; Hydrogenated 1,3-diazines
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P3/00—Fungicides
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P7/00—Arthropodicides
    • A01P7/02—Acaricides
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P7/00—Arthropodicides
    • A01P7/04—Insecticides

Abstract

The invention discloses a pyridine ether compound containing pyrimidinamine shown in formula (I) and a preparation method and application of an isomer or a salt thereof.
Figure DDA0002520885890000011
In the formula, R and R 1 、R 2 、R 3 、R 4 And W has the definitions given in the specification. The compound of formula (I) has insecticidal/acaricidal or fungicidal biological activity, and especially has high activity on diseases.

Description

Pyridylether compound containing pyrimidinamine and preparation and application thereof
Technical Field
The invention belongs to the field of insecticidal/acaricidal and bactericidal agents, and particularly relates to pyridylether compounds containing pyrimidinylamines and having insecticidal/acaricidal and bactericidal biological activities, a preparation method thereof, insecticidal/acaricidal and bactericidal compositions containing the compounds, and application and methods for controlling pests/acarids and harmful bacteria by using the compounds.
Background
CN109776427A discloses the following structural formulae of pyriminone hydrochloride, acetate or maleate S1, S2, S3, S4 and S5 containing pyrimidinamine, and does not disclose the structural features and biological activities thereof. Based on the investigation, the non-salt compounds D1, D2, D3, D4 and D5 and other pyridine ether compounds containing pyrimidine amine are not found.
Figure BDA0002520885880000011
WO2016/184378 discloses that pyrazole ether compounds D6 and D7, etc., containing pyrimidineamines also have insecticidal/acaricidal activity.
Figure BDA0002520885880000012
In order to obtain novel active molecules, the inventor carries out intensive research on pyridine ether compounds containing pyrimidinamine and finds that the novel pyridine ether compounds containing pyrimidinamine have broad-spectrum and high-efficiency biological activity.
Disclosure of Invention
The invention provides a pyridine ether compound containing pyrimidinamine and having biological activity of preventing and controlling pests/mites, harmful bacteria and the like as shown in a formula (I), an isomer thereof or a salt of the compound as shown in the formula (I):
Figure BDA0002520885880000013
wherein:
r is selected from C 1 -C 12 Alkyl radical, C 2 -C 12 Alkenyl radical, C 2 -C 12 Alkynyl, C 3 -C 12 Cycloalkyl or C 3 -C 12 A heterocyclic group;
II.R 1 is selected from C 1 -C 12 Alkyl radical, C 2 -C 12 Alkenyl radical, C 2 -C 12 Alkynyl, C 3 -C 12 Cycloalkyl or C 3 -C 12 A heterocyclic group;
III.R 2 、R 3 、R 4 are identical or different and are selected from the group consisting of hydrogen, nitro, cyano, halogen, C 1 -C 12 Alkyl radical, C 1 -C 12 Alkoxy or C 1 -C 12 An alkylthio group;
w is selected from hydrogen, C 1 -C 12 Alkyl radical, C 2 -C 12 Alkenyl radical, C 2 -C 12 Alkynyl, C 3 -C 12 Cycloalkyl or C 3 -C 12 A heterocyclic group;
v, and R 1 The carbon to which is attached is in S configuration, R configuration or R/S configuration in any ratio;
I. in II, III or IV, the hydrogen atoms in the alkyl, alkenyl, alkynyl, cycloalkyl or heterocyclyl groups may be partially or fully substituted by the same or different substituents selected from the group consisting of: halogen, nitro, cyano, amino, hydroxy, C 1 -C 6 Alkyl radical, C 1 -C 6 Alkoxy radical, C 1 -C 6 Alkylthio radical, C 1 -C 6 An alkylamino group;
in the definitions of the compounds (I) given above, the terms used, whether used alone or in compound words, represent the following substituents:
halogen: fluorine, chlorine, bromine, iodine;
alkyl groups: refers to straight or branched chain alkyl;
an alkenyl group; refers to a straight or branched chain alkyl group, and a double bond may be present at any position;
alkynyl; refers to a straight or branched chain alkyl group, and may have a triple bond at any position;
halogenation: refers to a compound in which hydrogen atoms are partially or totally substituted by halogen atoms;
cycloalkyl: refers to a saturated or unsaturated cycloalkyl group;
heterocyclic group: saturated or unsaturated heterocycloalkyl in which at least 1N, O or S is present;
a salt of a compound represented by the formula (I): refers to salts of compounds of formula (I) with organic or inorganic acids; the organic acid means a carboxylic acid or a sulfonic acid such as acetic acid, trifluoroacetic acid, chloroacetic acid, propionic acid, butyric acid, oxalic acid, adipic acid, lauric acid, citric acid, maleic acid, fumaric acid, benzoic acid, methylbenzoic acid, phthalic acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid or dodecylbenzenesulfonic acid, etc.; inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, or carbonic acid, and the like.
Preferred compounds of the invention are compounds of formula (I) and isomers thereof or salts of compounds of formula (I) wherein:
r is selected from C 1 -C 6 Alkyl, halo C 1 -C 6 Alkyl radical, C 3 -C 6 Cycloalkyl or halo C 3 -C 6 A cycloalkyl group;
II.R 1 is selected from C 1 -C 6 Alkyl, halo C 1 -C 6 Alkyl radical, C 3 -C 6 Cycloalkyl or halo C 3 -C 6 A cycloalkyl group;
III.R 2 、R 3 、R 4 are the same or different and are selected from hydrogen, nitro, halogen, C 1 -C 6 Alkyl or halo C 1 -C 6 An alkyl group;
w is selected from hydrogen, C 1 -C 6 Alkyl, halo C 1 -C 6 Alkyl radical, C 3 -C 6 Cycloalkyl or halo C 3 -C 6 A cycloalkyl group;
v, and R 1 The carbon attached is in S configuration, R configuration or R/S configuration in any ratio.
Preferred compounds of the invention are compounds of formula (I) and isomers thereof or salts of compounds of formula (I) wherein:
r is selected from C 1 -C 6 Alkyl, halo C 1 -C 6 Alkyl radical, C 3 -C 6 Cycloalkyl or halo C 3 -C 6 A cycloalkyl group;
II.R 1 is selected from C 1 -C 6 Alkyl, halo C 1 -C 6 Alkyl radical, C 3 -C 6 Cycloalkyl or halo C 3 -C 6 A cycloalkyl group;
III.R 2 、R 3 、R 4 are the same or different in nature and are,selected from hydrogen, halogen, difluoromethyl, trifluoromethyl, trichloromethyl;
w is selected from hydrogen or methyl; when W is selected from hydrogen, the compound of formula (I) is shown as formula (I-1), and the salt of the compound of formula (I) is shown as formula (I-3); when W is selected from methyl, the compound of formula (I) is shown as formula (I-2), and the salt of the compound of formula (I-2) is shown as formula (I-4); the Acid in the formula (I-3) and the formula (I-4) is an organic Acid or an inorganic Acid as defined above;
Figure BDA0002520885880000021
v, and R 1 The carbon attached is in the S configuration, R configuration or R/S configuration in any ratio.
Further preferred compounds of the invention are compounds of formula (I) and isomers thereof or salts of compounds of formula (I) wherein:
r is selected from C 1 -C 6 Alkyl, halo C 1 -C 6 Alkyl radical, C 3 -C 6 Cycloalkyl or halo C 3 -C 6 A cycloalkyl group;
II.R 1 is selected from C 1 -C 6 Alkyl, halo C 1 -C 6 Alkyl radical, C 3 -C 6 Cycloalkyl or halo C 3 -C 6 A cycloalkyl group;
III.R 2 、R 3 、R 4 are the same or different and are selected from hydrogen, halogen, trifluoromethyl;
w is selected from hydrogen or methyl; when W is selected from hydrogen, the compound shown in formula (I-1) is I-1A, I-1B, I-1C, I-1D, I-1E, I-1F, I-1G, I-1H, I-1I, I-1J, I-1K, I-1L, I-1M, I-1N, I-1O, I-1P, I-1Q, I-1R, I-1S, I-1T, I-1U, I-1V, I-1W or I-1X; when W is selected from methyl, the compound shown in formula (I-2) is I-2A, I-2B, I-2C, I-2D, I-2E, I-2F, I-2G, I-2H, I-2I, I-2J, I-2K, I-2L, I-2M, I-2N, I-2O, I-2P, I-2Q, I-2R, I-2S, I-2T, I-2U, I-2V, I-2W or I-2X;
Figure BDA0002520885880000031
Figure BDA0002520885880000041
the compound salt shown in formula (I-1) is I-3A, I-3B, I-3C, I-3D, I-3E, I-3F, I-3G, I-3H, I-3I, I-3J, I-3K, I-3L, I-3M, I-3N, I-3O, I-3P, I-3Q, I-3R, I-3S, I-3T, I-3U, I-3V, I-3W or I-3X; the compound salt shown in formula (I-2) is I-4A, I-4B, I-4C, I-4D, I-4E, I-4F, I-4G, I-4H, I-4I, I-4J, I-4K, I-4L, I-4M, I-4N, I-4O, I-4P, I-4Q, I-4R, I-4S, I-4T, I-4U, I-4V, I-4W or I-4X;
RS stands for R 1 The carbon to which is attached is of the configuration R/S in any ratio, S representing the bond with R 1 The carbon to which is attached being of S configuration, R representing a bond with R 1 The attached carbon is in the R configuration.
Still further preferred compounds of the invention are those of the formulae I-1A, I-1B, I-1C, I-1D, I-1E, I-1F, I-1G, I-1H, I-1I, I-1J, I-1K, I-1L, I-1M, I-1N, I-1O, I-1P, I-1Q, I-1R, I-1S, I-1T, I-1U, I-1V, I-1W, I-1X, I-2A, I-2B, I-2C, I-2D, I-2E, I-2F, I-2G, I-2H, I-2I, I-2J, I-2K, I-2L, I-2M, I-2N, I-2O, I-2P, I-2Q, I-2R, I-2S, I-2J, I-2K, I-2L, I-2M, I-2N, I-2O, I-2P, I-2Q, I-2R, I-2W, I-2X or I-1M,
wherein: r and R 1 Are identical or different and are selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, chloromethyl, fluoromethyl, bromomethyl, iodomethyl, dichloromethyl, difluoromethyl, dibromomethyl, diiodomethyl, trichloromethyl, trifluoromethyl, tribromomethyl, triiodomethyl, 2-trifluoroethyl, 1-fluoroethyl, 1-chloroethyl, 1-bromoethyl, 1-fluoroisopropyl, 1-chloroisopropyl, 1-bromoisopropyl, methoxymethyl, methoxyethyl, ethoxymethyl, cyclopropyl, cyclopentyl, cyclohexyl, 1-oxocyclopentyl, 2-allylic, 2-propargyl, 3-chloro-2-allyl, 3-dichloro-2-allyl, 3-difluoro-2-allyl, heptafluoroisopropyl or 1-methoxyhexafluoroisopropyl;
<xnotran> , , , , , , , , , , , , , , , , , , I-3A, I-3B, I-3C, I-3D, I-3E, I-3F, I-3G, I-3H, I-3I, I-3J, I-3K, I-3L, I-3M, I-3N, I-3O, I-3P, I-3Q, I-3R, I-3S, I-3T, I-3U, I-3V, I-3W, I-3X, I-4A, I-4B, I-4C, I-4D, I-4E, I-4F, I-4G, I-4H, I-4I, I-4J, I-4K, I-4L, I-4M, I-4N, I-4O, I-4P, I-4Q, I-4R, I-4S, I-4T, I-4U, I-4V, I-4W I-4X. </xnotran>
Particularly preferred compounds of the formula (I) according to the invention are the compounds shown in Table 1 or their salts with hydrochloric acid, sulfuric acid, phosphoric acid, nitric acid, formic acid, acetic acid, trifluoroacetic acid, oxalic acid, methanesulfonic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, benzoic acid, phthalic acid, maleic acid, fumaric acid, sorbic acid, malic acid, tartaric acid or citric acid.
TABLE 1 Compounds of formula (I) which are particularly preferred according to the invention
Figure BDA0002520885880000051
Figure BDA0002520885880000061
Tables 2,3, 4 and 5 show R and R in the formula (I) 1 ，R 2 、R 3 Or R 4 The moiety of W is a specific substituent, but they are not limited to these substituents. Table 6 lists some specific acids of the Acid in formula (I-3) or formula (I-4), but the Acid is not limited to these acids.
TABLE 2 specific substituents for moieties from which R is selected in the general formula (I)
Figure BDA0002520885880000081
TABLE 3 partial specific substituents of formula (I) from which R1 is selected
Figure BDA0002520885880000082
TABLE 4 general formula (I) R 2 、R 3 Or R 4 Selected from the group consisting of the moiety-specific substituents
No R 2 、R 3 Or R 4 No R 2 、R 3 Or R 4 No R 2 、R 3 Or R 4 No R 2 、R 3 Or R 4
4-1 H 4-2 F 4-3 Cl 4-4 Br
4-5 CH 3 4-6 CH 2 CH 3 4-7 CH 2 CH 2 CH 3 4-8 C(CH 3 ) 3
4-9 CH 2 Cl 4-10 CH 2 F 4-11 CH 2 Br 4-12 CHCl 2
4-13 CHF 2 4-14 CHBr 2 4-15 CCl 3 4-16 CH 2 CF 3
4-17 CF 3 4-18 CHFCH 3 4-19 CHClCH 3 4-20 CHBrCH 3
4-21 CF(CH 3 ) 2 4-22 CCl(CH 3 ) 2 4-23 CBr(CH 3 ) 2 4-24 I
4-25 CF(CF 3 ) 2 4-26 NO 2 4-27 CN 4-28 OCH 3
4-29 OCF 3 4-30 OCH 2 CH 3 4-31 OCH 2 CF 3 4-32 OCH 2 CHF 2
TABLE 5 partial specific substituents of formula (I) from which w is selected
Figure BDA0002520885880000091
TABLE 6 partial acids selected from the group consisting of acids in the general formula (I-3) and the formula (I-4)
No Acid No Acid No Acid No Acid
6-1 Hydrochloric acid 6-2 Sulfuric acid 6-3 Phosphoric acid 6-4 Nitric acid
6-5 Carbonic acid 6-6 Formic acid 6-7 Acetic acid 6-8 Trifluoroacetic acid
6-9 Propionic acid 6-10 Butyric acid 6-11 Cyclopentanoic acid 6-12 Oxalic acid
6-13 Adipic acid 6-14 Benzoic acid 6-15 Para methyl benzoic acid 6-16 Phthalic acid
6-17 Methanesulfonic acid 6-18 Trifluoromethanesulfonic acid 6-19 Benzene sulfonic acid 6-20 P-toluenesulfonic acid
6-21 Dodecyl benzene sulfonic acid 6-22 Lauric acid 6-23 Maleic acid 6-24 Fumaric acid
6-25 Sorbic acid 6-26 Malic acid 6-27 Citric acid 6-28 Tartaric acid
<xnotran> I-1A, I-1B, I-1C, I-1D, I-1E, I-1F, I-1G, I-1H, I-1I, I-1J, I-1K, I-1L, I-1M, I-1N, I-1O, I-1P, I-1Q, I-1R, I-1S, I-1T, I-1U, I-1V, I-1W, I-1X, I-2A, I-2B, I-2C, I-2D, I-2E, I-2F, I-2G, I-2H, I-2I, I-2J, I-2K, I-2L, I-2M, I-2N, I-2O, I-2P, I-2Q, I-2R, I-2S, I-2T, I-2U, I-2V, I-2W I-2X , . </xnotran>
<xnotran> I-3A, I-3B, I-3C, I-3D, I-3E, I-3F, I-3G, I-3H, I-3I, I-3J, I-3K, I-3L, I-3M, I-3N, I-3O, I-3P, I-3Q, I-3R, I-3S, I-3T, I-3U, I-3V, I-3W, I-3X, I-4A, I-4B, I-4C, I-4D, I-4E, I-4F, I-4G, I-4H, I-4I, I-4J, I-4K, I-4L, I-4M, I-4N, I-4O, I-4P, I-4Q, I-4R, I-4S, I-4T, I-4U, I-4V, I-4W I-4X , . </xnotran>
When R = CH 3 ，R 1 The substituent groups are shown in the table 3, the I-1A represents compounds with the numbers of I-1A1-1-I-1A1-40, I-1B1-1-I-1B1-40, I-1C1-1-I-1C1-40, I-1D1-1-I-1D1-40, I-1E1-1-I-1E1-40, I-1F1-1-I-1F1-40, I-1G1-1-I-1G1-40, I-1H1-1-I-1H1-40, I-1I1-1-I-1I1-40, I-1J1-1-I-1J1-40, I-1K1-40, I-1-I-1K 1-40I-1L 1-1-I-1L1-40, I-1M1-1-I-1M1-40, I-1N1-1-I-1N1-40, I-1O1-1-I-1O1-40, I-1P1-1-I-1P1-40, I-1Q1-1-I-1Q1-40, I-1R1-1-I-1R1-40, I-1S1-1-I-1S1-40, I-1T1-1-I-1T1-40, I-1U1-1-I-1U1-40, I-1V1-1-I-1V1-40, I-1W1-1-I-1W1-40, I-1-I-1W 1-40, I-1X1-1-I-1X1-40; the I-2A represents a compound which is numbered as I-2A1-1-I-2A1-40, I-2B1-1-I-2B1-40, I-2C1-1-I-2C1-40, I-2D1-1-I-2D1-40, I-2E1-1-I-2E 1-40I-2F 1-1-I-2F1-40, I-2G1-1-I-2G1-40, I-2H1-1-I-2H1-40, I-2I1-1-I-2I1-40, I-2J1-1-I-2J1-40, I-2K1-1-I-2K 1-40I-2L 1-1-I-2L1-40, I-2M1-1-I-2M1-40, I-2N1-1-I-2N1-40, I-2O1-1-I-2O1-40, I-2P1-1-I-2P1-40, I-2Q1-1-I-2Q1-40, I-2R1-1-I-2R1-40, I-2S1-1-I-2S1-40, I-2T1-1-I-2T1-40, I-2U1-1-I-2U1-40, I-2V1-1-I-2V1-40, I-2W1-1-I-2W1-40, I-2L 1-1-I-2W1-40, I-2X1-1-I-2X1-40;
when R = CH 2 CH 3 ，R 1 The substituent groups are shown in the table 3, the I-1A represents compounds with the numbers of I-1A2-1-I-1A2-40, I-1B2-1-I-1B2-40, I-1C2-1-I-1C2-40, I-1D2-1-I-1D2-40, I-1E2-1-I-1E2-40, I-1F2-1-I-1F2-40, I-1G2-1-I-1G2-40, I-1H2-1-I-1H2-40, I-1I2-1-I-1I2-40, I-1J2-1-I-1J2-40, I-1K2-1-I-1K2-40, I-1A 2-1-I-1B2-40, I-1B2-40 and B2-40I-1L 2-1-I-1L2-40, I-1M2-1-I-1M2-40, I-1N2-1-I-1N2-40, I-1O2-1-I-1O2-40, I-1P2-1-I-1P2-40, I-1Q2-1-I-1Q2-40, I-1R2-1-I-1R2-40, I-1S2-1-I-1S2-40, I-1T2-1-I-1T2-40, I-1U2-1-I-1U2-40, I-1V2-1-I-1V2-40, I-1W2-1-I-1W2-40, I-1X2-1-I-1X2-40; the I-2A represents a compound which is numbered as I-2A2-1-I-2A2-40, I-2B2-1-I-2B2-40, I-2C2-1-I-2C2-40, I-2D2-1-I-2D2-40, I-2E2-1-I-2E2-40, I-2F2-1-I-2F2-40, I-2G2-1-I-2G2-40, I-2H2-1-I-2H2-40, I-2I2-1-I-2I 2-40I-2J 2-1-I-2J2-40, I-2K2-1-I-2K2-40, I-2L2-1-I-2L2-40, I-2M2-1-I-2M2-40, I-2N2-1-I-2N2-40, I-2O2-1-I-2O2-40, I-2P2-1-I-2P2-40, I-2Q2-1-I-2Q2-40, I-2R2-1-I-2R2-40, I-2S2-1-I-2S2-40、I-2T2-1-I-2T2-40、 I-2U2-1-I-2U2-40、I-2V2-1-I-2V2-40、I-2W2-1-I-2W2-40、I-2X2-1-I-2X2-40；
When R = CHF 2 ，R 1 The substituent groups are shown in the table 3, I-1A represents compounds with the numbers of I-1A3-1-I-1A3-40, I-1B3-1-I-1B3-40, I-1C3-1-I-1C3-40, I-1D3-1-I-1D3-40, I-1E3-1-I-1E3-40, I-1F3-1-I-1F3-40, I-1G3-1-I-1G3-40, I-1H3-1-I-1H3-40, I-1I3-1-I-1I3-40, I-1J3-1-I-1J3-40, I-1K3-1-I-1K3-40, I-1-I-1K 3-40I-1L 3-1-I-1L3-40, I-1M3-1-I-1M3-40, I-1N3-1-I-1N3-40, I-1O3-1-I-1O3-40, I-1P3-1-I-1P3-40, I-1Q3-1-I-1Q3-40, I-1R3-1-I-1R3-40, I-1S3-1-I-1S3-40, I-1T3-1-I-1T3-40, I-1U3-1-I-1U3-40, I-1V3-1-I-1V3-40, I-1W3-1-I-1W3-40, I-1N 3-1W 3-40, I-1X3-1-I-1X3-40; the I-2A represents a compound which is numbered as I-2A3-1-I-2A3-40, I-2B3-1-I-2B3-40, I-2C3-1-I-2C3-40, I-2D3-1-I-2D3-40, I-2E3-1-I-2E3-40, I-2F3-1-I-2F3-40, I-2G3-1-I-2G3-40, I-2H3-1-I-2H3-40, I-2I3-1-I-2I3-40, I-2J3-1-I-2J3-40, I-2K3-1-I-2K 3-40I-2L 3-1-I-2L3-40, I-2M3-1-I-2M3-40, I-2N3-1-I-2N3-40, I-2O3-1-I-2O3-40, I-2P3-1-I-2P3-40, I-2Q3-1-I-2Q3-40, I-2R3-1-I-2R3-40, I-2S3-1-I-2S3-40, I-2T3-1-I-2T3-40, I-2U3-1-I-2U3-40, I-2V3-1-I-2V3-40, I-2W3-1-I-2W3-40, I-2X3-1-I-2X3-40;
when R = CF 3 ，R 1 The substituent groups are shown in the table 3, I-1A represents the compound numbers of I-1A4-1-I-1A4-40, I-1B4-1-I-1B4-40, I-1C4-1-I-1C4-40, I-1D4-1-I-1D4-40, I-1E4-1-I-1E4-40, I-1F4-1-I-1F4-40, I-1G4-1-I-1G4-40, I-1H4-1-I-1H4-40, I-1I4-1-I-1I4-40, I-1J4-1-I-1J4-40, I-1K 4-40I-1L 4-1-I-1L4-40, I-1M4-1-I-1M4-40, I-1N4-1-I-1N4-40, I-1O4-1-I-1O4-40, I-1P4-1-I-1P4-40, I-1Q4-1-I-1Q4-40, I-1R4-1-I-1R4-40, I-1S4-1-I-1S4-40, I-1T4-1-I-1T4-40, I-1U4-1-I-1U4-40, I-1V4-1-I-1V4-40, I-1W4-1-I-1W4-40, I-1X4-1-I-1X4-40; I-2A represents a compound which is numbered sequentially as I-2A4-1-I-2A4-40, I-2B4-1-I-2B4-40, I-2C4-1-I-2C4-40, I-2D4-1-I-2D4-40, I-2E4-1-I-2E4-40, I-2F4-1-I-2F4-40, I-2G4-1-I-2G4-40, I-2H4-1-I-2H4-40, I-2I4-1-I-2I4-40, I-2J4-1-I-2J4-40, I-2K4-1-I-2K4-40, I-2L4-1-I-2L4-40, I-2M4-1-I-2M4-40、I-2N4-1-I-2N4-40、I-2O4-1-I-2O4-40、 I-2P4-1-I-2P4-40、I-2Q4-1-I-2Q4-40、I-2R4-1-I-2R4-40、I-2S4-1-I-2S4-40、I-2T4-1-I-2T4-40、 I-2U4-1-I-2U4-40、I-2V4-1-I-2V4-40、I-2W4-1-I-2W4-40、I-2X4-1-I-2X4-40；
When R = CHClCH 3 ，R 1 The substituent groups are shown in the table 3, the I-1A represents the compound numbers of I-1A5-1-I-1A5-40, I-1B5-1-I-1B5-40, I-1C5-1-I-1C5-40, I-1D5-1-I-1D5-40, I-1E5-1-I-1E 5-40I-1F 5-1-I-1F5-40, I-1G5-1-I-1G5-40, I-1H5-1-I-1H5-40, I-1I5-1-I-1I5-40, I-1J5-1-I-1J5-40, I-1K5-1-I-1K 5-40I-1L 5-1-I-1L5-40, I-1M5-1-I-1M5-40, I-1N5-1-I-1N5-40, I-1O5-1-I-1O5-40, I-1P5-1-I-1P5-40, I-1Q5-1-I-1Q5-40, I-1R5-1-I-1R5-40, I-1S5-1-I-1S5-40, I-1T5-1-I-1T5-40, I-1U5-1-I-1U5-40, I-1V5-1-I-1V5-40, I-1W5-1-I-1W5-40, I-1X5-1-I-1X5-40; the I-2A represents a compound which is numbered as I-2A5-1-I-2A5-40, I-2B5-1-I-2B5-40, I-2C5-1-I-2C5-40, I-2D5-1-I-2D5-40, I-2E5-1-I-2E5-40, I-2F5-1-I-2F5-40, I-2G5-1-I-2G5-40, I-2H5-1-I-2H5-40, I-2I5-1-I-2I5-40, I-2J5-1-I-2J5-40, I-2K5-1-I-2K 5-40I-2L 5-1-I-2L5-40, I-2M5-1-I-2M5-40, I-2N5-1-I-2N5-40, I-2O5-1-I-2O5-40, I-2P5-1-I-2P5-40, I-2Q5-1-I-2Q5-40, I-2R5-1-I-2R5-40, I-2S5-1-I-2S5-40, I-2T5-1-I-2T5-40, I-2U5-1-I-2U5-40, I-2V5-1-I-2V5-40, I-2W5-1-I-2W5-40, I-2X5-1-I-2X5-40;
when R = CHFCH 3 ，R 1 The substituent groups are shown in the table 3, I-1A represents the compound numbers of I-1A6-1-I-1A6-40, I-1B6-1-I-1B6-40, I-1C6-1-I-1C6-40, I-1D6-1-I-1D6-40, I-1E6-1-I-1E6-40, I-1F6-1-I-1F6-40, I-1G6-1-I-1G6-40, I-1H6-1-I-1H6-40, I-1I6-1-I-1I6-40, I-1J6-1-I-1J6-40, I-1K6-1-I-1K6-40, I-1-I-1K 6-40I-1L 6-1-I-1L6-40, I-1M6-1-I-1M6-40, I-1N6-1-I-1N6-40, I-1O6-1-I-1O6-40, I-1P6-1-I-1P6-40, I-1Q6-1-I-1Q6-40, I-1R6-1-I-1R6-40, I-1S6-1-I-1S6-40, I-1T6-1-I-1T6-40, I-1U6-1-I-1U6-40, I-1V6-1-I-1V6-40, I-1W6-1-I-1W6-40, I-1X6-1-I-1X6-40; the I-2A represents a compound with the serial number of I-2A6-1-I-2A6-40, I-2B6-1-I-2B6-40, I-2C6-1-I-2C6-40, I-2D6-1-I-2D6-40, I-2E6-1-I-2E6-40, I-2F6-1-I-2F6-40 and I-2G6-1-I-2G6-40、I-2H6-1-I-2H6-40、I-2I6-1-I-2I6-40、I-2J6-1-I-2J6-40、 I-2K6-1-I-2K6-40、I-2L6-1-I-2L6-40、I-2M6-1-I-2M6-40、I-2N6-1-I-2N6-40、I-2O6-1-I-2O6-40、 I-2P6-1-I-2P6-40、I-2Q6-1-I-2Q6-40、I-2R6-1-I-2R6-40、I-2S6-1-I-2S6-40、I-2T6-1-I-2T6-40、 I-2U6-1-I-2U6-40、I-2V6-1-I-2V6-40、I-2W6-1-I-2W6-40、I-2X6-1-I-2X6-40；
When R = cyclopropyl, R 1 The substituent groups are shown in the table 3, the I-1A represents the compound numbers of I-1A7-1-I-1A7-40, I-1B7-1-I-1B7-40, I-1C7-1-I-1C7-40, I-1D7-1-I-1D7-40, I-1E7-1-I-1E7-40, I-1F7-1-I-1F7-40, I-1G7-1-I-1G7-40, I-1H7-1-I-1H7-40, I-1I7-1-I-1I7-40, I-1J7-1-I-1J7-40, I-1K7-1-I-1K7-40, I-1-I-1K 7-40I-1L 7-1-I-1L7-40, I-1M7-1-I-1M7-40, I-1N7-1-I-1N7-40, I-1O7-1-I-1O7-40, I-1P7-1-I-1P7-40, I-1Q7-1-I-1Q7-40, I-1R7-1-I-1R7-40, I-1S7-1-I-1S7-40, I-1T7-1-I-1T7-40, I-1U7-1-I-1U7-40, I-1V7-1-I-1V7-40, I-1W7-1-I-1W7-40, I-1U 7-1-I-1W7-40, I-1X7-1-I-1X7-40; I-2A represents a compound which is numbered as I-2A7-1-I-2A7-40, I-2B7-1-I-2B7-40, I-2C7-1-I-2C7-40, I-2D7-1-I-2D7-40, I-2E7-1-I-2E7-40, I-2F7-1-I-2F7-40, I-2G7-1-I-2G7-40, I-2H7-1-I-2H7-40, I-2I7-1-I-2I7-40, I-2J7-1-I-2J7-40, I-2K7-1-I-2K 7-40I-2L 7-1-I-2L7-40, I-2M7-1-I-2M7-40, I-2N7-1-I-2N7-40, I-2O7-1-I-2O7-40, I-2P7-1-I-2P7-40, I-2Q7-1-I-2Q7-40, I-2R7-1-I-2R7-40, I-2S7-1-I-2S7-40, I-2T7-1-I-2T7-40, I-2U7-1-I-2U7-40, I-2V7-1-I-2V7-40, I-2W7-1-I-2W7-40, I-2L 7-1-I-2W7-40, I-2X7-l-I-2X7-40;
when R = 2-allyl, R 1 The substituent groups are shown in the table 3, I-1A represents compounds with the numbers of I-1A8-1-I-1A8-40, I-1B8-1-I-1B8-40, I-1C8-1-I-1C8-40, I-1D8-1-I-1D8-40, I-1E8-1-I-1E8-40, I-1F8-1-I-1F8-40, I-1G8-1-I-1G8-40, I-1H8-1-I-1H8-40, I-1I8-1-I-1I8-40, I-1J 8-1I-1J 8-40, I-1K 8-40I-1L 8-1-I-1L8-40, I-1M8-1-I-1M8-40, I-1N8-1-I-1N8-40, I-1O8-1-I-1O8-40, I-1P8-1-I-1P8-40, I-1Q8-1-I-1Q8-40, I-1R8-1-I-1R8-40, I-1S8-1-I-1S8-40, I-1T8-1-I-1T8-40, I-1U8-1-I-1U8-40, I-1V8-1-I-1V8-40, I-1W8-1-I-1W8-40, I-1N 8-1W 8-40, I-1X8-1-I-1X8-40; I-2A represents a compound with the number of I-2A8-1-I-2A8-40 in sequence、I-2B8-1-I-2B8-40、I-2C8-1-I-2C8-40、I-2D8-1-I-2D8-40、I-2E8-1-I-2E8-40、 I-2F8-1-I-2F8-40、I-2G8-1-I-2G8-40、I-2H8-1-I-2H8-40、I-2I8-1-I-2I8-40、I-2J8-1-I-2J8-40、 I-2K8-1-I-2K8-40、I-2L8-1-I-2L8-40、I-2M8-1-I-2M8-40、I-2N8-1-I-2N8-40、I-2O8-1-I-2O8-40、 I-2P8-1-I-2P8-40、I-2Q8-1-I-2Q8-40、I-2R8-1-I-2R8-40、I-2S8-1-I-2S8-40、I-2T8-1-I-2T8-40、 I-2U8-1-I-2U8-40、I-2V8-1-I-2V8-40、I-2W8-1-I-2W8-40、I-2X8-1-I-2X8-40：
When R = 2-propargyl, R 1 The substituent groups are shown in the table 3, I-1A represents the compound numbers of I-1A9-1-I-1A9-40, I-1B9-1-I-1B9-40, I-1C9-1-I-1C9-40, I-1D9-1-I-1D9-40, I-1E9-1-I-1E9-40, I-1F9-1-I-1F9-40, I-1G9-1-I-1G9-40, I-1H9-1-I-1H9-40, I-1I9-1-I-1I9-40, I-1J9-1-I-1J9-40, I-1K9-1-I-1K 9-40I-1L 9-1-I-1L9-40, I-1M9-1-I-1M9-40, I-1N9-1-I-1N9-40, I-1O9-1-I-1O9-40, I-1P9-1-I-1P9-40, I-1Q9-1-I-1Q9-40, I-1R9-1-I-1R9-40, I-1S9-1-I-1S9-40, I-1T9-1-I-1T9-40, I-1U9-1-I-1U9-40, I-1V9-1-I-1V9-40, I-1W9-1-I-1W9-40, I-1N 9-1W 9-40, I-1X9-1-I-1X9-40; the I-2A represents a compound which is numbered as I-2A9-1-I-2A9-40, I-2B9-1-I-2B9-40, I-2C9-1-I-2C9-40, I-2D9-1-I-2D9-40, I-2E9-1-I-2E9-40, I-2F9-1-I-2F9-40, I-2G9-1-I-2G9-40, I-2H9-1-I-2H9-40, I-2I9-1-I-2I9-40, I-2J9-1-I-2J9-40, I-2K9-1-I-2K 9-40I-2L 9-1-I-2L9-40, I-2M9-1-I-2M9-40, I-2N9-1-I-2N9-40, I-2O9-1-I-2O9-40, I-2P9-1-I-2P9-40, I-2Q9-1-I-2Q9-40, I-2R9-1-I-2R9-40, I-2S9-1-I-2S9-40, I-2T9-1-I-2T9-40, I-2U9-1-I-2U9-40, I-2V9-1-I-2V9-40, I-2W9-1-I-2W9-40, I-2L 9-1-I-2W9-40, I-2X9-1-I-2X9-40.
When R = CH 3 ，R 1 The substituent group is shown in a table 3, the acid is shown in a table 6, the I-3A represents a compound number of I-3A1-1-1-I-3A1-40-28, I-3B 1-1-I-3B1-40-28, I-3C1-1-1-I-3C1-40-28, I-3D 1-1-I-3D 1-40-28, I-3E1-1-1-I-3E1-40-28, I-3F 1-1-I-3F1-40-28, I-3G1-1-1-I-3G 1-40-28I-3H 1-1-1-I-3H 1-40-28, I-3I 1-1-I-3I1-40-28, I-3J 1-1-I-3J1-40-28, I-3K 1-1-I-3K1-40-28, I-3L 1-1-I-3L 1-40-28, I-3M 1-1-I-3M1-40-28, I-3N 1-1-I-3N1-40-28, I-3O1-1-1-I-3O1-40-28, I-3P1-1-1-I-3P1-40-28. I-3Q1-1-1-I-3Q1-40-28, I-3R 1-1-I-3R1-40-28, I-3S 1-1-I-3S1-40-28, I-3T 1-1-I-3T1-40-28, I-3U 1-1-I-3U1-40-28, I-3V1-1-1-I-3V1-40-28, I-3W 1-1-I-3W 1-40-28, I-3X1-1-1-I-3X1-40-28; I-4A represents a compound which is numbered as I-4A1-1-1-I-4A1-40-28, I-4B1-1-1-I-4B1-40-28, I-4C 1-1-I-4C1-40-28, I-4D 1-1-I-4D1-40-28, I-4E 1-1-I-4E1-40-28, I-4F 1-1-I-4F1-40-28, I-4G 1-1-I-4G1-40-28, I-4H1-1-1-I-4H 1-40-28I-4I 1-1-I-4I1-40-28, I-4J 1-1-I-4J1-40-28, I-4K 1-1-I-4K1-40-28, I-4L 1-1-I-4L1-40-28, I-4M 1-1-I-4M1-40-28, I-4N 1-1-I-4N1-40-28, I-4O 1-1-I-4O1-40-28, I-4P 1-1-I-4P1-40-28, I-4Q 1-1-I-4Q1-40-28, I-4R1-1-1-I-4R1-40-28, I-4S 1-1-I-4S1-40-28, I-4T 1-1-I-4T1-40-28, I-4U 1-1-I-4U1-40-28, I-4V 1-1-I-4V1-40-28, I-4W 1-1-I-4W1-40-28, I-4X 1-1-I-4X1-40-28;
when R = CH 2 CH 3 ，R 1 The substituent group is shown in a table 3, the acid is shown in a table 6, the I-3A represents the compound numbers I-3A 2-1-I-3A 2-40-28, I-3B 2-1-I-3B 2-40-28, I-3C 2-1-I-3C 2-40-28, I-3D 2-1-I-3D 2-40-28, I-3E 2-1-I-3E 2-40-28, I-3F 2-1-I-3F 2-40-28, I-3G 2-1-I-3G 2-40-28, I-3H 2-1-I-3H 2-40-28I-3I 2-1-I-3I 2-40-28, I-3J 2-1-I-3J 2-40-28, I-3K 2-1-I-3K 2-40-28, I-3L 2-1-I-3L 2-40-28, I-3M 2-1-I-3M 2-40-28, I-3N 2-1-I-3N 2-40-28, I-3O 2-1-I-3O 2-40-28, I-3P 2-1-I-3P 2-40-28, I-3Q 2-1-I-3Q 2-40-28, I-3R 2-1-I-3R 2-40-28, I-3S 2-1-I-3S 2-40-28, I-3T 2-1-I-3T 2-40-28, I-3U 2-1-I-3U 2-40-28, I-3V 2-1-I-3V 2-40-28, I-3W 2-1-I-3W 2-40-28, I-3X 2-1-I-3X 2-40-28; I-4A represents a compound which is numbered as I-4A 2-1-1-I-4A 2-40-28, I-4B 2-1-I-4B 2-40-28, I-4C 2-1-I-4C 2-40-28, I-4D 2-1-I-4D 2-40-28, I-4E 2-1-I-4E 2-40-28, I-4F 2-1-I-4F 2-40-28, I-4G 2-1-I-4G 2-40-28, I-4H 2-1-I-4H 2-40-28I-4I 2-1-I-4I 2-40-28, I-4J 2-1-I-4J 2-40-28, I-4K 2-1-I-4K 2-40-28, I-4L 2-1-I-4L 2-40-28, I-4M 2-1-I-4M 2-40-28, I-4N 2-1-I-4N 2-40-28, I-4O 2-1-I-4O 2-40-28, I-4P 2-1-I-4P 2-40-28, I-4Q 2-1-I-4Q 2-40-28, I-4R2-1-1-I-4R2-40-28, I-4S 2-1-I-4S 2-40-28, I-4T2-1-1- I-4T2-40-28、I-4U2-1-1-I-4U2-40-28、I-4V2-1-1-I-4V2-40-28、I-4W2-1-1-I-4W2-40-28、 I-4X2-1-1-I-4X2-40-28；
When R = CHF 2 ，R 1 The substituent group is shown in a table 3, the acid is shown in a table 6, the I-3A represents the compound numbers I-3A3-1-1-I-3A3-40-28, I-3B 3-1-I-3B 3-40-28, I-3C 3-1-I-3C 3-40-28, I-3D 3-1-I-3D 3-40-28, I-3E 3-1-I-3E 3-40-28, I-3F 3-1-I-3F 3-40-28, I-3G 3-1-I-3G 3-40-28, I-3H 3-1-I-3H 3-40-28I-3I 3-1-I-3I 3-40-28, I-3J 3-1-I-3J 3-40-28, I-3K 3-1-I-3K 3-40-28, I-3L 3-1-I-3L 3-40-28, I-3M 3-1-I-3M 3-40-28, I-3N 3-1-I-3N 3-40-28, I-3O 3-1-I-3O 3-40-28, I-3P 3-1-I-3P 3-40-28, I-3Q 3-1-I-3Q 3-40-28, I-3M 3-1-I-3M 3-40-28, I-3Q 3-1-I-3Q 3-40-28, I-3R 3-1-I-3R 3-40-28, I-3S 3-1-I-3S 3-40-28, I-3T 3-1-I-3T 3-40-28, I-3U 3-1-I-3U 3-40-28, I-3V 3-1-I-3V 3-40-28, I-3W 3-1-I-3W 3-40-28, I-3X 3-1-I-3X 3-40-28; I-4A represents a compound which is numbered as I-4A 3-1-1-I-4A 3-40-28, I-4B 3-1-I-4B 3-40-28, I-4C 3-1-I-4C 3-40-28, I-4D 3-1-I-4D 3-40-28, I-4E 3-1-I-4E 3-40-28, I-4F 3-1-I-4F 3-40-28, I-4G 3-1-I-4G 3-40-28, I-4H 3-1-I-4H 3-40-28I-4I 3-1-I-4I 3-40-28, I-4J 3-1-I-4J 3-40-28, I-4K 3-1-I-4K 3-40-28, I-4L 3-1-I-4L 3-40-28, I-4M 3-1-I-4M 3-40-28, I-4N 3-1-I-4N 3-40-28, I-4O 3-1-I-4O 3-40-28, I-4P 3-1-I-4P 3-40-28, I-4Q 3-1-I-4Q 3-40-28, I-4M 3-1-I-4P 3-40-28, I-4Q 3-1-I-4Q 3-40-28, I-4R3-1-1-I-4R3-40-28, I-4S 3-1-I-4S 3-40-28, I-4T 3-1-I-4T 3-40-28, I-4U 3-1-I-4U 3-40-28, I-4V 3-1-I-4V 3-40-28, I-4W 3-1-I-4W 3-40-28, I-4X 3-1-I-4X 3-40-28;
when R = CF 3 ，R 1 The substituent group is shown in a table 3, the acid is shown in a table 6, the I-3A represents the compound number which is sequentially I-3A4-1-1-I-3A4-40-28, I-3B 4-1-I-3B 4-40-28, I-3C 4-1-I-3C 4-40-28, I-3D 4-1-I-3D 4-40-28, I-3E 4-1-I-3E 4-40-28, I-3F 4-1-I-3F 4-40-28, I-3G 4-1-I-3G 4-40-28, I-3H 4-1-I-3H 4-40-28I-3I 4-1-I-3I 4-40-28, I-3J 4-1-I-3J 4-40-28, I-3K 4-1-I-3K 4-40-28, I-3L 4-1-I-3L 4-40-28, I-3M 4-1-I-3M 4-40-28, I-3N 4-1-I-3N 4-40-28, I-3O 4-1-I-3O 4-40-28, I-3P 4-1-I-3P 4-40-28, I-3Q 4-1-I-3Q 4-40-28, I-3R4-1-1-I-3R4-40-28, I-3S4-1-1-I-3S4-40-28, I-3T 4-1-I-3T 4-40-28, I-3U 4-1-I-3U 4-40-28, I-3V 4-1-I-3V 4-40-28, I-3W 4-1-I-3W 4-40-28, I-3X 4-1-I-3X 4-40-28; I-4A represents a compound which is numbered as I-4A4-1-1-I-4A4-40-28, I-4B 4-1-I-4B 4-40-28, I-4C 4-1-I-4C 4-40-28, I-4D 4-1-I-4D 4-40-28, I-4E 4-1-I-4E 4-40-28, I-4F 4-1-I-4F 4-40-28, I-4G 4-1-I-4G 4-40-28, I-4H 4-1-I-4H 4-40-28I-4I 4-1-I-4I 4-40-28, I-4J 4-1-I-4J 4-40-28, I-4K 4-1-I-4K 4-40-28, I-4L 4-1-I-4L 4-40-28, I-4M 4-1-I-4M 4-40-28, I-4N 4-1-I-4N 4-40-28, I-4O 4-1-I-4O 4-40-28, I-4P 4-1-I-4P 4-40-28, I-4Q 4-1-I-4Q 4-40-28, I-4R4-1-1-I-4R4-40-28, I-4S 4-1-I-4S 4-40-28, I-4T 4-1-I-4T 4-40-28, I-4U 4-1-I-4U 4-40-28, I-4V 4-1-I-4V 4-40-28, I-4W 4-1-I-4W 4-40-28, I-4X 4-1-I-4X 4-40-28;
when R = CHClCH 3 ，R 1 The substituent group is shown in a table 3, the acid is shown in a table 6, the I-3A represents a compound number of I-3A5-1-1-I-3A5-40-28, I-3B 5-1-I-3B 5-40-28, I-3C 5-1-I-3C 5-40-28, I-3D 5-1-I-3D 5-40-28, I-3E 5-1-I-3E 5-40-28, I-3F 5-1-I-3F 5-40-28, I-3G 5-1-I-3G 5-40-28, I-3H 5-1-I-3H 5-40-28I-3I 5-1-I-3I 5-40-28, I-3J 5-1-I-3J 5-40-28, I-3K 5-1-I-3K 5-40-28, I-3L 5-1-I-3L 5-40-28, I-3M 5-1-I-3M 5-40-28, I-3N 5-1-I-3N 5-40-28, I-3O 5-1-I-3O 5-40-28, I-3P 5-1-I-3P 5-40-28, I-3Q 5-1-I-3Q 5-40-28, I-3R 5-1-I-3R 5-40-28, I-3S 5-1-I-3S 5-40-28, I-3T 5-1-I-3T 5-40-28, I-3U 5-1-I-3U 5-40-28, I-3V 5-1-I-3V 5-40-28, I-3W 5-1-I-3W 5-40-28, I-3X 5-1-I-3X 5-40-28; I-4A represents a compound which is numbered as I-4A 5-1-1-I-4A 5-40-28, I-4B 5-1-I-4B 5-40-28, I-4C 5-1-I-4C 5-40-28, I-4D 5-1-I-4D 5-40-28, I-4E 5-1-I-4E 5-40-28, I-4F 5-1-I-4F 5-40-28, I-4G 5-1-I-4G 5-40-28, I-4H 5-1-I-4H 5-40-28I-4I 5-1-I-4I 5-40-28, I-4J 5-1-I-4J 5-40-28, I-4K 5-1-I-4K 5-40-28, I-4L 5-1-I-4L 5-40-28, I-4M 5-1-I-4M 5-40-28, I-4N 5-1-I-4N 5-40-28, I-4O 5-1-I-4O 5-40-28, I-4P 5-1-I-4P 5-40-28, I-4Q 5-1-I-4Q 5-40-28, I-4R5-1-1-I-4R5-40-28, I-4S 5-1-I-4S 5-40-28, I-4T 5-1-I-4T 5-40-28, I-4U 5-1-I-4U 5-40-28, I-4V 5-1-I-4V 5-40-28-4W5-1-1- I-4W5-40-28、I-4X5-1-1-I-4X5-40-28；
When R = CHFCH 3 ，R 1 The substituent group is shown in a table 3, the acid is shown in a table 6, the I-3A represents the compound numbers I-3A6-1-1-I-3A6-40-28, I-3B 6-1-I-3B 6-40-28, I-3C 6-1-I-3C 6-40-28, I-3D 6-1-I-3D 6-40-28, I-3E 6-1-I-3E 6-40-28, I-3F 6-1-I-3F 6-40-28, I-3G 6-1-I-3G 6-40-28, I-3H 6-1-I-3H 6-40-28I-3I 6-1-I-3I 6-40-28, I-3J 6-1-I-3J 6-40-28, I-3K 6-1-I-3K 6-40-28, I-3L 6-1-I-3L 6-40-28, I-3M 6-1-I-3M 6-40-28, I-3N 6-1-I-3N 6-40-28, I-3O 6-1-I-3O 6-40-28, I-3P 6-1-I-3P 6-40-28, I-3Q 6-1-I-3Q 6-40-28, I-3R6-1-1-I-3R6-40-28, I-3S 6-1-I-3S 6-40-28, I-3T 6-1-I-3T 6-40-28, I-3U 6-1-I-3U 6-40-28, I-3V 6-1-I-3V 6-40-28, I-3W 6-1-I-3W 6-40-28, I-3X 6-1-I-3X 6-40-28; I-4A represents a compound which is numbered as I-4A6-1-1-I-4A6-40-28, I-4B 6-1-I-4B 6-40-28, I-4C 6-1-I-4C 6-40-28, I-4D 6-1-I-4D 6-40-28, I-4E 6-1-I-4E 6-40-28, I-4F 6-1-I-4F 6-40-28, I-4G 6-1-I-4G 6-40-28, I-4H 6-1-I-4H 6-40-28I-4I 6-1-I-4I 6-40-28, I-4J 6-1-I-4J 6-40-28, I-4K 6-1-I-4K 6-40-28, I-4L 6-1-I-4L 6-40-28, I-4M 6-1-I-4M 6-40-28, I-4N 6-1-I-4N 6-40-28, I-4O 6-1-I-4O 6-40-28, I-4P 6-1-I-4P 6-40-28, I-4Q 6-1-I-4Q 6-40-28, I-4R6-1-1-I-4R6-40-28, I-4S 6-1-I-4S 6-40-28, I-4T 6-1-I-4T 6-40-28, I-4U 6-1-I-4U 6-40-28, I-4V 6-1-I-4V 6-40-28, I-4W 6-1-I-4W 6-40-28, I-4X 6-1-I-4X 6-40-28;
when R = cyclopropyl, R 1 The substituent group is shown in a table 3, the acid is shown in a table 6, the I-3A represents a compound number of I-3A7-1-1-I-3A7-40-28, I-3B 7-1-I-3B 7-40-28, I-3C 7-1-I-3C 7-40-28, I-3D 7-1-I-3D 7-40-28, I-3E 7-1-I-3E 7-40-28, I-3F 7-1-I-3F 7-40-28, I-3G 7-1-I-3G 7-40-28, I-3H 7-1-I-3H 7-40-28I-3I 7-1-I-3I 7-40-28, I-3J 7-1-I-3J 7-40-28, I-3K 7-1-I-3K 7-40-28, I-3L 7-1-I-3L 7-40-28, I-3M 7-1-I-3M 7-40-28, I-3N 7-1-I-3N 7-40-28, I-3O 7-1-I-3O 7-40-28, I-3P 7-1-I-3P 7-40-28, I-3Q 7-1-I-3Q 7-40-28, I-3R7-1-1-I-3R7-40-28, I-3S 7-1-I-3S 7-40-28, I-3T 7-1-I-3T 7-40-28, I-3U 7-1-I-3U 7-40-28, I-3V 7-1-I-3V7-40-28, I-3W 7-1-1-I-3W 7-40-28, I-3X 7-1-I-3X 7-40-28; I-4A represents a compound which is numbered as I-4A7-1-1-I-4A7-40-28, I-4B 7-1-I-4B 7-40-28, I-4C 7-1-I-4C 7-40-28, I-4D 7-1-I-4D 7-40-28, I-4E 7-1-I-4E 7-40-28, I-4F 7-1-I-4F 7-40-28, I-4G 7-1-I-4G 7-40-28, I-4H 7-1-I-4H 7-40-28I-4I 7-1-I-4I 7-40-28, I-4J 7-1-I-4J 7-40-28, I-4K 7-1-I-4K 7-40-28, I-4L 7-1-I-4L 7-40-28, I-4M 7-1-I-4M 7-40-28, I-4N 7-1-I-4N 7-40-28, I-4O 7-1-I-4O 7-40-28, I-4P 7-1-I-4P 7-40-28, I-4Q 7-1-I-4Q 7-40-28, I-4R7-1-1-I-4R7-40-28, I-4S 7-1-I-4S 7-40-28, I-4T 7-1-I-4T 7-40-28, I-4U 7-1-I-4U 7-40-28, I-4V 7-1-I-4V 7-40-28, I-4W 7-1-I-4W 7-40-28, I-4X 7-1-I-4X 7-40-28;
when R = 2-allyl, the compound is, the substituent of R1 is shown in a table 3, the acid is shown in a table 6, the I-3A represents the compound numbers I-3A 8-1-I-3A 8-40-28, I-3B 8-1-I-3B 8-40-28, I-3C 8-1-I-3C 8-40-28, I-3D 8-1-I-3D 8-40-28, I-3E 8-1-I-3E 8-40-28, I-3F 8-1-I-3F 8-40-28, I-3G 8-1-I-3G 8-40-28I-3H 8-1-1-I-3H 8-40-28, I-3I 8-1-I-3I 8-40-28, I-3J 8-1-I-3J 8-40-28, I-3K 8-1-I-3K 8-40-28, I-3L 8-1-I-3L 8-40-28, I-3M 8-1-I-3M 8-40-28, I-3N 8-1-I-3N 8-40-28, I-3O 8-1-I-3O 8-40-28, I-3P 8-1-I-3P 8-40-28, I-3Q8-1-1-I-3Q8-40-28, I-3R 8-1-I-3R 8-40-28, I-3S 8-1-I-3S 8-40-28, I-3T 8-1-I-3T 8-40-28, I-3U 8-1-I-3U 8-40-28, I-3V 8-1-I-3V 8-40-28, I-3W 8-1-I-3W 8-40-28, I-3X 8-1-I-3X 8-40-28; I-4A represents a compound which is numbered as I-4A8-1-1-I-4A8-40-28, I-4B 8-1-I-4B 8-40-28, I-4C 8-1-I-4C 8-40-28, I-4D 8-1-I-4D 8-40-28, I-4E 8-1-I-4E 8-40-28, I-4F 8-1-I-4F 8-40-28, I-4G 8-1-I-4G 8-40-28, I-4H 8-1-I-4H 8-40-28I-4I 8-1-I-4I 8-40-28, I-4J 8-1-I-4J 8-40-28, I-4K 8-1-I-4K 8-40-28, I-4L 8-1-I-4L 8-40-28, I-4M 8-1-I-4M 8-40-28, I-4N 8-1-I-4N 8-40-28, I-4O 8-1-I-4O 8-40-28, I-4P 8-1-I-4P 8-40-28, I-4Q 8-1-I-4Q 8-40-28, I-4R8-1-1-I-4R8-40-28, I-4S 8-1-I-4S 8-40-28, I-4T 8-1-I-4T 8-40-28, I-4U 8-1-I-4U 8-40-28, I-4V 8-1-I-4V 8-40-28, I-4W 8-1-I-4W 8-40-28, I-4X 8-1-I-4X 8-40-28;
when R = 2-propargyl group, the substituent of R1 is shown in a table 3, the acid is shown in a table 6, the I-3A represents the compound numbers I-3A 9-1-I-3A 9-40-28, I-3B 9-1-I-3B 9-40-28, I-3C 9-1-I-3C 9-40-28, I-3D 9-1-I-3D 9-40-28, I-3E 9-1-I-3E 9-40-28, I-3F 9-1-I-3F 9-40-28, I-3G 9-1-I-3G 9-40-28I-3H 9-1-1-I-3H 9-40-28, I-3I 9-1-I-3I 9-40-28, I-3J 9-1-I-3J 9-40-28, I-3K 9-1-I-3K 9-40-28, I-3L 9-1-I-3L 9-40-28, I-3M 9-1-I-3M 9-40-28, I-3N 9-1-I-3N 9-40-28, I-3O 9-1-I-3O 9-40-28, I-3P 9-1-I-3P 9-40-28, I-3Q9-1-1-I-3Q9-40-28, I-3R 9-1-I-3R 9-40-28, I-3S 9-1-I-3S 9-40-28, I-3T 9-1-I-3T 9-40-28, I-3U 9-1-I-3U 9-40-28, I-3V 9-1-I-3V 9-40-28, I-3W 9-1-I-3W 9-40-28, I-3X 9-1-I-3X 9-40-28; I-4A represents a compound which is numbered as I-4A9-1-1-I-4A9-40-28, I-4B 9-1-I-4B 9-40-28, I-4C 9-1-I-4C 9-40-28, I-4D 9-1-I-4D 9-40-28, I-4E 9-1-I-4E 9-40-28, I-4F 9-1-I-4F 9-40-28, I-4G 9-1-I-4G 9-40-28, I-4H 9-1-I-4H 9-40-28I-4I 9-1-I-4I 9-40-28, I-4J 9-1-I-4J 9-40-28, I-4K 9-1-I-4K 9-40-28, I-4L 9-1-I-4L 9-40-28, I-4M 9-1-I-4M 9-40-28, I-4N 9-1-I-4N 9-40-28, I-4O 9-1-I-4O 9-40-28, I-4P 9-1-I-4P 9-40-28, I-4Q 9-1-I-4Q 9-40-28, I-4R9-1-1-I-4R9-40-28, I-4S 9-1-I-4S 9-40-28, I-4T 9-1-I-4T 9-40-28, I-4U 9-1-I-4U 9-40-28, I-4V 9-1-I-4V 9-40-28, I-4W 9-1-I-4W 9-40-28, I-4X 9-1-I-4X 9-40-28.
The compounds of the present invention may exist in the form of one or more isomers. Isomers include enantiomers, diastereomers, geometric isomers and cis-trans isomers. The compounds of formula (I) according to the invention, in which the carbon-carbon double bonds are linked to different substituents, may form geometrical isomers (different configurations are denoted by Z and E, respectively), and the invention includes both the Z-and E-isomers and mixtures thereof in any proportion. The compound shown in the formula (I) forms stereoisomers (R and S respectively represent different configurations) due to the fact that four different substituents are connected to one carbon atom of the compound, and the compound comprises an R-type isomer, an S-type isomer and a mixture of the R-type isomer and the S-type isomer in any proportion. The invention relates to a compound shown in formula (I), wherein more than 2 substituents are connected on a cycloalkyl or a heterocycloalkyl to form cis-trans isomers (different configurations are respectively represented by cis and trans), and the invention comprises cis isomers and trans isomers and mixtures of the cis isomers and the trans isomers in any proportion.
<xnotran> , I-1A, I-1B, I-1C, I-1D, I-1E, I-1F, I-1G, I-1H, I-1I, I-1J, I-1K, I-1L, I-1M, I-1N, I-1O, I-1P, I-1Q, I-1R, I-1S, I-1T, I-1U, I-1V, I-1W, I-1X, I-2A, I-2B, I-2C, I-2D, I-2E, I-2F, I-2G, I-2H, I-2I, I-2J, I-2K, I-2L, I-2M, I-2N, I-2O, I-2P, I-2Q, I-2R, I-2S, I-2T, I-2U, I-2V, I-2W I-2X , . </xnotran> The compounds represented by formula I-1A, I-1D, I-1G, I-1J, I-1M, I-1P, I-1S, I-1V, I-2A, I-2D, I-2G, I-2J, I-2M, I-2P, I-2S or I-2V represent mixtures of R-type isomers and S-type isomers in any ratio; the compounds represented by formula I-1B, I-1E, I-1H, I-1K, I-1N, I-1Q, I-1T, I-1W, I-2B, I-2E, I-2H, I-2K, I-2N, I-2Q, I-2T or I-2W represent S-type isomers; the compounds represented by formula I-1C, I-1F, I-1I, I-1L, I-1O, I-1R, I-1U, I-1X, I-2C, I-2F, I-2I, I-2L, I-2O, I-2R, I-2U or I-2X represent R-type isomers.
The invention also relates to a composition for controlling pests and harmful bacteria, comprising a biologically effective amount of a compound of formula (I) and at least one further diluent selected from the group consisting of surfactants, solid diluents and liquid diluents.
The invention also relates to a composition for controlling pests and harmful bacteria, comprising a biologically effective amount of a compound of formula (I) and an effective amount of at least one further biologically active compound or agent.
The invention also relates to a method for controlling pests, harmful bacteria, which comprises contacting a biologically effective amount of a compound of formula (I) with the pests, harmful bacteria or their environment. Also disclosed is a method for controlling pests or harmful bacteria by contacting the pests or harmful bacteria or their environment with a biologically effective amount of a compound of formula (I) or a mixture comprising a compound of formula (I) and a biologically effective amount of at least one additional compound or agent.
The compounds of formula (I) according to the invention have a broad spectrum of activity: some compounds can be used for preventing and controlling harmful germs and pests; and some compounds have high biological activity to some target harmful germs, so that good effect can be obtained under low dosage.
Preferred compositions of the invention are those containing the preferred compounds described above. Preferred methods are those using the preferred compounds described above.
The compounds of the present invention are further illustrated by, but not limited to, the compounds of formula (I) listed in Table 7. The melting points given in the present invention are uncorrected. When the compound of formula (I) of the present invention is a viscous solid, some viscous solids will solidify to form a non-viscous solid after standing; when the compound of formula (I) of the present invention is a viscous liquid, some of the viscous liquid will solidify after standing; the compound of the invention can be observed in LC-MS (APCI) to obtain a molecular ion peak; process for preparing compounds 1 H NMR internal Standard TMS, CDCl 3 As a solvent.
TABLE 7
Figure BDA0002520885880000171
Figure BDA0002520885880000181
Figure BDA0002520885880000191
Figure BDA0002520885880000201
The salts of the compounds of the present invention are illustrated in Table 8, but are not intended to limit the invention.
Table 8 salts of some of the compounds
Figure BDA0002520885880000202
Figure BDA0002520885880000211
The compound of formula (I) of the present invention can be obtained by the reaction formula 1 shown below; the (II) in the reaction formula 1 can be obtained by the reaction formula 2 shown below; (IV) in the reaction formula 2 can be obtained by the reaction formula 3 shown below; (III) in the reaction formula 1, (V) in the reaction formula 2, (VI) and (VIII) in the reaction formula 3 can be synthesized by purchasing or referring to relevant documents; l in the reaction formula 1, the reaction formula 2 and the reaction formula 3 may be the same or different and represents a leaving group of fluorine, chlorine, bromine or iodine, etc., R in the reaction formula 3 2 A salt of the compound represented by the formula (I) may be obtained by the following reaction formula 4; the Acid in the reaction formula 4 is an organic Acid or an inorganic Acid, and other substituents are as defined above unless otherwise specified.
Reaction formula 1:
Figure BDA0002520885880000212
reaction formula 2:
Figure BDA0002520885880000213
reaction formula 3:
Figure BDA0002520885880000214
reaction formula 4:
Figure BDA0002520885880000215
the compounds of formula (I) may be prepared by (scheme 1): reacting a compound of formula (II) with a compound of formula (III) in a suitable solvent such as dichloromethane, dichloroethane, toluene, xylene, N-dimethylformamide, N-methylpyrrolidone, dimethylsulfoxide, pyridine, tetrahydrofuran, methanol, ethanol, isopropanol, acetone, butanone, methyl isobutyl ketone, acetonitrile, ethyl acetate, dioxane, or the like, at a temperature of-10 ℃ to the reflux temperature of the system, in the absence of a base or in the presence of a suitable base, which may be selected from alkali metal hydrides such as sodium hydride, to obtain a compound of formula (I), which reaction can be accelerated when the reaction is carried out in the presence of a base; alkali metal hydroxides such as sodium hydroxide or potassium hydroxide; alkali metal carbonates such as sodium carbonate or potassium carbonate; alkali metal alkoxides such as sodium methoxide or sodium ethoxide; organic amines, such as pyridine, triethylamine or diisopropylethylamine.
The compound of formula (II) may be prepared by (equation 2): reacting a compound of formula (IV) with a compound of formula (V) in a suitable solvent such as dichloromethane, dichloroethane, toluene, xylene, N-dimethylformamide, N-methylpyrrolidone, dimethylsulfoxide, pyridine, tetrahydrofuran, methanol, ethanol, isopropanol, acetone, butanone, methyl isobutyl ketone, acetonitrile, ethyl acetate, dioxane, or the like, at a temperature of-10 ℃ to the reflux temperature of the system, in the absence of a base or in the presence of a suitable base, which may be selected from alkali metal hydrides such as sodium hydride, to obtain a compound of formula (II), which reaction can be accelerated when the reaction is carried out in the presence of a base; alkali metal hydroxides such as sodium hydroxide or potassium hydroxide; alkali metal carbonates such as sodium carbonate or potassium carbonate; alkali metal alkoxides such as sodium methoxide or sodium ethoxide; organic amines, such as pyridine, triethylamine or diisopropylethylamine.
The compound of formula (IV) may be prepared by (reaction formula 3): reacting the compound of formula (VI) with a chlorinating agent such as chlorine or sulfonyl chloride at 0-50 ℃ in a solvent-free or suitable solvent such as ethyl acetate, dichloromethane, trichloromethane, dichloroethane, acetone, butanone or methyl isobutyl ketone, etc. to obtain a compound of formula (VII); reacting a compound of formula (VII) with a compound of formula (VIII) in a suitable solvent such as methanol, ethanol, propanol, isopropanol, dichloromethane, dichloroethane, toluene, xylene, N-dimethylformamide, N-methylpyrrolidone, dimethylsulfoxide, pyridine, tetrahydrofuran, acetone, methyl ethyl ketone or methyl isobutyl ketone, etc., in the presence of a suitable base such as triethylamine, pyridine, sodium methoxide, sodium ethoxide, sodium hydride, potassium hydroxide, potassium carbonate, sodium hydroxide or sodium carbonate, etc., at 5 ℃ to 50 ℃ to obtain a compound of formula (IX); reacting a compound of formula (IX) with a halogenating agent such as phosphorus oxychloride or phosphorus oxybromide in the presence of a suitable base such as triethylamine, pyridine, sodium methoxide, sodium ethoxide, sodium hydride, potassium hydroxide, potassium carbonate, sodium hydroxide or sodium carbonate to give a compound of formula (IV);
salts of compounds of formula (I) may be prepared by (equation 4): reacting the compound of the formula (I) with Acid at the temperature of 0-system reflux temperature in one or two suitable solvents selected from dichloromethane, dichloroethane, trichloromethane, toluene, xylene, acetone, methyl ethyl ketone, methyl isobutyl ketone, N-dimethylformamide, tetrahydrofuran, ethyl acetate, methanol, ethanol, isopropanol, dioxane and the like to obtain the compound salt of the formula (I).
Specific synthetic methods are set forth in more detail in the examples below.
The compound of formula (I) provided by the invention has broad-spectrum bioactivity at the dosage of 7.5-2250 g of active ingredient per hectare, and can be used for preventing and treating harmful germs and harmful insects or mites. Some compounds have good harmful germ prevention and treatment effects, and good effects can be obtained at very low dosage.
The compound of formula (I) provided by the invention has bioactivity, and the compound has good bioactivity, and particularly shows activity in the aspects of preventing and controlling agricultural, horticultural, flower and sanitary pests and harmful bacteria. Pests as used herein include, but are not limited to:
harmful pathogenic bacteria: phytophthora species, erysiphe species, gibberella species, venturia species, sclerotinia species, rhizoctonia species, botrytis species, pyricularia species, fusarium species. Such as rice blast (Pyricularia oryzae); stripe rust (Puccinia striiformis), leaf rust (Puccinia recondita); barley and wheat powdery mildew (Erysiphe graminis), cucumber powdery mildew (spoharoteca to ligenea), apple powdery mildew (podosphaea leucotricha) and grape powdery mildew (podosphaea leucotricha); sheath and glume blight of wheat (Septoria nodorum). Helminthosporium, mortierella, sclerotiella herpotrichoides, pseudocercospora herpotrichoides, and wheat take-all (Gaeumunnomyces graminis) on cereals. Cercospora arachidicola (Cercospora arachidicola) and Cercospora black spot (Cercospora personata); apple ring rot pathogen (Botryosphaeria berenggiana f.sp. Piricola), apple rot pathogen (cytopora sp.); urospora disease on beet, soybean and rice. Tomato, cucumber, grape gray mold (Botrytis cinerea). Diseases of the genus Geobacillus on vegetables such as cucumber. Anthracnose in cucumber, apple scab, cucumber downy mildew, grape downy mildew, blight in potato and tomato, the monad Thanatephorus cupmeris on rice and other rhizoctonia species on other hosts such as wheat and barley, vegetables; sclerotinia sclerotiorum (sclerotiorum); wheat scab (Gibberella zeae); phytophthora capsici (Phytophythora capsicii).
Harmful insects: lepidopteran pests such as oriental armyworm, prodenia litura, diamondback moth, beet armyworm, cabbage caterpillar, orthopteran such as cockroach, thysanoptera such as cotton thrips, rice thrips, melon thrips, homopteran such as leafhopper, plant hopper, aphid, hymenopteran such as leaf bee larva, dipteran such as aedes, culex, fly; acarina pest mites such as Panonychus citri, tetranychus gossypii, tetranychus urticae, etc.
The compounds of formula (I) of the present invention are effective for controlling pests, harmful bacteria, alone, and they can also be used together with other biochemical substances such as insecticides, nematocides, acaricides and bactericides.
Agricultural formulations containing the compound of formula (I) as an active ingredient provided by the present invention may be formulated into any desired dosage form, such as dry compressed granules, flowable compositions, granules, wettable powders, water dispersible granules, emulsifiable concentrates, powders, powder concentrates, microemulsions, suspensions, emulsifiable concentrates, aqueous emulsions, soluble liquids, aqueous solutions, dispersible liquids, suitable adjuvants including carrier diluents and other adjuvants such as spreaders, emulsifiers, wetting agents, dispersants, stickers and disintegrants. These formulations comprise the compounds of the present invention in admixture with an inert, pharmacologically acceptable solid or liquid diluent.
Examples of the compositions of the present invention may also be formulated into any desired dosage form such as dry compressed granules, flowable compositions, granules, wettable powders, water dispersible granules, emulsifiable concentrates, dusts, powdered concentrates, microemulsions, suspensions, emulsifiable concentrates, emulsions in water, soluble liquids, mists, dispersible liquids, suitable adjuvants including carrier diluents) and other adjuvants such as spreaders, emulsifiers, wetting agents, dispersants, stickers and disintegrants. These formulations comprise the compounds of the present invention in admixture with an inert, pharmacologically acceptable solid or liquid diluent.
The present invention will be further described with reference to the following examples, but the present invention is not limited thereto.
Synthetic examples
EXAMPLE 1 this example illustrates the preparation of Compound I-1B2-1
Figure BDA0002520885880000231
Adding sulfonyl chloride (0.33 mol) dropwise into a solution of propionylacetic acid ethyl ester (0.30 mol) and dichloromethane (50 mL) at the temperature of-5 ℃ under the condition of stirring, and naturally heating to room temperature after the addition of sulfonyl chloride is finished to react completely. The reaction solution was poured into ice water, the organic layer was separated, the aqueous layer was extracted with dichloromethane, the organic phases were combined and dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give the title product as a pale yellow liquid which was used directly in the next reaction.
5-chloro-6-ethyl pyrimidine-4-alcohol is added with 30 percent methanol solution of sodium methoxide (0.63 mol) dropwise into solution of formamidine acetate (0.33 mol) and methanol (50 mL) at the temperature of 5-10 ℃ under the stirring condition, after the dropwise addition is finished, the solution is continuously stirred for 2-3h, the obtained ethyl 2-chloro-3-oxopentanoate is added dropwise, and the mixture is naturally heated to room temperature to react completely. After removing methanol, ethyl acetate was added, insoluble matter was filtered off, and the filtrate was concentrated to give the title compound as a yellow solid 23.61g and used directly in the next reaction.
4, 5-dichloro-6-ethyl pyrimidine is added into phosphorus oxychloride (0.35 mol) in batches under the condition of stirring at 0-5 ℃, and triethylamine (0.17 mol) is added dropwise after the 5-chloro-6-ethyl pyrimidine-4-alcohol (0.15 mol) is completely dissolved. Naturally heating to room temperature, reacting for 6-10h until the reaction is complete, removing most of phosphorus oxychloride from the reactant, pouring into ice water, and adjusting the pH to be 7-8 by using potassium carbonate. After extraction with dichloromethane and drying of the organic layer over anhydrous sodium sulfate, the solvent was removed under reduced pressure to give 16.56g of the title compound.
(S) -2- ((5-chloro-6-ethylpyrimidin-4-yl) amino) propanol to a solution of 4, 5-dichloro-6-ethylpyrimidin (20 mmol) and potassium carbonate (30 mmol) in tetrahydrofuran (15 mL) was added dropwise (S) -2-aminopropanol (24 mmol) at room temperature with stirring, and after stirring for 15-30min, the temperature was raised to 60-90 ℃ to complete the reaction. The reaction mixture was cooled, poured into ice water, extracted with dichloromethane, and the organic layer was dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure to obtain the titled compound (3.12 g).
Adding sodium hydride (6 mmol) in batches to a solution of (S) -2- ((5-chloro-6-ethylpyrimidin-4-yl) amino) propanol (5 mmol) in N, N-dimethylformamide (10 mL) at 0-5 ℃ under stirring conditions, stirring for 15-30min, adding 2, 3-dichloropyridine (5 mmol) in batches, and naturally heating to room temperature to react for 8-16h until the reaction is complete. The reaction product was poured into ice water, extracted with dichloromethane, and the organic layer was dried over anhydrous sodium sulfate, and the solvent was removed to give a crude product, which was subjected to column chromatography with ethyl acetate and petroleum ether to give the titled compound 0.96g.
EXAMPLE 2 this example illustrates the preparation of Compound I-2D3-1
Figure BDA0002520885880000241
2-chloro-3-oxo-4, 4-difluorobutyric acid ethyl ester is added with sulfonyl chloride (0.33 mol) dropwise into a solution of difluoroacetoacetic acid ethyl ester (0.30 mol) and dichloromethane (50 mL) at the temperature of-5 ℃ under stirring, and after the addition, the mixture is naturally heated to room temperature for reaction till the reaction is complete. The reaction solution was poured into ice water, the organic layer was separated, the aqueous layer was extracted with dichloromethane, the organic phases were combined and dried over anhydrous sodium sulfate, and concentrated to give the title compound, which was used in the next reaction.
5-chloro-2-methyl-6-difluoromethylpyrimidin-4-ol is added into a solution of acetamidine hydrochloride (0.33 mol) and methanol (50 mL) with 30% methanol solution of sodium methoxide (0.63 mol) dropwise at the temperature of 5-10 ℃ and under the stirring condition, the mixture is continuously stirred for 2-3h after the dropwise addition, the ethyl 2-chloro-3-oxo-4, 4-difluorobutyrate obtained in the previous step is added dropwise, and the mixture is naturally heated to room temperature for reaction till the reaction is complete. After removing methanol, ethyl acetate was added, insoluble matter was filtered off, and the filtrate was concentrated to give 32.90g of the title product as a yellow solid, which was used directly in the next reaction.
4, 5-dichloro-2-methyl-6-difluoromethylpyrimidine at 0-5 ℃ under stirring, adding 5-chloro-2-methyl-6-difluoromethylpyrimidin-4-ol (0.15 mol) in batches to phosphorus oxychloride (0.35 mol), and after complete dissolution, dropwise adding triethylamine (0.17 mol). And naturally heating to room temperature, reacting for 6-10h until the reaction is complete, removing most of phosphorus oxychloride from the reactant, pouring into ice water, and adjusting the pH value to be 7-8 by using potassium carbonate. After extraction with dichloromethane and drying of the organic layer over anhydrous sodium sulfate, the solvent was removed under reduced pressure to give the title compound (20.66 g).
(RS) -2- ((5-chloro-2-methyl-6-difluoromethylpyrimidin-4-yl) amino) propanol to a solution of 4, 5-dichloro-2-methyl-6-difluoromethylpyrimidine (20 mmol) and potassium carbonate (30 mmol) in tetrahydrofuran (15 mL) at room temperature with stirring was added dropwise (RS) 2-aminopropanol (24 mmol) and the mixture was stirred for 15-30min and then warmed to 60-90 ℃ for completion of the reaction. The reaction mixture was cooled, poured into ice water, extracted with dichloromethane, and the organic layer was dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure to obtain 2.96g of the titled compound.
(RS) -N- (1- ((5-trifluoromethylpyridin-2-yl) oxy) propan-2-yl) -5-chloro-2-methyl-6-difluoromethylpyrimidin-4-amine to a solution of (RS) -2- ((5-chloro-2-methyl-6-difluoromethylpyrimidin-4-yl) amino) propanol (5 mmol) in N, N-dimethylformamide (10 mL) at 0-5 ℃ with stirring was added sodium hydride (6 mmol) in portions, after stirring for 15-30min, 2-chloro-5-trifluoromethylpyridine (5 mmol) was added in portions, and the reaction was allowed to warm to room temperature naturally for 8-16h to completion. The reaction product was poured into ice water, extracted with dichloromethane, and the organic layer was dried over anhydrous sodium sulfate, and the solvent was removed to give a crude product, which was subjected to column chromatography with ethyl acetate and petroleum ether to give the titled compound 0.95g.
EXAMPLE 3 this example illustrates the preparation of hydrochloride salt I-4D3-1-1 of Compound I-2D3-1
Figure BDA0002520885880000251
Hydrochloride of (RS) -N- (1- ((5-trifluoromethylpyridin-2-yl) oxy) propan-2-yl) -5-chloro-2-methyl-6-difluoromethylpyrimidin-4-amine to a solution of (RS) -N- (1- ((5-trifluoromethylpyridin-2-yl) oxy) propan-2-yl) -5-chloro-2-methyl-6-difluoromethylpyrimidin-4-amine (2 mmol) in ethyl acetate (10 mL) was added hydrogen chloride (20 mmol) with stirring at 15-25 deg.C, stirring was continued until complete reaction, excess hydrogen chloride and solvent were removed under reduced pressure, and the solvent was washed for further purification to afford the title.
The yields in the examples were not optimized, and other compounds of the present invention were synthesized by referring to examples 1 to 3, and if necessary, related references.
Formulation examples
Example 4 preparation of 10% tall oil
Weighing a proper amount (10 percent by weight) of the compound of the formula (I) provided by the invention, such as the compound 19154 in the table 1, a proper amount of cosolvent (such as ethyl acetate or acetone), a proper amount of pesticide auxiliary agent, a solvent (such as toluene) and the like, putting the mixture into a reaction kettle, firstly adding a certain amount of solvent (such as toluene) and defoamer, stirring for 10-30 min, then adding a proper amount of stabilizer, synergist, penetrant and the like, continuously stirring for 10-30 min, adjusting the pH value, then putting an effective amount of solvent into the kettle, uniformly stirring, and then discharging to obtain the 10 percent emulsifiable solution of the compound I-2D 3-1.
EXAMPLE 5 preparation of 20% wettable powder
Weighing a proper amount (20 percent by weight) of the compound of the formula (I) provided by the invention, such as the compound 19154 in the table 1, sodium dodecyl sulfate (2 percent by weight), sodium lignin sulfonate (10 percent by weight) and kaolin which is complemented to 100 percent, mixing together, and crushing in a crusher until the granules reach the standard.
Examples of bioassay
The compound of the invention is subjected to biological activity screening tests such as sterilization, disinsection/acarid killing and the like, and partial test results are as follows.
EXAMPLE 6 insecticidal Activity against aphids (Aphisfabae)
The dipping method comprises the following steps: the test compound is dissolved in a suitable solvent such as acetone or N, N-dimethylformamide, diluted to the desired concentration with clear water containing 0.2% Tween80 emulsifier, and the blank containing no test compound is set as a control and the treatment is repeated 3 times. The broad bean aphids are inoculated on the just-emerged bean seedlings, each plant is inoculated with more than 20 heads, then the bean seedlings and the test insects are immersed in the compound liquid medicine of the formula (I) of the invention, the bean seedlings are taken out after 5 seconds, the redundant liquid medicine is absorbed, the bean seedlings are inserted into absorbent sponge and covered by a glass tube, the number of the living and dead insects is checked after 24 hours, and the average value is taken. Active mortality) is divided into A, B, C and D grades in percentage relative to a blank control, wherein 100% or more of mortality is more than or equal to 90% of A grade, 90% or more of mortality is more than or equal to 70% of B grade, 70% or more of mortality is more than or equal to 50% of C grade, and 50% or more of mortality is more than or equal to 0 of D grade. Some of the results are listed below:
under the concentration of 500mg/L, compounds I-1B1-1, I-1B2-1, I-1B3-1, I-1D1-1, I-1D3-1, I-1D5-1, I-1E1-1, I-1E2-1, I-1E3-2, I-1G3-1, I-1H1-1, I-1H2-1, I-1H3-2, I-1J1-1, I-1J5-1, I-1K1-1, I-1K2-2, I-1K3-1, I-1K3-2, I-1M3-1, I-1N1-1, I-1N 2-1I-1N 3-1, I-1P3-1, I-1Q2-1, I-1Q3-2, I-1W2-1, I-2B1-1, I-2B3-1, I-2D1-1, I-2D3-1, I-2E1-1, I-2E2-1, I-2E3-2, I-2H1-1, I-2H2-1, I-2H3-1, I-2J1-1, I-2J3-1, I-2K1-1, I-2K2-2, I-2K3-1, I-2K3-2, I-2N1-1, I-2N2-1, I-2N3-1, I-2Q3-2, I-2W2-1 and the like have A-level activity on aphids; under the same condition, the activities of D2 and D4 on aphids are A grade, D6 is B grade, and D7 is C grade;
the compounds I-1B3-1, I-1H2-1, I-1H3-1, I-1K1-1, I-1K2-1, I-1K3-1, I-1Q2-1, I-2E3-1, I-2H2-1, I-2H3-1, I-2K1-1, I-2K2-1, I-2K3-1 and I-2Q3-2 and the like have class A activity on aphids, and the compounds I-2E1-1, I-1E2-1, I-2H1-1, I-1H3-2, I-1J1-1, I-1N2-1 and I-1Q3-2 and the like have class B activity at a concentration of 50 mg/L;
at a concentration of 12.5mg/L, the compounds I-1E3-1, I-1H2-1, I-1K3-1, I-2H2-1, I-2H3-1, I-2J3-1 and I-2K2-1 have A-level activity on aphids, and the compounds I-1D3-1, I-1G3-1, I-1H3-2, I-1K3-2, I-2K3-1 and I-2K3-2 have B-level activity on aphids;
I-1K2-1 and the like are selected for deep screening, and the results show that the compound I-2K3-1 and the like have LC effect on aphids 50 LC of I-2H3-1 and the like on aphids with values lower than 1.50 mg/L 50 LC with value of 1.50-2.00mg/L, I-1K3-1, I-2J3-1 and I-2K3-2 for aphid 50 LC of 2.00-2.50mg/L for aphids, such as I-1E3-1, I-1G3-1, I-1H2-1, I-1K2-1, I-1P3-1, I-2E3-2 and I-2K2-1 50 LC of 2.50-5.00mg/L, I-1D3-1 and I-1K3-2, etc. for aphid 50 LC of 5.00-8.00mg/L for aphids, such as I-1H3-1, I-1H3-2, I-2E3-1 and I-2Q3-2 50 Values higher than 8.00mg/L. LC of D2 against aphids under the same conditions 50 LC of D4 to aphid with value higher than 2.00mg/L 50 Values higher than 8.00mg/L.
Example 7 evaluation of acaricidal Activity on Tetranychus urticae (Tetranychus urticae)
The method comprises the following steps: dissolving the compound in a suitable solvent such as N, N-dimethylformamide, diluting with water containing 0.2% Tween80 emulsifier to desired concentration, setting blank containing no test compound as blank control, and repeating the treatment for 3 times; selecting bean seedlings with good growth vigor to inoculate red spiders, cutting the bean seedlings with mites after the red spiders colonize, soaking the bean seedlings in the prepared liquid medicine of the compound shown in the formula (I) for 10 seconds, taking out the bean seedlings, absorbing the redundant liquid medicine by using filter paper, inserting the bean seedlings into a water-containing beaker, culturing the bean seedlings in an observation room, and checking the number of the alive and dead mites after 48 hours, wherein each bean seedling has 100-200 mites. The results were averaged. The activity was graded as in example 6. Some of the results are listed below:
<xnotran> 500mg/L , I-1B1-1, I-1B2-1, I-1B3-1, I-1D1-1, I-1D3-1, I-1E1-1, I-1E3-1, I-1E3-2, I-1G3-1, I-1H2-1, I-1H3-1, I-1H3-2, I-1J1-1, I-1J5-1, I-1K1-1, 1-1K2-1, I-1K2-2, I-1K3-1, I-1K3-2, I-1M3-1, I-1N1-1, I-1N2-1, I-1N3-1, I-1P3-1, I-1Q2-1, I-1Q3-2, I-2D3-1, I-2E1-1, I-2E2-1, I-2E3-1, I-2E3-2, I-2H1-1, I-2H2-1, I-2H3-1, I-2J1-1, I-2K1-1, I-2K2-1, I-2K3-1, I-2K3-2, I-2N1-1, I-2N2-1 I-2N3-1 A , I-1E2-1, I-1W2-1, I-2D1-1, I-2Q3-2 I-2W2-1 B ; </xnotran> Under the same condition, the activity of D2 and D4 to red spider is A grade, D6 is B grade, and D7 is C grade;
at a concentration of 50mg/L, the compounds I-1B3-1, I-1H2-1, I-1K2-1, I-1N3-1, I-1Q2-1, I-1Q3-2 and I-2K3-1, etc. have class A activity against red spider, the compounds I-1H3-1, I-2H1-1, I-2H2-1, I-2K1-1 and I-2K2-1, etc. have class B activity, the compounds I-1B1-1, I-1H3-2, I-1K1-1, I-2E3-1 and I-2N1-1, etc. have class C activity; under the same condition, the activity of D2 on red spider is B grade;
at a concentration of 12.5mg/L, the compounds I-1K2-1 and the like have B-grade activity on red spider, and I-1B1-1, I-1H2-1 and the like have C-grade activity; under the same conditions, the activity of D2 and D4 on red spider is grade D.
Example 8 evaluation of biological Activity of armyworm (Mythimna separata)
A Potter spraying method: the test compound is dissolved in a suitable solvent such as N, N-dimethylformamide and diluted to the desired concentration with clear water containing 0.2% Tween80 emulsifier, and the blank containing no test compound is set as a control. Fresh and tender corn leaves are cut into segments with basically consistent sizes and placed into a culture dish (phi 90 mm) which is previously padded with filter paper. Then 10 heads of mythimna separata larvae of 3 years old are inoculated into the dish, the dish is put under a Potter spray tower for quantitative spraying, the amount of the spraying liquid is 1ml, and the spraying is repeated for 3 times per concentration. And after the treatment is finished, covering the dish cover, placing the dish cover in a recovery room for culture, regularly observing, checking and recording the death condition of the test insects after 72 hours, calculating the death rate, and averaging the results. The activity was graded as in example 6. Some of the results are as follows:
at a concentration of 500mg/L, the compounds I-1D3-1, I-1E3-1, I-1G3-1, I-1H2-1, I-1K3-2, I-1P3-1, I-2D1-1, I-2H3-1 and I-2K2-1 have class A activity against armyworms, and I-1B2-1, I-1E1-1, I-1K1-1, I-2B3-1, I-2H1-1, I-2J1-1, I-2K3-1 and I-2Q3-2 have class B activity; under the same conditions, D4 has A-grade activity on armyworms, and D2, D6 and D7 have no activity on armyworms.
Under the concentration of 200mg/L, the compounds I-1G3-1, I-1H2-1 and the like have A-level activity on armyworms, and I-2K2-1 and the like have B-level activity; under the same conditions, the activity of D4 on armyworm is B grade.
Example 9 fungicidal Activity against wheat powdery mildew (Erisiphe grimmins)
Pot culture method: dissolving the test compound in a suitable solvent such as N, N-dimethylformamide, and diluting with sterile water containing 0.2% Tween80 emulsifier to the desired concentration; taking pots with straight stems of about 15cm, sowing 20 plump and robust seeds of wheat in each pot, and allowing the seeds to grow into two leaves and one core for testing; spraying the prepared wheat seedling plant with a medicament with a certain concentration, and inoculating germs after one day. Repeating the treatment for 3 times, and additionally setting a blank without the compound to be detected as a blank contrast and a commercial fungicide flusilazole as a commercial contrast; and (5) after the culture is carried out in a moisture-preserving and proper-temperature way until blank control is carried out, checking the area of the lesion spots and calculating the control effect of the medicament. The activity is divided into four grades A, B, C and D relative to a blank control in percentage, wherein 100% or more of control effect is grade A, 90% or more of control effect is grade B, 70% or more of control effect is grade C, and 50% or more of control effect is grade D, wherein the control effect is grade D. Some of the results are as follows:
<xnotran> 500mg/L , I-1B1-1, I-1B2-1, I-1B3-1, I-1D3-1, I-1E1-1, I-1E2-1, I-1E3-1, I-1E3-2, I-1G3-1, I-1H1-1, I-1H3-1, I-1H3-2, I-1J1-1, I-1J5-1, I-1K1-1, I-1N1-1I-1K2-1, I-1K3-1, I-1K3-2, I-1K2-2, I-1M3-1, I-1N2-1, I-1N3-1, I-1P3-1, I-1Q3-2, I-2B1-1, I-2B2-1, I-2B3-1, I-2D1-1, I-2D3-1, I-2E1-1, I-2E2-1, I-2E3-1, I-2E3-2, I-2H1-1, I-2H2-1, I-2H3-1, I-2J3-1, I-2K1-1, I-2K2-1, I-2K2-2, I-2K3-1, I-2K3-2, I-2N1-1, I-2N2-1, I-2N3-1 I-1Q2-1 A , I-1D1-1, I-1H2-1, </xnotran> I-2D5-1, I-2J1-1, I-2M5-1, I-2Q3-2 and the like have B-level activity; under the same conditions, the activity of D2 on wheat powdery mildew is grade C, the activities of D4, D6 and flusilazole are grade A, and the activity of D7 on wheat powdery mildew is less than grade A.
<xnotran> 100mg/L , I-1B1-1, I-1B3-1, I-1D3-1, I-1E1-1, I-1E2-1, I-1E3-1, I-1H1-1, I-1H3-1, I-1J1-1, I-1K1-1, I-1K3-1, I-1K3-2, I-1N2-1, I-1N3-1, I-1Q3-2, I-2B2-1, I-2B3-1, I-2D1-1, I-2D3-1, I-2E1-1, I-2E3-1, I-2E3-2, I-2H3-1, I-1H3-2, I-2J3-1, I-2K1-1, I-2K2-1, I-2K3-1, I-2K3-2, I-2N1-1 I-2N2-1 A , I-1D1-1, I-1E3-2, I-1G3-1, I-1H2-1, I-1K2-1, I-1N1-1, I-1P3-1, I-2B1-1, I-2H1-1, I-2N3-1 I-2Q3-2 B , , D4 D , D6 A . </xnotran>
Under the concentration of 50mg/L, compounds I-1E2-1, I-1E3-1, I-1H1-1, I-1H3-2, I-1J1-1, I-1K3-2, I-1N 3-1I-1Q 3-2, I-2B2-1, I-2E3-2, I-2H3-1, I-2K2-1, I-2K3-2 and I-2N1-1, etc. have class A activity on wheat powdery mildew, I-1B1-1, I-1B3-1, I-1D1-1, I-1D3-1, I-1E1-1, I-1G3-1, I-1K2-1, I-1N1-1, I-1N2-1, I-1P3-1, I-2B1-1, I-2B3-1, I-2D1-1, I-2D3-1, I-2E1-1, I-2H1-1, I-2J3-1, I-2K1-1, I-2N2-1, I-2N3-1, I-2Q3-2 and the like have class B activity.
I-1K2-1 and the like are selected for deep screening, and the results show that the ED of the compounds I-1E3-1, I-1H3-1 and the like on wheat powdery mildew 50 All values are lower than 1.00mg/L, and ED (effective dose) of I-1B3-1, I-1E2-1, I-1K2-2, I-1K3-1, I-1K3-2, I-2H1-1, I-2K2-1, I-2N1-1, I-2N3-1 and the like on wheat powdery mildew is 50 The value is 1.00-2.00mg/L, and ED for wheat powdery mildew such as I-1D3-1, I-1G3-1, I-1H1-1, I-1K2-1, I-1N1-1, I-1N2-1, I-1N3-1, I-1P3-1, I-1Q3-2, I-2B1-1, I-2B3-1, I-2E1-1, I-2E3-2, I-2H2-1, I-2H3-1, I-1H3-2, I-1J1-1, I-2K2-2, I-2K3-1, I-2K3-2 and I-2Q3-2 50 The value is 2.00-5.00mg/L, ED of I-1B1-1, I-1D1-1, I-1E1-1, I-1H2-1, I-2B2-1, I-2N2-1 and the like on wheat powdery mildew 50 Values higher than 5.00mg/L; ED of D6 and Flusilazole against wheat powdery mildew under the same conditions 50 The value was less than 2.00mg/L.
Example 10 fungicidal Activity against corn rust Puccinia Polysora)
Pot culture method: dissolving the compound in a suitable solvent such as N, N-dimethylformamide, diluting with sterile water containing 0.2% of Tween80 emulsifier to desired concentration, and setting blank containing no compound to be tested as blank control and commercial bactericide tebuconazole as commercial control; repeat 4 times per treatment; cutting diseased corn leaf, washing spore with 0.05% Tween80 or other suitable surfactant aqueous solution, filtering with 2-4 layers of gauze to obtain a filtrate with a concentration of 1 × 10 5 spores/mL of suspension; spraying the liquid medicine of the compound to be detected when the corn grows to 2 leaves and 1 heart stage, spraying and inoculating the spore suspension after 1 day, transferring the inoculated corn to a moisturizing cabinet at the relative humidity of more than 95 percent and the temperature of 20-22 ℃, and culturing for 15-24 hours under the low-light condition and the illumination intensity of 5000-10000 Lux); and (5) when the blank control disease leaf rate reaches more than 50%, investigating the disease occurrence condition of each treatment, and calculating the control effect. The activity was graded as in example 9. The following are partial results:
<xnotran> 500mg/L , I-1B1-1, I-1B3-1, I-1D3-1, I-1E1-1, I-1E2-1, I-1E3-1, I-1E3-2, I-1H2-1, I-1H3-1, I-1H3-2, I-1J1-1, I-1K1-1, I-1K2-1, I-1K2-2, I-1K3-1, I-1K3-2, I-1N2-1, I-1N3-1, I-1Q2-1, I-1Q3-2, I-1W2-1, I-2B1-1, I-2B2-1, I-2B3-1, I-2D3-1, I-2E2-1, I-2E3-1, I-2E3-2, I-2H2-1, I-2H3-1, I-2J1-1, I-2J3-1, I-2K1-1, I-2K2-1, I-2K3-1, I-2K3-2, I-2N1-1, I-2N2-1, I-2N3-1 I-2Q3-2 A , I-1B2-1, I-lD1-1, I-1G3-1, I-1P3-1, I-2D1-1, I-2D5-1, I-2E1-1, I-2H1-1, I-2J5-1, </xnotran> I-2K2-2, I-2M5-1 and the like have B-level activity; under the same conditions, the activity of D2 on the corn rust is grade C, the activity of D4 and tebuconazole is grade A, the activity of D6 is grade B, and the activity of D7 is grade D.
The compounds I-1B1-1, I-1B3-1, I-1E2-1, I-1E3-2, I-1H2-1, I-1H3-2, I-1K3-1, I-1K3-2, I-1N2-1, I-1N3-1, I-1Q3-2, I-2B2-1, I-2B3-1, I-2E3-2, I-2H2-1, I-2H3-1, I-2K3-1, I-2N1-1, I-2N2-1, I-2N3-1 and I-2Q3-2 have class A activity on corn rust at a concentration of 100mg/L, I-1B2-1, I-1D3-1, I-1E1-1, I-1G3-1, I-1J1-1, I-1K2-1, I-1P3-1, I-1W2-1, I-2H1-1, I-2J3-1, I-2K2-1 and I-2K3-2, etc. have class B activity; under the same condition, the activity of D4 to the corn rust is grade C, and D6 is grade B;
the compounds I-1B1-1, I-1B3-1, I-1E1-1, I-1E2-1, I-1E3-2, I-1H3-1, I-1K1-1, I-1K2-1, I-1K3-1, I-2E3-2, I-1K3-2, I-2Q3-2, I-2N1-1, I-2B2-1, I-2E3-1, I-2K3-1, I-2N3-1, and I-2B3-1, etc. have class A activity on corn rust at a concentration of 50mg/L, I-1B2-1, I-1E1-1, I-1G3-1, I-1H2-1, I-1H3-2, I-1J1-1, I-1K1-1, I-1N2-1, I-1P3-1, I-1Q3-2, I-2H2-1, I-2H3-1, I-2J3-1, I-2N2-1 and I-1N3-1, etc. have B-level activity; under the same conditions, the activity of D4 on the corn rust is grade D, and D6 is grade B.
I-1K2-1 and the like are selected for deep screening, and the results show that the ED of the compounds I-1B3-1, I-2B3-1 and the like on corn rust disease 50 The value is less than 0.50mg/L, and ED of I-1B1-1, I-2B2-1, I-2E3-1 and the like on corn rust disease 50 The ED for corn rust such as I-1E2-1, I-1E3-1, I-1H3-1, I-1N2-1, I-2H3-1, I-2J3-1 and I-2N1-1 with a value of 0.50-1.00mg/L 50 The value is 1.00-2.00mg/L, the ED for corn rust disease such as I-1B2-1, I-1G3-1, I-1H1-1, I-1H2-1, I-1H3-2, I-1J1-1, I-1K3-1, I-1N1-1, I-1N3-1, I-1P3-1, I-1Q3-2, I-2B3-1, I-2E3-2, I-2H3-1, I-2K3-2, I-2N2-1 and I-2Q3-2 50 The value is 2.00-5.00mg/L, ED of I-1B1-1, I-1E3-2, I-1K1-1, I-1K2-2, I-1K3-2, I-1W2-1, I-2H2-1, I-2K2-1 and I-2Q3-2 for corn rust 50 Values higher than 5.00mg/L; ED of D6 and tebuconazole against corn rust under the same conditions 50 The value is 1.50-2.00mg/L.
Example 10 fungicidal Activity against Rice sheath blight disease (Rhizoctonia solani))
Pot culture method: dissolving the test compound in a suitable solvent such as N, N-dimethylformamide, diluting with sterile water containing 0.1% Tween80 emulsifier to desired concentration, and repeating the treatment for 4 times while setting blank containing no test compound as control; transferring the rhizoctonia solani to a PDA (PDA) plate for activation culture, transferring to a PD (PD) culture medium, and culturing in a constant-temperature water bath for 4 days. Crushing the cultured mycelium pellets by a homogenizer and blending the crushed mycelium pellets into bacterial suspension with a certain concentration by using clear water. The cucumber was used for the experiment when it had grown to flatten two cotyledons. Spraying the liquid medicine, spraying the bacterial suspension to the surface of the seedling after 24 hours, and performing moisturizing culture. And observing the disease condition of the seedlings, and when the disease condition of the control treatment is obvious, beginning to investigate the disease condition of each treatment and calculating the medicament control effect. The activity was graded as in example 9. The results show that the compound of the invention has activity on the rice sheath blight disease, for example, under the concentration of 500mg/L, the compound I-1B2-1 and the like have B-level control effect on the rice sheath blight disease; under the same condition, D4, D6 and D7 have D-grade control effect on rice sheath blight disease.
Example 12 fungicidal Activity against Gibberella zeae) of Gibberella tritici
The method comprises the following steps: dissolving the test compound in a suitable solvent such as N, N-dimethylformamide, diluting with sterile water containing 0.2% Tween80 emulsifier to the desired concentration, and repeating the treatment for 4 times, with blank containing no test compound as control; 3mL of the liquid medicine is taken by a pipette and added into 27mL of potato agar culture medium PDA) which is cooled to 45 ℃, and the liquid medicine is poured into a culture dish after being fully shaken up; after cooling, taking a hypha block with the diameter of 6mm from the edge of a germ colony cultured for 7 days by using an inoculating needle, and transferring the hypha block to the center of a culture dish, wherein the hypha surface faces downwards; after the treatment, the culture dish is placed in a constant-temperature biochemical incubator at 28 ℃ for culture, the growth diameter of hyphae is measured after 4 days, EXCEL statistical software is adopted for analysis and the hypha growth inhibition rate is calculated, the activity is divided into four grades A, B, C and D in percentage relative to a blank control, the A grade is that the inhibition rate is greater than or equal to 90% in 100%, the B grade is that the inhibition rate is greater than or equal to 70%, the C grade is that the inhibition rate is greater than or equal to 70%, and the D grade is that the inhibition rate is greater than or equal to 0% in 50%.
The bactericidal activity of the compound on phytophthora capsici (phytophthora capsaici), alternaria alternata (Alternaria alternata), botrytis cinerea (Botrytis cinerea) and sclerotinia sclerotiorum (sclerotiorum) is respectively measured by adopting a method for measuring the bactericidal activity of the fusarium graminearum. The following are partial results:
at a concentration of 25mg/L, the compounds I-1E1-1, I-1E2-1, I-1H1-1, I-1K2-1, I-1N1-1, I-1N3-1, I-1Q2-1, I-1W2-1, I-2B3-1, I-2E2-1, I-2E3-1, I-2H2-1, I-2J3-1, I-2K1-1 and I-2N1-1, etc. have C-grade activity on Gibberella cerealis; under the same conditions, D2, D4, D6 and D7 had class D activity against Fusarium graminearum.
At the concentration of 25mg/L, the compounds I-1E3-2, I-1H1-1, I-1K3-2, I-1N1-1, I-1N3-1, I-1Q2-1, I-2D1-1, I-2E2-1, I-2E3-2, I-2H2-1, I-2J1-1, I-2K2-1, I-2K3-2 and the like have C-level activity on phytophthora capsici; under the same condition, D2 and D4 have C-grade activity to phytophthora capsici and D6 and D7 have D-grade activity.
At a concentration of 25mg/L, the compound I-2J1-1 and the like have B-level activity on alternaria alternata, and the compound I-1B2-1, I-1H1-1, I-1K2-2, I-1M3-1, I-1N1-1, I-1N3-1, I-1Q2-1, I-2E3-2, I-2H2-1, I-2H3-1, I-2K2-1, I-2N1-1, I-2N2-1 and the like have C-level activity on alternaria alternata; under the same conditions, D2, D4, D6 and D7 have D-grade activity on alternaria alternata.
At the concentration of 25mg/L, the compound I-2J1-1 and the like have B-level activity on cucumber botrytis cinerea, and the compound I-1K2-1, I-1M3-1, I-1N3-1, I-1W2-1, I-2E2-1, I-2H3-1, I-2K2-1 and the like have C-level activity on cucumber botrytis cinerea; under the same conditions, D4 has C-level activity on cucumber botrytis cinerea, and D2, D6 and D7 have D-level activity.
Under the concentration of 25mg/L, the compound I-2J1-1 and the like have B-grade activity on Sclerotinia sclerotiorum, and the compound I-1K2-1, I-1M3-1, I-1N3-1, I-1W2-1, I-2E2-1, I-2H3-1, I-2K2-1 and the like have C-grade activity on Sclerotinia sclerotiorum; under the same conditions, the activity of D4 on Sclerotinia sclerotiorum is grade C, and the activities of D2, D6 and D7 are grade D.

Claims (5)

1. Pyridine ether compounds containing pyrimidine amine with biological activity:
Figure FDA0003806053250000011
characterized in that the compound of formula (I) is:
(S) -N- (1- ((3-chloropyridin-2-yl) oxy) propan-2-yl) -5-chloro-6-methylpyrimidin-4-amine;
(S) -N- (1- ((3-chloropyridin-2-yl) oxy) propan-2-yl) -5-chloro-6-ethylpyrimidin-4-amine;
(S) -N- (1- ((3-chloropyridin-2-yl) oxy) propan-2-yl) -5-chloro-6-difluoromethylpyrimidin-4-amine;
(S) -N- (1- ((5-trifluoromethylpyridin-2-yl) oxy) propan-2-yl) -5-chloro-6-methylpyrimidin-4-amine;
(S) -N- (1- ((5-trifluoromethylpyridin-2-yl) oxy) propan-2-yl) -5-chloro-6-ethylpyrimidin-4-amine;
(S) -N- (1- ((5-trifluoromethylpyridin-2-yl) oxy) propan-2-yl) -5-chloro-6-difluoromethylpyrimidin-4-amine;
(S) -N- (1- ((5-trifluoromethylpyridin-2-yl) oxy) but-2-yl) -5-chloro-6-difluoromethylpyrimidin-4-amine;
(S) -N- (1- ((3, 5-dichloropyridin-2-yl) oxy) propan-2-yl) -5-chloro-6-methylpyrimidin-4-amine;
(S) -N- (1- ((3, 5-dichloropyridin-2-yl) oxy) propan-2-yl) -5-chloro-6-ethylpyrimidin-4-amine;
(S) -N- (1- ((3, 5-dichloropyridin-2-yl) oxy) propan-2-yl) -5-chloro-6-difluoromethylpyrimidin-4-amine;
(S) -N- (1- ((3, 5-dichloropyridin-2-yl) oxy) but-2-yl) -5-chloro-6-difluoromethylpyrimidin-4-amine;
(S) -N- (1- ((3-chloro-5-trifluoromethylpyridin-2-yl) oxy) propan-2-yl) -5-chloro-6-methylpyrimidin-4-amine;
(S) -N- (1- ((3-chloro-5-trifluoromethylpyridin-2-yl) oxy) propan-2-yl) -5-chloro-6-ethylpyrimidin-4-amine;
(S) -N- (1- ((3-chloro-5-trifluoromethylpyridin-2-yl) oxy) butan-2-yl) -5-chloro-6-ethylpyrimidin-4-amine;
(S) -N- (1- ((3-chloro-5-trifluoromethylpyridin-2-yl) oxy) propan-2-yl) -5-chloro-6-difluoromethylpyrimidin-4-amine;
(S) -N- (1- ((3-chloro-5-trifluoromethylpyridin-2-yl) oxy) butan-2-yl) -5-chloro-6-difluoromethylpyrimidin-4-amine;
(S) -N- (1- ((3, 5, 6-trichloropyridin-2-yl) oxy) propan-2-yl) -5-chloro-6-methylpyrimidin-4-amine;
(S) -N- (1- ((3, 5, 6-trichloropyridin-2-yl) oxy) propan-2-yl) -5-chloro-6-ethylpyrimidin-4-amine;
(S) -N- (1- ((3, 5, 6-trichloropyridin-2-yl) oxy) propan-2-yl) -5-chloro-6-difluoromethylpyrimidin-4-amine;
(S) -N- (1- ((3-fluoro-5-chloropyridin-2-yl) oxy) propan-2-yl) -5-chloro-6-ethylpyrimidin-4-amine;
(S) -N- (1- ((3-fluoro-5-chloropyridin-2-yl) oxy) but-2-yl) -5-chloro-6-difluoromethylpyrimidin-4-amine;
(S) -N- (1- ((5-nitropyridin-2-yl) oxy) propan-2-yl) -5-chloro-6-ethylpyrimidin-4-amine;
(S) -N- (1- ((3-chloropyridin-2-yl) oxy) propan-2-yl) -5-chloro-2, 6-dimethylpyrimidin-4-amine;
(S) -N- (1- ((3-chloropyridin-2-yl) oxy) propan-2-yl) -5-chloro-2-methyl-6-ethylpyrimidin-4-amine;
(S) -N- (1- ((3-chloropyridin-2-yl) oxy) propan-2-yl) -5-chloro-2-methyl-6-difluoromethylpyrimidin-4-amine;
(S) -N- (1- ((5-trifluoromethylpyridin-2-yl) oxy) propan-2-yl) -5-chloro-2, 6-dimethylpyrimidin-4-amine;
(S) -N- (1- ((5-trifluoromethylpyridin-2-yl) oxy) propan-2-yl) -5-chloro-2-methyl-6-ethylpyrimidin-4-amine;
(S) -N- (1- ((5-trifluoromethylpyridin-2-yl) oxy) propan-2-yl) -5-chloro-2-methyl-6-difluoromethylpyrimidin-4-amine;
(S) -N- (1- ((5-trifluoromethylpyridin-2-yl) oxy) but-2-yl) -5-chloro-2-methyl-6-difluoromethylpyrimidin-4-amine;
(S) -N- (1- ((3, 5-dichloropyridin-2-yl) oxy) propan-2-yl) -5-chloro-2, 6-dimethylpyrimidin-4-amine;
(S) -N- (1- ((3, 5-dichloropyridin-2-yl) oxy) propan-2-yl) -5-chloro-2-methyl-6-ethylpyrimidin-4-amine;
(S) -N- (1- ((3, 5-dichloropyridin-2-yl) oxy) propan-2-yl) -5-chloro-2-methyl-6-difluoromethylpyrimidin-4-amine;
(S) -N- (1- ((3-chloro-5-trifluoromethylpyridin-2-yl) oxy) propan-2-yl) -5-chloro-2, 6-dimethylpyrimidin-4-amine;
(S) -N- (1- ((3-chloro-5-trifluoromethylpyridin-2-yl) oxy) propan-2-yl) -5-chloro-2-methyl-6-ethylpyrimidin-4-amine;
(S) -N- (1- ((3-chloro-5-trifluoromethylpyridin-2-yl) oxy) butan-2-yl) -5-chloro-2-methyl-6-ethylpyrimidin-4-amine;
(S) -N- (1- ((3-chloro-5-trifluoromethylpyridin-2-yl) oxy) propan-2-yl) -5-chloro-2-methyl-6-difluoromethylpyrimidin-4-amine;
(S) -N- (1- ((3-chloro-5-trifluoromethylpyridin-2-yl) oxy) but-2-yl) -5-chloro-2-methyl-6-difluoromethylpyrimidin-4-amine;
(S) -N- (1- ((3, 5, 6-trichloropyridin-2-yl) oxy) propan-2-yl) -5-chloro-2, 6-dimethylpyrimidin-4-amine;
(S) -N- (1- ((3, 5, 6-trichloropyridin-2-yl) oxy) propan-2-yl) -5-chloro-2-methyl-6-ethylpyrimidin-4-amine;
(S) -N- (1- ((3, 5, 6-trichloropyridin-2-yl) oxy) propan-2-yl) -5-chloro-2-methyl-6-difluoromethylpyrimidin-4-amine;
(S) -N- (1- ((3-fluoro-5-chloropyridin-2-yl) oxy) butan-2-yl) -5-chloro-2-methyl-6-difluoromethylpyrimidin-4-amine.
2. The process for preparing pyridylether compounds containing pyrimidinamines according to claim 1, wherein the compound of formula (I) is prepared by the reaction shown below:
reaction formula 1:
Figure FDA0003806053250000021
reaction formula 2:
Figure FDA0003806053250000022
reaction formula 3:
Figure FDA0003806053250000023
reacting a compound of formula (II) with a compound of formula (III) in the presence of a suitable base selected from the group consisting of alkali metal hydride sodium hydride, alkali metal hydroxide sodium hydroxide or potassium hydroxide, alkali metal carbonate sodium carbonate or potassium carbonate, alkali metal alkoxide sodium methoxide or sodium ethoxide or organic amine pyridine, triethylamine, diisopropylethylamine, or a solvent selected from dichloromethane, dichloroethane, toluene, xylene, N-dimethylformamide, N-methylpyrrolidone, dimethylsulfoxide, pyridine, tetrahydrofuran, methanol, ethanol, isopropanol, acetone, butanone, methyl isobutyl ketone, acetonitrile, ethyl acetate, or dioxane at a temperature of-10 ℃ to system reflux temperature to obtain a compound of formula (I);
reacting the compound of formula (IV) with the compound of formula (V) in a solvent of dichloromethane, dichloroethane, toluene, xylene, N-dimethylformamide, N-methylpyrrolidone, dimethylsulfoxide, pyridine, tetrahydrofuran, methanol, ethanol, isopropanol, acetone, butanone, methyl isobutyl ketone, acetonitrile, ethyl acetate or dioxane at a temperature of-10 ℃ to the system reflux temperature in the absence of a base or a suitable base selected from the group consisting of sodium hydride alkali metal hydrides, sodium hydroxide or potassium hydroxide alkali metal carbonates or potassium carbonate, sodium methoxide or sodium ethoxide or organic amine pyridine, triethylamine or diisopropylethylamine;
reacting the compound of formula (VI) with a chlorinating agent chlorine or sulfonyl chloride at 0-50 ℃ in the absence of a solvent or in a solvent of ethyl acetate, dichloromethane, trichloromethane, dichloroethane, acetone, butanone or methyl isobutyl ketone to obtain a compound of formula (VII); reacting a compound of formula (VII) with a compound of formula (VIII) in the presence of the bases triethylamine, pyridine, sodium methoxide, sodium ethoxide, sodium hydride, potassium hydroxide, potassium carbonate, sodium hydroxide or sodium carbonate at 5-50 ℃ in the solvents methanol, ethanol, propanol, isopropanol, dichloromethane, dichloroethane, toluene, xylene, N-dimethylformamide, N-methylpyrrolidone, dimethyl sulfoxide, pyridine, tetrahydrofuran, acetone, butanone or methyl isobutyl ketone to obtain a compound of formula (IX); reacting the compound shown in the formula (IX) with a halogenating agent phosphorus oxychloride or phosphorus tribromooxy in the presence of alkali triethylamine, pyridine, sodium methoxide, sodium ethoxide, sodium hydride, potassium hydroxide, potassium carbonate, sodium hydroxide or sodium carbonate to obtain a compound shown in the formula (IV);
in the formula, R and R 1 、R 2 、R 3 、R 4 W has the meaning given in claim 1, R 5 Is methyl or ethyl, L is a leaving group, in formula (III) L is fluorine, chlorine, bromine or iodine, in formula (IV) L is chlorine or bromine.
3. The use of pyridylether compounds containing pyrimidinamines according to claim 1, characterized by insecticidal/acaricidal or fungicidal biological activity at a dosage of 7.5 to 2250 g of active principle per hectare.
4. Use of the pyridylether compounds containing pyrimidinamines according to claim 1 for the preparation of medicaments having insecticidal/acaricidal or fungicidal activity.
5. An insecticidal/acaricidal or fungicidal composition, comprising: the pyriproxyfen-containing compounds according to claim 1 as active ingredient in an amount of 0.5 to 90% by weight, and an acceptable carrier.
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Citations (2)

* Cited by examiner, † Cited by third party
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US5668140A (en) * 1991-05-17 1997-09-16 Hoechst Aktiengesellschaft Substituted 4-aminopyrimidines, processes for their preparation, and their use as pesticides
CN109776427A (en) * 2017-11-13 2019-05-21 沈阳中化农药化工研发有限公司 Double aminated compounds of pyrimidine and application thereof

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5668140A (en) * 1991-05-17 1997-09-16 Hoechst Aktiengesellschaft Substituted 4-aminopyrimidines, processes for their preparation, and their use as pesticides
CN109776427A (en) * 2017-11-13 2019-05-21 沈阳中化农药化工研发有限公司 Double aminated compounds of pyrimidine and application thereof

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