WO2018184579A1 - Triazole compound and use thereof in agriculture - Google Patents

Triazole compound and use thereof in agriculture Download PDF

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Publication number
WO2018184579A1
WO2018184579A1 PCT/CN2018/081979 CN2018081979W WO2018184579A1 WO 2018184579 A1 WO2018184579 A1 WO 2018184579A1 CN 2018081979 W CN2018081979 W CN 2018081979W WO 2018184579 A1 WO2018184579 A1 WO 2018184579A1
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WO
WIPO (PCT)
Prior art keywords
alkyl
halo
substituted
alkenyl
alkynyl
Prior art date
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PCT/CN2018/081979
Other languages
French (fr)
Inventor
Yitao LI
Jian Lin
Wenqiang YAO
Junxing XU
Yang Wu
Xinshuo LIU
Original Assignee
Dongguan Hec Tech R&D Co., Ltd.
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Publication date
Application filed by Dongguan Hec Tech R&D Co., Ltd. filed Critical Dongguan Hec Tech R&D Co., Ltd.
Priority to EP18781838.0A priority Critical patent/EP3606910A4/en
Publication of WO2018184579A1 publication Critical patent/WO2018184579A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D249/12—Oxygen or sulfur atoms
    • 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
    • A01N43/64—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with three nitrogen atoms as the only ring hetero atoms
    • A01N43/647—Triazoles; Hydrogenated triazoles
    • A01N43/653—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • 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
    • A01N51/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds having the sequences of atoms O—N—S, X—O—S, N—N—S, O—N—N or O-halogen, regardless of the number of bonds each atom has and with no atom of these sequences forming part of a heterocyclic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • the present invention provides a novel triazole compound and a preparation method thereof, a composition containing the compound and their use in agriculture.
  • the present invention provides a novel triazole compound having fungicidal activity.
  • the invention provides a novel fungicidal compound having an excellent controlling effect on plant diseases, a fungicidal composition and formulation containing the fungicidal compound, and use thereof.
  • a compound having Formula (A) or a stereoisomer, an N-oxide or a salt thereof is provided herein.
  • each of R 1 and R 2 is independently H, alkyl, alkoxyalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, cycloalkylalkyl, heterocyclylalkyl, arylalkyl, halo substituted arylalkyl or heteroarylalkyl; or R 1 and R 2 , together with the N atom to which they are attached, form a heterocyclyl or heteroaryl group;
  • heterocyclyl or heteroaryl group formed from R 1 and R 2 , together with the N atom to which they are attached is optionally substituted with one or more R 12 ;
  • R 3 is H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, aryl or haloaryl;
  • w 0, 1 or 2;
  • each R a and R b is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl or cycloalkyl;
  • x 0, 1, 2, 3, 4, 5 or 6;
  • R 5 and R 6 together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 15 ;
  • R 6 and R 7 together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 16 ;
  • R 7 and R 8 together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 17 ;
  • R 8 and R 9 together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 18 ;
  • each of R c , R d , R m , R n , R y1 , R x and R y is independently H, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl;
  • each R 1 , R 2 , R 3 , R 5 , R 6 , R 7 , R 8 , R 9 , R a , R b , R c , R d , R m , R n , R x and R y is optionally substituted with one, two, three, four, five or six R 10 ;
  • R z is C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halo C 1-6 alkyl, halo C 2-6 alkenyl, halo C 2-6 alkynyl, C 3-8 cycloalkyl, 3-12 membered heterocyclyl, C 6-10 aryl or C 1-9 heteroaryl;
  • each R 15 , R 16 , R 17 and R 18 is independently H, halogen, cyano, nitro, alkyl, alkenyl, alkynyl, alkoxy, alkylamino, haloalkyl or haloalkoxy;
  • R 7 is not unsubstituted or substituted phenoxy, unsubstituted or substituted pyridyloxy or unsubstituted or substituted naphthyloxy.
  • provided herein is a compound having Formula (I) or a stereoisomer, an N-oxide or a salt thereof,
  • each of R 1 and R 2 is independently H, alkyl, alkoxyalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, cycloalkylalkyl, heterocyclylalkyl, arylalkyl, halo substituted arylalkyl or heteroarylalkyl; or R 1 and R 2 , together with the N atom to which they are attached, form a heterocyclyl or heteroaryl group;
  • heterocyclyl or heteroaryl group formed from R 1 and R 2 , together with the N atom to which they are attached is optionally substituted with one or more R 12 ;
  • R 3 is H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, aryl or haloaryl;
  • each R a and R b is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl or cycloalkyl;
  • x 0, 1, 2, 3, 4, 5 or 6;
  • R 5 and R 6 together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 15 ;
  • R 6 and R 7 together with the carbon atoms to which they are attached, optionally form a benzene ring or naphthalene ring; and wherein the benzene ring or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 16 ;
  • R 7 and R 8 together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 17 ;
  • R 8 and R 9 together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 18 ;
  • each of R c , R d , R m , R n , R y1 , R x and R y is independently H, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl;
  • each R 1 , R 2 , R 3 , R 5 , R 6 , R 7 , R 8 , R 9 , R a , R b , R c , R d , R m , R n , R x and R y is optionally substituted with one, two, three, four, five or six R 10 ;
  • R z is C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halo C 1-6 alkyl, halo C 2-6 alkenyl, halo C 2-6 alkynyl, C 3-8 cycloalkyl, 3-12 membered heterocyclyl, C 6-10 aryl or C 1-9 heteroaryl;
  • each R 15 , R 16 , R 17 and R 18 is independently H, halogen, cyano, nitro, alkyl, alkenyl, alkynyl, alkoxy, alkylamino, haloalkyl or haloalkoxy;
  • R 7 is not unsubstituted or substituted phenoxy, unsubstituted or substituted pyridyloxy or unsubstituted or substituted naphthyloxy.
  • each of R 1 and R 2 is independently H, C 1-6 alkyl, C 1-6 alkoxy-C 1-6 -alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, C 2-10 heterocyclyl, C 6-10 aryl, C 1-9 heteroaryl, C 3-8 cycloalkyl-C 1-6 -alkyl, C 2-10 heterocyclyl-C 1-6 -alkyl, C 6-10 aryl-C 1-6 -alkyl, halo substituted C 6-10 aryl-C 1-6 -alkyl or C 1-9 heteroaryl-C 1-6 -alkyl; or R 1 and R 2 , together with the N atom to which they are attached, form a 3-8 membered heterocyclyl or C 1-9 heteroaryl group;
  • R 3 is H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halo C 1-6 alkyl, halo C 2-6 alkenyl, halo C 2-6 alkynyl, C 6-10 aryl or halo C 6-10 aryl ;
  • each R a and R b is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halo C 1-6 alkyl, halo C 2-6 alkenyl, halo C 2-6 alkynyl or C 3-8 cycloalkyl;
  • x 0, 1, 2, 3, 4, 5 or 6;
  • R 5 and R 6 together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 15 ;
  • R 6 and R 7 together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 16 ;
  • R 7 and R 8 together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 17 ;
  • R 8 and R 9 together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 18 ;
  • each of R c , R d , R m , R n , R y1 , R x and R y is independently H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halo C 1-6 alkyl, halo C 2-6 alkenyl, halo C 2-6 alkynyl, C 3-6 cycloalkyl, 3-8 membered heterocyclyl, C 6-10 aryl or C 1-5 heteroaryl;
  • each R 1 , R 2 , R 3 , R 5 , R 6 , R 7 , R 8 , R 9 , R a , R b , R c , R d , R m , R n , R x and R y is optionally substituted with one, two, three, four, five or six R 10 ;
  • R z is C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, halo C 1-4 alkyl, halo C 2-4 alkenyl, halo C 2-4 alkynyl, C 3-6 cycloalkyl, 3-8 membered heterocyclyl, C 6-10 aryl or C 1-5 heteroaryl;
  • each R 15 , R 16 , R 17 and R 18 is independently H, halogen, cyano, nitro, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 alkylamino, halo C 1-6 alkyl or halo C 1-6 alkoxy;
  • R 7 is not unsubstituted or substituted phenoxy, unsubstituted or substituted pyridyloxy or unsubstituted or substituted naphthyloxy.
  • each of R 1 and R 2 is independently H, C 1-4 alkyl, C 1-3 alkoxy-C 1-3 -alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 3-6 cycloalkyl, C 2-6 heterocyclyl, C 6-10 aryl, C 1-5 heteroaryl, C 3-6 cycloalkyl-C 1-4 -alkyl, C 2-6 heterocyclyl-C 1-4 -alkyl, C 6-10 aryl-C 1-4 -alkyl, halo substituted C 6-10 aryl-C 1-4 -alkyl or C 1-5 heteroaryl-C 1-4 -alkyl; or R 1 and R 2 , together with the N atom to which they are attached, form the following sub-structures:
  • each of p 1 and p 2 is independently 0, 1, or 2;
  • q 0, 1 or 2;
  • each X 2 , X 3 , X 4 and X 5 is independently N or CH;
  • sub-structure (i) , (ii) , (iii) or (iv) is optionally substituted with one or more R 12 .
  • R 3 is H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, halo C 1-4 alkyl, halo C 2-4 alkenyl, halo C 2-4 alkynyl, C 6-10 aryl or halo C 6-10 aryl.
  • R 3 is H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, -CH 3 , -CHF 2 , -CH 2 F, -CH 2 CH 3 , -CH 2 CH 2 F, -CH 2 CHF 2 , -CH 2 CH 2 CH 3 , -CH (CH 3 ) 2 , -C (CH 3 ) 3 , phenyl, 2-fluorophenyl, 3-fluorophenyl or 4-fluorophenyl.
  • R 5 and R 6 together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 15 ;
  • R 6 and R 7 together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 16 ;
  • R 7 and R 8 together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 17 ;
  • R 8 and R 9 together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 18 ;
  • each of R c , R d , R m , R n , R y1 , R x and R y is independently H, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, halo C 1-4 alkyl, halo C 2-4 alkenyl, halo C 2-4 alkynyl, C 3-6 cycloalkyl, 3-6 membered heterocyclyl, C 6-10 aryl or C 1-5 heteroaryl;
  • each R 5 , R 6 , R 7 , R 8 , R 9 , R c , R d , R m , R n , R y1 , R x and R y is optionally substituted with one, two, three, four, five or six R 10 ; and wherein R 10 is as defined herein;
  • each R 15 , R 16 , R 17 and R 18 is independently H, halogen, cyano, nitro, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 alkoxy, C 1-4 alkylamino, halo C 1-4 alkyl or halo C 1-4 alkoxy.
  • each R 5 , R 7 , R 8 , R 9 , R 15a , R 15b , R 15c , R 15d , R 16a , R 16b , R 16c , R 16d , R 16e , R 16f , R 18a , R 18b , R 18c and R 18d is independently H, halo, cyano, nitro, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 alkylamino, halo C 1-6 alkyl or halo C 1-6 alkoxy.
  • each R 5 , R 7 , R 8 , R 9 , R 15a , R 15b , R 15c , R 15d , R 16a , R 16b , R 16c , R 16d , R 16e , R 16f , R 18a , R 18b , R 18c and R 18d is independently H, halo, cyano, nitro, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 alkoxy, C 1-4 alkylamino, halo C 1-4 alkyl or halo C 1-4 alkoxy.
  • each R 5 , R 7 , R 8 , R 9 , R 15a , R 15b , R 15c , R 15d , R 16a , R 16b , R 16c , R 16d , R 16e , R 16f , R 18a , R 18b , R 18c and R 18d is independently H, F, Cl, Br, I, cyano, nitro, methyl, ethyl, n-propyl, isopropyl, t-butyl, vinyl, propenyl, allyl, ethynyl, propinyl, propargyl, methoxy, ethoxy, isopropoxy, t-butoxy, difluoromethyl, trifluoromethyl, difluoromethoxy, trifluoromethoxy, dimethylamino or diethylamino.
  • each R a and R b is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, halo C 1-4 alkyl, halo C 2-4 alkenyl, halo C 2-4 alkynyl or C 3-6 cycloalkyl;
  • R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R a , R b and x are as defined herein.
  • R 3 , R 5 , R 6 , R 7 , R 8 , R 9 , R a , R b and x are as defined herein.
  • composition comprising the compound disclosed herein.
  • the composition further comprises an agrochemically acceptable surfactant and carrier.
  • provided herein is use of the compound or composition disclosed herein for controlling plant diseases.
  • the plant disease is caused by plant pathogenic fungi.
  • provided herein is a method of controlling plant diseases by using the compound or composition disclosed herein.
  • provided herein is the compound or composition disclosed herein for use in controlling plant diseases.
  • provided herein is use of the compound or composition disclosed herein in the manufacture of a fungicide.
  • the compound of Formula (A) or (I) can exist in different stereoisomeric or optical isomeric or tautomeric forms. All such isomers and tautomers and mixtures thereof with various proportions, and isotopic forms such as a compound containing deuterium are included within the scope of the invention.
  • Isotopically enriched compounds have structures depicted by the formulas given herein except that one or more atoms are replaced by an atom having a selected atomic mass or mass number.
  • isotopes that can be incorporated into compounds of the invention include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorous, sulfur, fluorine, and chlorine, such as 2 H, 3 H, 11 C, 13 C, 14 C, 15 N, 17 O, 18 O, 18 F, 31 P, 32 P, 35 S, 36 Cl, 125 I, respectively.
  • Any asymmetric atom (e.g., carbon or the like) of the compound (s) disclosed herein can be present in racemic or enantiomerically enriched, for example the (R) -, (S) -or (R, S) -configuration.
  • grammatical articles “a” , “an” and “the” are intended to include “at least one” or “one or more” unless otherwise indicated herein or clearly contradicted by the context.
  • the articles are used herein to refer to one or more than one (i.e. at least one) of the grammatical objects of the article.
  • a component means one or more components, and thus, possibly, more than one component is contemplated and may be employed or used in an implementation of the described embodiments.
  • Stereoisomers refers to compounds which have identical chemical constitution, but differ with regard to the arrangement of the atoms or groups in space. Stereoisomers include enantiomer, diastereomers, conformer (rotamer) , geometric (cis/trans) isomer, atropisomer, etc.
  • Enantiomers refers to two stereoisomers of a compound which are non-superimposable mirror images of one another.
  • Diastereomer refers to a stereoisomer with two or more centers of chirality and whose molecules are not mirror images of one another. Diastereomers have different physical properties, e.g. melting points, boling points, spectral properties or biological activities. Mixture of diastereomers may separate under high resolution analytical procedures such as electrophoresis and chromatography such as HPLC.
  • optically active compounds Many organic compounds exist in optically active forms, i.e., they have the ability to rotate the plane of plane-polarized light.
  • the prefixes D and L, or R and S are used to denote the absolute configuration of the molecule about its chiral center (s) .
  • the prefixes d and l or (+) and (-) are employed to designate the sign of rotation of plane-polarized light by the compound, with (-) or l meaning that the compound is levorotatory.
  • a compound prefixed with (+) or d is dextrorotatory.
  • a specific stereoisomer may be referred to as an enantiomer, and a mixture of such stereoisomers is called an enantiomeric mixture.
  • a 50: 50 mixture of enantiomers is referred to as a racemic mixture or a racemate, which may occur where there has been no stereoselection or stereospecificity in a chemical reaction or process.
  • any asymmetric atom (e.g., carbon or the like) of the compound (s) disclosed herein can be present in racemic or enantiomerically enriched, for example the (R) -, (S) -or (R, S) -configuration.
  • each asymmetric atom has at least 50 %enantiomeric excess, at least 60 %enantiomeric excess, at least 70 %enantiomeric excess, at least 80 %enantiomeric excess, at least 90 %enantiomeric excess, at least 95 %enantiomeric excess, or at least 99 %enantiomeric excess in the (R) -or (S) -configuration.
  • the compounds can be present in the form of one of the possible stereoisomers or as mixtures thereof, such as racemates and diastereoisomer mixtures, depending on the number of asymmetric carbon atoms.
  • Optically active (R) -and (S) -isomers may be prepared using chiral synthons or chiral reagents, or resolved using conventional techniques. If the compound contains a double bond, the substituent may be E or Z configuration. If the compound contains a disubstituted cycloalkyl, the cycloalkyl substituent may have a cis-or trans-configuration.
  • Any resulting mixtures of stereoisomers can be separated on the basis of the physicochemical differences of the constituents, into the pure or substantially pure geometric isomers, enantiomers, diastereomers, for example, by chromatography and/or fractional crystallization.
  • racemates of final products or intermediates can be resolved into the optical antipodes by methods known to those skilled in the art, e.g., by separation of the diastereomeric salts thereof.
  • Racemic products can also be resolved by chiral chromatography, e.g., high performance liquid chromatography (HPLC) using a chiral adsorbent.
  • HPLC high performance liquid chromatography
  • enantiomer may be obtained by asymmetric synthesis.
  • compounds disclosed herein may optionally be substituted with one or more substituents, such as are illustrated generally below, or as exemplified by particular classes, subclasses, and species of the invention.
  • substituents such as are illustrated generally below, or as exemplified by particular classes, subclasses, and species of the invention.
  • the phrase “optionally substituted” is used interchangeably with the phrase “substituted or unsubstituted” .
  • substituted refers to the replacement of one or more hydrogen radicals in a given structure with the radical of a specified substituent.
  • an optionally substituted group may have a substituent at each substitutable position of the group.
  • substituent When more than one position in a given structure can be substituted with more than one substituent selected from a specified group, the substituent may be either the same or different at each position. Specifically, one example of “one or more” refers to one, two, three, four, five, six, seven, eight, nine or ten.
  • substituents of compounds disclosed herein include, but are not limited to, deuterium (D or H 2 ) , F, Cl, Br, I, cyano, hydroxy, nitro, amino, carboxy, alkyl, alkoxy, alkoxyalkyl, alkoxyalkoxy, alkoxyalkylamino, aryloxy, heteroaryloxy, heterocyclyloxy, arylalkoxy, heteroarylalkoxy, heterocyclylalkoxy, cycloalkylalkoxy, alkylamino, alkylaminoalkyl, alkylaminoalkylamino, cycloalkylamino, cycloalkylalkylamino, alkylthio, haloalkyl, haloalkoxy, hydroxy-substituted alkyl, hydroxy-substituted alkylamino, cyano-substituted alkyl, cyano-substituted alkoxy, cyano-
  • substituents of compounds disclosed herein are disclosed in groups or in ranges. It is specifically intended that the invention include each and every individual subcombination of the members of such groups and ranges.
  • the term “C 1 -C 6 alkyl” or “C 1-6 alkyl” is specifically intended to individually disclose methyl, ethyl, C 3 alkyl, C 4 alkyl, C 5 alkyl, and C 6 alkyl.
  • alkyl refers to a saturated linear or branched-chain monovalent hydrocarbon group of 1-20 carbon atoms, wherein the alkyl group is optionally substituted with one or more substituents described herein. Unless otherwise stated, the alkyl group contains 1-20 carbon atoms. In some embodiments, the alkyl group contains 1-12 carbon atoms. In some embodiments, the alkyl group contains 1-8 carbon atoms. In other embodiments, the alkyl group contains 1-6 carbon atoms. In still other embodiments, the alkyl group contains 1-4 carbon atoms. In yet other embodiments, the alkyl group contains 1-3 carbon atoms.
  • alkyl group examples include methyl (Me, -CH 3 ) , ethyl (Et, -CH 2 CH 3 ) , n-propyl (n-Pr, -CH 2 CH 2 CH 3 ) , isopropyl (i-Pr, -CH (CH 3 ) 2 ) , n-butyl (n-Bu, -CH 2 CH 2 CH 2 CH 3 ) , i-butyl (i-Bu, -CH 2 CH (CH 3 ) 2 ) , s-butyl (s-Bu, -CH (CH 3 ) CH 2 CH 3 ) , t-butyl (t-Bu, -C (CH 3 ) 3 ) , n-pentyl (-CH 2 CH 2 CH 2 CH 3 ) , 2-pentyl (-CH (CH 3 ) CH 2 CH 2 CH 3 ) , 3-pentyl (-CH (CH 2 CH 3 ) ) , n
  • alkylene refers to a saturated divalent hydrocarbon group derived from a straight or branched chain saturated hydrocarbon by the removal of two hydrogen atoms. Unless otherwise stated, the alkylene group contains 1-12 carbon atoms. In some embodiments, the alkylene group contains 1-8 carbon atoms. In other embodiments, the alkylene group contains 1-6 carbon atoms. In still other embodiments, the alkylene group contains 1-4 carbon atoms. In yet other embodiments, the alkylene group contains 1-3 carbon atoms. In yet other embodiments, the alkylene group contains 1-2 carbon atoms.
  • Some non-limiting examples of such group include methylene (-CH 2 -) , ethylene (-CH 2 CH 2 -) , propylene (-CH 2 CH 2 CH 2 -) , -CH (CH 3 ) CH 2 -, -C (CH 3 ) 2 -, -CH 2 CH 2 CH (CH 3 ) -, -CH 2 CH 2 C (CH 3 ) 2 -, and the like.
  • alkenyl refers to a linear or branched-chain monovalent hydrocarbon radical of 2 to 12 carbon atoms with at least one site of unsaturation, i.e., a carbon-carbon, sp 2 double bond, wherein the alkenyl radical may be optionally substituted independently with one or more substituents described herein, and includes radicals having “cis” and “trans” orientations, or alternatively, “E” and “Z” orientations.
  • the alkenyl contains 2 to 8 carbon atoms.
  • the alkenyl contains 2 to 6 carbon atoms.
  • the alkenyl contains 2 to 4 carbon atoms.
  • alkynyl refers to a linear or branched chain monovalent hydrocarbon radical of 2 to 12 carbon atoms with at least one carbon-carbon, sp triple bond.
  • alkoxy refers to an alkyl group, as previously defined, attached to the parent molecular moiety via an oxygen atom.
  • alkoxy group include methoxy (MeO, -OCH 3 ) , ethoxy (EtO, -OCH 2 CH 3 ) , 1-propoxy (n-PrO, n-propoxy, -OCH 2 CH 2 CH 3 ) , 2-propoxy (i-PrO, i-propoxy, -OCH (CH 3 ) 2 ) , and so on.
  • alkylthio refers to an alkyl group, as previously defined, attached to the parent molecular moiety via a sulphur atom. Wherein the alkyl group is as defined herein. Some non-limiting examples of the alkylthio group include -SCH 3 , -SCH 2 CH 3 , -SCH 2 CH 2 CH 3 , -SCH (CH 3 ) 2 , and so on.
  • cycloalkyl refers to a monovalent or multivalent saturated ring having 3 to 12 carbon atoms as a monocyclic, bicyclic, or tricyclic ring system. In some embodiments, the cycloalkyl group contains 3 to 10 carbon atoms. In other embodiments, the cycloalkyl group contains 3 to 8 carbon atoms. In still other embodiments, the cycloalkyl group contains 3 to 6 carbon atoms.
  • the cycloalkyl radical is optionally substituted with one or more substituents described herein.
  • Some examples include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, cyclohendecyl and cyclododecyl, etc.
  • the ring sulfur atom can be optionally oxygenized to S-oxide and the ring nitrogen atom can be optionally oxygenized to N-oxide.
  • heterocyclyl examples include, but are not limited to, oxiranyl, azetidinyl, oxetanyl, thietanyl, pyrrolidinyl (e.g. 2-pyrrolidinyl) , 2-pyrrolinyl, 3-pyrrolinyl, pyrazolidinyl, imidazolinyl, imidazolidinyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothienyl, dihydrothienyl, 1, 3-dioxolanyl, dithiolanyl, tetrahydropyranyl, dihydropyranyl, 2H-pyranyl, 4H-pyranyl, tetrahydrothiopyranyl, piperidinyl (2-piperidinyl, 3-piperidinyl, 4-piperidinyl) , morpholinyl, thiomorpholinyl, 1-oxothiomorpholinyl,
  • heterocyclyl wherein the ring sulfur atom is oxidized is sulfolanyl, 1, 1-dioxo-thiomorpholinyl. And wherein the carbocyclyl group is optionally substituted with one or more substituents described herein.
  • 3-12 membered heterocyclyl typically describes the number of ring atoms of a molecule.
  • piperidinyl is an example of a 6 membered heterocyclyl group.
  • unsaturated refers to a moiety having one or more units of unsaturation.
  • heteroatom refers to one or more of oxygen, sulfur, nitrogen, phosphorus and silicon, including any oxidized form of nitrogen, sulfur, and phosphorus; the quaternized form of any basic nitrogen; or a substitutable nitrogen of a heterocyclic ring, for example, N (as in 3, 4-dihydro-2H-pyrrolyl) , NH (as in pyrrolidinyl) or NR (as in N-substituted pyrrolidinyl) .
  • halogen refers to fluorine (F) , chlorine (Cl) , bromine (Br) or iodine (I) .
  • aryl refers to monocyclic, bicyclic and tricyclic carbocyclic ring systems having a total of six to fourteen ring members, or six to twelve ring members, or six to ten ring members, wherein at least one ring in the system is aromatic, wherein each ring in the system contains 3 to 7 ring members and that has a single point or multipoint of attachment to the rest of the molecule.
  • aryl and “aromatic ring” can be used interchangeably herein. Examples of the aryl group would include phenyl, naphthyl, and anthryl.
  • the aryl radical is optionally substituted with one or more substituents described herein.
  • heteroaryl refers to monocyclic, bicyclic and tricyclic carbocyclic ring systems having a total of five to twelve ring members, or five to ten ring members, or five to six ring members, wherein at least one ring in the system is aromatic, and in which at least one ring member is selected from heteroatom, and wherein each ring in the system contains 5 to 7 ring members and that has a single point or multipoint of attachment to the rest of the molecule.
  • heteroaryl and “heteroaromatic ring” or “heteroaromatic compound” can be used interchangeably herein.
  • the heteroaryl group is optionally substituted with one or more substituents disclosed herein.
  • a 5-10 membered heteroaryl comprises 1, 2, 3 or 4 heteroatoms independently selected from O, S and N.
  • heteroaryl ring examples include 2-furanyl, 3-furanyl, N-imidazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, N-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, pyridazinyl (e.g., 3-pyridazinyl) , 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, tetrazolyl (e.g., 5-tetrazolyl) , triazolyl (e.g., 2-triazolyl and 5-triazolyl) , 2-thienyl, 3-
  • Salts of the compound disclosed herein include those derived from alkali or alkaline earth metals and those derived from ammonia and amines.
  • Preferred cations include sodium, potassium, magnesium, and aminium (ammonium) cations of the formula N + (R 19 R 20 R 21 R 22 ) , wherein each R 19 , R 20 , R 21 and R 22 is independently selected from H, C 1 -C 6 alkyl and C 1 -C 6 hydroxyalkyl.
  • Salts of the compound having Formula (I) can be prepared by treatment of the compound having Formula (I) with a metal hydroxide, such as sodium hydroxide, or with an amine, such as ammonia, trimethylamine, diethanolamine, 2-methylthiopropylamine, bisallylamine, 2-butoxyethylamine, morpholine, cyclododecylamine, or benzylamine.
  • a metal hydroxide such as sodium hydroxide
  • an amine such as ammonia, trimethylamine, diethanolamine, 2-methylthiopropylamine, bisallylamine, 2-butoxyethylamine, morpholine, cyclododecylamine, or benzylamine.
  • acceptable salts can be formed from organic and inorganic acids, for example, acetic, propionic, lactic, citric, tartaric, succinic, fumaric, maleic, malonic, mandelic, malic, phthalic, hydrochloric, hydrobromic, phosphoric, nitric, sulfuric, methanesulfonic, naphthalenesulfonic, benzenesulfonic, toluenesulfonic, camphorsulfonic, and similarly known acceptable acids.
  • organic and inorganic acids for example, acetic, propionic, lactic, citric, tartaric, succinic, fumaric, maleic, malonic, mandelic, malic, phthalic, hydrochloric, hydrobromic, phosphoric, nitric, sulfuric, methanesulfonic, naphthalenesulfonic, benzenesulfonic, toluenesulfonic, camphorsulfonic, and similarly
  • the invention provides a novel fungicidal compound having an excellent controlling effect on plant diseases, a fungicidal composition and formulation containing the fungicidal compound, and use thereof.
  • a compound having Formula (A) or a stereoisomer, an N-oxide or a salt thereof is provided herein.
  • each of R 1 and R 2 is independently H, alkyl, alkoxyalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, cycloalkylalkyl, heterocyclylalkyl, arylalkyl, halo substituted arylalkyl or heteroarylalkyl; or R 1 and R 2 , together with the N atom to which they are attached, form a heterocyclyl or heteroaryl group;
  • heterocyclyl or heteroaryl group formed from R 1 and R 2 , together with the N atom to which they are attached is optionally substituted with one or more R 12 ;
  • R 3 is H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, aryl or haloaryl;
  • w is 0 , 1 or 2;
  • each R a and R b is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl or cycloalkyl;
  • x 0, 1, 2, 3, 4, 5 or 6;
  • R 5 and R 6 together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 15 ;
  • R 6 and R 7 together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 16 ;
  • R 7 and R 8 together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 17 ;
  • R 8 and R 9 together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 18 ;
  • each of R c , R d , R m , R n , R y1 , R x and R y is independently H, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl;
  • each R 1 , R 2 , R 3 , R 5 , R 6 , R 7 , R 8 , R 9 , R a , R b , R c , R d , R m , R n , R x and R y is optionally substituted with one, two, three, four, five or six R 10 ;
  • R z is C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halo C 1-6 alkyl, halo C 2-6 alkenyl, halo C 2-6 alkynyl, C 3-8 cycloalkyl, 3-12 membered heterocyclyl, C 6-10 aryl or C 1-9 heteroaryl;
  • each R 15 , R 16 , R 17 and R 18 is independently H, halogen, cyano, nitro, alkyl, alkenyl, alkynyl, alkoxy, alkylamino, haloalkyl or haloalkoxy;
  • R 7 is not unsubstituted or substituted phenoxy, unsubstituted or substituted pyridyloxy or unsubstituted or substituted naphthyloxy.
  • provided herein is a compound having Formula (I) or a stereoisomer, an N-oxide or a salt thereof,
  • each of R 1 and R 2 is independently H, alkyl, alkoxyalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, cycloalkylalkyl, heterocyclylalkyl, arylalkyl, halo substituted arylalkyl or heteroarylalkyl; or R 1 and R 2 , together with the N atom to which they are attached, form a heterocyclyl or heteroaryl group;
  • heterocyclyl or heteroaryl group formed from R 1 and R 2 , together with the N atom to which they are attached is optionally substituted with one or more R 12 ;
  • R 3 is H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, aryl or haloaryl;
  • each R a and R b is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl or cycloalkyl;
  • x 0, 1, 2, 3, 4, 5 or 6;
  • R 5 and R 6 together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 15 ;
  • R 6 and R 7 together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 16 ;
  • R 7 and R 8 together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 17 ;
  • R 8 and R 9 together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 18 ;
  • each of R c , R d , R m , R n , R y1 , R x and R y is independently H, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl;
  • each R 1 , R 2 , R 3 , R 5 , R 6 , R 7 , R 8 , R 9 , R a , R b , R c , R d , R m , R n , R x and R y is optionally substituted with one, two, three, four, five or six R 10 ;
  • R z is C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halo C 1-6 alkyl, halo C 2-6 alkenyl, halo C 2-6 alkynyl, C 3-8 cycloalkyl, 3-12 membered heterocyclyl, C 6-10 aryl or C 1-9 heteroaryl;
  • each R 15 , R 16 , R 17 and R 18 is independently H, halogen, cyano, nitro, alkyl, alkenyl, alkynyl, alkoxy, alkylamino, haloalkyl or haloalkoxy;
  • R 7 is not unsubstituted or substituted phenoxy, unsubstituted or substituted pyridyloxy or unsubstituted or substituted naphthyloxy.
  • each of R 1 and R 2 is independently H, C 1-6 alkyl, C 1-6 alkoxy-C 1-6 -alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, C 2-10 heterocyclyl, C 6-10 aryl, C 1-9 heteroaryl, C 3-8 cycloalkyl-C 1-6 -alkyl, C 2-10 heterocyclyl-C 1-6 -alkyl, C 6-10 aryl-C 1-6 -alkyl, halo substituted C 6-10 aryl-C 1-6 -alkyl or C 1-9 heteroaryl-C 1-6 -alkyl; or R 1 and R 2 , together with the N atom to which they are attached, form 3-8 membered heterocyclyl or C 1-9 heteroaryl;
  • R 12 is as defined herein.
  • R 3 is H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halo C 1-6 alkyl, halo C 2-6 alkenyl, halo C 2-6 alkynyl, C 6-10 aryl or halo C 6-10 aryl.
  • R 14 is as defined herein.
  • each R a and R b is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halo C 1-6 alkyl, halo C 2-6 alkenyl, halo C 2-6 alkynyl or C 3-8 cycloalkyl;
  • x is 0, 1, 2, 3, 4, 5 or 6.
  • R 5 and R 6 together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 15 ;
  • R 6 and R 7 together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 16 ;
  • R 7 and R 8 together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 17 ;
  • R 8 and R 9 together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 18 ;
  • R c , R d , R m , R n , R p , R q , R 15 , R 16 , R 17 , R 18 , R x and R y are as defined herein.
  • R y1 is as defined herein.
  • each of R c , R d , R m , R n , R y1 , R x and R y is independently H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halo C 1-6 alkyl, halo C 2-6 alkenyl, halo C 2-6 alkynyl, C 3-6 cycloalkyl, 3-8 membered heterocyclyl, C 6-10 aryl or C 1-5 heteroaryl.
  • each R 1 , R 2 , R 3 , R 5 , R 6 , R 7 , R 8 , R 9 , R a , R b , R c , R d , R m , R n , R x and R y is optionally substituted with one, two, three, four, five or six R 10 ;
  • R 10 is as defined herein.
  • R z is as defined herein.
  • R z is C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, halo C 1-4 alkyl, halo C 2-4 alkenyl, halo C 2-4 alkynyl, C 3-6 cycloalkyl, 3-8 membered heterocyclyl, C 6-10 aryl or C 1-5 heteroaryl.
  • each R 15 , R 16 , R 17 and R 18 is independently H, halogen, cyano, nitro, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 alkylamino, halo C 1-6 alkyl or halo C 1-6 alkoxy.
  • each of R 1 and R 2 is independently H, C 1-4 alkyl, C 1-3 alkoxy-C 1-3 -alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 3-6 cycloalkyl, C 2-6 heterocyclyl, C 6-10 aryl, C 1-5 heteroaryl, C 3-6 cycloalkyl-C 1-4 -alkyl, C 2-6 heterocyclyl-C 1-4 -alkyl, C 6-10 aryl-C 1-4 -alkyl, halo substituted C 6-10 aryl-C 1-4 -alkyl or C 1-5 heteroaryl-C 1-4 -alkyl; or R 1 and R 2 , together with the N atom to which they are attached, form the following sub-structures:
  • each of p 1 and p 2 is independently 0, 1 or 2;
  • q 0, 1 or 2;
  • each X 2 , X 3 , X 4 and X 5 is independently N or CH;
  • sub-structure (i) , (ii) , (iii) or (iv) is optionally substituted with one or more R 12 ;
  • R 12 is as defined herein.
  • R 3 is H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, halo C 1-4 alkyl, halo C 2-4 alkenyl, halo C 2-4 alkynyl, C 6-10 aryl or halo C 6-10 aryl.
  • R 3 is H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, -CH 3 , -CHF 2 , -CH 2 F, -CH 2 CH 3 , -CH 2 CH 2 F, -CH 2 CHF 2 , -CH 2 CH 2 CH 3 , -CH (CH 3 ) 2 , -C (CH 3 ) 3 , phenyl, 2-fluorophenyl, 3-fluorophenyl or 4-fluorophenyl.
  • R 14 is as defined herein.
  • each R a and R b is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, halo C 1-4 alkyl, halo C 2-4 alkenyl, halo C 2-4 alkynyl or C 3-6 cycloalkyl.
  • R c , R d , R m , R n , R p , R q , R x and R y are as defined herein.
  • R y1 is as defined herein.
  • each of R c , R d , R m , R n , R y1 , R x and R y is independently H, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, halo C 1-4 alkyl, halo C 2-4 alkenyl, halo C 2-4 alkynyl, C 3-6 cycloalkyl, 3-6 membered heterocyclyl, C 6-10 aryl or C 1-5 heteroaryl.
  • R 5 and R 6 together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 15 ;
  • R 15 is as defined herein.
  • R 6 and R 7 together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 16 ;
  • R 16 is as defined herein.
  • R 7 and R 8 together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 17 ;
  • R 17 is as defined herein.
  • R 8 and R 9 together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 18 ;
  • R 18 is as defined herein.
  • each R 5 , R 6 , R 7 , R 8 , R 9 , R c , R d , R m , R n , R y1 , R x and R y is optionally substituted with one, two, three, four, five or six R 10 ;
  • R 10 is as defined herein.
  • each R 15 , R 16 , R 17 and R 18 is independently H, halogen, cyano, nitro, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 alkoxy, C 1-4 alkylamino, halo C 1-4 alkyl or halo C 1-4 alkoxy.
  • each R 5 , R 7 , R 8 , R 9 , R 15a , R 15b , R 15c , R 15d , R 16a , R 16b , R 16c , R 16d , R 16e , R 16f , R 18a , R 18b , R 18c and R 18d is independently H, halo, cyano, nitro, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 alkylamino, halo C 1-6 alkyl or halo C 1-6 alkoxy.
  • each R 5 , R 7 , R 8 , R 9 , R 15a , R 15b , R 15c , R 15d , R 16a , R 16b , R 16c , R 16d , R 16e , R 16f , R 18a , R 18b , R 18c and R 18d is independently H, halo, cyano, nitro, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 alkoxy, C 1-4 alkylamino, halo C 1-4 alkyl or halo C 1-4 alkoxy.
  • each R 5 , R 7 , R 8 , R 9 , R 15a , R 15b , R 15c , R 15d , R 16a , R 16b , R 16c , R 16d , R 16e , R 16f , R 18a , R 18b , R 18c and R 18d is independently H, F, Cl, Br, I, cyano, nitro, methyl, ethyl, n-propyl, isopropyl, t-butyl, vinyl, propenyl, allyl, ethynyl, propinyl, propargyl, methoxy, ethoxy, isopropoxy, t-butoxy, difluoromethyl, trifluoromethyl, difluoromethoxy, trifluoromethoxy, dimethylamino or diethylamino.
  • each R a and R b is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, halo C 1-4 alkyl, halo C 2-4 alkenyl, halo C 2-4 alkynyl or C 3-6 cycloalkyl;
  • provided herein is a compound having Formula (Ia) or a stereoisomer, an N-oxide or a salt thereof,
  • each R 5 , R 6 , R 7 , R 8 and R 9 is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, alkyl, haloalkyl, alkenyl, alkoxy or haloalkoxy;
  • R 5 and R 6 together with the carbon atoms to which they are attached, optionally form a benzene ring; and wherein the benzene ring is optionally substituted with one, two, three or four substituents selected from F, Cl, Br, I, cyano, nitro, alkyl, alkenyl, alkynyl, alkoxy, alkylamino, haloalkyl or haloalkoxy.
  • each R 5 , R 6 , R 7 , R 8 and R 9 is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, C 1-6 alkyl, halo C 1-6 alkyl, C 2-6 alkenyl, C 1-6 alkoxy or halo C 1-6 alkoxy;
  • R 5 and R 6 together with the carbon atoms to which they are attached, optionally form a benzene ring; and wherein the benzene ring is optionally substituted with one, two, three or four substituents selected from F, Cl, Br, I, cyano, nitro, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, halo C 1-6 alkyl or halo C 1-6 alkoxy.
  • each R 5 , R 6 , R 7 , R 8 and R 9 is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, C 1-4 alkyl, halo C 1-4 alkyl, C 2-4 alkenyl, C 1-4 alkoxy or halo C 1-4 alkoxy;
  • R 5 and R 6 together with the carbon atoms to which they are attached, optionally form a benzene ring; and wherein the benzene ring is optionally substituted with one, two, three or four substituents selected from F, Cl, Br, I, cyano, nitro, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkylamino, halo C 1-4 alkyl or halo C 1-4 alkoxy.
  • R 5 and R 6 together with the carbon atoms to which they are attached, optionally form a benzene ring; and wherein the benzene ring is optionally substituted with one, two, three or four substituents selected from F, Cl, Br, I, cyano, nitro, -CH 3 , -CF 3 , -OCH 3 or -OCF 3 .
  • provided herein is a compound having one of the following structures or a stereoisomer, an N-oxide or a salt thereof,
  • R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R a , R b and x are as defined herein.
  • R 3 , R 5 , R 6 , R 7 , R 8 , R 9 , R a , R b and x are as defined herein.
  • composition comprising the compound disclosed herein. Unless otherwise indicated, all tautomers, racemates, hydrates, solvates, metabolites, metabolic precursors or prodrugs of the compounds of Formula (A) , (I) or (Ia) disclosed herein are within the scope of the present invention.
  • composition disclosed herein further comprises an agrochemically acceptable surfactant and carrier.
  • provided herein is use of the compound or the composition disclosed herein for controlling plant diseases; specifically for use as a fungicide.
  • the plant disease is caused by plant pathogenic fungi.
  • the compound of the invention can generally be used as an active ingredient of fungicides in a composition, i.e. formulation, usually including an agrochemically acceptable surfactant and carrier.
  • the above surfactant may be any common surfactant in the field of pesticide formulation, the optimization disclosed herein is one or more of emulsifier, dispersant and wetting agent.
  • the carrier may be any common carrier in the field of pesticide formulation, including any silicate, carbonate, sulfate, oxide, phosphate, plant carrier, synthetic carrier.
  • silica kaolin, diatomite, clay, talc, organic bentonite, pumice, titanium dioxide, dextrin, cellulose powder, light calcium carbonate, soluble starch, corn starch, sawdust powder, urea, amine fertilizer, a mixture of urea and amine fertilizer, glucose, maltose, sucrose, anhydrous potassium carbonate, anhydrous sodium carbonate, anhydrous potassium bicarbonate, anhydrous sodium bicarbonate, attapulgite, a mixture of anhydrous potassium carbonate and anhydrous potassium bicarbonate, a mixture of anhydrous sodium carbonate and anhydrous sodium bicarbonate.
  • the above emulsifier may be any common emulsifier in the field of pesticide formulation, specifically, the emulsifier may be one or more of calcium dodecylbenzenesulfonate, triphenylethylphenol polyoxyethylene ether phosphate, polyoxyethy fatty alcohol ether, alkyl phenol polyoxyethylene ether, alkyl phenol polyoxyethylene polyoxypropylene ether, fatty amines, ethylene oxide adduct of fatty amide, polyoxyethylene fatty acid ester, ethylene oxide adduct of rosin acid, polyol fatty acid ester and ethylene oxide adduct thereof, styrenyl phenyl polyoxyethylene ether, alkyl phenol formaldehyde resin polyoxyethylene ether, hydroxy terminated polyoxyethylene polyoxypropylene ether, styrenyl phenol formaldehyde resin polyoxyethylene polyoxypropylene ether and castor oil polyoxyethylene ether.
  • the above dispersant may be any common emulsifier in the field of pesticide formulation, specifically, the dispersant may be one or more of acrylic acid homopolymer sodium salt, maleic acid disodium salt, naphthalene sulfonated formaldehyde condensates sodium salt, rosin segmented polyoxyethylene ether polyoxypropylene sulfonates, hydroxy terminated polyoxyethylene polyoxypropylene ether segmented copolymer, triphenylethyl phenol polyoxyethylene ether phosphate, fatty alcohol polyoxyethylene ether phosphate and p-hydroxyphenyl lignin sulfonic acid sodium salt.
  • the above wetting agent may be any common wetting agent in the field of pesticide formulation, specifically, the dispersant may be one or more of lauryl sodium sulfate, sec-alkyl sodium sulfate, sodium dodecyl benzene sulfonate, fatty alcohol polyoxyethylene ether, alkyl naphthalene sulfonate, alkyl phenol resin polyoxyethylene ether sulfate.
  • the fungicide composition disclosed herein may also contain any common auxiliary for formulation in the field of pesticide formulation, specifically, the auxiliary for formulation may be one or more of solvent, cosolvent, thickener, antifreeze, capsule wall material, protective agent, defoamer, disintegrating agent, stabilizer, preservative and binder.
  • the auxiliary for formulation may be one or more of solvent, cosolvent, thickener, antifreeze, capsule wall material, protective agent, defoamer, disintegrating agent, stabilizer, preservative and binder.
  • the above solvent may be any common solvent in the field of pesticide formulation, specifically, the solvent may be one or more of organic solvent, plant oil, mineral oil, solvent oil and water.
  • the organic solvent includes one or more of N-methyl pyrrolidone, tetrahydrofuran, dimethyl sulfoxide, N, N-dimethyl decyl amide, N, N-dimethyl formamide, trimethylbenzene, tetramethylbenzene, xylene, toluene, heptane, octane, methanol, isopropanol, butanol, tetrahydrofurfuryl alcohol, tributyl phosphate, 1, 4-dioxane and cyclohexanone.
  • the plant oil includes one or more of methylated plant oil, pine oleoresin-based plant oil, turpentine oil, epoxidized soybean oil, soybean oil, peanut oil, rapeseed oil, castor oil, corn oil and pine nut oil.
  • the mineral oil includes one or more of liquid-wax, engine oil, kerosene and lubricant.
  • the above solvent may be used as a cosolvent.
  • the above antifreeze may be any common antifreeze in the field of pesticide formulation, the optimization disclosed herein is one or more of glycol, propanediol, glycerol and urea.
  • the above thickener may be any common thickener in the field of pesticide formulation, specifically, the thickener may be one or more xanthan gum, polyvinyl alcohol, polyallyl alcohol, polyethylene glycol, silica, diatomaceous earth, kaolin, clay, sodium alginate, aluminum silicate magnesium silicate, sodium aluminosilicate, carboxymethyl cellulose, hydroxypropyl cellulose sodium and organobentonite.
  • the thickener may be one or more xanthan gum, polyvinyl alcohol, polyallyl alcohol, polyethylene glycol, silica, diatomaceous earth, kaolin, clay, sodium alginate, aluminum silicate magnesium silicate, sodium aluminosilicate, carboxymethyl cellulose, hydroxypropyl cellulose sodium and organobentonite.
  • the above capsule wall material may be any common capsule wall material in the field of pesticide formulation, the optimization disclosed herein is one or more of polyurethane, polyurea and urea formaldehyde resin.
  • the above protective agent may be any common protective agent in the field of pesticide formulation, the optimization disclosed herein is one or more of polyvinyl alcohol and/or polyethylene glycol.
  • the above defoamer may be any common defoamer in the field of pesticide formulation, the optimization disclosed herein is one or more of organo-siloxane, tributyl phosphate and silicone.
  • the above stabilizer is selected from one or more of triphenyl phosphite, epichlorohydrin and acetic anhydride.
  • the above preservative is selected from one or more of benzoic acid, sodium benzoate, 1, 2-benzothiazoline-3-one (BIT for short) , isothiazolinone and potassium sorbate.
  • the present invention also provides a formulation prepared from the above fungicide composition, the form of the formulation is missible oil, aqueous emulsion, microemulsion, soluble liquid agent, aqueous suspension, suspoemulsion, ultra low volume sprays, oil suspension, microcapsule suspension, water surface spreading oil, wettable powder, water dispersible granules, dry suspension, soluble powder, soluble granules, emulsifiable powder, emulsifiable granules, granules, solid micro capsule, effervescent tablets, effervescent granules, water floating dispersible granules or seed dressing agent.
  • the above formulations all may be prepared by the common methods in this field.
  • a preparation method of the above missible oil may include, for example, mixing every active component, solvent, cosolvent and emulsifier to form a homogeneous transparent oil phase, i.e. missible oil may be obtained.
  • a preparation method of the above aqueous emulsion may include, for example, mixing active component (s) , emulsifier (s) , cosolvent (s) and solvent (s) to form a homogeneous oil phase; mixing water, thickener (s) and antifreeze (s) , etc. to form a homogeneous water phase; adding the water phase into the oil phase (or adding the oil phase into the water phase) under high speed shearing to form a aqueous emulsion with good dispersivity.
  • a preparation method of the above microemulsion may include, for example, mixing active component (s) , emulsifier (s) and solvent (s) to form a homogeneous oil phase. Adding water gradually with stirring to form a homogeneous transparent microemulsion.
  • a preparation method of the above aqueous/oil suspension may include, for example, grinding active component (s) , sufactant (s) , and the like adjuvant (s) in a sand grinding kettle with water or oil as medium to a certain particle size and filtering; adding measured thickener (s) to the grinded mother liquor, sheating to homogeneous dispersion; obtaining oil suspension or aqueous suspension.
  • a preparation method of the above water dispersible granules or soluble granules may include, for example, mixing every active component, dispersant, wetting agent, carrier, etc. homogeneously; shredding to a certain particle size through airflow; adding water and kneading; prilling in a granulator; and then drying to get water dispersible granules or soluble granules.
  • a preparation method of the above wettable powder or soluble powder may include, for example, mixing every active component, adjuvant and other carrier, and the like fillers thoroughly, shredding by using a super micro mill.
  • the fungicide composition disclosed herein may be provided in a form of a finished product, i.e. every components in the composition had been mixed; also may be in a form of a separate preparation, and mixing them in a container before using, diluting with water selectively according to the required concentration of the active component.
  • the compounds of this invention are useful as plant diseases controlling agents.
  • the present invention therefore further comprises a method for controlling plant diseases caused by plant fungal pathogens, the method comprises applying an effective amount of a compound of the invention or a fungicide composition containing the compound to plants to be protected or parts thereof, or to plant seeds to be protectedd.
  • the compounds and/or compositions of this invention can control diseases caused by a broad spectrum of plant fungal pathogens in the Basidiomycete, Ascomycete, Oomycete and Deuteromycete classes. They are effective in controlling a broad spectrum of plant diseases, particularly foliar pathogens of ornamental, turf, vegetable, field, cereal, and fruit crops.
  • pathogens include: Oomycetes, including Phytophthora diseases such as Phytophthora infestans, Phytophthora megasperma, Phytophthora parasitica, Phytophthora cinnamomi and Phytophthora capsici, Pythium diseases such as Pythium aphanidermatum, and diseases in the Peronosporaceae family such as Plasmopara viticola, Peronospora spp. (including Peronospora tabacina and Peronospora parasitica) , Pseudoperonospora spp.
  • Phytophthora diseases such as Phytophthora infestans, Phytophthora megasperma, Phytophthora parasitica, Phytophthora cinnamomi and Phytophthora capsici
  • Pythium diseases such as Pythium aphanidermatum
  • diseases in the Peronosporaceae family
  • Botrytis diseases such as Botrytis cinerea, Monilinia fructicola, Sclerotinia diseases such as Sclerotinia sclerotiorum, Magnaporthe grisea, Phomopsis viticola, Helminthosporium diseases such as Helminthosporium tritici repentis, Pyrenophora teres, anthracnose diseases such as Glomerella or Colletotrichum spp.
  • Puccinia spp. such as Colletotrichum graminicola and Colletotrichum orbiculare
  • Basidiomycetes including rust diseases caused by Puccinia spp.
  • Puccinia recondita Puccinia striiformis, Puccinia hordei, Puccinia graminis and Puccinia arachidis
  • Hemileia vastatrix and Phakopsora pachyrhizi other pathogens including Rhizoctonia spp.
  • compositions or combinations also have activity against bacteria such as Erwinia amylovora, Xanthomonas campestris, Pseudomonas syringae, and other related species.
  • the use method of the fungicide composition disclosed herein is simple, which comprises applying the composition to crops or places for crops growth before or after germination of plant diseases by common methods, such as mix soil, spray, jet, pour, etc, the application amount is determined according to climatic conditions or crop states, in general, 10-5000 g per mu is applied, and which is diluted to 10-400 mg/L when applying, preferably, which is diluted to 100-300 mg/L.
  • the diluter is preferably water.
  • Fungicidal effect of the fungicide composition disclosed herein typically relates to extraneous factors such as climate, but the influence of climate can be reduced by using suitable formulation.
  • composition disclosed herein can be used mixing with other compounds having fungicidal, insecticidal, or herbicidal properties, also can be used mixing with nematocides, acaricides, protective agents, herbicide safeners, growth regulator, plant nutrients, or soil conditioners.
  • the preparation of the compounds of the present invention is represented by the following scheme. Unless otherwise mentioned, the compounds disclosed herein may be prepared by methods described herein. The raw materials, reagents, etc. used in the preparation of the compounds disclosed herein can be commercially purchased, or prepared according to the common methods in the field. In the present invention, if the chemical name of the compound doesn’t match the corresponding structure, the compound is characterized by the corresponding structure.
  • Compound of Formula (I) can be prepared by the procedure illustrated in scheme 1, and wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R a , R b and x are as defined herein; Y is Cl, Br or I.
  • Oxidizing reaction of compound (a) and chlorine at a certain temperature (e.g. -10 °C to 10°C) under a condition of an acid (e.g. hydrochloric acid, dilute sulfuric acid, acetic acid, etc. ) can give compound (b) ; nucleophilic substitution reaction of compound (c) and R 4 -NH 2 at a certain temperature (e.g.
  • compound (d) condensation reaction of compound (b) and compound (d) at a certain temperature (e.g. -10 °C to 40 °C) under a condition of a base (e.g. pyridine, triethylamine, potassium carbonate, etc. ) can give compound (e) ; condensation reaction of compound (e) and R 1 R 2 N-SO 2 Cl at a certain temperature (e.g. -10 °C to 40 °C) under a condition of a base (e.g. pyridine, triethylamine, potassium carbonate, etc. ) can give compound (I) .
  • a base e.g. sodium hydroxide, sodium hydride, potassium carbonate, etc.
  • Compound of Formula (I) can be prepared by the procedure illustrated in scheme 2, and wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R a , R b and x are as defined herein; Y is Cl, Br or I.
  • Oxidative coupling reaction of compound (a) and acyl chloride e.g. benzene sulfonyl chloride, p-toluene sulfonyl chloride
  • a certain temperature e.g. -10 °C to 40 °C
  • a base e.g. pyridine, triethylamine, potassium carbonate, etc.
  • compound (f) condensation reaction of compound (f) and R 1 R 2 N-SO 2 Cl at a certain temperature (e.g. -10 °C to 40 °C) under a condition of a base (e.g. pyridine, triethylamine, potassium carbonate, etc. ) can give compound (g) ; oxidation reaction of compound (g) and chlorine at a certain temperature (e.g. -10 °C to 10 °C) under a condition of an acid (e.g. hydrochloric acid, dilute sulfuric acid, acetic acid, etc. ) can give compound (h) ; condensation reaction of compound (h) and NH 2 -R 4 at a certain temperature (e.g.
  • compound (i) -10 °C to 40 °C) under a condition of a base (e.g. pyridine, triethylamine, potassium carbonate, etc. ) can give compound (i) ; nucleophilic substitution reaction of compound (i) and compound (c) at a certain temperature (e.g. -10 °C to 40 °C) under a condition of a base (e.g. sodium hydroxide, sodium hydride, potassium carbonate, etc. ) can give compound (I) .
  • a base e.g. pyridine, triethylamine, potassium carbonate, etc.
  • Compound of Formula (I) can be prepared by the procedure illustrated in scheme 3, and wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R a , R b and x are as defined herein.
  • Condensation reaction of compound (h) and compound (d) at a certain temperature (e.g. -10 °C to 40 °C) under a condition of a base (e.g. pyridine, triethylamine, potassium carbonate, etc. ) can give compound (I) .
  • Formylthiosemicarbazide (12 g, 0.1 mol) was added to a 250 mL single neck flask, and then water (130 mL) and sodium carbonate (21.2 g, 0.25 mol) were added. The mixture was heated to 100 °C and reated for 4 hours, and then cooled to room temperature slowly. The reaction mixture was adjusted with dilute hydrochloric acid to pH 4-5. The resulting mixture was stirred at -10 °C slowly to crystallize, and then filtered. The solid was dried to give a white solid (5.6 g, yield was 55%) .
  • 1, 2, 4-Triazole-3-thiol (3 g, 0.03 mol) was dissolved in a hydrochloric acid solution (2 mol/L, 50 mL) .
  • the solution was cooled to 0 °C and mixed homogeneously, and chlorine was then bubbled (30 g, over a period of one hour) , a white solid precipitated out gradually.
  • nitrogen was used to purge superfluous chlorine out at 0 °C.
  • the resulting mixture was filtered, and the solid was dried to give a white solid (3.2 g, yield was 75%) .
  • 5-p-Fluorophenyl-1, 2, 4-triazole-3-thiol (3.9 g, 0.02 mol) was dissolved in a mixed hydrochloric acid (2 mol/L, 80 mL) and methanol (10 mL) solution. The solution was cooled to 0 °C and mixed homogeneously, and chlorine was then bubbled (30 g, over a period of one hour) . After stopping chlorine bubbling, nitrogen was used to purge superfluous chlorine out at 0 °C. The resulting mixture was extracted with dichloromethane (100 mL ⁇ 3) , and the combined organic layers were dried over magnesium sulfate and concentrated to give a brown oil (2.25 g, yield was 43.1%) .
  • the intermediate compounds listed in table 1 can be obtained according to the similar methods of example G by replacing benzyl chloride to corresponding raw materials.
  • the intermediate compounds listed in table 2 can be obtained according to the similar methods of example H by using corresponding raw materials under certain conditions.
  • reaction mixture was transferred to a separatory funnel and allowed to stand until it was separated into layers, the organic layer was washed with water (30 mL) 3 times and the solvent was removed by evaporating on a rotary evaporator under vacuum. A white powder was obtained (47.23 g, yield was 86.2%) .
  • the intermediate compounds listed in table 3 can be obtained according to the similar methods of example M by using corresponding raw materials.
  • the intermediate compounds listed in table 4 can be obtained according to the similar methods of example O by using corresponding raw materials and conditions.
  • the intermediate compounds listed in table 5 can be obtained according to the similar methods of example P by using corresponding raw materials and conditions.
  • the intermediate compounds listed in table 6 can be obtained according to the similar methods of example Q by using corresponding raw materials and conditions.
  • N-benzyl-N-cyclopropyl-1H-1, 2, 4-triazole-3-sulfonamide (0.28 g, 1 mmol) in dry tetrahydrofuran (8 mL) was stirred at 0 °C under N 2 , and then sodium hydride (60%, 60 mg, 1.5 mmol, 3 batches) was added in portions. After the addition, the mixture was further stirred at 0 °C for 30 minutes and then warmed to room temperature, N, N-dimethylamino sulfonyl chloride (0.286 g, 2 mmol) was added dropwise slowly.
  • N-cyclopropyl-N- (4-fluorobenzyl) -1H-1, 2, 4-triazole-3-sulfonamide 0.296 g, 1.0 mmol
  • potassium carbonate 0.28 g, 2.0 mmol
  • DMF 10 mL
  • N, N-dimethylamino sulfonyl chloride 0.215 g, 1.5 mmol
  • the mixture was stirred at 25 °C for 8 hours and quenched with water (20 mL) .
  • the resulting mixture was extracted with ethyl acetate (15 mL ⁇ 3) .
  • N-cyclopropyl-5- (difluoromethyl) -N- (4-fluorobenzyl) -1H-1, 2, 4-triazole-3-sulfonamide 0.346 g, 1.0 mmol
  • potassium carbonate 0.28 g, 2.0 mmol
  • DMF 10 mL
  • N, N-dimethylamino sulfonyl chloride 0.215 g, 1.5 mmol
  • the mixture was stirred at 25 °C for 8 hours and quenched with water (20 mL) .
  • the resulting mixture was extracted with ethyl acetate (15 mL ⁇ 3) .
  • N-cyclopropyl-N- (4-fluorobenzyl) -5- (4-fluorophenyl) -1H-1, 2, 4-triazole-3-sulfonamide 0.390 g, 1.0 mmol
  • potassium carbonate 0.28 g, 2.0 mmol
  • DMF 10 mL
  • N, N-dimethylamino sulfonyl chloride 0.215 g, 1.5 mmol
  • the test targets Rhizoctonia Solani, Botrytis cinerea, Pseudoperonospora cubensis, Sphaerotheca Fuliginea.
  • Treating process the compound was dissolved in DMF to make 1%EC.
  • the fungicidal activities of the compounds of the invention were evaluated at a dose of 200 ppm, 100 ppm, 50 ppm, 25 ppm, 12.5 ppm and 6.25 ppm against the four test targets by adopting a pot culture method.
  • Plotted cucumber seedlings in one leaf period (removing the growing point) with consistent growth were selected.
  • the selected Plotted cucumber seedlings were air-dried naturally, and after 24 h, Pseudoperonospora cubensis were inoculated to the treated cucumber seedlings by spraying a sporangia suspension (2 ⁇ 10 5 to 3 ⁇ 10 5 cells/ml) , the sporangia suspension was prepared from sporangium obtained by washing down from the back of fresh cucumber leaves with cucumber downy mildew using a dipping distilled water brush. The inoculation was carried out by spraying uniformly on the cucumber seedlings with a sprayer (pressure is 0.1 MPa) .
  • the inoculated test materials were moved to a climatic chamber, the relative humidity was maintained at 100%, the temperature was at about 21 °C. After 24 h, moisture inducement was performed under the temperature of about 21 °C and the relative humidity of about 95%. After 5 days, an investigation on gradation was carried out on a morbidity case of the blank control group, the control effect was calculated according to the disease index.
  • Cucumber seedlings in one leaf period (removing the growing point) with consistent growth were selected.
  • spray treatment with the formulation, which were dried in the shade for 24 h.
  • Conidia of fresh powdery mildew fungus on cucumber leaves were washed drown, and filtered through double-layer gauze and then prepared to a suspension at a concentration of 1 ⁇ 10 5 cells/mL, the inoculation was carried out by spraying.
  • the inoculated test materials were moved to a climatic chamber, the relative humidity was maintained between 60%and 70%, and the temperature was maintained between 21 °C and 23 °C. After about 10 days, an investigation on gradation was carried out on a morbidity case of the blank control group, the control effect was calculated according to the disease index.
  • a leaf inoculation method was adopted. Cucumber seedlings in two leaf period with consistent growth were selected. After spraying the selected cucumber seedlings with the formulation and air drying, mycelial piece obtained from the cultures of fungus was inoculated to the leaves of the cucumber seedlings. The inoculated cucumber seedlings was cultivated at a certain moisture and at 24-26 °C in dark for 24 hours and in natural light for about 3 days. After complete morbidity of the control group, the scab diameter of every inoculation point was metered by using a caliper, and the control effect was calculated.
  • Corn seedlings in two leaf and one bud period with consistent growth were selected. After 24 h of spray treatment with the formulation and air drying, mycelial piece obtained from the cultures of fungus was inoculated to the leaves of the selected corn seedlings. The inoculated corn seedlings was cultivated at a certain moisture and at 25-26°C in dark for 24 hours and in natural light for about 3 days. After complete morbidity of the control group, the scab diameter of every inoculation point was metered by using a caliper, and the control effect was calculated.
  • Table A the control effects of the compounds of the invention at 200 ppm on cucumber downy mildew
  • Example Control effect (%) 1 100 8 100 9 100 10 100 11 100 12 100 13 100 14 100 15 100 16 100 17 100 21 100 24 100 27 100 38 100 40 100 42 100 43 100 44 100 57 98 60 100 62 100 64 100 65 100 67 100 68 100 69 100 71 100 74 100 75 100 76 100 77 100 81 100 91 98
  • Table B the control effects of the compounds of the invention at 100 ppm on cucumber downy mildew
  • results listed in tables A and B indicated that the compounds of the invention have an obvious control effect at various concentrations on cucumber downy mildew, especially at 6.25 ppm, the compounds of the invention, for example, example 9, example 12, example 13, example 14, example 17, example 31 and example 132, have a control effect on cucumber downy mildew more than 40%.
  • results listed in tables C and E indicated that the compounds of the invention have a better control effect on cucumber downy mildew than that of prior art.
  • the compounds of the invention have an obvious control effect on Rhizoctonia solani, Botrytis cinerea and Sphaerotheca fuliginea at 200 ppm, the control effect is more than 30%.
  • the process of test of inhibition rates to the first well in the first line of a 96 well plate was added a given amount of the test medicinal liquid, and then it was serially diluted in required multiple to the 8 th well, the density of the pathogens of cucumber brown spot in the logarithmic growth were measured by a microscopic count method, the pathogens were diluted to a concentration of 10 7 to 10 8 CFU/mL with a culture solution; the pathogen solution was added into the 96 well plate, and 100 ⁇ L was added per well, the 9 th and 10 th wells were used as controls.
  • inhibition rate (%) (1-sample OD value /control OD value) x 100%. The results were listed in table F.
  • the broaden research of the compounds of the invention found that these compound have prominent control effects on potato late blight, wheat root rot and soybean root rot.
  • the compound of the invention have certain control effects on cucumber brown spot, wheat scab, corn curvularia leaf spot, rape sclerotinia stem rot, cotton fusarium wilt, apple ring rot, apple leaf spot, citrus scab, anthracnose of grape, peach brown rot, peanut spot disease, watermelon wilt, mango rot were test by the same method.
  • the compounds of the invention are high safety to crops and fruit trees such as rice, cucumber, wheat, potato, corn, soybean, rape, cotton, apple, citrus, grape, peach, peanut, watermelon, mango and so on, there is no evident injury at the concentration in the range from 1 ppm to 200 ppm.

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Abstract

The present invention provides a triazole compound and use thereof in agriculture. In particularly, the present invention provides a triazole compound having Formula (A) and a preparation method thereof, a composition and formulation containing these compounds and their use as fungicides; wherein R 1, R 2, R 3, w, R 4, R 5, R 6, R 7, R 8, R 9, R a, R b and x are as defined herein.

Description

TRIAZOLE COMPOUND AND USE THEREOF IN AGRICULTURE
CROSS REFERENCE TO RELATED APPLICATIONS
This application claims priority and benefits of Chinese Patent Applications No. 201710216598.1, filed with State Intellectual Property Office on 05 April, 2017, and No. 201710893563.1, filed with State Intellectual Property Office on 28 September, 2017, the entire contents of which are incorporated herein by reference.
FIELD OF THE INVENTION
The present invention provides a novel triazole compound and a preparation method thereof, a composition containing the compound and their use in agriculture.
BACKGROUND OF THE INVENTION
The control of plant diseases caused by fungal plant pathogens is extremely important in achieving high crop efficiency. Plant disease damage to ornamental, vegetable, field, cereal and fruit crops can cause significant reduction in productivity and thus lead to increased costs. Many products are commercially available for these purposes, but there is a continuing need for new compounds that are more effective, less costly, less toxic, environmentally safer or have different sites of action.
The present invention provides a novel triazole compound having fungicidal activity.
SUMMARY OF THE INVENTION
The invention provides a novel fungicidal compound having an excellent controlling effect on plant diseases, a fungicidal composition and formulation containing the fungicidal compound, and use thereof.
In one aspect, provided herein is a compound having Formula (A) or a stereoisomer, an N-oxide or a salt thereof,
Figure PCTCN2018081979-appb-000001
wherein
each of R 1 and R 2 is independently H, alkyl, alkoxyalkyl, alkenyl, alkynyl, cycloalkyl,  heterocyclyl, aryl, heteroaryl, cycloalkylalkyl, heterocyclylalkyl, arylalkyl, halo substituted arylalkyl or heteroarylalkyl; or R 1 and R 2, together with the N atom to which they are attached, form a heterocyclyl or heteroaryl group;
wherein the heterocyclyl or heteroaryl group formed from R 1 and R 2, together with the N atom to which they are attached is optionally substituted with one or more R 12;
R 3 is H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, aryl or haloaryl;
w is 0, 1 or 2;
R 4 is H, alkyl, -C (=O) -alkyl, -alkylene-C (=O) -alkyl, -C (=O) -O-alkyl, -alkylene-C (=O) -O-alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, cycloalkylalkyl or heterocyclylalkyl; wherein R 4 is optionally substituted with one or more R 14;
each R a and R b is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl or cycloalkyl;
or R a and R b together form oxo (=O) ;
x is 0, 1, 2, 3, 4, 5 or 6;
each of R 5, R 6, R 7, R 8 and R 9 is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, -C (=O) -NR cR d, -NR m-C (=O) -R n, -NR p (OR q) , -C (=O) -R x, -C (=O) -OR y, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, hydroxy substituted alkyl, amino substituted alkyl, cyano substituted alkyl, alkoxy, haloalkoxy, hydroxy substituted alkoxy, amino substituted alkoxy, cyano substituted alkoxy, alkylamino, alkylthio or aryloxy;
wherein R 5 and R 6, together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 15;
wherein R 6 and R 7, together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 16;
wherein R 7 and R 8, together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 17;
wherein R 8 and R 9, together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally  substituted with one, two, three, four, five, six, seven, eight or nine R 18;
wherein each of R p and R q is independently H, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl or -C (=O) -OR y1;
wherein each of R c, R d, R m, R n, R y1, R x and R y is independently H, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl;
wherein each R 1, R 2, R 3, R 5, R 6, R 7, R 8, R 9, R a, R b, R c, R d, R m, R n, R x and R y is optionally substituted with one, two, three, four, five or six R 10;
each R 10, R 12 and R 14 is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, -C (=O) -OR z, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halo C 1-6 alkyl, halo C 2-6 alkenyl, halo C 2-6 alkynyl, hydroxy substituted C 1-6 alkyl, amino substituted C 1-6 alkyl, cyano substituted C 1-6 alkyl, C 1-6 alkoxy, halo C 1-6 alkoxy, hydroxy substituted C 1-6 alkoxy, amino substituted C 1-6 alkoxy, cyano substituted C 1-6 alkoxy, C 1-6 alkylamino, C 3-8 cycloalkyl, C 6-10 aryl or C 1-9 heteroaryl;
wherein R z is C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halo C 1-6 alkyl, halo C 2-6 alkenyl, halo C 2-6 alkynyl, C 3-8 cycloalkyl, 3-12 membered heterocyclyl, C 6-10 aryl or C 1-9 heteroaryl;
each R 15, R 16, R 17 and R 18 is independently H, halogen, cyano, nitro, alkyl, alkenyl, alkynyl, alkoxy, alkylamino, haloalkyl or haloalkoxy;
with the proviso that when R 1 and R 2 is methyl, R 3 is H, w is 2, R 4 is H and x is 0, R 7 is not unsubstituted or substituted phenoxy, unsubstituted or substituted pyridyloxy or unsubstituted or substituted naphthyloxy.
In some embodiments, provided herein is a compound having Formula (I) or a stereoisomer, an N-oxide or a salt thereof,
Figure PCTCN2018081979-appb-000002
wherein
each of R 1 and R 2 is independently H, alkyl, alkoxyalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, cycloalkylalkyl, heterocyclylalkyl, arylalkyl, halo substituted arylalkyl or heteroarylalkyl; or R 1 and R 2, together with the N atom to which they are attached, form a heterocyclyl or heteroaryl group;
wherein the heterocyclyl or heteroaryl group formed from R 1 and R 2, together with the N atom to which they are attached is optionally substituted with one or more R 12;
R 3 is H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, aryl or haloaryl;
R 4 is H, alkyl, -C (=O) -alkyl, -alkylene-C (=O) -alkyl, -C (=O) -O-alkyl, -alkylene-C (=O) -O-alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, cycloalkylalkyl or heterocyclylalkyl; wherein R 4 is optionally substituted with one or more R 14;
each R a and R b is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl or cycloalkyl;
or R a and R b together form oxo (=O) ;
x is 0, 1, 2, 3, 4, 5 or 6;
each of R 5, R 6, R 7, R 8 and R 9 is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, -C (=O) -NR cR d, -NR m-C (=O) -R n, -NR p (OR q) , -C (=O) -R x, -C (=O) -OR y, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, hydroxy substituted alkyl, amino substituted alkyl, cyano substituted alkyl, alkoxy, haloalkoxy, hydroxy substituted alkoxy, amino substituted alkoxy, cyano substituted alkoxy, alkylamino, alkylthio or aryloxy;
wherein R 5 and R 6, together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 15;
wherein R 6 and R 7, together with the carbon atoms to which they are attached, optionally form a benzene ring or naphthalene ring; and wherein the benzene ring or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 16;
wherein R 7 and R 8, together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 17;
wherein R 8 and R 9, together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 18;
wherein each of R p and R q is independently H, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl or -C (=O) -OR y1;
wherein each of R c, R d, R m, R n, R y1, R x and R y is independently H, alkyl, alkenyl, alkynyl,  haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl;
wherein each R 1, R 2, R 3, R 5, R 6, R 7, R 8, R 9, R a, R b, R c, R d, R m, R n, R x and R y is optionally substituted with one, two, three, four, five or six R 10;
each R 10, R 12 and R 14 is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, -C (=O) -OR z, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halo C 1-6 alkyl, halo C 2-6 alkenyl, halo C 2-6 alkynyl, hydroxy substituted C 1-6 alkyl, amino substituted C 1-6 alkyl, cyano substituted C 1-6 alkyl, C 1-6 alkoxy, halo C 1-6 alkoxy, hydroxy substituted C 1-6 alkoxy, amino substituted C 1-6 alkoxy, cyano substituted C 1-6 alkoxy, C 1-6 alkylamino, C 3-8 cycloalkyl, C 6-10 aryl or C 1-9 heteroaryl;
wherein R z is C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halo C 1-6 alkyl, halo C 2-6 alkenyl, halo C 2-6 alkynyl, C 3-8 cycloalkyl, 3-12 membered heterocyclyl, C 6-10 aryl or C 1-9 heteroaryl;
each R 15, R 16, R 17 and R 18 is independently H, halogen, cyano, nitro, alkyl, alkenyl, alkynyl, alkoxy, alkylamino, haloalkyl or haloalkoxy;
with the proviso that when R 1 and R 2 is methyl, R 3 is H, w is 2, R 4 is H and x is 0, R 7 is not unsubstituted or substituted phenoxy, unsubstituted or substituted pyridyloxy or unsubstituted or substituted naphthyloxy.
In some embodiments, each of R 1 and R 2 is independently H, C 1-6 alkyl, C 1-6 alkoxy-C 1-6-alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, C 2-10 heterocyclyl, C 6-10 aryl, C 1-9 heteroaryl, C 3-8 cycloalkyl-C 1-6-alkyl, C 2-10 heterocyclyl-C 1-6-alkyl, C 6-10 aryl-C 1-6-alkyl, halo substituted C 6-10 aryl-C 1-6-alkyl or C 1-9 heteroaryl-C 1-6-alkyl; or R 1 and R 2, together with the N atom to which they are attached, form a 3-8 membered heterocyclyl or C 1-9 heteroaryl group;
wherein the 3-8 membered heterocyclyl or C 1-9 heteroaryl group formed from R 1 and R 2, together with the N atom to which they are attached is optionally substituted with one or more R 12;
R 3 is H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halo C 1-6 alkyl, halo C 2-6 alkenyl, halo C 2-6 alkynyl, C 6-10 aryl or halo C 6-10 aryl ;
R 4 is H, C 1-6 alkyl, -C (=O) -C 1-6 alkyl, -C 1-6 alkylene-C (=O) -C 1-6 alkyl, -C (=O) -O-C 1-6 alkyl, -C 1-6 alkylene-C (=O) -O-C 1-6 alkyl, C 1-6 alkoxy, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, 3-12 membered heterocyclyl, C 6-10 aryl, C 6-10 aryl-C 1-6-alkyl, C 3-8 cycloalkyl-C 1-6-alkyl or C 2-10 heterocyclyl-C 1-6-alkyl; wherein R 4 is optionally substituted with one or more R 14;
each R a and R b is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halo C 1-6 alkyl, halo C 2-6 alkenyl, halo C 2-6 alkynyl or C 3-8  cycloalkyl;
or R a and R b together form oxo (=O) ;
x is 0, 1, 2, 3, 4, 5 or 6;
each of R 5, R 6, R 7, R 8 and R 9 is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, -C (=O) -NR cR d, -NR m-C (=O) -R n, -NR p (OR q) , -C (=O) -R x, -C (=O) -OR y, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halo C 1-6 alkyl, halo C 2-6 alkenyl, halo C 2-6 alkynyl, hydroxy substituted C 1-6 alkyl, amino substituted C 1-6 alkyl, cyano substituted C 1-6 alkyl, C 1-6 alkoxy, halo C 1-6 alkoxy, hydroxy substituted C 1-6 alkoxy, amino substituted C 1-6 alkoxy, cyano substituted C 1-6 alkoxy, C 1-6 alkylamino, C 1-6 alkylthio or C 6-10 aryloxy;
wherein R 5 and R 6, together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 15;
wherein R 6 and R 7, together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 16;
wherein R 7 and R 8, together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 17;
wherein R 8 and R 9, together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 18;
wherein each of R p and R q is independently H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halo C 1-6 alkyl, halo C 2-6 alkenyl, halo C 2-6 alkynyl, C 3-6 cycloalkyl, 3-8 membered heterocyclyl, C 6-10 aryl, C 1-6 heteroaryl or -C (=O) -OR y1;
wherein each of R c, R d, R m, R n, R y1, R x and R y is independently H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halo C 1-6 alkyl, halo C 2-6 alkenyl, halo C 2-6 alkynyl, C 3-6 cycloalkyl, 3-8 membered heterocyclyl, C 6-10 aryl or C 1-5 heteroaryl;
wherein each R 1, R 2, R 3, R 5, R 6, R 7, R 8, R 9, R a, R b, R c, R d, R m, R n, R x and R y is optionally substituted with one, two, three, four, five or six R 10;
each R 10, R 12 and R 14 is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, -C (=O) -OR z, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, halo C 1-4 alkyl, halo C 2-4 alkenyl, halo C 2-4  alkynyl, hydroxy substituted C 1-4 alkyl, amino substituted C 1-4 alkyl, cyano substituted C 1-4 alkyl, C 1-4 alkoxy, halo C 1-4 alkoxy, hydroxy substituted C 1-4 alkoxy, amino substituted C 1-4 alkoxy, cyano substituted C 1-4 alkoxy, C 1-4 alkylamino, C 3-6 cycloalkyl, C 6-10 aryl or C 1-5 heteroaryl;
wherein R z is C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, halo C 1-4 alkyl, halo C 2-4 alkenyl, halo C 2-4 alkynyl, C 3-6 cycloalkyl, 3-8 membered heterocyclyl, C 6-10 aryl or C 1-5 heteroaryl;
each R 15, R 16, R 17 and R 18 is independently H, halogen, cyano, nitro, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 alkylamino, halo C 1-6 alkyl or halo C 1-6 alkoxy;
with the proviso that when R 1 and R 2 is methyl, R 3 is H, w is 2, R 4 is H and x is 0, R 7 is not unsubstituted or substituted phenoxy, unsubstituted or substituted pyridyloxy or unsubstituted or substituted naphthyloxy.
In other embodiments, each of R 1 and R 2 is independently H, C 1-4 alkyl, C 1-3 alkoxy-C 1-3-alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 3-6 cycloalkyl, C 2-6 heterocyclyl, C 6-10 aryl, C 1-5 heteroaryl, C 3-6 cycloalkyl-C 1-4-alkyl, C 2-6 heterocyclyl-C 1-4-alkyl, C 6-10 aryl-C 1-4-alkyl, halo substituted C 6-10 aryl-C 1-4-alkyl or C 1-5 heteroaryl-C 1-4-alkyl; or R 1 and R 2, together with the N atom to which they are attached, form the following sub-structures:
Figure PCTCN2018081979-appb-000003
each of p 1 and p 2 is independently 0, 1, or 2;
q is 0, 1 or 2;
X 1 is -O-, -S-, -S (=O) -, -S (=O)  2-or -NH-;
wherein each X 2, X 3, X 4 and X 5 is independently N or CH;
wherein sub-structure (i) , (ii) , (iii) or (iv) is optionally substituted with one or more R 12.
In other embodiments, each of R 1 and R 2 is independently H, -CH 3, -CH 2CH 3, -CH 2CH 2CH 3, -CH (CH 3)  2, -CH 2CH=CH 2, -CH 2CH 2CH=CH 2, -CH 2CH=CHCH 3, -CH 2-O-CH 3, -CH 2CH 2-O-CH 3, -CH 2-O-CH 2CH 3, -CH 2CH 2-O-CH 2CH 3, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, benzyl, 4-fluorobenzyl or 4-cyanobenzyl;
or R 1 and R 2, together with the N atom to which they are attached, form the following sub-structures:
Figure PCTCN2018081979-appb-000004
In some embodiments, R 3 is H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, halo C 1-4 alkyl, halo C 2-4 alkenyl, halo C 2-4 alkynyl, C 6-10 aryl or halo C 6-10 aryl.
In other embodiments, R 3 is H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, -CH 3, -CHF 2, -CH 2F, -CH 2CH 3, -CH 2CH 2F, -CH 2CHF 2, -CH 2CH 2CH 3, -CH (CH 3)  2, -C (CH 3)  3, phenyl, 2-fluorophenyl, 3-fluorophenyl or 4-fluorophenyl.
In some embodiments, R 4 is H, C 1-4 alkyl, -C (=O) -C 1-4 alkyl, -C 1-4 alkylene-C (=O) -C 1-4 alkyl, -C (=O) -O-C 1-4 alkyl, -C 1-4 alkylene-C (=O) -O-C 1-4 alkyl, C 1-4 alkoxy, C 2-4 alkenyl, C 2-4 alkynyl, C 3-6 cycloalkyl, 3-10 membered heterocyclyl, C 6-10 aryl, C 6-10 aryl-C 1-3-alkyl, C 3-6 cycloalkyl-C 1-3-alkyl or C 2-6 heterocyclyl-C 1-3-alkyl; R 4 is optionally substituted with one, two, three, four or five R 14; each R 14 is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, -C (=O) -O-C 1-3 alkyl, C 1-3 alkyl, C 1-3 alkoxy, C 3-6 cycloalkyl or phenyl.
In other embodiments, R 4 is H, -CH 3, -CHF 2, -CH 2 (CN) , -CH 2CH 3, -CH (CN) CH 3, -CH 2CHF 3, -CH 2CH 2CH 3, -CH (CH 3)  2, -CH 2CH 2CH 2CH 3, -C (CH 3)  3, -CH 2CH=CH 2, -CH 2CH 2CH=CH 2, -CH 2CH=CHCH 3, -C (=O) -CH 3, -C (=O) -CH 2CH 3, -C (=O) -OCH 3, -C (=O) -OCH 2CH 3, -CH 2-C (=O) -OCH 3, -CH 2-C (=O) -OCH 2CH 3, -OCH 3, -OCH 2CH 3, -OCH 2CH 2CH 3, -OCH (CH 3)  2, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl or benzyl; or R 4 has the following sub-structures:
Figure PCTCN2018081979-appb-000005
In some embodiments, each of R 5, R 6, R 7, R 8 and R 9 is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, -C (=O) -NR cR d, -NR m-C (=O) -R n, -NR p (OR q) , -C (=O) -R x,  -C (=O) -OR y, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, halo C 1-4 alkyl, halo C 2-4 alkenyl, halo C 2-4 alkynyl, hydroxy substituted C 1-4 alkyl, amino substituted C 1-4 alkyl, cyano substituted C 1-4 alkyl, C 1-4 alkoxy, halo C 1-4 alkoxy, hydroxy substituted C 1-4 alkoxy, amino substituted C 1-4 alkoxy, cyano substituted C 1-4 alkoxy, C 1-4 alkylamino, C 1-4 alkylthio or C 6-10 aryloxy;
wherein R 5 and R 6, together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 15;
wherein R 6 and R 7, together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 16;
wherein R 7 and R 8, together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 17;
wherein R 8 and R 9, together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 18;
wherein each of R p and R q is independently H, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, halo C 1-3 alkyl, halo C 2-4 alkenyl, halo C 2-4 alkynyl, C 3-6 cycloalkyl, 3-6 membered heterocyclyl, C 6-10 aryl, C 1-5 heteroaryl or -C (=O) -OR y1;
wherein each of R c, R d, R m, R n, R y1, R x and R y is independently H, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, halo C 1-4 alkyl, halo C 2-4 alkenyl, halo C 2-4 alkynyl, C 3-6 cycloalkyl, 3-6 membered heterocyclyl, C 6-10 aryl or C 1-5 heteroaryl;
wherein each R 5, R 6, R 7, R 8, R 9, R c, R d, R m, R n, R y1, R x and R y is optionally substituted with one, two, three, four, five or six R 10; and wherein R 10 is as defined herein;
each R 15, R 16, R 17 and R 18 is independently H, halogen, cyano, nitro, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 alkoxy, C 1-4 alkylamino, halo C 1-4 alkyl or halo C 1-4 alkoxy.
In other embodiments, each R 5, R 6, R 7, R 8 and R 9 is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, -CH 3, -CH 2CH 3, -CH 2CH 2CH 3, -CH (CH 3)  2, -CH 2F, -CHF 2, -CF 3, -CH 2CH 2F, -CH 2CHF 2, -CH 2CF 3, -CH=CH 2, -CH 2-CH=CH 2, -OCH 3, -OCH 2CH 3, -OCH 2CH 2CH 3, -OCH (CH 3)  2, -OCF 3, -OCH 2CF 3, -NH-C (=O) -CH 3, -NH-C (=O) -CH 2CH 3, -NH-OH, -N (OH) -C (=O) -OCH 3, -N (OC (=O) OCH 3) -C (=O) -OCH 3, -C (=O) -CH 3,  -C (=O) -CH 2CH 3, -C (=O) -OCH 3, -C (=O) -OCH 2CH 3, -SCH 3, -SCH 2CH 3, -SCH 2CH 2CH 3, -SCH (CH 3)  2, phenoxy, halophenoxy, C 1-4 alkyl substituted phenoxy, C 1-4 alkoxy substituted phenoxy, C 1-4 haloalkyl substituted phenoxy or C 1-4 haloalkoxy substituted phenoxy.
In some embodiments, 
Figure PCTCN2018081979-appb-000006
has the following sub-structures:
Figure PCTCN2018081979-appb-000007
wherein
each R 5, R 7, R 8, R 9, R 15a, R 15b, R 15c, R 15d, R 16a, R 16b, R 16c, R 16d, R 16e, R 16f, R 18a, R 18b, R 18c and R 18d is independently H, halo, cyano, nitro, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 alkylamino, halo C 1-6 alkyl or halo C 1-6 alkoxy.
In other embodiments, each R 5, R 7, R 8, R 9, R 15a, R 15b, R 15c, R 15d, R 16a, R 16b, R 16c, R 16d, R 16e, R 16f, R 18a, R 18b, R 18c and R 18d is independently H, halo, cyano, nitro, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 alkoxy, C 1-4 alkylamino, halo C 1-4 alkyl or halo C 1-4 alkoxy.
In other embodiments, each R 5, R 7, R 8, R 9, R 15a, R 15b, R 15c, R 15d, R 16a, R 16b, R 16c, R 16d, R 16e, R 16f, R 18a, R 18b, R 18c and R 18d is independently H, F, Cl, Br, I, cyano, nitro, methyl, ethyl, n-propyl, isopropyl, t-butyl, vinyl, propenyl, allyl, ethynyl, propinyl, propargyl, methoxy, ethoxy, isopropoxy, t-butoxy, difluoromethyl, trifluoromethyl, difluoromethoxy, trifluoromethoxy, dimethylamino or diethylamino.
In some embodiments, each R a and R b is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, halo C 1-4 alkyl, halo C 2-4 alkenyl, halo C 2-4 alkynyl or C 3-6 cycloalkyl;
or R a and R b together form oxo (=O) .
In other embodiments, each R a and R b is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, -CH 3, -CH 2CH 3, -CH 2CH 2CH 3, -CH (CH 3)  2, -CH 2F, -CHF 2, -CF 3, -CH 2CH 2F, -CH 2CHF 2, -CH 2CF 3, -CH=CH 2, -CH 2-CH=CH 2, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl;
or R a and R b together form oxo (=O) .
In other aspect, provided herein is a method of preparing a compound of Formula (I) comprising
reacting a compound of Formula (e) with a disubstituted amino sulfonyl chloride to obtain the compound of formula (I) :
Figure PCTCN2018081979-appb-000008
wherein R 1, R 2, R 3, R 4, R 5, R 6, R 7, R 8, R 9, R a, R b and x are as defined herein.
In other aspect, provided herein is a compound having Formula (II) or a stereoisomer, an N-oxide or a salt thereof,
Figure PCTCN2018081979-appb-000009
wherein R 3, R 5, R 6, R 7, R 8, R 9, R a, R b and x are as defined herein.
In other aspect, provided herein is a composition comprising the compound disclosed herein.
In some embodiments, the composition further comprises an agrochemically acceptable surfactant and carrier.
In other aspect, provided herein is use of the compound or composition disclosed herein for controlling plant diseases.
In some embodiments, the plant disease is caused by plant pathogenic fungi.
In other aspect, provided herein is a method of controlling plant diseases by using the  compound or composition disclosed herein.
In other aspect, provided herein is the compound or composition disclosed herein for use in controlling plant diseases.
In other aspect, provided herein is use of the compound or composition disclosed herein in the manufacture of a fungicide.
The compound of Formula (A) or (I) can exist in different stereoisomeric or optical isomeric or tautomeric forms. All such isomers and tautomers and mixtures thereof with various proportions, and isotopic forms such as a compound containing deuterium are included within the scope of the invention.
Isotopically enriched compounds have structures depicted by the formulas given herein except that one or more atoms are replaced by an atom having a selected atomic mass or mass number. Examples of isotopes that can be incorporated into compounds of the invention include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorous, sulfur, fluorine, and chlorine, such as  2H,  3H,  11C,  13C,  14C,  15N,  17O,  18O,  18F,  31P,  32P,  35S,  36Cl,  125I, respectively.
Any asymmetric atom (e.g., carbon or the like) of the compound (s) disclosed herein can be present in racemic or enantiomerically enriched, for example the (R) -, (S) -or (R, S) -configuration.
The foregoing merely summarizes certain aspects disclosed herein and is not intended to be limiting in nature. These aspects and other aspects and embodiments are described more fully below.
DETAILED DESCRIPTION OF THE INVENTION
DEFINITIONS AND GENERAL TERMINOLOGY
Reference will now be made in detail to certain embodiments of the invention, examples of which are illustrated in the accompanying structures and formulas. The invention is intended to cover all alternatives, modifications, and equivalents which may be included within the scope of the present invention as defined by the claims. One skilled in the art will recognize many methods and materials similar or equivalent to those described herein, which could be used in the practice of the present invention. The present invention is in no way limited to the methods and materials described herein. In the event that one or more of the incorporated literature, patents, and similar materials differs from or contradicts this application, including but not limited to defined terms, term usage, described techniques, or the like, this application controls.
It is further appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, can also be provided in combination in a single embodiment. Conversely, various features of the invention which are, for brevity, described in the context of a single embodiment, can also be provided separately or in any suitable subcombination.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one skilled in the art to which this invention belongs. All patents and publications referred to herein are incorporated by reference in their entirety.
As used herein, the following definitions shall apply unless otherwise indicated. For purposes of this invention, the chemical elements are identified in accordance with the Periodic Table of the Elements, CAS version, and the Handbook of Chemistry and Physics, 75th Ed. 1994. Additionally, general principles of organic chemistry are described in “Organic Chemistry” , Thomas Sorrell, University Science Books, Sausalito: 1999, and Smith et al., “March’s Advanced Organic Chemistry” , John Wiley &Sons, New York: 2007, the entire contents of which are hereby incorporated by reference.
The grammatical articles “a” , “an” and “the” , as used herein, are intended to include “at least one” or “one or more” unless otherwise indicated herein or clearly contradicted by the context. Thus, the articles are used herein to refer to one or more than one (i.e. at least one) of the grammatical objects of the article. By way of example, “a component” means one or more components, and thus, possibly, more than one component is contemplated and may be employed or used in an implementation of the described embodiments.
The term “comprise” is an open expression, it means comprising the contents disclosed herein, but don’t exclude other contents.
“Stereoisomers” refers to compounds which have identical chemical constitution, but differ with regard to the arrangement of the atoms or groups in space. Stereoisomers include enantiomer, diastereomers, conformer (rotamer) , geometric (cis/trans) isomer, atropisomer, etc.
“Enantiomers” refers to two stereoisomers of a compound which are non-superimposable mirror images of one another.
“Diastereomer” refers to a stereoisomer with two or more centers of chirality and whose molecules are not mirror images of one another. Diastereomers have different physical properties, e.g. melting points, boling points, spectral properties or biological activities. Mixture of  diastereomers may separate under high resolution analytical procedures such as electrophoresis and chromatography such as HPLC.
Stereochemical definitions and conventions used herein generally follow S. P. Parker, Ed., McGraw-Hill Dictionary of Chemical Terms (1984) McGraw-Hill Book Company, New York; and Eliel, E. and Wilen, S., “Stereochemistry of Organic Compounds” , John Wiley &Sons, Inc., New York, 1994.
Many organic compounds exist in optically active forms, i.e., they have the ability to rotate the plane of plane-polarized light. In describing an optically active compound, the prefixes D and L, or R and S, are used to denote the absolute configuration of the molecule about its chiral center (s) . The prefixes d and l or (+) and (-) are employed to designate the sign of rotation of plane-polarized light by the compound, with (-) or l meaning that the compound is levorotatory. A compound prefixed with (+) or d is dextrorotatory. A specific stereoisomer may be referred to as an enantiomer, and a mixture of such stereoisomers is called an enantiomeric mixture. A 50: 50 mixture of enantiomers is referred to as a racemic mixture or a racemate, which may occur where there has been no stereoselection or stereospecificity in a chemical reaction or process.
Any asymmetric atom (e.g., carbon or the like) of the compound (s) disclosed herein can be present in racemic or enantiomerically enriched, for example the (R) -, (S) -or (R, S) -configuration. In certain embodiments, each asymmetric atom has at least 50 %enantiomeric excess, at least 60 %enantiomeric excess, at least 70 %enantiomeric excess, at least 80 %enantiomeric excess, at least 90 %enantiomeric excess, at least 95 %enantiomeric excess, or at least 99 %enantiomeric excess in the (R) -or (S) -configuration.
Depending on the choice of the starting materials and procedures, the compounds can be present in the form of one of the possible stereoisomers or as mixtures thereof, such as racemates and diastereoisomer mixtures, depending on the number of asymmetric carbon atoms. Optically active (R) -and (S) -isomers may be prepared using chiral synthons or chiral reagents, or resolved using conventional techniques. If the compound contains a double bond, the substituent may be E or Z configuration. If the compound contains a disubstituted cycloalkyl, the cycloalkyl substituent may have a cis-or trans-configuration.
Any resulting mixtures of stereoisomers can be separated on the basis of the physicochemical differences of the constituents, into the pure or substantially pure geometric isomers, enantiomers, diastereomers, for example, by chromatography and/or fractional  crystallization.
Any resulting racemates of final products or intermediates can be resolved into the optical antipodes by methods known to those skilled in the art, e.g., by separation of the diastereomeric salts thereof. Racemic products can also be resolved by chiral chromatography, e.g., high performance liquid chromatography (HPLC) using a chiral adsorbent. In particularly, enantiomer may be obtained by asymmetric synthesis.
As described herein, compounds disclosed herein may optionally be substituted with one or more substituents, such as are illustrated generally below, or as exemplified by particular classes, subclasses, and species of the invention. It will be appreciated that the phrase “optionally substituted” is used interchangeably with the phrase “substituted or unsubstituted” . In general, the term “substituted” refers to the replacement of one or more hydrogen radicals in a given structure with the radical of a specified substituent. Unless otherwise indicated, an optionally substituted group may have a substituent at each substitutable position of the group. When more than one position in a given structure can be substituted with more than one substituent selected from a specified group, the substituent may be either the same or different at each position. Specifically, one example of “one or more” refers to one, two, three, four, five, six, seven, eight, nine or ten. wherein substituents of compounds disclosed herein include, but are not limited to, deuterium (D or H 2) , F, Cl, Br, I, cyano, hydroxy, nitro, amino, carboxy, alkyl, alkoxy, alkoxyalkyl, alkoxyalkoxy, alkoxyalkylamino, aryloxy, heteroaryloxy, heterocyclyloxy, arylalkoxy, heteroarylalkoxy, heterocyclylalkoxy, cycloalkylalkoxy, alkylamino, alkylaminoalkyl, alkylaminoalkylamino, cycloalkylamino, cycloalkylalkylamino, alkylthio, haloalkyl, haloalkoxy, hydroxy-substituted alkyl, hydroxy-substituted alkylamino, cyano-substituted alkyl, cyano-substituted alkoxy, cyano-substituted alkylamino, amino-substituted alkyl, alkylacyl, heteroalkyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, heterocyclylacyl, aryl, arylalkyl, arylamino, heteroaryl, heteroarylalkyl, heteroarylamino, acylamino, sulfonyl, aminosulfonyl, and the like.
Furthermore, what need to be explained is that the phrase “each…is independently” and “each of…and…is independently” , unless otherwise stated, should be broadly understood. The specific options expressed by the same symbol are independent of each other in different groups; or the specific options expressed by the same symbol are independent of each other in same groups.
At various places in the present specification, substituents of compounds disclosed herein are disclosed in groups or in ranges. It is specifically intended that the invention include each and every individual subcombination of the members of such groups and ranges. For example, the term “C 1-C 6 alkyl” or “C 1-6 alkyl” is specifically intended to individually disclose methyl, ethyl, C 3 alkyl, C 4 alkyl, C 5 alkyl, and C 6 alkyl.
The term “alkyl” or “alkyl group” refers to a saturated linear or branched-chain monovalent hydrocarbon group of 1-20 carbon atoms, wherein the alkyl group is optionally substituted with one or more substituents described herein. Unless otherwise stated, the alkyl group contains 1-20 carbon atoms. In some embodiments, the alkyl group contains 1-12 carbon atoms. In some embodiments, the alkyl group contains 1-8 carbon atoms. In other embodiments, the alkyl group contains 1-6 carbon atoms. In still other embodiments, the alkyl group contains 1-4 carbon atoms. In yet other embodiments, the alkyl group contains 1-3 carbon atoms.
Some non-limiting examples of the alkyl group include methyl (Me, -CH 3) , ethyl (Et, -CH 2CH 3) , n-propyl (n-Pr, -CH 2CH 2CH 3) , isopropyl (i-Pr, -CH (CH 3)  2) , n-butyl (n-Bu, -CH 2CH 2CH 2CH 3) , i-butyl (i-Bu, -CH 2CH (CH 3)  2) , s-butyl (s-Bu, -CH (CH 3) CH 2CH 3) , t-butyl (t-Bu, -C (CH 3)  3) , n-pentyl (-CH 2CH 2CH 2CH 2CH 3) , 2-pentyl (-CH (CH 3) CH 2CH 2CH 3) , 3-pentyl (-CH (CH 2CH 3)  2) , 2-methyl-2-butyl (-C (CH 3)  2CH 2CH 3) , 3-methyl-2-butyl (-CH (CH 3) CH (CH 3)  2) , 3-methyl-1-butyl (-CH 2CH 2CH (CH 3)  2) , 2-methyl-1-butyl (-CH 2CH (CH 3) CH 2CH 3) , and so on.
The term “alkylene” refers to a saturated divalent hydrocarbon group derived from a straight or branched chain saturated hydrocarbon by the removal of two hydrogen atoms. Unless otherwise stated, the alkylene group contains 1-12 carbon atoms. In some embodiments, the alkylene group contains 1-8 carbon atoms. In other embodiments, the alkylene group contains 1-6 carbon atoms. In still other embodiments, the alkylene group contains 1-4 carbon atoms. In yet other embodiments, the alkylene group contains 1-3 carbon atoms. In yet other embodiments, the alkylene group contains 1-2 carbon atoms. Some non-limiting examples of such group include methylene (-CH 2-) , ethylene (-CH 2CH 2-) , propylene (-CH 2CH 2CH 2-) , -CH (CH 3) CH 2-, -C (CH 3)  2-, -CH 2CH 2CH (CH 3) -, -CH 2CH 2C (CH 3)  2-, and the like.
The term “alkenyl” refers to a linear or branched-chain monovalent hydrocarbon radical of 2 to 12 carbon atoms with at least one site of unsaturation, i.e., a carbon-carbon, sp 2 double bond, wherein the alkenyl radical may be optionally substituted independently with one or more substituents described herein, and includes radicals having “cis” and “trans” orientations, or  alternatively, “E” and “Z” orientations. In some embodiments, the alkenyl contains 2 to 8 carbon atoms. In other embodiments, the alkenyl contains 2 to 6 carbon atoms. In still other embodiments, the alkenyl contains 2 to 4 carbon atoms. Some non-limiting examples of the alkenyl group include ethenyl or vinyl (-CH=CH 2) , allyl (-CH 2CH=CH 2) , propenyl (CH 3-CH=CH-) , oxo substituted butenyl (CH 3-C (=O) -CH=CH-) , and so on.
The term “alkynyl” refers to a linear or branched chain monovalent hydrocarbon radical of 2 to 12 carbon atoms with at least one carbon-carbon, sp triple bond.
The term “alkoxy” refers to an alkyl group, as previously defined, attached to the parent molecular moiety via an oxygen atom. Some non-limiting examples of the alkoxy group include methoxy (MeO, -OCH 3) , ethoxy (EtO, -OCH 2CH 3) , 1-propoxy (n-PrO, n-propoxy, -OCH 2CH 2CH 3) , 2-propoxy (i-PrO, i-propoxy, -OCH (CH 3)  2) , and so on.
The term “alkylthio” refers to an alkyl group, as previously defined, attached to the parent molecular moiety via a sulphur atom. Wherein the alkyl group is as defined herein. Some non-limiting examples of the alkylthio group include -SCH 3, -SCH 2CH 3, -SCH 2CH 2CH 3, -SCH (CH 3)  2, and so on.
The term “cycloalkyl” refers to a monovalent or multivalent saturated ring having 3 to 12 carbon atoms as a monocyclic, bicyclic, or tricyclic ring system. In some embodiments, the cycloalkyl group contains 3 to 10 carbon atoms. In other embodiments, the cycloalkyl group contains 3 to 8 carbon atoms. In still other embodiments, the cycloalkyl group contains 3 to 6 carbon atoms. The cycloalkyl radical is optionally substituted with one or more substituents described herein. Some examples include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, cyclohendecyl and cyclododecyl, etc.
The term “heterocycle” , “heterocyclyl” , or “heterocyclic ring” as used interchangeably herein refers to a saturated or partially unsaturated monocyclic, bicyclic or tricyclic ring containing 3-15 ring atoms of which at least one ring atom is selected from nitrogen, sulfur and oxygen, and of which may, unless otherwise specified, be carbon or nitrogen linked, and of which a -CH 2-group can optionally be replaced by a -C (=O) -group. In heterocyclyl group, the ring sulfur atom can be optionally oxygenized to S-oxide and the ring nitrogen atom can be optionally oxygenized to N-oxide. Examples of heterocyclyl include, but are not limited to, oxiranyl, azetidinyl, oxetanyl, thietanyl, pyrrolidinyl (e.g. 2-pyrrolidinyl) , 2-pyrrolinyl,  3-pyrrolinyl, pyrazolidinyl, imidazolinyl, imidazolidinyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothienyl, dihydrothienyl, 1, 3-dioxolanyl, dithiolanyl, tetrahydropyranyl, dihydropyranyl, 2H-pyranyl, 4H-pyranyl, tetrahydrothiopyranyl, piperidinyl (2-piperidinyl, 3-piperidinyl, 4-piperidinyl) , morpholinyl, thiomorpholinyl, 1-oxothiomorpholinyl, 1, 1-dioxothiomorpholinyl, piperazinyl, dioxanyl, dithianyl, thioxanyl, homopiperazinyl, homopiperidinyl, oxepanyl, thiepanyl, 2-oxa-5-azabicyclo [2.2.1] hept-5-yl, tetrahydropyridyl. Some non-limiting examples of heterocyclyl wherein -CH 2-group is replaced by -C (=O) -moiety include 2-oxopyrrolidinyl, oxo-1, 3-thiazolidinyl, 2-piperidinonyl and 3, 5-dioxopiperidinyl. Some non-limited examples of heterocyclyl wherein the ring sulfur atom is oxidized is sulfolanyl, 1, 1-dioxo-thiomorpholinyl. And wherein the carbocyclyl group is optionally substituted with one or more substituents described herein.
The term “3-12 membered heterocyclyl” , “3-10 membered heterocyclyl” , “3-10 membered heterocyclyl” or “3-6 membered heterocyclyl” , wherein “3-12 membered” , “3-10 membered” , “3-8 membered” or “3-6 membered” typically describe the number of ring atoms of a molecule. For example, piperidinyl is an example of a 6 membered heterocyclyl group.
The term “unsaturated” refers to a moiety having one or more units of unsaturation.
The term “heteroatom” refers to one or more of oxygen, sulfur, nitrogen, phosphorus and silicon, including any oxidized form of nitrogen, sulfur, and phosphorus; the quaternized form of any basic nitrogen; or a substitutable nitrogen of a heterocyclic ring, for example, N (as in 3, 4-dihydro-2H-pyrrolyl) , NH (as in pyrrolidinyl) or NR (as in N-substituted pyrrolidinyl) .
The term “halogen” refers to fluorine (F) , chlorine (Cl) , bromine (Br) or iodine (I) .
The term “aryl” refers to monocyclic, bicyclic and tricyclic carbocyclic ring systems having a total of six to fourteen ring members, or six to twelve ring members, or six to ten ring members, wherein at least one ring in the system is aromatic, wherein each ring in the system contains 3 to 7 ring members and that has a single point or multipoint of attachment to the rest of the molecule. The term “aryl” and “aromatic ring” can be used interchangeably herein. Examples of the aryl group would include phenyl, naphthyl, and anthryl. The aryl radical is optionally substituted with one or more substituents described herein.
The term “heteroaryl” refers to monocyclic, bicyclic and tricyclic carbocyclic ring systems having a total of five to twelve ring members, or five to ten ring members, or five to six ring members, wherein at least one ring in the system is aromatic, and in which at least one ring  member is selected from heteroatom, and wherein each ring in the system contains 5 to 7 ring members and that has a single point or multipoint of attachment to the rest of the molecule. The term “heteroaryl” and “heteroaromatic ring” or “heteroaromatic compound” can be used interchangeably herein. The heteroaryl group is optionally substituted with one or more substituents disclosed herein. In one embodiment, a 5-10 membered heteroaryl comprises 1, 2, 3 or 4 heteroatoms independently selected from O, S and N.
Some non-limiting examples of the heteroaryl ring include 2-furanyl, 3-furanyl, N-imidazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, N-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, pyridazinyl (e.g., 3-pyridazinyl) , 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, tetrazolyl (e.g., 5-tetrazolyl) , triazolyl (e.g., 2-triazolyl and 5-triazolyl) , 2-thienyl, 3-thienyl, pyrazolyl, isothiazolyl, 1, 2, 3-oxadiazolyl, 1, 2, 5-oxadiazolyl, 1, 2, 4-oxadiazolyl, 1, 2, 3-triazolyl, 1, 2, 3-thiadiazolyl, 1, 3, 4-thiadiazolyl, 1, 2, 5-thiadiazolyl, pyrazinyl, 1, 3, 5-triazinyl, oxopyrimidinyl, oxopyridinyl; and the following bicycles, but are not limited to: benzimidazolyl, benzofuryl, benzotetrahydrofuryl, benzothienyl, indolyl (e.g., 2-indolyl) , benzopiperidyl, and so on.
Salts of the compound disclosed herein include those derived from alkali or alkaline earth metals and those derived from ammonia and amines. Preferred cations include sodium, potassium, magnesium, and aminium (ammonium) cations of the formula N + (R 19R 20R 21R 22) , wherein each R 19, R 20, R 21 and R 22 is independently selected from H, C 1-C 6 alkyl and C 1-C 6 hydroxyalkyl. Salts of the compound having Formula (I) can be prepared by treatment of the compound having Formula (I) with a metal hydroxide, such as sodium hydroxide, or with an amine, such as ammonia, trimethylamine, diethanolamine, 2-methylthiopropylamine, bisallylamine, 2-butoxyethylamine, morpholine, cyclododecylamine, or benzylamine.
When a compound of this invention contains a basic moiety, acceptable salts can be formed from organic and inorganic acids, for example, acetic, propionic, lactic, citric, tartaric, succinic, fumaric, maleic, malonic, mandelic, malic, phthalic, hydrochloric, hydrobromic, phosphoric, nitric, sulfuric, methanesulfonic, naphthalenesulfonic, benzenesulfonic, toluenesulfonic, camphorsulfonic, and similarly known acceptable acids.
DESCRIPTION OF COMPOUNDS OF THE INVENTION
The invention provides a novel fungicidal compound having an excellent controlling  effect on plant diseases, a fungicidal composition and formulation containing the fungicidal compound, and use thereof.
In one aspect, provided herein is a compound having Formula (A) or a stereoisomer, an N-oxide or a salt thereof,
Figure PCTCN2018081979-appb-000010
wherein
each of R 1 and R 2 is independently H, alkyl, alkoxyalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, cycloalkylalkyl, heterocyclylalkyl, arylalkyl, halo substituted arylalkyl or heteroarylalkyl; or R 1 and R 2, together with the N atom to which they are attached, form a heterocyclyl or heteroaryl group;
wherein the heterocyclyl or heteroaryl group formed from R 1 and R 2, together with the N atom to which they are attached is optionally substituted with one or more R 12;
R 3 is H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, aryl or haloaryl;
w is 0 , 1 or 2;
R 4 is H, alkyl, -C (=O) -alkyl, -alkylene-C (=O) -alkyl, -C (=O) -O-alkyl, -alkylene-C (=O) -O-alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, cycloalkylalkyl or heterocyclylalkyl; wherein R 4 is optionally substituted with one or more R 14;
each R a and R b is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl or cycloalkyl;
or R a and R b together form oxo (=O) ;
x is 0, 1, 2, 3, 4, 5 or 6;
each of R 5, R 6, R 7, R 8 and R 9 is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, -C (=O) -NR cR d, -NR m-C (=O) -R n, -NR p (OR q) , -C (=O) -R x, -C (=O) -OR y, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, hydroxy substituted alkyl, amino substituted alkyl, cyano substituted alkyl, alkoxy, haloalkoxy, hydroxy substituted alkoxy, amino substituted alkoxy, cyano substituted alkoxy, alkylamino, alkylthio or aryloxy;
wherein R 5 and R 6, together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 15;
wherein R 6 and R 7, together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 16;
wherein R 7 and R 8, together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 17;
wherein R 8 and R 9, together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 18;
wherein each of R p and R q is independently H, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl or -C (=O) -OR y1;
wherein each of R c, R d, R m, R n, R y1, R x and R y is independently H, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl;
wherein each R 1, R 2, R 3, R 5, R 6, R 7, R 8, R 9, R a, R b, R c, R d, R m, R n, R x and R y is optionally substituted with one, two, three, four, five or six R 10;
each R 10, R 12 and R 14 is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, -C (=O) -OR z, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halo C 1-6 alkyl, halo C 2-6 alkenyl, halo C 2-6 alkynyl, hydroxy substituted C 1-6 alkyl, amino substituted C 1-6 alkyl, cyano substituted C 1-6 alkyl, C 1-6 alkoxy, halo C 1-6 alkoxy, hydroxy substituted C 1-6 alkoxy, amino substituted C 1-6 alkoxy, cyano substituted C 1-6 alkoxy, C 1-6 alkylamino, C 3-8cycloalkyl, C 6-10 aryl or C 1-9 heteroaryl;
wherein R z is C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halo C 1-6 alkyl, halo C 2-6 alkenyl, halo C 2-6 alkynyl, C 3-8 cycloalkyl, 3-12 membered heterocyclyl, C 6-10 aryl or C 1-9 heteroaryl;
each R 15, R 16, R 17 and R 18 is independently H, halogen, cyano, nitro, alkyl, alkenyl, alkynyl, alkoxy, alkylamino, haloalkyl or haloalkoxy;
with the proviso that when R 1 and R 2 is methyl, R 3 is H, w is 2, R 4 is H and x is 0, R 7 is not unsubstituted or substituted phenoxy, unsubstituted or substituted pyridyloxy or unsubstituted or substituted naphthyloxy.
In some embodiments, provided herein is a compound having Formula (I) or a  stereoisomer, an N-oxide or a salt thereof,
Figure PCTCN2018081979-appb-000011
wherein
each of R 1 and R 2 is independently H, alkyl, alkoxyalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, cycloalkylalkyl, heterocyclylalkyl, arylalkyl, halo substituted arylalkyl or heteroarylalkyl; or R 1 and R 2, together with the N atom to which they are attached, form a heterocyclyl or heteroaryl group;
wherein the heterocyclyl or heteroaryl group formed from R 1 and R 2, together with the N atom to which they are attached is optionally substituted with one or more R 12;
R 3 is H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, aryl or haloaryl;
R 4 is H, alkyl, -C (=O) -alkyl, -alkylene-C (=O) -alkyl, -C (=O) -O-alkyl, -alkylene-C (=O) -O-alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, cycloalkylalkyl or heterocyclylalkyl; wherein R 4 is optionally substituted with one or more R 14;
each R a and R b is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl or cycloalkyl;
or R a and R b together form oxo (=O) ;
x is 0, 1, 2, 3, 4, 5 or 6;
each of R 5, R 6, R 7, R 8 and R 9 is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, -C (=O) -NR cR d, -NR m-C (=O) -R n, -NR p (OR q) , -C (=O) -R x, -C (=O) -OR y, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, hydroxy substituted alkyl, amino substituted alkyl, cyano substituted alkyl, alkoxy, haloalkoxy, hydroxy substituted alkoxy, amino substituted alkoxy, cyano substituted alkoxy, alkylamino, alkylthio or aryloxy;
wherein R 5 and R 6, together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 15;
wherein R 6 and R 7, together with the carbon atoms to which they are attached, optionally  form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 16;
wherein R 7 and R 8, together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 17;
wherein R 8 and R 9, together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 18;
wherein each of R p and R q is independently H, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl or -C (=O) -OR y1;
wherein each of R c, R d, R m, R n, R y1, R x and R y is independently H, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl;
wherein each R 1, R 2, R 3, R 5, R 6, R 7, R 8, R 9, R a, R b, R c, R d, R m, R n, R x and R y is optionally substituted with one, two, three, four, five or six R 10;
each R 10, R 12 and R 14 is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, -C (=O) -OR z, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halo C 1-6 alkyl, halo C 2-6 alkenyl, halo C 2-6 alkynyl, hydroxy substituted C 1-6 alkyl, amino substituted C 1-6 alkyl, cyano substituted C 1-6 alkyl, C 1-6 alkoxy, halo C 1-6 alkoxy, hydroxy substituted C 1-6 alkoxy, amino substituted C 1-6 alkoxy, cyano substituted C 1-6 alkoxy, C 1-6 alkylamino, C 3-8 cycloalkyl, C 6-10 aryl or C 1-9 heteroaryl;
wherein R z is C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halo C 1-6 alkyl, halo C 2-6 alkenyl, halo C 2-6 alkynyl, C 3-8 cycloalkyl, 3-12 membered heterocyclyl, C 6-10 aryl or C 1-9 heteroaryl;
each R 15, R 16, R 17 and R 18 is independently H, halogen, cyano, nitro, alkyl, alkenyl, alkynyl, alkoxy, alkylamino, haloalkyl or haloalkoxy;
with the proviso that when R 1 and R 2 is methyl, R 3 is H, w is 2, R 4 is H and x is 0, R 7 is not unsubstituted or substituted phenoxy, unsubstituted or substituted pyridyloxy or unsubstituted or substituted naphthyloxy.
In some embodiments, each of R 1 and R 2 is independently H, C 1-6 alkyl, C 1-6 alkoxy-C 1-6-alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, C 2-10 heterocyclyl, C 6-10 aryl, C 1-9 heteroaryl, C 3-8 cycloalkyl-C 1-6-alkyl, C 2-10 heterocyclyl-C 1-6-alkyl, C 6-10 aryl-C 1-6-alkyl, halo substituted C 6-10 aryl-C 1-6-alkyl or C 1-9 heteroaryl-C 1-6-alkyl; or R 1 and R 2, together with the N atom to which they are attached, form 3-8 membered heterocyclyl or C 1-9 heteroaryl;
wherein the 3-8 membered heterocyclyl or C 1-9 heteroaryl formed from R 1 and R 2, together with the N atom to which they are attached is optionally substituted with one or more R 12;
wherein R 12 is as defined herein.
In some embodiments, R 3 is H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halo C 1-6 alkyl, halo C 2-6 alkenyl, halo C 2-6 alkynyl, C 6-10 aryl or halo C 6-10 aryl.
In some embodiments, R 4 is H, C 1-6 alkyl, -C (=O) -C 1-6 alkyl, -C 1-6 alkylene-C (=O) -C 1-6 alkyl, -C (=O) -O-C 1-6 alkyl, -C 1-6 alkylene-C (=O) -O-C 1-6 alkyl, C 1-6 alkoxy, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, 3-12 membered heterocyclyl, C 6-10 aryl, C 6-10 aryl-C 1-6-alkyl, C 3-8 cycloalkyl-C 1-6-alkyl or C 2-10 heterocyclyl-C 1-6-alkyl; wherein R 4 is optionally substituted with one or more R 14;
wherein R 14 is as defined herein.
In some embodiments, each R a and R b is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halo C 1-6 alkyl, halo C 2-6 alkenyl, halo C 2-6 alkynyl or C 3-8 cycloalkyl;
or R a and R b together form oxo (=O) .
In some embodiments, x is 0, 1, 2, 3, 4, 5 or 6.
In some embodiments, each of R 5, R 6, R 7, R 8 and R 9 is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, -C (=O) -NR cR d, -NR m-C (=O) -R n, -NR p (OR q) , -C (=O) -R x, -C (=O) -OR y, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halo C 1-6 alkyl, halo C 2-6 alkenyl, halo C 2-6 alkynyl, hydroxy substituted C 1-6 alkyl, amino substituted C 1-6 alkyl, cyano substituted C 1-6 alkyl, C 1-6 alkoxy, halo C 1-6 alkoxy, hydroxy substituted C 1-6 alkoxy, amino substituted C 1-6 alkoxy, cyano substituted C 1-6 alkoxy, C 1-6 alkylamino, C 1-6 alkylthio or C 6-10 aryloxy;
wherein R 5 and R 6, together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 15;
wherein R 6 and R 7, together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 16;
wherein R 7 and R 8, together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally  substituted with one, two, three, four, five, six, seven, eight or nine R 17;
wherein R 8 and R 9, together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 18;
wherein R c, R d, R m, R n, R p, R q, R 15, R 16, R 17, R 18, R x and R y are as defined herein.
In some embodiments, wherein each of R p and R q is independently H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halo C 1-6 alkyl, halo C 2-6 alkenyl, halo C 2-6 alkynyl, C 3-6 cycloalkyl, 3-8 membered heterocyclyl, C 6-10 aryl, C 1-6 heteroaryl or -C (=O) -OR y1;
wherein R y1 is as defined herein.
In some embodiments, wherein each of R c, R d, R m, R n, R y1, R x and R y is independently H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halo C 1-6 alkyl, halo C 2-6 alkenyl, halo C 2-6 alkynyl, C 3-6 cycloalkyl, 3-8 membered heterocyclyl, C 6-10 aryl or C 1-5 heteroaryl.
In some embodiments, wherein each R 1, R 2, R 3, R 5, R 6, R 7, R 8, R 9, R a, R b, R c, R d, R m, R n, R x and R y is optionally substituted with one, two, three, four, five or six R 10;
wherein R 10 is as defined herein.
In some embodiments, each R 10, R 12 and R 14 is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, -C (=O) -OR z, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, halo C 1-4 alkyl, halo C 2-4 alkenyl, halo C 2-4 alkynyl, hydroxy substituted C 1-4 alkyl, amino substituted C 1-4 alkyl, cyano substituted C 1-4 alkyl, C 1-4 alkoxy, halo C 1-4 alkoxy, hydroxy substituted C 1-4 alkoxy, amino substituted C 1-4 alkoxy, cyano substituted C 1-4 alkoxy, C 1-4 alkylamino, C 3-6 cycloalkyl, C 6-10 aryl or C 1-5 heteroaryl;
wherein R z is as defined herein.
In some embodiments, wherein R z is C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, halo C 1-4 alkyl, halo C 2-4 alkenyl, halo C 2-4 alkynyl, C 3-6 cycloalkyl, 3-8 membered heterocyclyl, C 6-10 aryl or C 1-5 heteroaryl.
In some embodiments, each R 15, R 16, R 17 and R 18 is independently H, halogen, cyano, nitro, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 alkylamino, halo C 1-6 alkyl or halo C 1-6 alkoxy.
In some embodiments, each of R 1 and R 2 is independently H, C 1-4 alkyl, C 1-3 alkoxy-C 1-3-alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 3-6 cycloalkyl, C 2-6 heterocyclyl, C 6-10 aryl, C 1-5 heteroaryl, C 3-6 cycloalkyl-C 1-4-alkyl, C 2-6 heterocyclyl-C 1-4-alkyl, C 6-10 aryl-C 1-4-alkyl, halo  substituted C 6-10 aryl-C 1-4-alkyl or C 1-5 heteroaryl-C 1-4-alkyl; or R 1 and R 2, together with the N atom to which they are attached, form the following sub-structures:
Figure PCTCN2018081979-appb-000012
wherein each of p 1 and p 2 is independently 0, 1 or 2;
q is 0, 1 or 2;
X 1 is -O-, -S-, -S (=O) -, -S (=O)  2-or -NH-;
each X 2, X 3, X 4 and X 5 is independently N or CH;
wherein sub-structure (i) , (ii) , (iii) or (iv) is optionally substituted with one or more R 12;
wherein R 12 is as defined herein.
In other embodiments, each of R 1 and R 2 is independently H, -CH 3, -CH 2CH 3, -CH 2CH 2CH 3, -CH (CH 3)  2, -CH 2CH=CH 2, -CH 2CH 2CH=CH 2, -CH 2CH=CHCH 3, -CH 2-O-CH 3, -CH 2CH 2-O-CH 3, -CH 2-O-CH 2CH 3, -CH 2CH 2-O-CH 2CH 3, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, benzyl, 4-fluorobenzyl or 4-cyanobenzyl;
or R 1 and R 2, together with the N atom to which they are attached, form the following sub-structures:
Figure PCTCN2018081979-appb-000013
In some embodiments, R 3 is H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, halo C 1-4 alkyl, halo C 2-4 alkenyl, halo C 2-4 alkynyl, C 6-10 aryl or halo C 6-10 aryl.
In other embodiments, R 3 is H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, -CH 3, -CHF 2, -CH 2F, -CH 2CH 3, -CH 2CH 2F, -CH 2CHF 2, -CH 2CH 2CH 3, -CH (CH 3)  2, -C (CH 3)  3, phenyl, 2-fluorophenyl, 3-fluorophenyl or 4-fluorophenyl.
In some embodiments, R 4 is H, C 1-4 alkyl, -C (=O) -C 1-4 alkyl, -C 1-4 alkylene-C (=O) -C 1-4 alkyl, -C (=O) -O-C 1-4 alkyl, -C 1-4 alkylene-C (=O) -O-C 1-4 alkyl, C 1-4 alkoxy, C 2-4 alkenyl, C 2-4 alkynyl, C 3-6 cycloalkyl, 3-10 membered heterocyclyl, C 6-10 aryl, C 6-10 aryl-C 1-3-alkyl, C 3-6 cycloalkyl-C 1-3-alkyl or C 2-6 heterocyclyl-C 1-3-alkyl; wherein R 4 is optionally substituted with one, two, three, four or five R 14;
wherein R 14 is as defined herein.
In some embodiments, each R 14 is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, -C (=O) -O-C 1-3 alkyl, C 1-3 alkyl, C 1-3 alkoxy, C 3-6 cycloalkyl or phenyl.
In some embodiments, R 4 is H, -CH 3, -CHF 2, -CH 2 (CN) , -CH 2CH 3, -CH (CN) CH 3, -CH 2CHF 2, -CH 2CH 2CH 3, -CH (CH 3)  2, -CH 2CH 2CH 2CH 3, -C (CH 3)  3, -CH 2CH=CH 2, -CH 2CH 2CH=CH 2, -CH 2CH=CHCH 3, -C (=O) -CH 3, -C (=O) -CH 2CH 3, -C (=O) -OCH 3, -C (=O) -OCH 2CH 3, -CH 2-C (=O) -OCH 3, -CH 2-C (=O) -OCH 2CH 3, -OCH 3, -OCH 2CH 3, -OCH 2CH 2CH 3, -OCH (CH 3)  2, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl or benzyl; or R 4 has the following sub-structures:
Figure PCTCN2018081979-appb-000014
In some embodiments, each R a and R b is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, halo C 1-4 alkyl, halo C 2-4 alkenyl, halo C 2-4 alkynyl or C 3-6 cycloalkyl.
In some embodiments, each R a and R b is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, -CH 3, -CH 2CH 3, -CH 2CH 2CH 3, -CH (CH 3)  2, -CH=CH 2, -CH 2-CH=CH 2, -CH 2F, -CHF 2 or -CF 3.
In some embodiments, each of R 5, R 6, R 7, R 8 and R 9 is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, -C (=O) -NR cR d, -NR m-C (=O) -R n, -NR p (OR q) , -C (=O) -R x, -C (=O) -OR y, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, halo C 1-4 alkyl, halo C 2-4 alkenyl, halo C 2-4 alkynyl, hydroxy substituted C 1-4 alkyl, amino substituted C 1-4 alkyl, cyano substituted C 1-4 alkyl, C 1-4 alkoxy, halo C 1-4 alkoxy, hydroxy substituted C 1-4 alkoxy, amino substituted C 1-4 alkoxy, cyano substituted C 1-4 alkoxy, C 1-4 alkylamino, C 1-4 alkylthio or C 6-10 aryloxy;
wherein R c, R d, R m, R n, R p, R q, R x and R y are as defined herein.
In some embodiments, wherein each of R p and R q is independently H, C 1-3 alkyl, C 2-4  alkenyl, C 2-4 alkynyl, halo C 1-3 alkyl, halo C 2-4 alkenyl, halo C 2-4 alkynyl, C 3-6 cycloalkyl, 3-6 membered heterocyclyl, C 6-10 aryl, C 1-5 heteroaryl or -C (=O) -OR y1;
wherein R y1 is as defined herein.
In some embodiments, each of R c, R d, R m, R n, R y1, R x and R y is independently H, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, halo C 1-4 alkyl, halo C 2-4 alkenyl, halo C 2-4 alkynyl, C 3-6 cycloalkyl, 3-6 membered heterocyclyl, C 6-10 aryl or C 1-5 heteroaryl.
In some embodiments, wherein R 5 and R 6, together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 15;
wherein R 15 is as defined herein.
In some embodiments, wherein R 6 and R 7, together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 16;
wherein R 16 is as defined herein.
In some embodiments, wherein R 7 and R 8, together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 17;
wherein R 17 is as defined herein.
In some embodiments, wherein R 8 and R 9, together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 18;
wherein R 18 is as defined herein.
In some embodiments, wherein each R 5, R 6, R 7, R 8, R 9, R c, R d, R m, R n, R y1, R x and R y is optionally substituted with one, two, three, four, five or six R 10;
wherein R 10 is as defined herein.
In some embodiments, each R 15, R 16, R 17 and R 18 is independently H, halogen, cyano, nitro, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 alkoxy, C 1-4 alkylamino, halo C 1-4 alkyl or halo  C 1-4 alkoxy.
In other embodiments, each R 5, R 6, R 7, R 8 and R 9 is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, -CH 3, -CH 2CH 3, -CH 2CH 2CH 3, -CH (CH 3)  2, -CH 2F, -CHF 2, -CF 3, -CH 2CH 2F, -CH 2CHF 2, -CH 2CF 3, -CH=CH 2, -CH 2-CH=CH 2, -OCH 3, -OCH 2CH 3, -OCH 2CH 2CH 3, -OCH (CH 3)  2, -OCF 3, -OCH 2CF 3, -NH-C (=O) -CH 3, -NH-C (=O) -CH 2CH 3, -NH-OH, -N (OH) -C (=O) -OCH 3, -N (OC (=O) OCH 3) -C (=O) -OCH 3, -C (=O) -CH 3, -C (=O) -CH 2CH 3, -C (=O) -OCH 3, -C (=O) -OCH 2CH 3, -SCH 3, -SCH 2CH 3, -SCH 2CH 2CH 3, -SCH (CH 3)  2, phenoxy, halophenoxy, C 1-4 alkyl substituted phenoxy, C 1-4 alkoxy substituted phenoxy, C 1-4 haloalkyl substituted phenoxy or C 1-4 haloalkoxy substituted phenoxy.
In some embodiments, 
Figure PCTCN2018081979-appb-000015
has the following sub-structures:
Figure PCTCN2018081979-appb-000016
wherein
each R 5, R 7, R 8, R 9, R 15a, R 15b, R 15c, R 15d, R 16a, R 16b, R 16c, R 16d, R 16e, R 16f, R 18a, R 18b, R 18c and R 18d is independently H, halo, cyano, nitro, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 alkylamino, halo C 1-6 alkyl or halo C 1-6 alkoxy.
In other embodiments, each R 5, R 7, R 8, R 9, R 15a, R 15b, R 15c, R 15d, R 16a, R 16b, R 16c, R 16d, R 16e, R 16f, R 18a, R 18b, R 18c and R 18d is independently H, halo, cyano, nitro, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 alkoxy, C 1-4 alkylamino, halo C 1-4 alkyl or halo C 1-4 alkoxy.
In other embodiments, each R 5, R 7, R 8, R 9, R 15a, R 15b, R 15c, R 15d, R 16a, R 16b, R 16c, R 16d, R 16e, R 16f, R 18a, R 18b, R 18c and R 18d is independently H, F, Cl, Br, I, cyano, nitro, methyl, ethyl,  n-propyl, isopropyl, t-butyl, vinyl, propenyl, allyl, ethynyl, propinyl, propargyl, methoxy, ethoxy, isopropoxy, t-butoxy, difluoromethyl, trifluoromethyl, difluoromethoxy, trifluoromethoxy, dimethylamino or diethylamino.
In some embodiments, each R a and R b is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, halo C 1-4 alkyl, halo C 2-4 alkenyl, halo C 2-4 alkynyl or C 3-6 cycloalkyl;
or R a and R b together form oxo (=O) .
In other embodiments, each R a and R b is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, -CH 3, -CH 2CH 3, -CH 2CH 2CH 3, -CH (CH 3)  2, -CH 2F, -CHF 2, -CF 3, -CH 2CH 2F, -CH 2CHF 2, -CH 2CF 3, -CH=CH 2, -CH 2-CH=CH 2, -OCH 3, -OCH 2CH 3, -OCH 2CH 2CH 3, -OCH (CH 3)  2, -OCF 3, -OCH 2CF 3, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl;
or R a and R b together form oxo (=O) .
In some embodiments, provided herein is a compound having Formula (Ia) or a stereoisomer, an N-oxide or a salt thereof,
Figure PCTCN2018081979-appb-000017
wherein
each R 5, R 6, R 7, R 8 and R 9 is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, alkyl, haloalkyl, alkenyl, alkoxy or haloalkoxy;
wherein R 5 and R 6, together with the carbon atoms to which they are attached, optionally form a benzene ring; and wherein the benzene ring is optionally substituted with one, two, three or four substituents selected from F, Cl, Br, I, cyano, nitro, alkyl, alkenyl, alkynyl, alkoxy, alkylamino, haloalkyl or haloalkoxy.
In other embodiments, provided herein is a compound having Formula (Ia) or a stereoisomer, an N-oxide or a salt thereof, wherein each R 5, R 6, R 7, R 8 and R 9 is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, C 1-6 alkyl, halo C 1-6 alkyl, C 2-6 alkenyl, C 1-6 alkoxy or halo C 1-6 alkoxy;
wherein R 5 and R 6, together with the carbon atoms to which they are attached, optionally  form a benzene ring; and wherein the benzene ring is optionally substituted with one, two, three or four substituents selected from F, Cl, Br, I, cyano, nitro, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, halo C 1-6 alkyl or halo C 1-6 alkoxy.
In other embodiments, provided herein is a compound having Formula (Ia) or a stereoisomer, an N-oxide or a salt thereof, wherein each R 5, R 6, R 7, R 8 and R 9 is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, C 1-4 alkyl, halo C 1-4 alkyl, C 2-4 alkenyl, C 1-4 alkoxy or halo C 1-4 alkoxy;
wherein R 5 and R 6, together with the carbon atoms to which they are attached, optionally form a benzene ring; and wherein the benzene ring is optionally substituted with one, two, three or four substituents selected from F, Cl, Br, I, cyano, nitro, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkylamino, halo C 1-4 alkyl or halo C 1-4 alkoxy.
In other embodiments, provided herein is a compound having Formula (Ia) or a stereoisomer, an N-oxide or a salt thereof, wherein each R 5, R 6, R 7, R 8 and R 9 is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, -CH 3, -CH 2CH 3, -CH 2CH 2CH 3, -CH (CH 3)  2, -CH 2F, -CHF 2, -CF 3, -CH 2CH 2F, -CH 2CHF 2, -CH 2CF 3, -CH=CH 2, -OCH 3, -OCH 2CH 3, -OCH 2CH 2CH 3, -OCH (CH 3)  2, -OCF 3 or-OCH 2CF 3;
wherein R 5 and R 6, together with the carbon atoms to which they are attached, optionally form a benzene ring; and wherein the benzene ring is optionally substituted with one, two, three or four substituents selected from F, Cl, Br, I, cyano, nitro, -CH 3, -CF 3, -OCH 3 or -OCF 3.
In some embodiments, provided herein is a compound having one of the following structures or a stereoisomer, an N-oxide or a salt thereof,
Figure PCTCN2018081979-appb-000018
Figure PCTCN2018081979-appb-000019
Figure PCTCN2018081979-appb-000020
Figure PCTCN2018081979-appb-000021
Figure PCTCN2018081979-appb-000022
Figure PCTCN2018081979-appb-000023
Figure PCTCN2018081979-appb-000024
Figure PCTCN2018081979-appb-000025
Figure PCTCN2018081979-appb-000026
Figure PCTCN2018081979-appb-000027
Figure PCTCN2018081979-appb-000028
Figure PCTCN2018081979-appb-000029
In other aspect, provided herein is a method of preparing a compound of Formula (I) comprising
reacting a compound of Formula (e) with a disubstituted amino sulfonyl chloride to obtain the compound of Formula (I) :
Figure PCTCN2018081979-appb-000030
wherein R 1, R 2, R 3, R 4, R 5, R 6, R 7, R 8, R 9, R a, R b and x are as defined herein.
In other aspect, provided herein is a compound having Formula (II) or a stereoisomer, an N-oxide or a salt thereof,
Figure PCTCN2018081979-appb-000031
wherein R 3, R 5, R 6, R 7, R 8, R 9, R a, R b and x are as defined herein.
In other aspect, provided herein is a composition comprising the compound disclosed herein. Unless otherwise indicated, all tautomers, racemates, hydrates, solvates, metabolites,  metabolic precursors or prodrugs of the compounds of Formula (A) , (I) or (Ia) disclosed herein are within the scope of the present invention.
In some embodiments, the composition disclosed herein further comprises an agrochemically acceptable surfactant and carrier.
In other aspect, provided herein is use of the compound or the composition disclosed herein for controlling plant diseases; specifically for use as a fungicide. In some embodiments, the plant disease is caused by plant pathogenic fungi.
COMPOSITIONS OF THE COMPOUNDS OF THE INVENTION
The compound of the invention can generally be used as an active ingredient of fungicides in a composition, i.e. formulation, usually including an agrochemically acceptable surfactant and carrier.
The above surfactant may be any common surfactant in the field of pesticide formulation, the optimization disclosed herein is one or more of emulsifier, dispersant and wetting agent.
In addition to the above surfactants, the carrier may be any common carrier in the field of pesticide formulation, including any silicate, carbonate, sulfate, oxide, phosphate, plant carrier, synthetic carrier. Specifically, for example, one or more of silica, kaolin, diatomite, clay, talc, organic bentonite, pumice, titanium dioxide, dextrin, cellulose powder, light calcium carbonate, soluble starch, corn starch, sawdust powder, urea, amine fertilizer, a mixture of urea and amine fertilizer, glucose, maltose, sucrose, anhydrous potassium carbonate, anhydrous sodium carbonate, anhydrous potassium bicarbonate, anhydrous sodium bicarbonate, attapulgite, a mixture of anhydrous potassium carbonate and anhydrous potassium bicarbonate, a mixture of anhydrous sodium carbonate and anhydrous sodium bicarbonate.
The above emulsifier may be any common emulsifier in the field of pesticide formulation, specifically, the emulsifier may be one or more of calcium dodecylbenzenesulfonate, triphenylethylphenol polyoxyethylene ether phosphate, polyoxyethy fatty alcohol ether, alkyl phenol polyoxyethylene ether, alkyl phenol polyoxyethylene polyoxypropylene ether, fatty amines, ethylene oxide adduct of fatty amide, polyoxyethylene fatty acid ester, ethylene oxide adduct of rosin acid, polyol fatty acid ester and ethylene oxide adduct thereof, styrenyl phenyl polyoxyethylene ether, alkyl phenol formaldehyde resin polyoxyethylene ether, hydroxy terminated polyoxyethylene polyoxypropylene ether, styrenyl phenol formaldehyde resin  polyoxyethylene polyoxypropylene ether and castor oil polyoxyethylene ether.
The above dispersant may be any common emulsifier in the field of pesticide formulation, specifically, the dispersant may be one or more of acrylic acid homopolymer sodium salt, maleic acid disodium salt, naphthalene sulfonated formaldehyde condensates sodium salt, rosin segmented polyoxyethylene ether polyoxypropylene sulfonates, hydroxy terminated polyoxyethylene polyoxypropylene ether segmented copolymer, triphenylethyl phenol polyoxyethylene ether phosphate, fatty alcohol polyoxyethylene ether phosphate and p-hydroxyphenyl lignin sulfonic acid sodium salt.
The above wetting agent may be any common wetting agent in the field of pesticide formulation, specifically, the dispersant may be one or more of lauryl sodium sulfate, sec-alkyl sodium sulfate, sodium dodecyl benzene sulfonate, fatty alcohol polyoxyethylene ether, alkyl naphthalene sulfonate, alkyl phenol resin polyoxyethylene ether sulfate.
The fungicide composition disclosed herein may also contain any common auxiliary for formulation in the field of pesticide formulation, specifically, the auxiliary for formulation may be one or more of solvent, cosolvent, thickener, antifreeze, capsule wall material, protective agent, defoamer, disintegrating agent, stabilizer, preservative and binder.
The above solvent may be any common solvent in the field of pesticide formulation, specifically, the solvent may be one or more of organic solvent, plant oil, mineral oil, solvent oil and water.
Wherein the organic solvent includes one or more of N-methyl pyrrolidone, tetrahydrofuran, dimethyl sulfoxide, N, N-dimethyl decyl amide, N, N-dimethyl formamide, trimethylbenzene, tetramethylbenzene, xylene, toluene, heptane, octane, methanol, isopropanol, butanol, tetrahydrofurfuryl alcohol, tributyl phosphate, 1, 4-dioxane and cyclohexanone.
The plant oil includes one or more of methylated plant oil, pine oleoresin-based plant oil, turpentine oil, epoxidized soybean oil, soybean oil, peanut oil, rapeseed oil, castor oil, corn oil and pine nut oil.
The mineral oil includes one or more of liquid-wax, engine oil, kerosene and lubricant.
Also, the above solvent may be used as a cosolvent.
The above antifreeze may be any common antifreeze in the field of pesticide formulation, the optimization disclosed herein is one or more of glycol, propanediol, glycerol and urea.
The above thickener may be any common thickener in the field of pesticide formulation, specifically, the thickener may be one or more xanthan gum, polyvinyl alcohol, polyallyl alcohol, polyethylene glycol, silica, diatomaceous earth, kaolin, clay, sodium alginate, aluminum silicate magnesium silicate, sodium aluminosilicate, carboxymethyl cellulose, hydroxypropyl cellulose sodium and organobentonite.
The above capsule wall material may be any common capsule wall material in the field of pesticide formulation, the optimization disclosed herein is one or more of polyurethane, polyurea and urea formaldehyde resin.
The above protective agent may be any common protective agent in the field of pesticide formulation, the optimization disclosed herein is one or more of polyvinyl alcohol and/or polyethylene glycol.
The above defoamer may be any common defoamer in the field of pesticide formulation, the optimization disclosed herein is one or more of organo-siloxane, tributyl phosphate and silicone.
The above stabilizer is selected from one or more of triphenyl phosphite, epichlorohydrin and acetic anhydride.
The above preservative is selected from one or more of benzoic acid, sodium benzoate, 1, 2-benzothiazoline-3-one (BIT for short) , isothiazolinone and potassium sorbate.
The present invention also provides a formulation prepared from the above fungicide composition, the form of the formulation is missible oil, aqueous emulsion, microemulsion, soluble liquid agent, aqueous suspension, suspoemulsion, ultra low volume sprays, oil suspension, microcapsule suspension, water surface spreading oil, wettable powder, water dispersible granules, dry suspension, soluble powder, soluble granules, emulsifiable powder, emulsifiable granules, granules, solid micro capsule, effervescent tablets, effervescent granules, water floating dispersible granules or seed dressing agent. The above formulations all may be prepared by the common methods in this field.
A preparation method of the above missible oil may include, for example, mixing every active component, solvent, cosolvent and emulsifier to form a homogeneous transparent oil phase, i.e. missible oil may be obtained.
A preparation method of the above aqueous emulsion may include, for example, mixing active component (s) , emulsifier (s) , cosolvent (s) and solvent (s) to form a homogeneous oil phase;  mixing water, thickener (s) and antifreeze (s) , etc. to form a homogeneous water phase; adding the water phase into the oil phase (or adding the oil phase into the water phase) under high speed shearing to form a aqueous emulsion with good dispersivity.
A preparation method of the above microemulsion may include, for example, mixing active component (s) , emulsifier (s) and solvent (s) to form a homogeneous oil phase. Adding water gradually with stirring to form a homogeneous transparent microemulsion.
A preparation method of the above aqueous/oil suspension may include, for example, grinding active component (s) , sufactant (s) , and the like adjuvant (s) in a sand grinding kettle with water or oil as medium to a certain particle size and filtering; adding measured thickener (s) to the grinded mother liquor, sheating to homogeneous dispersion; obtaining oil suspension or aqueous suspension.
A preparation method of the above water dispersible granules or soluble granules may include, for example, mixing every active component, dispersant, wetting agent, carrier, etc. homogeneously; shredding to a certain particle size through airflow; adding water and kneading; prilling in a granulator; and then drying to get water dispersible granules or soluble granules.
A preparation method of the above wettable powder or soluble powder may include, for example, mixing every active component, adjuvant and other carrier, and the like fillers thoroughly, shredding by using a super micro mill.
The fungicide composition disclosed herein may be provided in a form of a finished product, i.e. every components in the composition had been mixed; also may be in a form of a separate preparation, and mixing them in a container before using, diluting with water selectively according to the required concentration of the active component.
USE OF THE COMPOUNDS AND COMPOSITIONS
The compounds of this invention are useful as plant diseases controlling agents. The present invention therefore further comprises a method for controlling plant diseases caused by plant fungal pathogens, the method comprises applying an effective amount of a compound of the invention or a fungicide composition containing the compound to plants to be protected or parts thereof, or to plant seeds to be protectedd. The compounds and/or compositions of this invention can control diseases caused by a broad spectrum of plant fungal pathogens in the Basidiomycete, Ascomycete, Oomycete and Deuteromycete classes. They are effective in controlling a broad spectrum of plant diseases, particularly foliar pathogens of ornamental, turf,  vegetable, field, cereal, and fruit crops. These pathogens include: Oomycetes, including Phytophthora diseases such as Phytophthora infestans, Phytophthora megasperma, Phytophthora parasitica, Phytophthora cinnamomi and Phytophthora capsici, Pythium diseases such as Pythium aphanidermatum, and diseases in the Peronosporaceae family such as Plasmopara viticola, Peronospora spp. (including Peronospora tabacina and Peronospora parasitica) , Pseudoperonospora spp. (including Pseudoperonospora cubensis) and Bremia lactucae; Ascomycetes, including Alternaria diseases such as Alternaria solani and Alternaria brassicae, Guignardia diseases such as Guignardia bidwell, Venturia diseases such as Venturia inaequalis, Septoria diseases such as Septoria nodorum and Septoria tritici, powdery mildew diseases such as Erysiphe spp. (including Erysiphe graminis and Erysiphe
Figure PCTCN2018081979-appb-000032
) , Uncinula necatur, Sphaerotheca fuligena and Podosphaera leucotricha, Pseudocercosporella herpotrichoides, Botrytis diseases such as Botrytis cinerea, Monilinia fructicola, Sclerotinia diseases such as Sclerotinia sclerotiorum, Magnaporthe grisea, Phomopsis viticola, Helminthosporium diseases such as Helminthosporium tritici repentis, Pyrenophora teres, anthracnose diseases such as Glomerella or Colletotrichum spp. (such as Colletotrichum graminicola and Colletotrichum orbiculare) , and Gaeumannomyces graminis; Basidiomycetes, including rust diseases caused by Puccinia spp. (such as Puccinia recondita, Puccinia striiformis, Puccinia hordei, Puccinia graminis and Puccinia arachidis) , Hemileia vastatrix and Phakopsora pachyrhizi; other pathogens including Rhizoctonia spp. (such as Rhizoctonia solani) ; Fusarium diseases such as Fusarium roseum, Fusarium graminearum and Fusarium oxysporum; Verticillium dahliae; Sclerotium rolfsii; Rynchosporium secalis; Cercosporidium personatum, Cercospora arachidicola and Cercospora beticola; and other genera and species closely related to these pathogens. In addition to their fungicidal activity, the compositions or combinations also have activity against bacteria such as Erwinia amylovora, Xanthomonas campestris, Pseudomonas syringae, and other related species.
The use method of the fungicide composition disclosed herein is simple, which comprises applying the composition to crops or places for crops growth before or after germination of plant diseases by common methods, such as mix soil, spray, jet, pour, etc, the application amount is determined according to climatic conditions or crop states, in general, 10-5000 g per mu is applied, and which is diluted to 10-400 mg/L when applying, preferably, which is diluted to 100-300 mg/L. The diluter is preferably water.
Fungicidal effect of the fungicide composition disclosed herein typically relates to extraneous factors such as climate, but the influence of climate can be reduced by using suitable formulation.
The composition disclosed herein can be used mixing with other compounds having fungicidal, insecticidal, or herbicidal properties, also can be used mixing with nematocides, acaricides, protective agents, herbicide safeners, growth regulator, plant nutrients, or soil conditioners.
GENERAL SYNTHETIC PROCEDURES
The preparation of the compounds of the present invention is represented by the following scheme. Unless otherwise mentioned, the compounds disclosed herein may be prepared by methods described herein. The raw materials, reagents, etc. used in the preparation of the compounds disclosed herein can be commercially purchased, or prepared according to the common methods in the field. In the present invention, if the chemical name of the compound doesn’t match the corresponding structure, the compound is characterized by the corresponding structure.
Scheme 1
Figure PCTCN2018081979-appb-000033
Figure PCTCN2018081979-appb-000034
Compound of Formula (I) can be prepared by the procedure illustrated in scheme 1, and wherein R 1, R 2, R 3, R 4, R 5, R 6, R 7, R 8, R 9, R a, R b and x are as defined herein; Y is Cl, Br or I. Oxidizing reaction of compound (a) and chlorine at a certain temperature (e.g. -10 ℃ to 10℃) under a condition of an acid (e.g. hydrochloric acid, dilute sulfuric acid, acetic acid, etc. ) can give compound (b) ; nucleophilic substitution reaction of compound (c) and R 4-NH 2 at a certain temperature (e.g. -10 ℃ to 30℃) under a condition of a base (e.g. sodium hydroxide, sodium hydride, potassium carbonate, etc. ) can give compound (d) ; condensation reaction of compound (b) and compound (d) at a certain temperature (e.g. -10 ℃ to 40 ℃) under a condition of a base (e.g. pyridine, triethylamine, potassium carbonate, etc. ) can give compound (e) ; condensation reaction of compound (e) and R 1R 2N-SO 2Cl at a certain temperature (e.g. -10 ℃ to 40 ℃) under a condition of a base (e.g. pyridine, triethylamine, potassium carbonate, etc. ) can give compound (I) .
Scheme 2
Figure PCTCN2018081979-appb-000035
Figure PCTCN2018081979-appb-000036
Compound of Formula (I) can be prepared by the procedure illustrated in scheme 2, and wherein R 1, R 2, R 3, R 4, R 5, R 6, R 7, R 8, R 9, R a, R b and x are as defined herein; Y is Cl, Br or I. Oxidative coupling reaction of compound (a) and acyl chloride (e.g. benzene sulfonyl chloride, p-toluene sulfonyl chloride) at a certain temperature (e.g. -10 ℃ to 40 ℃) under a condition of a base (e.g. pyridine, triethylamine, potassium carbonate, etc. ) can give compound (f) ; condensation reaction of compound (f) and R 1R 2N-SO 2Cl at a certain temperature (e.g. -10 ℃ to 40 ℃) under a condition of a base (e.g. pyridine, triethylamine, potassium carbonate, etc. ) can give compound (g) ; oxidation reaction of compound (g) and chlorine at a certain temperature (e.g. -10 ℃ to 10 ℃) under a condition of an acid (e.g. hydrochloric acid, dilute sulfuric acid, acetic acid, etc. ) can give compound (h) ; condensation reaction of compound (h) and NH 2-R 4 at a certain temperature (e.g. -10 ℃ to 40 ℃) under a condition of a base (e.g. pyridine, triethylamine, potassium carbonate, etc. ) can give compound (i) ; nucleophilic substitution reaction of compound (i) and compound (c) at a certain temperature (e.g. -10 ℃ to 40 ℃) under a condition of a base (e.g. sodium hydroxide, sodium hydride, potassium carbonate, etc. ) can give compound (I) .
Scheme 3
Figure PCTCN2018081979-appb-000037
Compound of Formula (I) can be prepared by the procedure illustrated in scheme 3, and wherein R 1, R 2, R 3, R 4, R 5, R 6, R 7, R 8, R 9, R a, R b and x are as defined herein. Condensation reaction of compound (h) and compound (d) at a certain temperature (e.g. -10 ℃ to 40 ℃) under a condition of a base (e.g. pyridine, triethylamine, potassium carbonate, etc. ) can give compound (I) .
The following abbreviations are used throughout the specification:
g gram; mg milligram; mol mole; mmol millimole; h hour/hours; min minute/minutes; L liter/liters; mL, ml milliliter/milliliters; M mol/L; PE petroleum ether; EtOAc ethyl acetate; DMF N, N-dimethylformamide; THF tetrahydrofuran
Examples
Example A Synthesis of intermediate 3-mercapto-1, 2, 4-triazole
Figure PCTCN2018081979-appb-000038
To a 100 mL flask were added formic acid (24.2 g, 0.52 mol) , water (25 mL) and thiosemicarbazide (20 g, 0.22 mol) . The mixture was heated to 105 ℃ and reacted for half an hour. And then the mixture was cooled to room temperature slowly, and then cooled to -10 ℃ to crystallize slowly. The resulting mixture was filtered and the solid was dried to give formylthiosemicarbazide (white solid, 22.3 g, yield was 85%) .
Formylthiosemicarbazide (12 g, 0.1 mol) was added to a 250 mL single neck flask, and then water (130 mL) and sodium carbonate (21.2 g, 0.25 mol) were added. The mixture was heated to 100 ℃ and reated for 4 hours, and then cooled to room temperature slowly. The reaction mixture was adjusted with dilute hydrochloric acid to pH 4-5. The resulting mixture was stirred at -10 ℃ slowly to crystallize, and then filtered. The solid was dried to give a white solid (5.6 g, yield was 55%) .
1H-NMR (400 MHz, DMSO-d 6) : δ (ppm) 8.24 (s, 1H) , 13.2 (s, 1H) , 13.5 (s, 1H) ;
13C NMR (100 MHz, DMSO-d 6) : δ (ppm) 140.7, 166.1.
Example B Synthesis of intermediate 1H-1, 2, 4-triazole-3-sulfonyl chloride
Figure PCTCN2018081979-appb-000039
1, 2, 4-Triazole-3-thiol (3 g, 0.03 mol) was dissolved in a hydrochloric acid solution (2 mol/L, 50 mL) . The solution was cooled to 0 ℃ and mixed homogeneously, and chlorine was then bubbled (30 g, over a period of one hour) , a white solid precipitated out gradually. After stopping chlorine bubbling, nitrogen was used to purge superfluous chlorine out at 0 ℃. The resulting mixture was filtered, and the solid was dried to give a white solid (3.2 g, yield was  75%) .
1H-NMR (400 MHz, DMSO-d 6) : δ (ppm) 9.31 (s, 1H) , 13.9 (s, 1H) ;
13C NMR (100 MHz, DMSO-d 6) : δ (ppm) 143.6, 157.1.
Example C Synthesis of intermediate 5-difluoromethyl-3-mercapto-1, 2, 4-triazole
Figure PCTCN2018081979-appb-000040
A suspension of thiosemicarbazide (4.45 g, 0.049 mol) in xylene (200 mL) was heated to 40 ℃ and stirred, and then difluoroacetic acid (5.76 g, 0.06 mol) was added dropwise slowly. After the addition, the mixture was reacted at 40 ℃ for 30 minutes. And then the mixture was heated to 160 ℃ and refluxed in the flask equipped with a water separator for 4 hours. The resulting mixture was cooled to room temperature and stood for 10 hours. A solid precipitated out and the precipitated solid was filtered and dissolved in ethyl acetate (200 mL) . The solution was washed with a dilute hydrochloric acid solution (1 M, 50 mL) and water (50 mL × 3) , and then dried over magnesium sulfate and concentrated to give a yellow solid (5.42 g, yield was 73.3%) .
1H-NMR (400 MHz, DMSO-d 6) : δ (ppm) 14.3 (s, 1H) , 13.9 (s, 1H) , 7.1 (t, 1H) ;
19F NMR (DMSO-d 6) : δ (ppm) -118.6.
Example D Synthesis of intermediate 5-difluoromethyl-1H-1, 2, 4-triazole-3-sulfonyl chloride
Figure PCTCN2018081979-appb-000041
5-Difluoromethyl-1, 2, 4-triazole-3-thiol (8.9 g, 0.059 mol) was dissolved in a hydrochloric acid solution (2 mol/L, 125 mL) . The solution was cooled to 0 ℃ and mixed homogeneously, and chlorine was then bubbled (60 g, over a period of one hour) . After stopping chlorine bubbling, nitrogen was used to purge superfluous chlorine out at 0 ℃. The resulting mixture was extracted with dichloromethane (100 mL × 3) , and the combined organic layers were dried over magnesium sulfate and concentrated to give a yellow oil (5.89 g, yield was 46%) .
1H-NMR (400 MHz, CDCl 3) : δ (ppm) 6.9 (t, 1H) ;
13C NMR (100 MHz, CDCl 3) : δ (ppm) 162.9, 151.6, 109.1;
19F NMR (CDCl 3) : δ (ppm) -118.0.
Example E Synthesis of intermediate 5-p-fluorophenyl-3-mercapto-1, 2, 4-triazole
Figure PCTCN2018081979-appb-000042
A solution of p-fluorobenzoyl chloride (3.16 g, 0.02 mol) in THF (60 mL) was cooled to 5 ℃ and stirred, thiosemicarbazide was then added in portions (3.64 g, 0.04 mol, 6 batches) . After the addition, the mixture was warmed to room temperature and reacted for 4 hours. After the reaction was completed, the reaction was quenched with a saturated aqueous sodium bicarbonate solution (20 mL) . The resulting mixture was extracted with ethyl acetate (100 mL × 3) . The combined organic layers were washed with saturated aqueous sodium bicarbonate solution (50 mL) and sodium chloride aqueous solution (100 mL) , and dried over magnesium sulfate and concentrated to give a white solid (4.0 g, yield was 94%) .
The above obtained solid (p-fluorobenzoylthiosemicarbazide, 4.26 g) was dissolved in a sodium hydroxide (4 g, 0.1 mol) aqueous solution (60 mL) . The solution was heated to 85 ℃ and stirred for 4 hours. And then the solution was cooled to room temperature slowly and adjusted to pH 5. A solid precipitated out, and the solid was filtered and dried to give a white solid (3.1 g, yield was 85%) .
1H-NMR (400 MHz, DMSO-d 6) : δ (ppm) 13.7 (s, 1H) , 7.9 (t, 2H) , 7.4 (t, 2H) ;
13C NMR (100 MHz, DMSO-d 6) : δ (ppm) 167.5, 164.5, 162.8, 149.9, 128.6, 122.5, 116.8, 116.5.
Example F Synthesis of intermediate 5- (4-fluorophenyl) -1H-1, 2, 4-triazole-3-sulfonyl chloride
Figure PCTCN2018081979-appb-000043
5-p-Fluorophenyl-1, 2, 4-triazole-3-thiol (3.9 g, 0.02 mol) was dissolved in a mixed hydrochloric acid (2 mol/L, 80 mL) and methanol (10 mL) solution. The solution was cooled to 0 ℃ and mixed homogeneously, and chlorine was then bubbled (30 g, over a period of one hour) . After stopping chlorine bubbling, nitrogen was used to purge superfluous chlorine out at 0 ℃. The resulting mixture was extracted with dichloromethane (100 mL × 3) , and the combined  organic layers were dried over magnesium sulfate and concentrated to give a brown oil (2.25 g, yield was 43.1%) .
Example G Synthesis of intermediate N-benzylcyclopropanamine
Figure PCTCN2018081979-appb-000044
A mixture of cyclopropane (3.3 g, 0.058 mol) , potassium carbonate (20 g, 0.15 mol) and DMF (80 mL) in a 250 mL flask was stirred at room temperature, and then a solution of benzyl chloride (5.11 g, 0.04 mol) in DMF (20 mL) was added dropwise slowly over one hour. After the addition, the mixture was stirred at room temperature for 48 hours and water (80 mL) was added. The resulting mixture was extracted with diethyl ether (100 mL × 3) . The combined organic layers were washed with saturated sodium chloride aqueous solution (100 mL × 2) , dried over magnesium sulfate, and concentrated. The residue was purified by column chromatography eluted with EtOAc/PE ( (v/v) = 1/4) to give a yellow liquid (3.06 g, yield was 52%) .
1H-NMR (400 MHz, DMSO-d 6) : δ (ppm) 7.3～7.2 (m, 5H) , 3.7 (s, 2H) , 2.0 (m, 1H) , 0.3～0.4 (m, 4H) ;
13C NMR (100 MHz, DMSO-d 6) : δ (ppm) 141.6, 128.4, 126.8, 53.4, 30.1, 6.6.
The intermediate compounds listed in table 1 can be obtained according to the similar methods of example G by replacing benzyl chloride to corresponding raw materials.
Table 1
Figure PCTCN2018081979-appb-000045
Example H Synthesis of intermediate N- (4- (trifluoromethoxy) phenyl) -1H-1, 2, 4-triazole-3-sulfonylamide
Figure PCTCN2018081979-appb-000046
A mixture of p-trifluoromethoxyaniline (3.18 g, 0.018 mol) , triethylamine (2.22 g, 0.022 mol) and tetrahydrofuran (30 mL) in a 100 mL single neck flask was stirred at room temperature homogeneously, and then a solution of 1H-1, 2, 4-triazole-3-sulfonyl chloride (3.32 g, 0.02 mol) in THF (15 mL) was added dropwise over one hour. After the reaction mixture was reacted for 12 hours, water (20 mL) was added, and the resulting mixture was adjusted with hydrochloric acid to pH 5. The mixture was extracted with diethyl ether (100 mL × 3) . The combined organic layers were dried over magnesium sulfate and concentrated. The residue was washed with n-hexane to give a gray white solid (2.5 g, yield was 46%) .
1H-NMR (400 MHz, DMSO-d 6) : δ (ppm) 14.8 (s, 1H) , 10.9 (s, 1H) , 8.7 (s, 1H) , 7.3～7.1 (m, 3H) ;
13C NMR (100 MHz, DMSO-d 6) : δ (ppm) 161.4, 146.3, 144.7, 137.0, 122.4, 121.7, 114.6.
The intermediate compounds listed in table 2 can be obtained according to the similar methods of example H by using corresponding raw materials under certain conditions.
Table 2
Figure PCTCN2018081979-appb-000047
Figure PCTCN2018081979-appb-000048
Figure PCTCN2018081979-appb-000049
Example I Synthesis of intermediate N- (4-fluorobenzyl) -N-cyclopropylsulfonyl chloride
Figure PCTCN2018081979-appb-000050
A solution of sulfonyl chloride (13.4 g, 0.1 mol) in dichloromethane (20 mL) was stirred at room temperature homogeneously, and then a solution of triethylamine (2.02 g, 0.02 mol) and N- (4-fluorobenzyl) cyclopropanamine (1.65 g, 0.01 mol) in dichloromethane (10 mL) was added dropwise slowly at room temperature. After the addition, the mixture was heated to 70 ℃ and refluxed for 3 hours. The reaction mixture was evaporated under reduced pressure to distill unreacted sulfonyl chloride and solvents off to give a yellow oil.
Example J Synthesis of intermediate 1, 2-di (1H-1, 2, 4-triazol-3-yl) disulfane
Figure PCTCN2018081979-appb-000051
To a solution of 3-mercapto-1, 2, 4-triazole (50.50 g, 0.50 mol) in dichloromethane (300 mL) was added pyridine (39.50 g, 0.50 mol) . Benzene sulfonyl chloride (44.20 g, 0.25 mol) was added to the solution with stirring at 0 ℃ over 2 hours. After the addition, the mixture was stirred for 16 hours. Dichloromehtane was removed by evaporating on a rotary evaporator under vacuum, water (300 mL) was added to the residue under mechanical stirring, and the mixture was stirred for 1 hour. The mixture was filtered, the filter cake was washed with water (500 mL) and ethyl acetate (200 mL) respectively, and then air-dried to give a yellow powder (46.54 g, yield was 93.1%) .
LC-MS: (M+1) m/z = 201.3.
Example K Synthesis of intermediate 3, 3'-disulfanediylbis (N, N-dimethyl-1H-1, 2, 4-triazole-1-sulfonamide)
Figure PCTCN2018081979-appb-000052
To a solution of 1, 2-di (1H-1, 2, 4-triazol-3-yl) disulfane (40.00 g, 0.20 mol) in N, N-dimethylformamide (200 mL) was added potassium carbonate (41.40 g, 0.30 mol) under N 2. The mixture was stirred at 0 ℃. And then N, N-dimethylamino sulfonyl chloride (64.34 g, 0.45 mol) was added dropwise over 2 hours, the mixture was further reacted for 6 hours. After the reaction was completed, the reaction mixture was poured into water, and the resulting mixture was stirred for 1 hour. The mixture was filtered. The filter cake was air dried to give a white powder (73.94 g, yield was 89.3%) .
LC-MS: (M+1) m/z = 415.2.
Example L Synthesis of intermediate 1- (N, N-dimethylamino sulfonyl) -1H-1, 2, 4-triazole-3-sulfonyl chloride
Figure PCTCN2018081979-appb-000053
To a solution of 3, 3’-disulfanediylbis (N, N-dimethyl-1H-1, 2, 4-triazole-1-sulfonamide) (41.40 g, 0.10 mol) in 1, 2-dichloroethane (300 mL) was added water (300 mL) , the mixture was cooled to 0 ℃, and acetic acid (100 mL) was added. The temperature was controlled between 10 ℃ and 25 ℃, chlorine (35.50 g, 0.50 mol) was bubbled over 2 hours. The mixture was further reacted for half an hour. After the reaction was completed, the reaction mixture was transferred to a separatory funnel and allowed to stand until it was separated into layers, the  organic layer was washed with water (30 mL) 3 times and the solvent was removed by evaporating on a rotary evaporator under vacuum. A white powder was obtained (47.23 g, yield was 86.2%) .
Example M Synthesis of intermediate N 3-cyclopropyl-N 1, N 1-dimethyl-1H-1, 2, 4-triazole-1, 3-disulfonamide
Figure PCTCN2018081979-appb-000054
A mixture of cyclopropylamine (1.14 g, 0.02 mol) , triethylamine (2.22 g, 0.022 mol) and tetrahydrofuran (30 mL) in a 100 mL three neck flask was stirred at 0 ℃ under N 2. A solution of 1- (N, N-dimethylamino sulfonyl) -1H-1, 2, 4-triazole-3-sulfonyl chloride (6.04 g, 0.02 mol) in tetrahydrofuran (20 mL) was added dropwise over 10 min, there was white smoke produced and a white solid precipitated out gradually. After the addition, the reaction was further carried out at room temperature for 2 hours, and the solid was filtered out, the filtrate was concentrated on a rotary evaporator under vacuum to give a light yellow solid. The solid was recrystallized (EtOAc/PE (v/v) = 5/1) to get a white solid (4.42 g, yield was 75.1%)
1H NMR (400 MHz, DMSO-d 6) : δ (ppm) 9.30 (s, 1H) , 7.49 (s, 1H) , 2.96 (s, 6H) , 2.48 (m, 1H) , 0.63～0.56 (m, 2H) , 0.50～0.43 (m, 2H) .
LC-MS: (M+1) m/z = 296.3.
The intermediate compounds listed in table 3 can be obtained according to the similar methods of example M by using corresponding raw materials.
Table 3
Figure PCTCN2018081979-appb-000055
Figure PCTCN2018081979-appb-000056
Example N Synthesis of intermediate N-benzylprop-2-en-1-amine
Figure PCTCN2018081979-appb-000057
To a mixture of benzylamine (1.07 g, 10.0 mmol) , potassium carbonate (2.8 g, 20.0 mmol) and DMF (30 mL) in a 100 mL three neck flask was added 3-bromoprop-1-ene (1.2 g, 10.0 mmol) dropwise slowly. The mixture was stirred at 25 ℃ for 8 hours and quenched with water (30 mL) . The resulting mixture was extracted with ethyl acetate (20 mL × 3) . The combined organic layers was washed with saturated aqueous NaCl and dried over anhydrous magnesium sulfate. The mixture was filtered, the filtrate was concentrated on a rotary evaporator under vacuum. The residue was purified by column chromatography (EtOAc/PE (v/v) = 1/5) to get a colorless liquid (1.10 g, yield was 75%) .
LC-MS: (M+1) m/z = 148.1.
Example O Synthesis of intermediate N-benzyloxetan-3-amine
Figure PCTCN2018081979-appb-000058
A mixture of oxetan-3-amine (2.19 g, 30.0 mmol) , benzaldehyde (1.06 g, 10.0 mmol) , anhydrous MgSO 4 (3.60 g, 30.0 mmol) and dichloromethane (30 mL) in a 100 mL three neck flask was stirred at 25 ℃ for 12 hours. The mixture was filtered, the filtrate was concentrated on a rotary evaporator under vacuum to get the intermediate imines. The intermediate imines was dissolved in methanol (20 mL) , and NaBH 4 (0.38 g, 10.0 mmol) was added into the solution slowly. The resulting mixture was stirred at 25 ℃ for 5 hours and concentrated on a rotary evaporator. The residue was purified by column chromatography (EtOAc/PE (v/v) = 1/5) to give a colorless liquid (1.45 g, yield was 89%) .
LC-MS: (M+1) m/z = 164.1.
The intermediate compounds listed in table 4 can be obtained according to the similar methods of example O by using corresponding raw materials and conditions.
Table 4
Figure PCTCN2018081979-appb-000059
Figure PCTCN2018081979-appb-000060
Figure PCTCN2018081979-appb-000061
Example P Synthesis of intermediate 4-methylpiperazine-1-sulfonyl chloride
Figure PCTCN2018081979-appb-000062
To a mixture of 1-methylpiperazine (2.00 g, 0.02 mol) and triethylamine (4.04 g, 0.04 mol) in a 100 mL flask at 0 ℃ was added a solution of sulfoxide chloride (5.40 g, 0.04 mol) in dichloromethane (30 mL) dropwise. After the addition, the mixture was stirred at 0 ℃ for 2 hours and quenched with water. The organic phase was seperated and dried over anhydrous magnesium sulfate, and then concentrated to get a light yellow oil (3.30 g, yield was 83%) .
LC-MS: (M+1) m/z = 199.0.
The intermediate compounds listed in table 5 can be obtained according to the similar methods of example P by using corresponding raw materials and conditions.
Table 5
Figure PCTCN2018081979-appb-000063
Figure PCTCN2018081979-appb-000064
Example Q Synthesis of intermediate N- (1-phenylethyl) cyclopropanamine
Figure PCTCN2018081979-appb-000065
A mixture of cyclopropylamine (1.71 g, 30.0 mmol) , acetophenone (1.20 g, 10.0 mmol) and toluene (30 mL) in a 100 mL three neck flask was heated to 110 ℃ and refluxed for 12 hours. The mixture was cooled and concentrated on a rotary evaporator under vacuum to get the intermediate imine. The intermediate imine was dissolved in methanol (20 mL) , and NaBH 4 (0.38 g, 10.0 mmol) was added slowly into the solution. The resulting mixture was stirred at 25 ℃ for 5 hours and concentrated on a rotary evaporator. The residue was purified by column chromatography (EtOAc/PE (v/v) = 1/5) to give a colorless liquid (0.85 g, yield was 53%) .
LC-MS: (M+1) m/z = 162.1.
The intermediate compounds listed in table 6 can be obtained according to the similar  methods of example Q by using corresponding raw materials and conditions.
Table 6
Figure PCTCN2018081979-appb-000066
Figure PCTCN2018081979-appb-000067
Example R Synthesis of intermediate N 3- (2, 2-difluoroethyl) -N 1, N 1-dimethyl-1H-1, 2, 4-triazole-1, 3-disulfonamide
Figure PCTCN2018081979-appb-000068
A mixture of 2, 2-difluoroethylamine (0.41 g, 5.0 mmol) , triethylamine (1.01 g, 10.0 mol) and tetrahydrofuran (20 mL) in a 100 mL single neck flask was stirred homogeneously at room temperature, and then 1- (N, N-dimethylamino sulfonyl) -1H-1, 2, 4-triazole-3-sulfonyl chloride (1.37 g, 5.0 mmol) was added. The mixture was stirred at 25 ℃ for 12 hours and quenched with water (30 mL) . The resulting mixture was extracted with ethyl acetate (20 mL × 3) . The combined organic layers were dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated on a rotary evaporator under vacuum. The residue was purified by column chromatography (EtOAc/PE (v/v) = 1/3) to get a white solid (1.10 g, yield was 69%) .
LC-MS: (M+1) m/z =320.0.
Example 1 Synthesis of compound N 3-benzyl-N 3-cyclopropyl-N 1, N 1-dimethyl-1H-1, 2, 4-triazole-1, 3-disulfonamide
Figure PCTCN2018081979-appb-000069
A solution of N-benzyl-N-cyclopropyl-1H-1, 2, 4-triazole-3-sulfonamide (0.28 g, 1 mmol)  in dry tetrahydrofuran (8 mL) was stirred at 0 ℃ under N 2, and then sodium hydride (60%, 60 mg, 1.5 mmol, 3 batches) was added in portions. After the addition, the mixture was further stirred at 0 ℃ for 30 minutes and then warmed to room temperature, N, N-dimethylamino sulfonyl chloride (0.286 g, 2 mmol) was added dropwise slowly. The resulting mixture was stirred at room temperature for 8 hours and quenched with water (5 mL) , extracted with ethyl acetate (10 mL × 3) . The combined organic layers were dried over magnesium sulfate and concentrated. The residue was purified by column chromatography (PE/EtOAc (v/v) = 5/1) to get a white powder (0.27 g, yield was 70.2%) .
1H-NMR (400 MHz, CDCl 3) : δ (ppm) 8.6 (s, 1H) , 7.4～7.3 (m, 5H) , 4.6 (s, 2H) , 3.0 (m, 6H) , 2.6～2.5 (m, 1H) , 0.8～0.6 (m, 4H) ;
13C NMR (100 MHz, CDCl 3) : δ (ppm) 163.0, 145.8, 135.9, 128.6, 128.4, 128.3, 127.8, 54.7, 38.8, 30.8, 7.3;
LC-MS: (M+1) m/z = 386.4.
Example 2 Synthesis of compound N 3-cyclopropyl-N 3- (4-fluorobenzyl) -N 1, N 1-dimethyl-1H-1, 2, 4-triazole-1, 3-disulfonamide
Figure PCTCN2018081979-appb-000070
To a mixture of N-cyclopropyl-N- (4-fluorobenzyl) -1H-1, 2, 4-triazole-3-sulfonamide (0.296 g, 1.0 mmol) , potassium carbonate (0.28 g, 2.0 mmol) and DMF (10 mL) in a 100 mL three neck flask was added N, N-dimethylamino sulfonyl chloride (0.215 g, 1.5 mmol) dropwise slowly. The mixture was stirred at 25 ℃ for 8 hours and quenched with water (20 mL) . The resulting mixture was extracted with ethyl acetate (15 mL × 3) . The combined organic layers was washed with saturated aqueous NaCl and dried over anhydrous magnesium sulfate. The mixture was filtered, the filtrate was concentrated on a rotary evaporator under vacuum. The residue was purified by column chromatography (EtOAc/PE (v/v) = 1/3) to get a white solid (0.250 g, yield was 62%) .
1H NMR (400 MHz, CDCl 3) : δ (ppm) 8.6 (s, 1H) , 7.4 (dd, 2H) , 7.0 (t, 2H) , 4.5 (s, 2H) , 3.0 (m, 6H) , 2.5 (m, 1H) , 0.8～0.7 (m, 4H) ;
13C NMR (100 MHz, CDCl 3) : δ (ppm) 163.4, 146.0, 130.3, 115.5, 115.3, 53.9, 39.0, 30.5, 7.3;
LC-MS: (M+1) m/z = 404.4.
Example 3 Synthesis of compound N 3-cyclopropyl-5- (difluoromethyl) -N 3- (4-fluorobenzyl) -N 1, N 1-dimethyl-1H-1, 2, 4-triazole-1, 3-disulfonamide
Figure PCTCN2018081979-appb-000071
To a mixture of N-cyclopropyl-5- (difluoromethyl) -N- (4-fluorobenzyl) -1H-1, 2, 4-triazole-3-sulfonamide (0.346 g, 1.0 mmol) , potassium carbonate (0.28 g, 2.0 mmol) and DMF (10 mL) in a 100 mL three neck flask was added N, N-dimethylamino sulfonyl chloride (0.215 g, 1.5 mmol) dropwise slowly. The mixture was stirred at 25 ℃ for 8 hours and quenched with water (20 mL) . The resulting mixture was extracted with ethyl acetate (15 mL × 3) . The combined organic layers was washed with saturated aqueous NaCl and dried over anhydrous magnesium sulfate. The mixture was filtered, the filtrate was concentrated on a rotary evaporator under vacuum. The residue was purified by column chromatography (EtOAc/PE (v/v) = 1/3) to get a white solid (0.222 g, yield was 51%) .
1H-NMR (400 MHz, DMSO-d 6) : δ (ppm) 7.4～7.3 (m, 2H) , 7.3～7.1 (m, 3H) , 4.4 (s, 2H) , 2.9 (m, 6H) , 2.1 (m, 1H) , 0.6～0.7 (m, 4H) ;
LC-MS: (M+1) m/z = 454.5.
Example 4 Synthesis of compound N 1, N 1-dimethyl-N 3- (3- (trifluoromethyl) phenyl) -1H-1, 2, 4-triazole-1, 3-disulfonamide
Figure PCTCN2018081979-appb-000072
A mixture of 3- (trifluoromethyl) aniline (0.81 g, 5.0 mmol) , pyridine (0.79 g, 10.0 mol) and tetrahydrofuran (20 mL) in a 100 mL single neck flask was stirred homogeneously at room temperature, and then 1- (N, N-dimethylamino sulfonyl) -1H-1, 2, 4-triazole-3-sulfonyl chloride (1.37 g, 5.0 mmol) was added. The mixture was stirred at 25 ℃ for 12 hours and quenched with water (30 mL) . The resulting mixture was extracted with ethyl acetate (20 mL × 3) . The combined organic layers were dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated on a rotary evaporator under vacuum. The residue was purified by column  chromatography (EtOAc/PE (v/v) = 1/3) to get a white solid (1.40 g, yield was 70%) .
LC-MS: (M+1) m/z = 400.0.
Example 5 Synthesis of compound N 3-cyclopropyl-N 3- (4-fluorobenzyl) -5- (4-fluorophenyl) -N 1, N 1-dimethyl-1H-1, 2, 4-triazole-1, 3-disulfonamide
Figure PCTCN2018081979-appb-000073
To a mixture of N-cyclopropyl-N- (4-fluorobenzyl) -5- (4-fluorophenyl) -1H-1, 2, 4-triazole-3-sulfonamide (0.390 g, 1.0 mmol) , potassium carbonate (0.28 g, 2.0 mmol) and DMF (10 mL) in a 100 mL three neck flask was added N, N-dimethylamino sulfonyl chloride (0.215 g, 1.5 mmol) dropwise slowly. The mixture was stirred at 25 ℃ for 8 hours and quenched with water (20 mL) . The resulting mixture was extracted with ethyl acetate (15 mL × 3) . The combined organic layers was washed with saturated aqueous NaCl and dried over anhydrous magnesium sulfate. The mixture was filtered, the filtrate was concentrated on a rotary evaporator under vacuum. The residue was purified by column chromatography (EtOAc/PE (v/v) = 1/3) to get a white solid (0.303 g, yield was 61%) .
1H-NMR (400 MHz, DMSO-d 6) : δ (ppm) 7.8～7.7 (m, 2H) , 7.3～7.2 (m, 7H) , 4.2 (s, 1H) , 3.0 (m, 6H) , 2.2 (m, 1H) , 0.7～0.6 (m, 4H) ;
LC-MS: (M+1) m/z = 498.5.
Example 6 Synthesis of compound N 3- (2-chloro-4-fluorophenyl) -5- (difluoromethyl) -N 1, N 1-dimethyl-1H-1, 2, 4-triazole-1, 3-disulfonamide
Figure PCTCN2018081979-appb-000074
A solution of N- (2-chloro-4-fluorophenyl) -5- (difluoromethyl) -1H-1, 2, 4-triazole-3-sulfonamide (0.360 g, 1 mmol) in dry pyridine (10 mL) was stirred at room temperature under N 2 for 2 hours, and then N, N-dimethylamino sulfonyl chloride (0.286 g, 2 mmol) was added dropwise by syringe slowly. After the addition, the mixture was stirred at room temperature for 24 hours and quenched with water (10 mL) , extracted with ethyl acetate (20 mL × 3) . The combined organic layers were washed with saturated aqueous sodium bicarbonate solution (10  mL × 2) and dried over magnesium sulfate and concentrated. The residue was purified by column chromatography (PE/EtOAc (v/v) = 5/1) to get a light yellow powder (0.168 g, yield was 39.0%) .
1H-NMR (400MHz, DMSO-d 6) : δ (ppm) 7.5～7.4 (m, 1H) , 7.3 (t, 1H) , 7.2 (m, 2H) , 3.0 (m, 6H) ;
LC-MS: (M+1) m/z = 433.9.
Example 7 Synthesis of compound N 1, N 3-dicyclopropyl-5- (difluoromethyl) -N 1, N 3-bis (4-fluorobenzyl) -1H-1, 2, 4-triazole-1, 3-disulfonamide
Figure PCTCN2018081979-appb-000075
A solution of N-cyclopropyl-5- (difluoromethyl) -N- (4-fluorobenzyl) -1H-1, 2, 4-triazole-3-sulfonamide (0.350 g, 1 mmol) in dry tetrahydrofuran (8 mL) was stirred at 0 ℃ under N 2, and then sodium hydride (60%, 60 mg, 1.5 mmol, 3 batches) was added in portions. After the addition, the mixture was further stirred at 0 ℃ for 30 minutes and then warmed to room temperature, N- (4-fluorobenzyl) -N-cyclopropyl sulfonyl chloride (0.526 g, 2 mmol) was added dropwise slowly. The resulting mixture was stirred at room temperature for 8 hours and quenched with water (5 mL) , extracted with ethyl acetate (10 mL × 3) . The combined organic layers were dried over magnesium sulfate and concentrated. The residue was purified by column chromatography (PE/EtOAc (v/v) = 5/1) . A light yellow powder was obtained (0.217 g, yield was 38.1%) .
1H-NMR (400 MHz, DMSO-d 6) : δ (ppm) 7.4～7.1 (m, 8H) , 6.9 (t, 1H) , 4.3 (s, 4H) , 2.2 (m, 2H) , 0.6～0.4 (m, 8H) ;
LC-MS: (M+1) m/z = 574.2.
Example 8 Synthesis of compound N 3-cyclopropyl-N 1, N 1-dimethyl-N 3- (naphth-2-yl-methyl) -1H-1, 2, 4-triazole-1, 3-disulfonamide
Figure PCTCN2018081979-appb-000076
A mixture of N 3-cyclopropyl-N 1, N 1-dimethyl-1H-1, 2, 4-triazole-1, 3-disulfonamide (0.400 g, 1.36 mmol) , potassium carbonate (0.276 g, 2.0 mmol) , 2-chloromehtylnaphthalene (0.320 g, 2.0 mmol) and DMF (30 mL) in a 100 mL three neck flask was stirred at room temperature overnight. Next day, the mixture was diluted with water (50 mL) . The resulting mixture was extracted with ethyl acetate (50 mL × 3) . The combined organic layers was washed with saturated aqueous NaCl and dried over magnesium sulfate. The mixture was filtered, the filtrate was concentrated on a rotary evaporator under vacuum. The residue was purified by column chromatography (EtOAc/PE (v/v) = 5/1) to get a white solid (0.370 g, yield was 63.0%) .
1H NMR (600 MHz, DMSO-d 6) : δ (ppm) 9.47 (s, 1H) , 7.93 (dd, 4H) , 7.58-7.51 (m, 3H) , 4.72 (s, 2H) , 2.99 (s, 6H) , 2.63 (m, 1H) , 0.78-0.69 (m, 4H) .
LC-MS: (M+1) m/z = 436.5.
Example 9 Synthesis of compound N 3-cyclopropyl-N 1, N 1-dimethyl-N 3- (naphth-1-yl-methyl) -1H-1, 2, 4-triazole-1, 3-disulfonamide
Figure PCTCN2018081979-appb-000077
A mixture of N 3-cyclopropyl-N 1, N 1-dimethyl-1H-1, 2, 4-triazole-1, 3-disulfonamide (0.400 g, 1.36 mmol) , potassium carbonate (0.276 g, 2.0 mmol) , 1-chloromehtylnaphthalene (0.320 g, 2.0 mmol) and DMF (30 mL) in a 100 mL three neck flask was stirred at room temperature overnight. Next day, the mixture was diluted with water (50 mL) . The resulting mixture was extracted with ethyl acetate (50 mL × 3) . The combined organic layers was washed with saturated aqueous NaCl and dried over magnesium sulfate. The mixture was filtered, the filtrate was concentrated on a rotary evaporator under vacuum to get a yellow liquid (0.516 g, yield was 87.2%) .
1H NMR (600 MHz, DMSO-d 6) : δ (ppm) 9.54 (s, 1H) , 8.22 (d, 1H) , 7.98 (dd, 2H) , 7.65-7.53 (m, 4H) , 5.04 (s, 2H) , 3.04 (s, 6H) , 2.58 (m, 1H) , 0.63-0.53 (m, 4H) .
LC-MS: (M+1) m/z = 436.3.
The compounds listed in table 7 can be obtained with reference to the schemes or specific examples of the invention by using corresponding raw materails and conditions.
Table 7
Figure PCTCN2018081979-appb-000078
Figure PCTCN2018081979-appb-000079
Figure PCTCN2018081979-appb-000080
Figure PCTCN2018081979-appb-000081
Figure PCTCN2018081979-appb-000082
Figure PCTCN2018081979-appb-000083
Figure PCTCN2018081979-appb-000084
Figure PCTCN2018081979-appb-000085
Figure PCTCN2018081979-appb-000086
Figure PCTCN2018081979-appb-000087
Figure PCTCN2018081979-appb-000088
Figure PCTCN2018081979-appb-000089
Figure PCTCN2018081979-appb-000090
Figure PCTCN2018081979-appb-000091
Figure PCTCN2018081979-appb-000092
Figure PCTCN2018081979-appb-000093
Figure PCTCN2018081979-appb-000094
Figure PCTCN2018081979-appb-000095
Figure PCTCN2018081979-appb-000096
Figure PCTCN2018081979-appb-000097
Figure PCTCN2018081979-appb-000098
Figure PCTCN2018081979-appb-000099
Figure PCTCN2018081979-appb-000100
Figure PCTCN2018081979-appb-000101
Figure PCTCN2018081979-appb-000102
Figure PCTCN2018081979-appb-000103
Figure PCTCN2018081979-appb-000104
Figure PCTCN2018081979-appb-000105
Figure PCTCN2018081979-appb-000106
Figure PCTCN2018081979-appb-000107
Figure PCTCN2018081979-appb-000108
Figure PCTCN2018081979-appb-000109
Figure PCTCN2018081979-appb-000110
Figure PCTCN2018081979-appb-000111
Figure PCTCN2018081979-appb-000112
Figure PCTCN2018081979-appb-000113
Figure PCTCN2018081979-appb-000114
Figure PCTCN2018081979-appb-000115
Figure PCTCN2018081979-appb-000116
Figure PCTCN2018081979-appb-000117
Figure PCTCN2018081979-appb-000118
The Biological Examples of the invention
The test targets: Rhizoctonia Solani, Botrytis cinerea, Pseudoperonospora cubensis, Sphaerotheca Fuliginea.
Treating process: the compound was dissolved in DMF to make 1%EC. The fungicidal activities of the compounds of the invention were evaluated at a dose of 200 ppm, 100 ppm, 50 ppm, 25 ppm, 12.5 ppm and 6.25 ppm against the four test targets by adopting a pot culture method.
Test method
(1) Pseudoperonospora cubensis
Plotted cucumber seedlings in one leaf period (removing the growing point) with consistent growth were selected. After spray treatment with the formulation, the selected Plotted cucumber seedlings were air-dried naturally, and after 24 h, Pseudoperonospora cubensis were  inoculated to the treated cucumber seedlings by spraying a sporangia suspension (2×10 5 to 3×10 5 cells/ml) , the sporangia suspension was prepared from sporangium obtained by washing down from the back of fresh cucumber leaves with cucumber downy mildew using a dipping distilled water brush. The inoculation was carried out by spraying uniformly on the cucumber seedlings with a sprayer (pressure is 0.1 MPa) . The inoculated test materials were moved to a climatic chamber, the relative humidity was maintained at 100%, the temperature was at about 21 ℃. After 24 h, moisture inducement was performed under the temperature of about 21 ℃ and the relative humidity of about 95%. After 5 days, an investigation on gradation was carried out on a morbidity case of the blank control group, the control effect was calculated according to the disease index.
(2) Sphaerotheca fuliginea
Cucumber seedlings in one leaf period (removing the growing point) with consistent growth were selected. After spray treatment with the formulation, which were dried in the shade for 24 h. Conidia of fresh powdery mildew fungus on cucumber leaves were washed drown, and filtered through double-layer gauze and then prepared to a suspension at a concentration of 1×10 5 cells/mL, the inoculation was carried out by spraying. The inoculated test materials were moved to a climatic chamber, the relative humidity was maintained between 60%and 70%, and the temperature was maintained between 21 ℃ and 23 ℃. After about 10 days, an investigation on gradation was carried out on a morbidity case of the blank control group, the control effect was calculated according to the disease index.
(3) Botrytis cinerea
A leaf inoculation method was adopted. Cucumber seedlings in two leaf period with consistent growth were selected. After spraying the selected cucumber seedlings with the formulation and air drying, mycelial piece obtained from the cultures of fungus was inoculated to the leaves of the cucumber seedlings. The inoculated cucumber seedlings was cultivated at a certain moisture and at 24-26 ℃ in dark for 24 hours and in natural light for about 3 days. After complete morbidity of the control group, the scab diameter of every inoculation point was metered by using a caliper, and the control effect was calculated.
(4) Rhizoctonia solani
Corn seedlings in two leaf and one bud period with consistent growth were selected. After 24 h of spray treatment with the formulation and air drying, mycelial piece obtained from  the cultures of fungus was inoculated to the leaves of the selected corn seedlings. The inoculated corn seedlings was cultivated at a certain moisture and at 25-26℃ in dark for 24 hours and in natural light for about 3 days. After complete morbidity of the control group, the scab diameter of every inoculation point was metered by using a caliper, and the control effect was calculated.
Experiment results were shown in tables A to E.
Table A the control effects of the compounds of the invention at 200 ppm on cucumber downy mildew
Example Control effect (%)
1 100
8 100
9 100
10 100
11 100
12 100
13 100
14 100
15 100
16 100
17 100
21 100
24 100
27 100
38 100
40 100
42 100
43 100
44 100
57 98
60 100
62 100
64 100
65 100
67 100
68 100
69 100
71 100
74 100
75 100
76 100
77 100
81 100
91 98
92 100
93 100
95 100
101 100
116 100
117 100
122 100
123 100
124 100
125 100
126 100
127 100
Table B the control effects of the compounds of the invention at 100 ppm on cucumber downy mildew
Example Control effect (%)
8 100
9 100
12 100
13 100
14 100
15 100
16 100
17 100
24 100
27 100
31 100
38 100
42 100
43 100
44 100
60 100
62 100
65 100
67 100
68 100
69 98
71 100
74 100
76 100
77 100
81 100
95 100
116 100
117 100
122 100
123 100
124 100
125 100
132 100
Table C comparison between the control effects of the compounds of the invention at various concentrations, cyazofamid and the compounds of WO 2017118193 on cucumber downy mildew
Figure PCTCN2018081979-appb-000119
Figure PCTCN2018081979-appb-000120
Table D comparison between control effects of the compounds of the invention at various concentrations and amisulbrom on cucumber downy mildew
Figure PCTCN2018081979-appb-000121
Figure PCTCN2018081979-appb-000122
Table E comparison of control effects of the compounds of the invention at various concentrations and the compounds of WO 9401419 on cucumber downy mildew
Figure PCTCN2018081979-appb-000123
Figure PCTCN2018081979-appb-000124
The results listed in tables A and B indicated that the compounds of the invention have an obvious control effect at various concentrations on cucumber downy mildew, especially at 6.25 ppm, the compounds of the invention, for example, example 9, example 12, example 13, example 14, example 17, example 31 and example 132, have a control effect on cucumber downy mildew more than 40%. The results listed in tables C and E indicated that the compounds of the invention have a better control effect on cucumber downy mildew than that of prior art. In addition, the compounds of the invention have an obvious control effect on Rhizoctonia solani, Botrytis cinerea and Sphaerotheca fuliginea at 200 ppm, the control effect is more than 30%.
Test of inhibition rates of the invention
The process of test of inhibition rates: to the first well in the first line of a 96 well plate was added a given amount of the test medicinal liquid, and then it was serially diluted in required multiple to the 8 th well, the density of the pathogens of cucumber brown spot in the logarithmic growth were measured by a microscopic count method, the pathogens were diluted to a concentration of 10 7 to 10 8 CFU/mL with a culture solution; the pathogen solution was added into the 96 well plate, and 100 μL was added per well, the 9 th and 10 th wells were used as controls. Each gradient was repeated 5 to 8 times, after the culture plate was cultivated at 37 ℃ for 2.5 hours, 10 μL of tetrazolium bromide solution was added per well, and then which was further cultivated for 1.5 hours and centrifuged at 3000 r/min for 10 min. The supernatant medium was discarded. At last, to the each well of the 96 well plate was added 200 μL SDS solution (i.e. Sodium dodecyl sulfate) , the plate was shook for several minutes, after complete dissolution of the blue crystal, and read on an ELSIA detector.
The control effects on rice blast, potato late blight, wheat root rot, wheat scab, corn curvularia leaf spot, soybean root rot, rape sclerotinia stem rot, cotton fusarium wilt, apple ring rot, apple leaf spot, citrus scab, anthracnose of grape, peach brown rot, peanut spot disease, watermelon wilt, mango rot were test by the same method.
Calculating Formula of the inhibition rate is: inhibition rate (%) = (1-sample OD value /control OD value) x 100%. The results were listed in table F.
Table F the control effects of the compounds of the invention on various pathogens
Figure PCTCN2018081979-appb-000125
The broaden research of the compounds of the invention found that these compound have prominent control effects on potato late blight, wheat root rot and soybean root rot. In addition, the compound of the invention have certain control effects on cucumber brown spot, wheat scab, corn curvularia leaf spot, rape sclerotinia stem rot, cotton fusarium wilt, apple ring rot, apple leaf spot, citrus scab, anthracnose of grape, peach brown rot, peanut spot disease, watermelon wilt, mango rot were test by the same method.
Meanwhile, the compounds of the invention are high safety to crops and fruit trees such as rice, cucumber, wheat, potato, corn, soybean, rape, cotton, apple, citrus, grape, peach, peanut, watermelon, mango and so on, there is no evident injury at the concentration in the range from 1 ppm to 200 ppm.
Some preferred embodiments of the invention have been described above. However, the invention is not limited to the details described above, the present invention may be modified in various simple manners within the scope of the concept of the present invention, those variations thus also belong to the scope of the invention.

Claims (22)

  1. A compound having Formula (A) or a stereoisomer, an N-oxide or a salt thereof,
    Figure PCTCN2018081979-appb-100001
    wherein
    each of R 1 and R 2 is independently H, alkyl, alkoxyalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, cycloalkylalkyl, heterocyclylalkyl, arylalkyl, halo substituted arylalkyl or heteroarylalkyl; or R 1 and R 2, together with the N atom to which they are attached, form a heterocyclyl or heteroaryl group;
    wherein the heterocyclyl or heteroaryl group formed from R 1 and R 2, together with the N atom to which they are attached is optionally substituted with one or more R 12;
    R 3 is H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, aryl or haloaryl;
    w is 0, 1 or 2;
    R 4 is H, alkyl, -C (=O) -alkyl, -alkylene-C (=O) -alkyl, -C (=O) -O-alkyl, -alkylene-C (=O) -O-alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, cycloalkylalkyl or heterocyclylalkyl; wherein R 4 is optionally substituted with one or more R 14;
    each R a and R b is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl or cycloalkyl;
    or R a and R b together form oxo (=O) ;
    x is 0, 1, 2, 3, 4, 5 or 6;
    each of R 5, R 6, R 7, R 8 and R 9 is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, -C (=O) -NR cR d, -NR m-C (=O) -R n, -NR p (OR q) , -C (=O) -R x, -C (=O) -OR y, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, hydroxy substituted alkyl, amino substituted alkyl, cyano substituted alkyl, alkoxy, haloalkoxy, hydroxy substituted alkoxy, amino substituted alkoxy, cyano substituted alkoxy, alkylamino, alkylthio or aryloxy;
    wherein R 5 and R 6, together with the carbon atoms to which they are attached, optionally  form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 15;
    wherein R 6 and R 7, together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 16;
    wherein R 7 and R 8, together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 17;
    wherein R 8 and R 9, together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 18;
    wherein each of R p and R q is independently H, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl or -C (=O) -OR y1;
    wherein each of R c, R d, R m, R n, R y1, R x and R y is independently H, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl;
    wherein each R 1, R 2, R 3, R 5, R 6, R 7, R 8, R 9, R a, R b, R c, R d, R m, R n, R x and R y is optionally substituted with one, two, three, four, five or six R 10;
    each R 10, R 12 and R 14 is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, -C (=O) -OR z, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halo C 1-6 alkyl, halo C 2-6 alkenyl, halo C 2-6 alkynyl, hydroxy substituted C 1-6 alkyl, amino substituted C 1-6 alkyl, cyano substituted C 1-6 alkyl, C 1-6 alkoxy, halo C 1-6 alkoxy, hydroxy substituted C 1-6 alkoxy, amino substituted C 1-6 alkoxy, cyano substituted C 1-6 alkoxy, C 1-6 alkylamino, C 3-8 cycloalkyl, C 6-10 aryl or C 1-9 heteroaryl;
    wherein R z is C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halo C 1-6 alkyl, halo C 2-6 alkenyl, halo C 2-6 alkynyl, C 3-8 cycloalkyl, 3-12 membered heterocyclyl, C 6-10 aryl or C 1-9 heteroaryl;
    each R 15, R 16, R 17 and R 18 is independently H, halogen, cyano, nitro, alkyl, alkenyl, alkynyl, alkoxy, alkylamino, haloalkyl or haloalkoxy;
    with the proviso that when R 1 and R 2 is methyl, R 3 is H, w is 2, R 4 is H and x is 0, R 7 is not unsubstituted or substituted phenoxy, unsubstituted or substituted pyridyloxy or unsubstituted or substituted naphthyloxy.
  2. The compound of claim 1 having Formula (I) or a stereoisomer, an N-oxide or a salt thereof,
    Figure PCTCN2018081979-appb-100002
    wherein
    each of R 1 and R 2 is independently H, alkyl, alkoxyalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, cycloalkylalkyl, heterocyclylalkyl, arylalkyl, halo substituted arylalkyl or heteroarylalkyl; or R 1 and R 2, together with the N atom to which they are attached, form a heterocyclyl or heteroaryl group;
    wherein the heterocyclyl or heteroaryl group formed from R 1 and R 2, together with the N atom to which they are attached is optionally substituted with one or more R 12;
    R 3 is H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, aryl or haloaryl;
    R 4 is H, alkyl, -C (=O) -alkyl, -alkylene-C (=O) -alkyl, -C (=O) -O-alkyl, -alkylene-C (=O) -O-alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, cycloalkylalkyl or heterocyclylalkyl; wherein R 4 is optionally substituted with one or more R 14;
    each R a and R b is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl or cycloalkyl;
    or R a and R b together form oxo (=O) ;
    x is 0, 1, 2, 3, 4, 5 or 6;
    each of R 5, R 6, R 7, R 8 and R 9 is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, -C (=O) -NR cR d, -NR m-C (=O) -R n, -NR p (OR q) , -C (=O) -R x, -C (=O) -OR y, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, hydroxy substituted alkyl, amino substituted alkyl, cyano substituted alkyl, alkoxy, haloalkoxy, hydroxy substituted alkoxy, amino substituted alkoxy, cyano substituted alkoxy, alkylamino, alkylthio or aryloxy;
    wherein R 5 and R 6, together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 15;
    wherein R 6 and R 7, together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally  substituted with one, two, three, four, five, six, seven, eight or nine R 16;
    wherein R 7 and R 8, together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 17;
    wherein R 8 and R 9, together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 18;
    wherein each of R p and R q is independently H, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl or -C (=O) -OR y1;
    wherein each of R c, R d, R m, R n, R y1, R x and R y is independently H, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl;
    wherein each R 1, R 2, R 3, R 5, R 6, R 7, R 8, R 9, R a, R b, R c, R d, R m, R n, R x and R y is optionally substituted with one, two, three, four, five or six R 10;
    each R 10, R 12 and R 14 is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, -C (=O) -OR z, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halo C 1-6 alkyl, halo C 2-6 alkenyl, halo C 2-6 alkynyl, hydroxy substituted C 1-6 alkyl, amino substituted C 1-6 alkyl, cyano substituted C 1-6 alkyl, C 1-6 alkoxy, halo C 1-6 alkoxy, hydroxy substituted C 1-6 alkoxy, amino substituted C 1-6 alkoxy, cyano substituted C 1-6 alkoxy, C 1-6 alkylamino, C 3-8 cycloalkyl, C 6-10 aryl or C 1-9 heteroaryl;
    wherein R z is C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halo C 1-6 alkyl, halo C 2-6 alkenyl, halo C 2-6 alkynyl, C 3-8 cycloalkyl, 3-12 membered heterocyclyl, C 6-10 aryl or C 1-9 heteroaryl;
    each R 15, R 16, R 17 and R 18 is independently H, halogen, cyano, nitro, alkyl, alkenyl, alkynyl, alkoxy, alkylamino, haloalkyl or haloalkoxy;
    with the proviso that when R 1 and R 2 is methyl, R 3 is H, w is 2, R 4 is H and x is 0, R 7 is not unsubstituted or substituted phenoxy, unsubstituted or substituted pyridyloxy or unsubstituted or substituted naphthyloxy.
  3. The compound of claim 1 or 2, wherein
    each of R 1 and R 2 is independently H, C 1-6 alkyl, C 1-6 alkoxy-C 1-6-alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, C 2-10 heterocyclyl, C 6-10 aryl, C 1-9 heteroaryl, C 3-8 cycloalkyl-C 1-6-alkyl, C 2-10 heterocyclyl-C 1-6-alkyl, C 6-10 aryl-C 1-6-alkyl, halo substituted C 6-10 aryl-C 1-6-alkyl or C 1-9 heteroaryl-C 1-6-alkyl; or R 1 and R 2, together with the N atom to which they are attached, form a 3-8 membered heterocyclyl or C 1-9 heteroaryl group;
    wherein the 3-8 membered heterocyclyl or C 1-9 heteroaryl group formed from R 1 and R 2, together with the N atom to which they are attached is optionally substituted with one or more R 12;
    R 3 is H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halo C 1-6 alkyl, halo C 2-6 alkenyl, halo C 2-6 alkynyl, C 6-10 aryl or halo C 6-10 aryl ;
    R 4 is H, C 1-6 alkyl, -C (=O) -C 1-6 alkyl, -C 1-6 alkylene-C (=O) -C 1-6 alkyl, -C (=O) -O-C 1-6 alkyl, -C 1-6 alkylene-C (=O) -O-C 1-6 alkyl, C 1-6 alkoxy, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, 3-12 membered heterocyclyl, C 6-10 aryl, C 6-10 aryl-C 1-6-alkyl, C 3-8 cycloalkyl-C 1-6-alkyl or C 2-10 heterocyclyl-C 1-6-alkyl; wherein R 4 is optionally substituted with one or more R 14;
    each R a and R b is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halo C 1-6 alkyl, halo C 2-6 alkenyl, halo C 2-6 alkynyl or C 3-8 cycloalkyl;
    or R a and R b together form oxo (=O) ;
    x is 0, 1, 2, 3, 4, 5 or 6;
    each of R 5, R 6, R 7, R 8 and R 9 is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, -C (=O) -NR cR d, -NR m-C (=O) -R n, -NR p (OR q) , -C (=O) -R x, -C (=O) -OR y, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halo C 1-6 alkyl, halo C 2-6 alkenyl, halo C 2-6 alkynyl, hydroxy substituted C 1-6 alkyl, amino substituted C 1-6 alkyl, cyano substituted C 1-6 alkyl, C 1-6 alkoxy, halo C 1-6 alkoxy, hydroxy substituted C 1-6 alkoxy, amino substituted C 1-6 alkoxy, cyano substituted C 1-6 alkoxy, C 1-6 alkylamino, C 1-6 alkylthio or C 6-10 aryloxy;
    wherein R 5 and R 6, together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 15;
    wherein R 6 and R 7, together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 16;
    wherein R 7 and R 8, together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 17;
    wherein R 8 and R 9, together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally  substituted with one, two, three, four, five, six, seven, eight or nine R 18;
    wherein each of R p and R q is independently H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halo C 1-6 alkyl, halo C 2-6 alkenyl, halo C 2-6 alkynyl, C 3-6 cycloalkyl, 3-8 membered heterocyclyl, C 6-10 aryl, C 1-6 heteroaryl or -C (=O) -OR y1;
    wherein each of R c, R d, R m, R n, R y1, R x and R y is independently H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halo C 1-6 alkyl, halo C 2-6 alkenyl, halo C 2-6 alkynyl, C 3-6 cycloalkyl, 3-8 membered heterocyclyl, C 6-10 aryl or C 1-5 heteroaryl;
    wherein each R 1, R 2, R 3, R 5, R 6, R 7, R 8, R 9, R a, R b, R c, R d, R m, R n, R x and R y is optionally substituted with one, two, three, four, five or six R 10;
    each R 10, R 12 and R 14 is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, -C (=O) -OR z, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, halo C 1-4 alkyl, halo C 2-4 alkenyl, halo C 2-4 alkynyl, hydroxy substituted C 1-4 alkyl, amino substituted C 1-4 alkyl, cyano substituted C 1-4 alkyl, C 1-4 alkoxy, halo C 1-4 alkoxy, hydroxy substituted C 1-4 alkoxy, amino substituted C 1-4 alkoxy, cyano substituted C 1-4 alkoxy, C 1-4 alkylamino, C 3-6 cycloalkyl, C 6-10 aryl or C 1-5 heteroaryl;
    wherein R z is C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, halo C 1-4 alkyl, halo C 2-4 alkenyl, halo C 2-4 alkynyl, C 3-6 cycloalkyl, 3-8 membered heterocyclyl, C 6-10 aryl or C 1-5 heteroaryl;
    each R 15, R 16, R 17 and R 18 is independently H, halogen, cyano, nitro, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 alkylamino, halo C 1-6 alkyl or halo C 1-6 alkoxy;
    with the proviso that when R 1 and R 2 is methyl, R 3 is H, w is 2, R 4 is H and x is 0, R 7 is not unsubstituted or substituted phenoxy, unsubstituted or substituted pyridyloxy or unsubstituted or substituted naphthyloxy.
  4. The compound of any one of claims 1 to 3, wherein
    each of R 1 and R 2 is independently H, C 1-4 alkyl, C 1-3 alkoxy-C 1-3-alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 3-6 cycloalkyl, C 2-6 heterocyclyl, C 6-10 aryl, C 1-5 heteroaryl, C 3-6 cycloalkyl-C 1-4-alkyl, C 2-6 heterocyclyl-C 1-4-alkyl, C 6-10 aryl-C 1-4-alkyl, halo substituted C 6-10 aryl-C 1-4-alkyl or C 1-5 heteroaryl-C 1-4-alkyl; or R 1 and R 2, together with the N atom to which they are attached, form the following sub-structures:
    Figure PCTCN2018081979-appb-100003
    each of p 1 and p 2 is independently 0, 1, or 2;
    q is 0, 1 or 2;
    X 1 is -O-, -S-, -S (=O) -, -S (=O)  2-or -NH-;
    each X 2, X 3, X 4 and X 5 is independently N or CH;
    wherein sub-structure (i) , (ii) , (iii) or (iv) is optionally substituted with one or more R 12.
  5. The compound of any one of claims 1 to 4, wherein
    each of R 1 and R 2 is independently H, -CH 3, -CH 2CH 3, -CH 2CH 2CH 3, -CH (CH 3)  2, -CH 2CH=CH 2, -CH 2CH 2CH=CH 2, -CH 2CH=CHCH 3, -CH 2-O-CH 3, -CH 2CH 2-O-CH 3, -CH 2-O-CH 2CH 3, -CH 2CH 2-O-CH 2CH 3, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, benzyl, 4-fluorobenzyl or 4-cyanobenzyl;
    or R 1 and R 2, together with the N atom to which they are attached, form the following sub-structures:
    Figure PCTCN2018081979-appb-100004
  6. The compound of any one of claims 1 to 5, wherein
    R 3 is H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, halo C 1-4 alkyl, halo C 2-4 alkenyl, halo C 2-4 alkynyl, C 6-10 aryl or halo C 6-10 aryl.
  7. The compound of any one of claims 1 to 6, wherein
    R 3 is H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, -CH 3, -CHF 2, -CH 2F, -CH 2CH 3, -CH 2CH 2F, -CH 2CHF 2, -CH 2CH 2CH 3, -CH (CH 3)  2, -C (CH 3)  3, phenyl, 2-fluorophenyl, 3-fluorophenyl or 4-fluorophenyl.
  8. The compound of any one of claims 1 to 7, wherein
    R 4 is H, C 1-4 alkyl, -C (=O) -C 1-4 alkyl, -C 1-4 alkylene-C (=O) -C 1-4 alkyl, -C (=O) -O-C 1-4 alkyl, -C 1-4 alkylene-C (=O) -O-C 1-4 alkyl, C 1-4 alkoxy, C 2-4 alkenyl, C 2-4 alkynyl, C 3-6 cycloalkyl, 3-10 membered heterocyclyl, C 6-10 aryl, C 6-10 aryl-C 1-3-alkyl, C 3-6 cycloalkyl-C 1-3-alkyl or C 2-6 heterocyclyl-C 1-3-alkyl; wherein R 4 is optionally substituted with one, two, three, four or five R 14;
    each R 14 is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, -C (=O) -O-C 1-3 alkyl, C 1-3 alkyl, C 1-3 alkoxy, C 3-6 cycloalkyl or phenyl.
  9. The compound of any one of claims 1 to 8, wherein
    R 4 is H, -CH 3, -CHF 2, -CH 2 (CN) , -CH 2CH 3, -CH (CN) CH 3, -CH 2CHF 2, -CH 2CH 2CH 3,  -CH(CH 3)  2, -CH 2CH 2CH 2CH 3, -C (CH 3)  3, -CH 2CH=CH 2, -CH 2CH 2CH=CH 3, -CH 2CH=CHCH 3, -C (=O) -CH 3, -C (=O) -CH 2CH 3, -C (=O) -OCH 3, -C (=O) -OCH 2CH 3, -CH 2-C (=O) -OCH 3, -CH 2-C (=O) -OCH 2CH 3, -OCH 3, -OCH 2CH 3, -OCH 2CH 2CH 3, -OCH (CH 3)  2, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl or benzyl; or R 4 has the following sub-structure:
    Figure PCTCN2018081979-appb-100005
  10. The compound of any one of claims 1 to 9, wherein
    each of R 5, R 6, R 7, R 8 and R 9 is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, -C (=O) -NR cR d, -NR m-C (=O) -R n, -NR p (OR q) , -C (=O) -R x, -C (=O) -OR y, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, halo C 1-4 alkyl, halo C 2-4 alkenyl, halo C 2-4 alkynyl, hydroxy substituted C 1-4 alkyl, amino substituted C 1-4 alkyl, cyano substituted C 1-4 alkyl, C 1-4 alkoxy, halo C 1-4 alkoxy, hydroxy substituted C 1-4 alkoxy, amino substituted C 1-4 alkoxy, cyano substituted C 1-4 alkoxy, C 1-4 alkylamino, C 1-4 alkylthio or C 6-10 aryloxy;
    wherein R 5 and R 6, together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 15;
    wherein R 6 and R 7, together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 16;
    wherein R 7 and R 8, together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 17;
    wherein R 8 and R 9, together with the carbon atoms to which they are attached, optionally form a benzene or naphthalene ring; and wherein the benzene or naphthalene ring is optionally substituted with one, two, three, four, five, six, seven, eight or nine R 18;
    wherein each of R p and R q is independently H, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, halo C 1-3 alkyl, halo C 2-4 alkenyl, halo C 2-4 alkynyl, C 3-6 cycloalkyl, 3-6 membered heterocyclyl, C 6-10 aryl, C 1-5 heteroaryl or -C (=O) -OR y1;
    wherein each of R c, R d, R m, R n, R y1, R x and R y is independently H, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, halo C 1-4 alkyl, halo C 2-4 alkenyl, halo C 2-4 alkynyl, C 3-6 cycloalkyl, 3-6 membered heterocyclyl, C 6-10 aryl or C 1-5 heteroaryl;
    wherein each R 5, R 6, R 7, R 8, R 9, R c, R d, R m, R n, R y1, R x and R y is optionally substituted with one, two, three, four, five or six R 10;
    each R 15, R 16, R 17 and R 18 is independently H, halogen, cyano, nitro, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 alkoxy, C 1-4 alkylamino, halo C 1-4 alkyl or halo C 1-4 alkoxy.
  11. The compound of any one of claims 1 to 10, wherein
    each R 5, R 6, R 7, R 8 and R 9 is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, -CH 3, -CH 2CH 3, -CH 2CH 2CH 3, -CH (CH 3)  2, -CH 2F, -CHF 2, -CF 3, -CH 2CH 2F, -CH 2CHF 2, -CH 2CF 3, -CH=CH 2, -CH 2-CH=CH 2, -OCH 3, -OCH 2CH 3, -OCH 2CH 2CH 3, -OCH (CH 3)  2, -OCF 3, -OCH 2CF 3, -NH-C (=O) -CH 3, -NH-C (=O) -CH 2CH 3, -NH-OH, -N (OH) -C (=O) -OCH 3, -N (OC (=O) OCH 3) -C (=O) -OCH 3, -C (=O) -CH 3, -C (=O) -CH 2CH 3, -C (=O) -OCH 3, -C (=O) -OCH 2CH 3, -SCH 3, -SCH 2CH 3, -SCH 2CH 2CH 3, -SCH (CH 3)  2, phenoxy, halophenoxy, C 1-4 alkyl substituted phenoxy, C 1-4 alkoxy substituted phenoxy, C 1-4 haloalkyl substituted phenoxy or C 1-4 haloalkoxy substituted phenoxy.
  12. The compound of any one of claims 1 to 11, wherein
    Figure PCTCN2018081979-appb-100006
    has the following sub-structure:
    Figure PCTCN2018081979-appb-100007
    Figure PCTCN2018081979-appb-100008
    wherein
    each R 5, R 7, R 8, R 9, R 15a, R 15b, R 15c, R 15d, R 16a, R 16b, R 16c, R 16d, R 16e, R 16f, R 18a, R 18b, R 18c and R 18d is independently H, halo, cyano, nitro, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 alkylamino, halo C 1-6 alkyl or halo C 1-6 alkoxy.
  13. The compound of any one of claims 1 to 12, wherein
    each R 5, R 7, R 8, R 9, R 15a, R 15b, R 15c, R 15d, R 16a, R 16b, R 16c, R 16d, R 16e, R 16f, R 18a, R 18b, R 18c and R 18d is independently H, halo, cyano, nitro, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 alkoxy, C 1-4 alkylamino, halo C 1-4 alkyl or halo C 1-4 alkoxy.
  14. The compound of any one of claims 1 to 13, wherein
    each R 5, R 7, R 8, R 9, R 15a, R 15b, R 15c, R 15d, R 16a, R 16b, R 16c, R 16d, R 16e, R 16f, R 18a, R 18b, R 18c and R 18d is independently H, F, Cl, Br, I, cyano, nitro, methyl, ethyl, n-propyl, isopropyl, t-butyl, vinyl, propenyl, allyl, ethynyl, propinyl, propargyl, methoxy, ethoxy, isopropoxy, t-butoxy, difluoromethyl, trifluoromethyl, difluoromethoxy, trifluoromethoxy, dimethylamino or diethylamino.
  15. The compound of any one of claims 1 to 14, wherein
    each R a and R b is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, halo C 1-4 alkyl, halo C 2-4 alkenyl, halo C 2-4 alkynyl or C 3-6 cycloalkyl;
    or R a and R b together form oxo (=O) .
  16. The compound of any one of claims 1-15, wherein
    each R a and R b is independently H, F, Cl, Br, I, hydroxy, cyano, nitro, amino, carboxy, -CH 3, -CH 2CH 3, -CH 2CH 2CH 3, -CH (CH 3)  2, -CH 2F, -CHF 2, -CF 3, -CH 2CH 2F, -CH 2CHF 2, -CH 2CF 3, -CH=CH 2, -CH 2-CH=CH 2, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl;
    or R a and R b together form oxo (=O) .
  17. The compound of any one of claims 1 to 16 having one of the following structures or a stereoisomer, an N-oxide or a salt thereof,
    Figure PCTCN2018081979-appb-100009
    Figure PCTCN2018081979-appb-100010
    Figure PCTCN2018081979-appb-100011
    Figure PCTCN2018081979-appb-100012
    Figure PCTCN2018081979-appb-100013
    Figure PCTCN2018081979-appb-100014
    Figure PCTCN2018081979-appb-100015
    Figure PCTCN2018081979-appb-100016
    Figure PCTCN2018081979-appb-100017
    Figure PCTCN2018081979-appb-100018
    Figure PCTCN2018081979-appb-100019
  18. A method of preparing a compound of Formula (I) comprising reacting a compound of Formula (e) with a disubstituted amino sulfonyl chloride to obtain the compound of Formula (I) :
    Figure PCTCN2018081979-appb-100020
    wherein R 1, R 2, R 3, R 4, R 5, R 6, R 7, R 8, R 9, R a, R b and x are as defined in any one of claims 2 to 16.
  19. A compound having Formula (II) or a stereoisomer, an N-oxide or a salt thereof,
    Figure PCTCN2018081979-appb-100021
    wherein R 3, R 5, R 6, R 7, R 8, R 9, R a, R b and x are as defined in any one of claims 1 to 3, 6 to 7 and 10 to 16.
  20. A composition comprising a compound of any one of claims 1 to 17.
  21. The composition of claim 20 further comprising an agrochemically acceptable surfactant and carrier.
  22. Use of a compound of any one of claims 1 to 17 or a composition of claim 20 or 21 for controlling plant diseases.
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CN113429356A (en) * 2020-03-23 2021-09-24 东莞市东阳光农药研发有限公司 Triazole sulfonamide derivative and application thereof in agriculture
CN113929665A (en) * 2020-06-29 2022-01-14 东莞市东阳光农药研发有限公司 Aryl-substituted triazole sulfonamide derivative and preparation method and application thereof
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CN113929665A (en) * 2020-06-29 2022-01-14 东莞市东阳光农药研发有限公司 Aryl-substituted triazole sulfonamide derivative and preparation method and application thereof
CN115039784A (en) * 2021-03-08 2022-09-13 东莞市东阳光农药研发有限公司 Composition and application thereof in agriculture
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