WO2019223664A1

WO2019223664A1 - Oxazoline derivatives and uses in agriculture thereof

Info

Publication number: WO2019223664A1
Application number: PCT/CN2019/087680
Authority: WO
Inventors: Yitao LI; Jian Lin; Weilin CHI; Shuiming ZENG; Jianing REN; Pengfei Qiu; Xiaodan Guo
Original assignee: Dongguan Hec Pesticides R&d Co Ltd
Current assignee: Dongguan Hec Pesticides R&d Co Ltd
Priority date: 2018-05-22
Filing date: 2019-05-21
Publication date: 2019-11-28
Anticipated expiration: 2020-11-22
Also published as: CN110511216A; CN110511216B

Abstract

Provided are isoxazoline derivatives having formula (Ia), or a stereoisomer, an N-oxide or a salt thereof, preparation methods thereof, compositions containing these compounds and uses in agriculture thereof, particularly uses as active ingredients of herbicide for controlling unwanted plants.

Description

ISOXAZOLINE DERIVATIVES AND THEIR USES IN AGRICULTURE

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to Chinese Patent Application Serial No. 201810497022.1, filed with the State Intellectual Property Office of China on May 22, 2018; Chinese Patent Application Serial No. 201810802955.7, filed with the State Intellectual Property Office of China on July 20, 2018; and Chinese Patent Application Serial No. 201910063372.1, filed with the State Intellectual Property Office of China on January 23, 2019, which are hereby incorporated by reference in their entireties and for all purposes as if specifically and fully set forth herein.

FIELD

The invention provides a novel isoxazoline derivative and preparation method thereof; composition containing the compound and their uses in agriculture.

BACKGROUND ART

Isoxazoline compounds are a class of compounds with excellent biological activities, and their herbicidal activities have been described in literatures such as WO 2002062770, WO 2003000686 and WO 2003010165. However, the compounds of the invention described in detail below are not described in these documents.

The active ingredients known from the above cited documents have disadvantages in use, for example, (a) no or only insufficient herbicidal effect on ruderal plants, (b) too narrow spectrum of ruderal plant to be controlled, or (c) too low selectivity for useful plant crops.

Therefore, there is a need to provide a chemical active ingredient that can be advantageously used as herbicide or plant growth regulator.

SUMMARY OF THE INVENTION

The present invention provides a novel isoxazoline compound having excellent herbicidal action and excellent selectivity between crops and weeds.

In one aspect, provided herein is a compound having Formula (Ia) or a stereoisomer, an N-oxide or a salt thereof:

wherein,

each of R ¹ and R ² is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, alkyl, haloalkyl, cycloalkyl or cycloalkylalkyl; or, R ¹ and R ² together with the carbon atom to which they are attached, form a 3-to 12-membered ring;

each of R ³ and R ⁴ is independently hydrogen, bromine, iodine, amino, nitro, hydroxy, carboxy, alkyl, cycloalkyl or cycloalkylalkyl; or, R ³ and R ⁴ together with the carbon atom to which they are attached, form a 3-to 12-membered ring;

n is 0, 1 or 2;

each of R ⁵ and R ⁶ is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, alkyl, alkenyl or alkynyl; or, R ⁵ and R ⁶ together with the carbon atom to which they are attached, form a 3-to 12-membered ring;

X is fluorine, chlorine or bromine;

Y is alkyl, haloalkyl, alkoxyalkyl, alkylaminoalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, -C (=O) -alkyl, -S (=O) ₂-alkyl, -C (=O) -cycloalkyl, -S (=O) ₂-cycloalkyl, -C (=O) -heterocyclyl, -S (=O) ₂-heterocyclyl, -C (=O) -aryl, -S (=O) ₂-aryl, -C (=O) -heteroaryl or -S (=O) ₂-heteroaryl;

wherein Y is optionally substituted with 1, 2, 3, 4, 5 or 6 substitutents selected from Y ^a; and each Y ^a is independently fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkoxy, alkylamino, alkylthio, cycloalkyl, heterocyclyl, aryl or heteroaryl;

with the proviso that:

(1) when Y is methyl, X is chlorine, R ⁵ and R ⁶ are hydrogen, n is 0, 1 or 2, R ³ and R ⁴ are hydrogen, and R ¹ is methyl, R ² is not methyl or chloromethyl;

(2) when Y is methyl, X is chlorine, R ⁵ and R ⁶ are hydrogen, n is 0, 1 or 2; R ³ and R ⁴ are hydrogen, and R ² is methyl, R ¹ is not methyl or chloromethyl;

(3) when Y is unsubstituted phenyl, X is chlorine, R ⁵ and R ⁶ are hydrogen, n is 0, 1 or 2, R ³ and R ⁴ are hydrogen, and R ¹ is methyl, R ² is not methyl or chloromethyl;

(4) when Y is unsubstituted phenyl, X is chlorine, R ⁵ and R ⁶ are hydrogen, n is 0, 1 or 2, R ³ and R ⁴ are hydrogen, and R ² is methyl, R ¹ is not methyl or chloromethyl;

(5) when Y is ethyl or isopropyl, X is chlorine on the 5 position of pyrazole ring, R ⁵ and R ⁶ are hydrogen, n is 0 or 2; R ³ and R ⁴ are hydrogen, and R ¹ is methyl, R ² is not chloromethyl; or

(6) when Y is ethyl or isopropyl, X is chlorine on the 5 position of pyrazole ring, R ⁵ and R ⁶ are hydrogen, n is 0 or 2, R ³ and R ⁴ are hydrogen, and R ² is methyl, R ¹ is not chloromethyl.

In some embodiments, provided herein is a compound having Formula (II) or a stereoisomer, an N-oxide or a salt thereof,

wherein,

X is fluorine, chlorine or bromine;

n is 0, 1 or 2;

each of R ⁸, R ⁹, R ¹⁰, R ¹¹ and R ¹² is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkoxy, alkylamino, alkylthio, cycloalkyl, heterocyclyl, aryl or heteroaryl;

or, R ⁸ and R ⁹ together with the carbon atom to which they are attached, form a 3 to 12-membered ring;

or, R ⁸ and R ⁹ together with the carbon atom to which they are attached, form -C (=O) -;

or, R ¹⁰, R ¹¹ and R ¹² together with the carbon atom to which they are attached, form -C≡CR ¹³ or -CR ¹⁴=CR ¹⁵R ¹⁶; wherein each of R ¹³, R ¹⁴, R ¹⁵ and R ¹⁶ is independently hydrogen, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl or haloalkynyl;

or, R ¹⁰, R ¹¹ and R ¹² together with the carbon atom to which they are attached, form optionally substituted C _6-14 aryl, optionally substituted C _1-9 heteroaryl, optionally substituted C _3-12 cycloalkyl or optionally substituted C _2-12 heterocyclyl;

or -CR ⁸R ⁹-CR ¹⁰R ¹¹R ¹² is optionally substituted C _10-14 aryl, optionally substituted C _1-9 heteroaryl, optionally substituted C _3-12 cycloalkyl, optionally substituted C _2-12 heterocyclyl, unsubstituted phenyl or substituted phenyl;

wherein the substituted or optionally substituted groups described above, the number of the substituents on the substituted or optionally substituted groups is 1, 2, 3, 4, 5 or 6; and the substituents may be the same or different; wherein the substituents are fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkoxy, alkylamino, alkylthio, cycloalkyl, heterocyclyl, aryl or heteroaryl;

with the proviso that:

(a) when -CR ⁸R ⁹-CR ¹⁰R ¹¹R ¹² is unsubstituted phenyl, X is chlorine, R ⁵ and R ⁶ are hydrogen, n is 0, 1 or 2, R ³ and R ⁴ are hydrogen, and R ¹ is methyl, R ² is not methyl or chloromethyl;

(b) when -CR ⁸R ⁹-CR ¹⁰R ¹¹R ¹² is unsubstituted phenyl, X is chlorine, R ⁵ and R ⁶ are hydrogen, n is 0, 1 or 2, R ³ and R ⁴ are hydrogen, and R ² is methyl, R ¹ is not methyl or chloromethyl;

(c) when -CR ⁸R ⁹-CR ¹⁰R ¹¹R ¹² is ethyl or isopropyl, X is chlorine on the 5 position of pyrazole ring, R ⁵ and R ⁶ are hydrogen, n is 0 or 2, R ³ and R ⁴ are hydrogen, and R ¹ is methyl, R ² is not chloromethyl; or

(d) when -CR ⁸R ⁹-CR ¹⁰R ¹¹R ¹² is ethyl or isopropyl, X is chlorine on the 5 position of pyrazole ring, R ⁵ and R ⁶ are hydrogen, n is 0 or 2, R ³ and R ⁴ are hydrogen, and R ² is methyl, R ¹ is not chloromethyl.

In some embodiments, provided herein is a compound having Formula (IIa) or a stereoisomer, an N-oxide or a salt thereof,

wherein R ¹, R ², R ³, R ⁴, R ⁵, R ⁶, R ⁸, R ⁹, R ¹⁰, R ¹¹ and R ¹² are as defined herein.

In some embodiments, the invention provides a compound having Formula (IIa) , or a stereoisomer, an N-oxide or a salt thereof, wherein:

each of R ¹ and R ² is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, C _1-6 alkyl, halo C _1-6 alkyl, C _3-6 cycloalkyl or C _3-6 cycloalkyl-C _1-6 alkyl; or, R ¹ and R ² together with the carbon atom to which they are attached, form a 3-to 8-membered ring;

each of R ³ and R ⁴ is independently hydrogen, bromine, iodine, amino, nitro, hydroxy, carboxy, C _1-6 alkyl, C _3-6 cycloalkyl or C _3-6cycloalkyl-C _1-6 alkyl; or, R ³ and R ⁴ together with the carbon atom to which they are attached, form a 3-to 8-membered ring;

each of R ⁵ and R ⁶ is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, C _1-6 alkyl, C _2-6 alkenyl _, or C _2-6 alkynyl; or, R ⁵ and R ⁶ together with the carbon atom to which they are attached, form a 3-to 8-membered ring;

each of R ⁸, R ⁹, R ¹⁰, R ¹¹ and R ¹² is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, C _1-6 alkyl, halo C _1-6 alkyl, C _2-6 alkenyl, halo C _2-6 alkenyl, C _2-6 alkynyl, halo C _2-6 alkynyl, C _1-6 alkoxy, C _1-6 alkylamino, C _1-6 alkylthio, C _3-6 cycloalkyl, C _2-8 heterocyclyl, C _6-10 aryl or C _1-9 heteroaryl;

or, R ⁸ and R ⁹, together with the carbon atom to which they are attached, form a 3 to 10-membered ring;

or, R ¹⁰, R ¹¹ and R ¹² together with the carbon atom to which they are attached, form -C≡CR ¹³ or -CR ¹⁴=CR ¹⁵R ¹⁶; wherein each of R ¹³, R ¹⁴, R ¹⁵ and R ¹⁶ is independently hydrogen, C _1-6 alkyl, halo C _1-6 alkyl, C _2-6 alkenyl, halo C _2-6 alkenyl, C _2-6 alkynyl or halo C _2-6 alkynyl;

or, R ¹⁰, R ¹¹ and R ¹² together with the carbon atom to which they are attached, form optionally substituted C _6-14 aryl, optionally substituted C _1-9 heteroaryl, optionally substituted C _3-10 cycloalkyl or optionally substituted C _2-10 heterocyclyl;

or -CR ⁸R ⁹-CR ¹⁰R ¹¹R ¹² is optionally substituted C _10-14 aryl, optionally substituted C _1-9 heteroaryl, optionally substituted C _3-10 cycloalkyl, optionally substituted C _2-10 heterocyclyl, unsubstituted phenyl or substituted phenyl;

wherein the substituted or optionally substituted groups described above, the number of the substituents on the substituted or optionally substituted groups is 1, 2, 3, 4, 5 or 6; and the substituents may be the same or different; wherein the substitutent is fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, C _1-6 alkyl, halo C _1-6 alkyl, C _2-6 alkenyl, halo C _2-6 alkenyl, C _2-6 alkynyl, halo C _2-6 alkynyl, C _1-6 alkoxy, C _1-6 alkylamino, C _1-6 alkylthio, C _3-8 cycloalkyl, C _2-10 heterocyclyl, C _6-14 aryl or C _1-9 heteroaryl;

with the proviso that:

(a) when -CR ⁸R ⁹-CR ¹⁰R ¹¹R ¹² is unsubstituted phenyl, R ⁵ and R ⁶ are hydrogen, R ³ and R ⁴ are hydrogen, and R ¹ is methyl, R ² is not methyl or chloromethyl;

(b) when -CR ⁸R ⁹-CR ¹⁰R ¹¹R ¹² is unsubstituted phenyl, R ⁵ and R ⁶ are hydrogen, R ³ and R ⁴ are hydrogen, and R ² is methyl, R ¹ is not methyl or chloromethyl;

(c) when -CR ⁸R ⁹-CR ¹⁰R ¹¹R ¹² is ethyl or isopropyl, R ⁵ and R ⁶ are hydrogen, R ³ and R ⁴ are hydrogen, and R ¹ is methyl, R ² is not chloromethyl; or

(d) when -CR ⁸R ⁹-CR ¹⁰R ¹¹R ¹² is ethyl or isopropyl, R ⁵ and R ⁶ are hydrogen, R ³ and R ⁴ are hydrogen, and R ² is methyl, R ¹ is not chloromethyl.

In some embodiments, provided herein is a compound having Formula (IIb) or a stereoisomer, an N-oxide or a salt thereof,

In some embodiments, the invention provides a compound having Formula (IIb) , or a stereoisomer, an N-oxide or a salt thereof, wherein:

each of R ³ and R ⁴ is independently hydrogen, bromine, iodine, amino, nitro, hydroxy, carboxy, C _1-6 alkyl, C _3-6 cycloalkyl or C _3-6 cycloalkyl-C _1-6 alkyl; or, R ³ and R ⁴ together with the carbon atom to which they are attached, form a 3-to 8-membered ring;

each of R ⁵ and R ⁶ is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl; or, R ⁵ and R ⁶ together with the carbon atom to which they are attached, form a 3-to 8-membered ring;

or, R ⁸ and R ⁹ together with the carbon atom to which they are attached, form a 3 to 10-membered ring;

with the proviso that:

(a) when -CR ⁸R ⁹-CR ¹⁰R ¹¹R ¹² is unsubstituted phenyl, R ⁵ and R ⁶ are hydrogen, R ³ and R ⁴ are hydrogen, and R ¹ is methyl, R ² is not methyl or chloromethyl; or

(b) when -CR ⁸R ⁹-CR ¹⁰R ¹¹R ¹² is unsubstituted phenyl, R ⁵ and R ⁶ are hydrogen, R ³ and R ⁴ are hydrogen, and R ² is methyl, R ¹ is not methyl or chloromethyl.

In some embodiments, provided herein is a compound having Formula (IIc) or a stereoisomer, an N-oxide or a salt thereof:

In some embodiments, the invention provides a compound having Formula (IIc) , or a stereoisomer, an N-oxide or a salt thereof, wherein:

wherein the substituted or optionally substituted groups described above, the number of the substituents on the substituted or optionally substituted groups is 1, 2, 3, 4, 5 or 6; and the substituents may be the same or different; wherein the substitutents are fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, C _1-6 alkyl, halo C _1-6 alkyl, C _2-6 alkenyl, halo C _2-6 alkenyl, C _2-6 alkynyl, halo C _2-6 alkynyl, C _1-6 alkoxy, C _1-6 alkylamino, C _1-6 alkylthio, C _3-8 cycloalkyl, C _2-10 heterocyclyl, C _6-14 aryl or C _1-9 heteroaryl.

In some embodiments, provided herein is a compound having Formula (IId) or a stereoisomer, an N-oxide or a salt thereof:

In some embodiments, the invention provides a compound having Formula (IId) , or a stereoisomer, an N-oxide or a salt thereof, wherein:

wherein the substituted or optionally substituted grpups described above, the number of the substituents on the substituted or optionally substituted groups is 1, 2, 3, 4, 5 or 6; and the substituents may be the same or different; wherein the substitutents are fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, C _1-6 alkyl, halo C _1-6 alkyl, C _2-6 alkenyl, halo C _2-6 alkenyl, C _2-6 alkynyl, halo C _2-6 alkynyl, C _1-6 alkoxy, C _1-6 alkylamino, C _1-6 alkylthio, C _3-8 cycloalkyl, C _2-10 heterocyclyl, C _6-14 aryl or C _1-9 heteroaryl.

In some embodiments, provided herein is a compound having Formula (II-1) or a stereoisomer, an N-oxide or a salt thereof:

wherein,

n is 0, 1 or 2;

X is fluorine, chlorine or bromine;

each of R ⁸ and R ⁹ is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkoxy, alkylamino, alkylthio, cycloalkyl, heterocyclyl, aryl or heteroaryl;

R ¹³ is hydrogen, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl or haloalkynyl.

In some embodiments, provided herein is a compound having Formula (IIa-1) or a stereoisomer, an N-oxide or a salt thereof:

wherein R ¹, R ², R ³, R ⁴, R ⁵, R ⁶, R ⁸, R ⁹ and R ¹³ are as defined herein.

In some embodiments, the invention provides a compound having Formula (IIa-1) , or a stereoisomer, an N-oxide or a salt thereof, wherein:

each of R ⁸ and R ⁹ is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, C _1-6 alkyl, halo C _1-6 alkyl, C _2-6 alkenyl, halo C _2-6 alkenyl, C _2-6 alkynyl, halo C _2-6 alkynyl, C _1-6 alkoxy, C _1-6 alkylamino, C _1-6 alkylthio, C _3-6 cycloalkyl, C _2-8 heterocyclyl, C _6-10 aryl or C _1-9 heteroaryl;

R ¹³ is hydrogen, C _1-6 alkyl, halo C _1-6 alkyl, C _2-6 alkenyl, halo C _2-6 alkenyl, C _2-6 alkynyl or halo C _2-6 alkynyl.

In some embodiments, provided herein is a compound having Formula (IIa-2) or a stereoisomer, an N-oxide or a salt thereof:

In some embodiments, the invention provides a compound having Formula (IIa-2) , or a stereoisomer, an N-oxide or a salt thereof, wherein:

In some embodiments, provided herein is a compound having Formula (II-5) or a stereoisomer, an N-oxide or a salt thereof:

wherein,

n is 0, 1 or 2;

X is fluorine, chlorine or bromine;

with the proviso that:

(i) when X is chlorine, R ⁵ and R ⁶ are hydrogen, n is 0, 1 or 2; and R ³ and R ⁴ are hydrogen, R ¹ and R ² can not be both methyl at the same time;

(ii) when X is chlorine on the 5 position of parazole ring, R ⁵ and R ⁶ are hydrogen, n is 0, 1 or 2; R ³ and R ⁴ are hydrogen, and R ² is methyl, R ¹ is not chloromethyl; or

(iii) when X is chlorine on the 5 position of parazole ring, R ⁵ and R ⁶ are hydrogen, n is 0, 1 or 2, R ³ and R ⁴ are hydrogen, and R ¹ is methyl, R ² is not chloromethyl.

In some embodiments, provided herein is a compound having Formula (IIa-17) or a stereoisomer, an N-oxide or a salt thereof:

wherein R ¹, R ², R ³, R ⁴, R ⁵, R ⁶ and X are as defined herein.

In some embodiments, the invention provides a compound having Formula (IIa-17) , or a stereoisomer, an N-oxide or a salt thereof, wherein:

X is fluorine, chlorine or bromine;

with the proviso that:

(1) when X is chlorine, R ⁵ and R ⁶ are hydrogen, and R ³ and R ⁴ are hydrogen, R ¹and R ² can not be both methyl at the same time;

(2) when X is chlorine, R ⁵ and R ⁶ are hydrogen, R ³ and R ⁴ are hydrogen, and R ² is methyl, R ¹ is not chloromethyl; or

(3) when X is chlorine, R ⁵ and R ⁶ are hydrogen, R ³ and R ⁴ are hydrogen, and R ¹ is methyl, R ² is not chloromethyl.

In some embodiments, provided herein is a compound having Formula (IIa-18) or a stereoisomer, an N-oxide or a salt thereof:

wherein R ¹, R ², R ³, R ⁴, R ⁵, R ⁶ and X are as defined herein.

In some embodiments, the invention provides a compound having Formula (IIa-18) , or a stereoisomer, an N-oxide or a salt thereof, wherein:

X is fluorine, chlorine or bromine;

with the proviso that:

(1) when X is chlorine, R ⁵ and R ⁶ are hydrogen, and R ³ and R ⁴ are hydrogen, R ¹ and R ² can not be both methyl at the same time.

In other embodiments, R ¹ and R ² are hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, C _1-4 alkyl, halo C _1-4 alkyl, C _3-6 cycloalkyl or C _3-6 cycloalkyl-C _1-3 alkyl; or, R ¹ and R ² together with the carbon atom to which they are attached, form a 3-to 6-membered ring;

each of R ³ and R ⁴ is independently hydrogen, bromine, iodine, amino, nitro, hydroxy, carboxy, C _1-3 alkyl, C _3-6 cycloalkyl or C _3-6 cycloalkyl-C _1-3 alkyl; or, R ³ and R ⁴ together with the carbon atom to which they are attached, form a 3-to 6-membered ring;

each of R ⁵ and R ⁶ is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, C _1-4 alkyl, C _2-4 alkenyl or C _2-4 alkynyl; or, R ⁵ and R ⁶ together with the carbon atom to which they are attached, form a 3-to 6-membered ring.

In other embodiments, each of R ¹ and R ² is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, methyl, ethyl, n-propyl, isopropyl, -CH ₂F, -CH ₂Cl, -CH ₂Br or -CF ₃;

each of R ³ and R ⁴ is independently hydrogen or bromine;

each of R ⁵ and R ⁶ is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy or methyl.

In other embodiments, provided herein is a compound having Formula (IIIa) or a stereoisomer, an N-oxide or a salt thereof:

wherein R ⁸, R ⁹, R ¹⁰, R ¹¹ and R ¹² are as defined herein.

In other embodiments, provided herein is a compound having Formula (IIIb) or a stereoisomer, an N-oxide or a salt thereof:

wherein R ⁸, R ⁹, R ¹⁰, R ¹¹ and R ¹² are as defined herein.

In other embodiments, provided herein is a compound having Formula (IIIc) or a stereoisomer, an N-oxide or a salt thereof:

wherein R ⁸, R ⁹, R ¹⁰, R ¹¹ and R ¹² are as defined herein.

In other embodiments, provided herein is a compound having Formula (IIId) or a stereoisomer, an N-oxide or a salt thereof:

wherein R ⁸, R ⁹, R ¹⁰, R ¹¹ and R ¹² is as defined herein.

In other embodiments, each of R ⁸, R ⁹, R ¹⁰, R ¹¹ and R ¹² is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, C _1-4 alkyl, halo C _1-4 alkyl, C _2-4 alkenyl, halo C _2-4 alkenyl, C _2-4 alkynyl, halo C _2-4 alkynyl, C _1-4 alkoxy, C _1-4 alkylamino, C _1-4 alkylthio, C _3-6 cycloalkyl, C _2-6 heterocyclyl, C _6-10 aryl or C _1-5 heteroaryl;

or, R ⁸ and R ⁹ together with the carbon atom to which they are attached, form a 3 to 8-membered ring;

or, R ¹⁰, R ¹¹ and R ¹² together with the carbon atom to which they are attached, form -C≡CR ¹³ or -CR ¹⁴=CR ¹⁵R ¹⁶; wherein each of R ¹³, R ¹⁴, R ¹⁵ and R ¹⁶ is independently hydrogen, C _1-4 alkyl, halo C _1-4 alkyl, C _2-4 alkenyl, halo C _2-4 alkenyl, C _2-4 alkynyl or halo C _2-4 alkynyl;

or, R ¹⁰, R ¹¹ and R ¹² together with the carbon atom to which they are attached, form optionally substituted C _6-10 aryl, optionally substituted C _1-6 heteroaryl, optionally substituted C _3-8 cycloalkyl or optionally substituted C _2-6 heterocyclyl;

or -CR ⁸R ⁹-CR ¹⁰R ¹¹R ¹² is optionally substituted C _10-14 aryl, optionally substituted C _1-6 heteroaryl, optionally substituted C _3-8 cycloalkyl, optionally substituted C _2-6 heterocyclyl, unsubstituted phenyl or substituted phenyl;

wherein the substituted or optionally substituted groups described above, the number of the substituents on the substituted or optionally substituted groups is 1, 2, 3, 4, 5 or 6; and the substituents may be the same or different; wherein the substitutents are fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, C _1-6 alkyl, halo C _1-4 alkyl, C _2-4 alkenyl, halo C _2-4 alkenyl, C _2-4 alkynyl, halo C _2-4 alkynyl, C _1-4 alkoxy, C _1-4 alkylamino, C _1-4 alkylthio, C _3-6 cycloalkyl, C _2-6 heterocyclyl, C _6-10 aryl or C _1-5 heteroaryl.

In other embodiments, each of R ⁸, R ⁹, R ¹⁰, R ¹¹ and R ¹² is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, -CH ₃, -CH ₂CH ₃, -CH ₂CH ₂CH ₃, -CH (CH ₃) ₂, -CH ₂F, -CHF ₂, -CH ₂Cl, -CH ₂Br, -CF ₃, -CH ₂CF ₃, -CH ₂CH ₂F, -CH ₂CH ₂Cl, -CH ₂CH ₂Br, -CH ₂CHF ₂, -CH ₂CH ₂CF ₃, -CH ₂CH ₂CH ₂F, -CH ₂CH ₂CH ₂Cl, -CH ₂CH ₂CH ₂Br, -CHFCH ₂CH ₃, -CHClCH ₂CH ₃, -CH=CH ₂, -CH ₂CH=CH ₂, CH ₃-CH=CH-, -C≡CH, -C≡CCH ₃, -CH ₂-C≡CH, -OCH ₃, -OCH ₂CH ₃, -OCH ₂CH ₂CH ₃, -OCH (CH ₃) ₂, -NHCH ₃, -N (CH ₃) ₂, -SCH ₃, -SCH ₂CH ₃, -SCH ₂CH ₂CH ₃, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or phenyl;

or, R ⁸ and R ⁹ together with the carbon atom to which they are attached, form C _3-6 cycloalkyl;

or, R ¹⁰, R ¹¹ and R ¹² together with the carbon atom to which they are attached, form -C≡CH or -CH=CH ₂;

or, R ¹⁰, R ¹¹ and R ¹² together with the carbon atom to which they are attached, form C _3-6 cycloalkyl, optionally halogen-substituted phenyl or C _2-6 heterocyclyl containing one oxygen atom;

or -CR ⁸R ⁹-CR ¹⁰R ¹¹R ¹² is C _3-6 cycloalkyl or halogen-substituted phenyl.

In other embodiments, provided herein is a compound having Formula (IIIe) or a stereoisomer, an N-oxide or a salt thereof:

wherein,

each of R ⁵ and R ⁶ is independently hydrogen or fluorine;

X is fluroine or chlorine;

R ^m is hydrogen, C _1-3 alkyl or halo C _1-3 alkyl;

R ^v is hydrogen, C _1-3 alkyl or halo C _1-3 alkyl;

R ^w is C _1-3 alkyl or halo C _1-3 alkyl.

In other embodiments, provided herein is a compound having Formula (IIIe) or a stereoisomer, an N-oxide or a salt thereof, wherein R ^m is hydrogen or methyl; R ^v is hydrogen or methyl; R ^w is methyl, isopropyl, difluoromethyl or tetrafluromethyl.

In other embodiments, provided herein is a compound having Formula (IIIf) or a stereoisomer, an N-oxide or a salt thereof:

wherein,

each of R ⁵ and R ⁶ is independently hydrogen or fluorine;

X is fluroine or chlorine;

R ^m is hydrogen, C _1-3 alkyl or halo C _1-3 alkyl;

R ^v is hydrogen, C _1-3 alkyl or halo C _1-3 alkyl;

R ^w is C _1-3 alkyl or halo C _1-3 alkyl.

In other embodiments, provided herein is a compound having Formula (IIIf) or a stereoisomer, an N-oxide or a salt thereof, wherein R ^m is hydrogen or methyl; R ^v is hydrogen or methyl; R ^w is methyl, isopropyl, difluoromethyl or tetrafluoromethyl.

In other embodiments, provided herein is a compound having Formula (IIIg) or a stereoisomer, an N-oxide or a salt thereof:

wherein X is fluroine or chlorine.

In other embodiments, provided herein is a compound having Formula (IIIh) or a stereoisomer, an N-oxide or a salt thereof:

wherein X is fluorine, chlorine or bromine.

In another aspect, the invention provides a composition comprising the compound disclosed herein, or a stereoisomer, an N-oxide or a salt thereof, and optionally further comprising at least one pesticidally acceptable adjuvant.

Furthermore, the invention provides a composition comprising the compound disclosed herein, or a stereoisomer, an N-oxide or a salt thereof as active component, and optionally further comprising at least one pesticidally acceptable adjuvant.

In another aspect, the invention provides use of the compound or the composition comprising the compound described herein in agriculture.

Furthermore, the invention provides the use of the compound or the composition comprising the compound described herein in the control of plant diseases.

Furthermore, the invention provides use of the compound or the composition comprising the compound described herein in agriculture for weed control.

In some embodiments, the invention provides the use of the compound or the composition comprising the compound described herein for controlling unwanted plants.

In another aspect, the invention provides a method for controlling the growth of weed in a growing field of useful plant comprising administering an effective amount of the compound disclosed herein to the field before weed emergence.

In some embodiments, the weed comprises broadleaf weed and grass weed. Furthermore, the broadleaf weed comprises aspiemarker, amaranthus retroflexus and eclipta prostrata; and the grass weed comprises crab grass, barnyard grass and green bristlegrass.

In some embodiments, the useful plant comprises soybean, peanut and sunflower.

In another aspect, the invention provides a method for controlling unwanted plants comprising applying an effective amount of the compound of the invention to a plant, a plant seed, soil in which or on which the plant grows, or a cultivation area.

The compound having Formula (Ia) , (II) , (IIa) , (IIb) , (IIc) , (IId) , (II-1) , (IIa-1) , (IIa-2) , (II-5) , (IIa-17) , (IIa-18) , (IIIa) , (IIIb) , (IIIc) , (IIId) , (IIIe) , (IIIf) , (IIIg) or (IIIh) may exist in different stereoisomers or optical isomers or tautomeric forms. The present invention encompasses all such isomers and tautomers, as well as mixtures thereof in various ratios, as well as isotopic forms such as compounds containing heavy hydrogen.

Any formula given herein is also intended to represent isotopically unenriched forms as well as isotopically enriched forms of the compounds. 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 and 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 disclosed herein, examples of which are illustrated in the accompanying structures and formulas. The invention is intended to cover all alternatives, modifications, and equivalents that may be included within the scope disclosed herein 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 disclosed herein. Described herein is in no way limited to the methods and materials. In the event that one or more of the incorporated literatures, 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 otherwise defined, 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 be applied unless otherwise indicated. For purposes disclosed herein, the chemical elements are identified in accordance with the Periodic Table of the Elements, CAS version, and the Handbook of Chemistry and Physics, 75 thEd. 1994. Additionally, general principles of organic chemistry are described in “Organic Chemistry” , Thomas Sorrell, University Science Books, Sausalito: 1999, and “March's Advanced Organic Chemistry” , by Michael B. Smith and Jerry March, John Wiley &Sons, New York: 2007, all of which are incorporated herein by reference in their entireties.

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, “acomponent” 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” refer 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 point, boiling point, spectral properties and reactivity. 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 Parker et al., McGraw-Hill Dictionary of Chemical Terms (1984) McGraw-Hill Book Company, New York and Eliel et al., Stereochemistry of Organic Compounds, John Wiley &Sons, Inc., New York, 1994. all of which are incorporated herein by reference.

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, wherein the compound with the prefix (-) or l means levorotatory. The compound with the prefix (+) or d means 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.

The term “room temperature” refers to the temperature is from about 15 ℃ to 35 ℃, or from about 20 ℃ to 30 ℃, or from about 23 ℃ to 28 ℃, or about 25 ℃. In the present invention, all numbers disclosed herein are approximate values, regardless whether or not the words "approximately " or "about" are used. The value of each number may have an approximate value varied by 1%, 2%, 3%, 4%or 5%.

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. Substituents described herein include, but are not limited to, deuterium, fluorine, chlorine, bromine, iodine, 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, alkylcarbonyl, heteroalkyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, heterocyclylcarbonyl, aryl, arylalkyl, arylamino, heteroaryl, heteroarylalkyl, heteroarylamino, carbonylamino, sulfonyl, aminosulfonyl and the like.

In addition, it should be specified that the descriptions of the description of “each…is independently” , “each (of) …and…is independently” and “…is independently” in the invention can be used interchangeably herein. It should have a general understanding that it can be expressed both in different groups in which same symbols expressed specific options do not affect each other and the same groups in which same symbols expressed specific options do not affect each other.

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 radical of 1 to 20 carbon atoms, wherein the alkyl radical may be optionally substituted with one or more substituents described herein. Unless otherwise specified, the alkyl group contains 1-20 carbon atoms. In some embodiments, the alkyl group contains 1-12 carbon atoms. In other embodiments, the alkyl group contains 1-10 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 other embodiments, the alkyl group contains 1-4 carbon atoms. In still 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) , isobutyl (i-Bu, -CH ₂CH (CH ₃) ₂) , sec-butyl (s-Bu, -CH (CH ₃) CH ₂CH ₃) , tert-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-l-butyl (-CH ₂CH ₂CH (CH ₃) ₂) , 2-methyl-l-butyl (-CH ₂CH (CH ₃) CH ₂CH ₃) , n-hexyl (-CH ₂CH ₂CH ₂CH ₂CH ₂CH ₃) , 2-hexyl (-CH (CH ₃) CH ₂CH ₂CH ₂CH ₃) , 3-hexyl (-CH (CH ₂CH ₃) (CH ₂CH ₂CH ₃) ) , 2-methyl-2-pentyl (-C (CH ₃) ₂CH ₂CH ₂CH ₃) , 3-methyl-2-pentyl (-CH (CH ₃) CH (CH ₃) CH ₂CH ₃) , 4-methyl-2-pentyl (-CH (CH ₃) CH ₂CH (CH ₃) ₂) , 3-methyl-3-pentyl (-C (CH ₃) (CH ₂CH ₃) ₂) , 2-methyl-3-pentyl (-CH (CH ₂CH ₃) CH (CH ₃) ₂) , 2, 3-dimethyl-2-butyl (-C (CH ₃) ₂CH (CH ₃) ₂) , 3, 3-dimethyl-2-butyl (-CH (CH ₃) C (CH ₃) ₃, n-heptyl and n-octyl, etc.

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 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 group contains 2-10 carbon atoms. In other embodiments, the alkyl group contains 2-8 carbon atoms. In some embodiments, the alkyl group contains 2-6 carbon atoms. In other embodiments, the alkyl group contains 2-4 carbon atoms. Examples of alkenyl includes, but are not limited to, vinyl (-CH=CH ₂) , allyl (-CH ₂CH=CH ₂) , propenyl (CH ₃-CH=CH-) , -CH ₂CH ₂CH=CH ₂, -CH ₂CH=CHCH ₃, -CH ₂CH ₂CH ₂CH=CH ₂, -CH ₂CH ₂CH=CHCH ₃, -CH ₂CH ₂CH ₂CH=CHCH ₃, etc.

The term “alkynyl” refers to a linear or branched monovalent hydrocarbon radical of 2 to 12 carbon atoms with at least one site of unsaturation, i.e., a carbon-carbon, sp triple bond, wherein the alkynyl radical may be optionally substituted with one or more substituents described herein. In some embodiments, the alkynyl group contains 2-10 carbon atoms; in some embodiments, the alkynyl group contains 2-8 carbon atoms; in other embodiments, the alkynyl group contains 2-6 carbon atoms; and in still other embodiments, the alkynyl group contains 2-4 carbon atoms. Examples of such alkynyl groups include, but are not limited to, -C≡CH, -C≡CCH ₃, -CH ₂-C≡CH, -CH ₂-C≡CCH ₃, -CH ₂CH ₂-C≡CH, -CH ₂-C≡CCH ₂CH ₃, -CH ₂CH ₂-C≡CH ₂CH ₃, and the like.

The term “alkoxy” refers to an alkyl group attached to the parent molecular moiety via an oxygen atom, wherein the alkyl group is as defined herein. Unless otherwise specified, the alkoxy group contains 1-12 carbon atoms. In some embodiments, the alkoxy group contains 1-10 carbon atoms. In other embodiments, the alkoxy group contains 1-8 carbon atoms. In some embodiments, the alkoxy group contains 1-6 carbon atoms. In other embodiments, the alkoxy group contains 1-4 carbon atoms. In other embodiments, the alkoxy group contains 1-4 carbon atoms. In still other embodiments, the alkoxy group contains 1-3 carbon atoms. The alkoxy group may be optionally substituted with one or more substituents disclosed herein.

Some non-limiting examples of 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) , 1-butoxy ( _n-BuO, n-butoxy, -OCH ₂CH ₂CH ₂CH ₃) , 2-methyl-l-propoxy (i-BuO, i-butoxy, -OCH ₂CH (CH ₃) ₂) , 2-butoxy (s-BuO, s-butoxy, -OCH (CH ₃) CH ₂CH ₃) , 2-methyl-2-propoxy (t-BuO, t-butoxy, -OC (CH ₃) ₃) , 1-pentoxy (n-pentoxy, -OCH ₂CH ₂CH ₂CH ₂CH ₃) , 2-pentoxy (-OCH (CH ₃) CH ₂CH ₂CH ₃) , 3-pentoxy (-OCH (CH ₂CH ₃) ₂) , 2-methyl-2-butoxy (-OC (CH ₃) ₂CH ₂CH ₃) , 3-methyl-2-butoxy (-OCH (CH ₃) CH (CH ₃) ₂) , 3-methyl-l-butoxy (-OCH ₂CH ₂CH (CH ₃) ₂) , 2-methyl-l-butoxy (-OCH ₂CH (CH ₃) CH ₂CH ₃) , and the like.

The term “alkylamino” refers to “N-alkylamino” and “N, N-dialkylamino” wherein amino groups are independently substituted with one alkyl radical or two alkyl radicals, respectively. In some embodiments, the alkylamino group is an alkylamino that contains one or two C _1-6 alkyl attached to the nitrogen atom. In some embodiments, the alkylamino group is a alkylamino that contains one C _1-3 alkyl group. Suitable alkylamino groups may be monoalkylamino or dialkylamino, examples of which include, but are not limited to, N-methylamino, N-ethylamino, N, N-dimethylamino, N, N-diethylamino, and the like.

The term “alkylthio” refers to a linear or branched-alkyl radical attached to the rest of the molecular via a divalent sulfur atom, and wherein the alkyl group is as defined herein. Some non-limiting examples of “alkylthio” include -SCH ₃, -SCH ₂CH ₃, -SCH ₂CH ₂CH ₃, and the like.

The term “halogen” or “halo” refers to fluorine (F) , chlorine (Cl) , bromine (Br) , or iodine (I) .

The terms "haloalkyl" refers to alkyl substituted with one or more halogen atoms. Examples of haloalkyl group include, but are not limited to, -CH ₂F, -CHF ₂, -CH ₂Cl, -CH ₂Br, -CF ₃, -CH ₂CF ₃, -CH ₂CH ₂F, -CH ₂CH ₂Cl, -CH ₂CH ₂Br, -CH ₂CHF ₂, -CH ₂CH ₂CF ₃, -CH ₂CH ₂CH ₂F, -CH ₂CH ₂CH ₂Cl, -CH ₂CH ₂CH ₂Br, -CHFCH ₂CH ₃, -CHClCH ₂CH ₃, and the like.

The terms "tetrafluoroethyl" refers to -CF ₂CHF ₂ or -CHFCF _3.

The term "haloalkoxy" refers to an alkoxy substituted with one or more halogen atoms. Examples of haloalkoxy group include, but are not limited to, -OCH ₂F, -OCHF ₂, -OCH ₂Cl, -OCH ₂Br, -OCF ₃, -OCH ₂CF ₃, -OCH ₂CH ₂F, -OCH ₂CH ₂Cl, -OCH ₂CH ₂Br, -OCH ₂CHF ₂, -OCH ₂CH ₂CF ₃, -OCH ₂CH ₂CH ₂F, -OCH ₂CH ₂CH ₂Cl, -OCH ₂CH ₂CH ₂Br, -OCHFCH ₂CH ₃, -OCHClCH ₂CH ₃, and the like.

The term "haloalkylamino" refers to an alkylamino substituted with one or more halogen atoms.

The term "haloalkylthio" refers to an alkylthio substituted with one or more halogen atoms.

The term "haloalkenyl" refers to an alkenyl substituted with one or more halogen atoms.

The term "haloalkynyl" refers to an alkenyl substituted with one or more halogen atoms.

The term “x-membered” where x is an integer typically describing the number of ring-forming atoms in a moiety and the number of ring-forming atoms is x. For example, piperidyl is an example of a 6-membered heterocyclyl group.

The term “3-to 12-membered ring"refers to the carbocyclic ring, heterocyclic ring or aromatic ring system having 3 to 12 ring members, i.e., optionally containing one or more heteroatoms, saturated, partial unsaturated or completely unsaturated ring system.

The term “3-to 10-membered ring" refers to the carbocyclic ring, heterocyclic ring or aromatic ring system having 3 to 10 ring members, i.e., optionally containing one or more heteroatoms, saturated, partial unsaturated or completely unsaturated ring system.

The term “3-to 8-membered ring"refers to the carbocyclic ring, heterocyclic ring or aromatic ring system having 3 to 8 ring members, i.e., optionally containing one or more heteroatoms, saturated, partial unsaturated or completely unsaturated ring system.

The term “3-to 6-membered ring" refers to the carbocyclic ring, heterocyclic ring or aromatic ring system having 3 to 6 ring members, i.e., optionally containing one or more heteroatoms, saturated, partial unsaturated or completely unsaturated ring system.

The term “carbocyclyl” , “carbocycle” or “carbocyclic ring” refers to a monovalent or multivalent, nonaromatic, saturated or partially unsaturated ring having 3 to 12 carbon atoms as a monocyclic, bicyclic or tricyclic ring system. A carbobicyclyl group includes a spiro carbobicyclyl group or a fused carbobicyclyl group. Suitable carbocyclyl groups include, but are not limited to, cycloalkyl, cycloalkenyl and cycloalkynyl. Further examples of carbocyclyl groups include cyclopropyl, cyclobutyl, cyclopentyl, 1-cyclopent-l-enyl, l-cyclopent-2-enyl, l-cyclopent-3-enyl, cyclohexyl, 1-cyclohex-l-enyl, l-cyclohex-2-enyl, l-cyclohex-3-enyl, cyclohexadienyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, cycloundecyl, cyclododecyl, and the like.

The term "cycloalkyl" refers to a monovalent or multivalent saturated monocyclic, bicyclic or tricyclic system containing 3-12 carbon atoms. In some embodiments, the cycloalkyl group contains 3-12 carbon atoms; in some embodiments, the cycloalkyl group contains 3-10 carbon atoms; in other embodiments, the cycloalkyl group contains 3-8 carbon atoms; and in still other embodiments, the cycloalkyl group contains 3-6 carbon atoms. The cycloalkyl group is optionally substituted with one or more substituents disclosed herein. Such examples include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclodecyl, cyclodecyl, cycloundecyl, cyclododecyl, adamantyl, and the like.

The term “cycloalkylalkyl” refers to an alkyl group substituted with cycloalkyl group, wherein the alkyl and cycloalkyl groups are as defined herein.

The term "cycloalkenyl" refers to a 3-to 12-membered monovalent or multivalent monocyclic, bicyclic, or tricyclic ring system containing at least one carbon-carbon double bond, wherein the ring system is non-aromatic. In one embodiment, the cycloalkenyl contains 3 to 10 carbon atoms. In other embodiment, the cycloalkenyl contains 3 to 8 carbon atoms. In still other embodiment, the cycloalkenyl contains 3 to 6 carbon atoms. The cycloalkenyl group is optionally substituted with one or more substituents disclosed herein. Some non-limiting examples include cyclobutenyl, cyclopentenyl, cyclohexenyl, cyclohexadienyl, and the like.

The term “unsaturated” refers to a moiety having one or more units of unsaturation.

The term "heteroatom" refers to oxygen (O) , sulfur (S) , nitrogen (N) , phosphorus (P) and silicon (Si) , including any oxidized form of nitrogen (N) , sulfur (S) , or phosphorus (P) ; primary amine, secondary amine, tertiary amine and quaternary ammonium forms; or a substitutable nitrogen of a heterocyclic ring, for example, N (as in 3, 4-dihydro-2H-pyrrolyl) , NH (as in pyrrolidyl) or NR (as in N-substituted pyrrolidyl) .

The term “heterocycle” , “heterocyclyl” , or “heterocyclic ring” as used interchangeably herein refers to a saturated or partially unsaturated non-aromatic monocyclic, bicyclic or tricyclic ring containing 3-15 ring atoms of which at least one ring atom is selected from nitrogen, sulfur and oxygen. In some embodiments, C _2-12 heterocyclyl refers to a saturated or partially unsaturated monocyclic, bicyclic or tricyclic ring containing 2-12 ring carbon atoms of which at least one ring atom is selected from nitrogen, sulfur and oxygen. In other embodiments, C _2-10 heterocyclyl refers to a saturated or partially unsaturated monocyclic, bicyclic or tricyclic ring containing 2-10 ring carbon atoms of which at least one ring atom is selected from nitrogen, sulfur and oxygen. In other embodiments, C _2-8 heterocyclyl refers to a saturated or partially unsaturated monocyclic, bicyclic or tricyclic ring containing 2-8 ring carbon atoms of which at least one ring atom is selected from nitrogen, sulfur and oxygen. In other embodiments, C _2-6 heterocyclyl refers to a saturated or partially unsaturated monocyclic, bicyclic or tricyclic ring containing 2-6 ring carbon atoms of which at least one ring atom is selected from nitrogen, sulfur and oxygen. Unless otherwise stated, the heterocyclyl group may be a carbon radical or a heteroatom radical, of which a -CH ₂-group may optionally be replaced by a -C (=O) -group. In which, the sulfur can be optionally oxygenized to S-oxide. The nitrogen atom can be optionally oxygenized to N-oxide. Some non-limiting examples of the heterocyclyl group include oxiranyl, azetidinyl, oxetanyl, thietanyl, pyrrolidyl (i.e., 2-pyrrolidyl) , 2-pyrrolinyl, 3-pyrrolinyl, pyrazolidinyl, imidazolinyl, imidazolidinyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothienyl, dihydrothienyl, 1, 3-dioxolanyl, dithiolanyl, tetrahydropyranyl, dihydropyranyl, 2H-pyranyl, 4H-pyranyl, tetrahydrothiopyranyl, piperidyl (2-piperidyl, 3-piperidyl, 4-piperidyl) , 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, tetrahydropyridinyl. 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, 3, 5-dioxopiperidinyl, and the like. Some non-limiting examples of heterocyclyl with oxidized ring sulfur atom include sulfolanyl and 1, 1-dioxo-thiomorpholinyl. The hetercyclyl group is optionally substituted with one or more substituents disclosed herein.

The term “C _2-6 heterocyclyl containing one oxygen atom” refers to a heterocyclyl containing 2 to 6 cabon atoms and one oxygen atom as ring members, such examples include, but are not limited to,

The term "heterocyclylalkyl" refers to an alkyl substituted with heterocyclyl, wherein the heterocyclyl and alkyl groups are as defined herein.

The term “heterocyclyloxy” refers to an optionally substituted heterocyclyl group attached to the parent molecular moiety via an oxygen atom, wherein the heterocyclyl group is as defined herein.

The term “aryl” refers to monocyclic, bicyclic and tricyclic carbocyclic ring systems having a total of 6 to 14 ring members, or 6 to12 ring members, or 6 to 10 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" may be used interchangeably with the term "aromatic ring" . Examples of aryl ring may include phenyl, indenyl, naphthyl and anthryl. The aryl group is optionally substituted with one or more substituents disclosed herein.

The term “arylalkyl” refers to an alkyl group substituted with one or more aryl groups, wherein the alkyl and aryl groups are as defined herein.

The term “aryloxy” refers to an optionally substituted aryl group attached to the rest of the molecule via an oxygen atom, wherein the aryl group is as defined herein.

The term “heteroaryl” refers to a monocyclic, bicyclic, or tricyclic ring system having a total of 5 to 12 ring members, preferably, 5 to 10 ring members, and more preferably 5 to 6 ring members, wherein at least one ring in the system is aromatic and at least one ring in the system contains one or more heteroatoms, and wherein each ring in the system contains 5 to 7 ring members and the heteroaryl group has one or more points of attachment to the rest of the molecule. The term “heteroaryl” may be used interchangeably with the term “heteroaryl ring” , “aromatic heterocyclic” , "heteroaromatic compound" or the term “heteroaromatic” . The heteroaryl group is optionally substituted with one or more substituents disclosed herein.

In some embodiment, the heteroaryl group is a 5-to 10-membered heteroaryl comprising 1, 2, 3 or 4 heteroatoms independently selected from O, S and N.

In other embodiments, the ring atom of the heteroaryl group comprises 1-9 carbon atoms and 1-4 heteroatoms selected from N, O or S; in another embodiment, the ring atom of the heteroaryl group comprises 1-5 carbon atoms and 1-4 heteroatoms selected from N, O or S.

In other embodiments, the heteroaryl group refers to a 5-membered or 6-membered heteroaryl containg 1-4 N atoms; in other embodiments, the heteroaryl group refers to a 5-membered heteroaryl containg 1-3 heteroatoms selected from N or O; in other embodiments, the heteroaryl group refers to a 5-membered heteroaryl containg 1-3 heteroatoms selected from N or S.

In some embodiments, C _1-9 heteroaryl refers to a hetereoaryl containg 1 to 9 carbon atoms as ring atoms. In other embodiments, C _1-6 heteroaryl refers to a hetereoaryl containg 1 to 6 carbon atoms as ring atoms. In other embodiments, C _1-5 heteroaryl refers to a hetereoaryl containg 1 to 5 carbon atoms as ring atoms.

Some non-limiting examples of heteroaryl group include 2-furyl, 3-furyl, 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, pyrimidonyl, pyridonyl, and the following non-limiting bicycles: benzimidazolyl, benzofuryl, tetrahydrobenzofuryl, benzothienyl, indolyl (e.g., 2-indolyl) , and the like.

The term “heteroarylalkyl” refers to an alkyl group substituted with one or more heteroaryl groups, wherein the alkyl and heteroaryl group are as defined herein.

The term “heteroaryloxy” refers to an optionally substituted heteroaryl group attached to the rest of the molecule via an oxygen atom, wherein the heteroaryl group is as defined herein.

The pyrazole ring number of the invention is as follows:

When the compounds of the invention comprise an acid moiety, salts of the compounds of the invention include those derived from alkali or alkaline earth metals and those derived from ammonia or amines. Preferred cations include sodium, potassium, magnesium, and ammonium cations having the formula N ⁺ (R ¹⁹R ²⁰R ²¹R ²²) , wherein each R ¹⁹, R ²⁰, R ²¹ and R ²² is independently selected from hydrogen, C ₁-C ₆ alkyl and C ₁-C ₆ hydroxyalkyl. The salt of the compound of Formula (I) , (Ia) , (II) , (IIa) , (IIb) , (IIc) , (IId) , (II-1) , (IIa-1) , (IIa-2) , (II-5) , (IIa-17) , (IIa-18) , (IIIa) , (IIIb) , (IIIc) , (IIId) , (IIIe) , (IIIf) , (IIIg) or (IIIh) can be obtained by using a metal hydroxide such as sodium hydroxide or an amine such as ammonia, trimethylamine, diethanolamine, 2-methylthiopropylamine, bisallylamine, 2-butoxyethylamine, morpholine, cyclododecylamine or benzylamine) to treat a compound of Formula (I) , (Ia) , (II) , (IIa) , (IIb) , (IIc) , (IId) , (II-1) , (IIa-1) , (IIa-2) , (II-5) , (IIa-17) , (IIa-18) , (IIIa) , (IIIb) , (IIIc) , (IIId) , (IIIe) , (IIIf) , (IIIg) or (IIIh) .

When the compound of the present invention contains a base moiety, an acceptable salt may be formed from organic acid and inorganic acid, such as acetic acid, propionic acid, lactic acid, citric acid, tartaric acid, succinic acid, fumaric acid, maleic acid, malonic acid, mandelic acid, malic acid, phthalic acid, hydrochloric acid, hydrobromic acid, phosphoric acid, nitric acid, sulfuric acid, methanesulfonic acid, naphthalenesulfonic acid, benzenesulfonic acid, toluenesulfonic acid, camphorsulfonic acid, and the known acceptable acid.

DETAILED DESCRIPTION OF THE COMPOUNDS OF THE INVENTION

The present invention is aimed to provide a novel isoxazoline compound, a herbicidal composition and formulation both containing the compound, and uses thereof.

In one aspect, provied herein is a compound having Formula (I) or a stereoisomer, an N-oxide or a salt thereof,

wherein,

each of R ¹ and R ² is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, alkyl, cycloalkyl or cycloalkylalkyl; or, R ¹ and R ² together with the carbon atom to which they are attached, form a 3-to 12-membered ring;

each of R ³ and R ⁴ is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, alkyl, cycloalkyl or cycloalkylalkyl; or, R ³ and R ⁴ together with the carbon atom to which they are attached, form a 3-to 12-membered ring;

n is 0, 1 or 2;

each of R ^a and R ^b is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, alkoxy, alkylamino, alkylthio, cycloalkyl, heterocyclyl, aryl or heteroaryl;

or, R ¹⁰, R ¹¹ and R ¹² together with the carbon atom to which they are attached, form optionally substituted C _6-14 aryl, optionally substituted C _1-9 heteroaryl, optionally substituted C _3-12 cycloalkyl or optionally substituted C _2-12 heterocyclyl (i.e.,

refers to

wherein Ay1 is optionally subsituted C _6-14 aryl, optionally substituted C _1-9 heteroaryl, optionally substituted C _3-12 cycloalkyl or optionally substituted C _2-12 heterocyclyl) ;

or, -CR ⁸R ⁹-CR ¹⁰R ¹¹R ¹² is optionally substituted C _10-14 aryl, optionally substituted C _1-9 heteroaryl, optionally substituted C _3-12 cycloalkyl, optionally substituted C _2-12 heterocyclyl, unsubstituted phenyl or substituted phenyl (i.e.,

refers to

wherein Ay2 is optionally substituted C _10-14 aryl, optionally substituted C _1-9 heteroaryl, optionally substituted C _3-12 cycloalkyl, optionally substituted C _2-12 heterocyclyl, unsubstituted phenyl or substituted phenyl) ;

wherein substituted or optionally substituted groups described above, the number of the substituents is 1, 2, 3, 4, 5 or 6; and the substituents may be the same or different; wherein the substituents are fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkoxy, alkylamino, alkylthio, cycloalkyl, heterocyclyl, aryl or heteroaryl;

with the proviso that, (i) R ^a is not -CF ₃; (ii) R ^b is not -CF ₃; (iii) when R ^a is phenyl, R ^b is not Cl; (iv) R ^a and R ^b can not be both Cl; (v) when R ^a is alkyl, R ⁸ and R ¹⁰ together with the carbon atoms to which they are attached form a 3-to 12-membered ring which is not benzene ring; (vi) when -CR ⁸R ⁹-CR ¹⁰R ¹¹R ¹² is unsubstituted phenyl, R ^a is chlorine, R ^b is difluoromethyl, R ⁵ and R ⁶ are hydrogen, n is 0, 1 or 2, R ³ and R ⁴ are hydrogen, and R ¹ is methyl, R ² is not mehtyl or chloromethyl; (vii) when -CR ⁸R ⁹-CR ¹⁰R ¹¹R ¹² is unsubstituted phenyl, R ^b is chlorine, R ^a is difluoromethyl, R ⁵ and R ⁶ are hydrogen, n is 0, 1 or 2, R ³ and R ⁴ are hydrogen, and R ¹ is methyl, R ² is not methyl or chloromethyl; (viii) when -CR ⁸R ⁹-CR ¹⁰R ¹¹R ¹² is unsubstituted phenyl, R ^a is chlorine, R ^b is difluoromethyl, R ⁵and R ⁶ are hydrogen, n is 0, 1 or 2, R ³ and R ⁴ are hydrogen, and R ² is methyl, R ¹ is not methyl or chloromethyl; or (ix) when -CR ⁸R ⁹-CR ¹⁰R ¹¹R ¹² is unsubstitued phenyl, R ^b is chlorine, R ^a is difluoromethyl, R ⁵ and R ⁶ are hydrogen, n is 0, 1 or 2, R ³ and R ⁴ are hydrogen, and R ² is methyl, R ¹ is not methyl or chloromethyl.

In other aspect, provided herein is a compound having Formula (Ia) or a stereoisomer, an N-oxide or a salt thereof,

wherein,

n is 0, 1 or 2;

X is fluorine, chlorine or bromine;

with the proviso that:

(4) when Y is unsubstituted phenyl, X is chlorine, each of R ⁵ and R ⁶ is independently hydrogen, n is 0, 1 or 2; each of R ³ and R ⁴ is independently hydrogen, and R ² is methyl, R ¹ is not methyl or chloromethyl;

(5) when Y is ethyl or isopropyl, X is chlorine on the 5 position of parazole ring, R ⁵ and R ⁶ are hydrogen, n is 0 or 2, R ³ and R ⁴ are hydrogen, and R ¹ is methyl, R ² is not chloromethyl; or

(6) when Y is ethyl or isopropyl, X is chlorine on the 5 position of parazole ring, R ⁵ and R ⁶ are hydrogen, n is 0 or 2, R ³ and R ⁴ are hydrogen, and R ² is methyl, R ¹ is not chloromethyl.

In some embodiments, Y is C _1-8 alkyl, halo C _1-8 alkyl, C _1-8 alkoxy-C _1-8 alkyl, C _1-8 alkylamino-C _1-8 alkyl, C _2-8 alkenyl, halo C _2-8 alkenyl, C _2-8 alkynyl, halo C _2-8 alkynyl, C _3-10 cycloalkyl, C _3-10 cycloalkyl-C _1-8 alkyl, C _2-12 heterocyclyl, C _2-12 heterocyclyl-C _1-8 alkyl, C _6-14 aryl, C _6-14 aryl-C _1-8alkyl, C _1-9 heteroaryl, C _1-9 heteroaryl-C _1-8 alkyl, -C (=O) -C _1-8 alkyl, -S (=O) ₂-C _1-8 alkyl, -C (=O) -C _3-10 cycloalkyl, -S (=O) ₂-C _3-10 cycloalkyl, -C (=O) -C _2-12 heterocyclyl, -S (=O) ₂-C _2-12 heterocyclyl, -C (=O) -C _6-14 aryl, -S (=O) ₂-C _6-14 aryl, -C (=O) -C _1-9 heteroaryl or -S (=O) ₂-C _1-9 heteroaryl;

wherein Y is optionally substituted with 1, 2, 3, 4, 5 or 6 Y ^a; each Y ^a is independently fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, C _1-6 alkyl, halo C _1-6 alkyl, C _2-6 alkenyl, halo C _2-6 alkenyl, C _2-6 alkynyl, halo C _2-6 alkynyl, C _1-6 alkoxy, C _1-6 alkylamino, C _1-6 alkylthio, C _3-6 cycloalkyl, C _2-6 heterocyclyl, C _6-10 aryl or C _1-9 heteroaryl.

In some embodiments, Y is C _1-6 alkyl, halo C _1-6 alkyl, C _1-6 alkoxy-C _1-6 alkyl, C _1-6 alkylamino-C _1-6 alkyl, C _2-6 alkenyl, halo C _2-6 alkenyl, C _2-6 alkynyl, halo C _2-6 alkynyl, C _3-8 cycloalkyl, C _3-8 cycloalkyl-C _1-6 alkyl, C _2-8 heterocyclyl, C _2-8 heterocyclyl-C _1-6 alkyl, C _6-10 aryl, C _6-10 aryl-C _1-6 alkyl, C _1-6 heteroaryl, C _1-6 heteroaryl-C _1-6 alkyl, -C (=O) -C _1-6 alkyl, -S (=O) ₂-C _1-6 alkyl, -C (=O) -C _3-8 cycloalkyl, -S (=O) ₂-C _3-8 cycloalkyl, -C (=O) -C _2-8 heterocyclyl, -S (=O) ₂-C _2-8 heterocyclyl, -C (=O) -C _6-10 aryl, -S (=O) ₂-C _6-10 aryl, -C (=O) -C _1-6 heteroaryl or -S (=O) ₂-C _1-6 heteroaryl;

wherein Y is optionally substituted with 1, 2, 3, 4, 5 or 6 Y ^a; each Y ^a is independently fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, C _1-4 alkyl, halo C _1-4 alkyl, C _2-4 alkenyl, halo C _2-4 alkenyl, C _2-4 alkynyl, halo C _2-4 alkynyl, C _1-4 alkoxy, C _1-4 alkylamino, C _1-4 alkylthio, C _3-6 cycloalkyl, C _2-6 heterocyclyl, C _6-10 aryl or C _1-6 heteroaryl.

In other embodiments, Y is C _1-4 alkyl, halo C _1-4 alkyl, C _1-4 alkoxy-C _1-4 alkyl, C _1-4 alkylamino-C _1-4 alkyl, C _2-4 alkenyl, halo C _2-4 alkenyl, C _2-4 alkynyl, halo C _2-4 alkynyl, C _3-6 cycloalkyl, C _3-6 cycloalkyl-C _1-3 alkyl, C _2-4 heterocyclyl, C _2-4 heterocyclyl-C _1-3 alkyl, C _6-10 aryl, C _6-10 aryl-C _1-4 alkyl, C _1-6 heteroaryl, C _1-6 heteroaryl-C _1-3 alkyl, -C (=O) -C _1-4 alkyl, -S (=O) ₂-C _1-4 alkyl, -C (=O) -C _3-6 cycloalkyl, -S (=O) ₂-C _3-6 cycloalkyl, -C (=O) -C _2-4 heterocyclyl, -S (=O) ₂-C _2-4 heterocyclyl, -C (=O) -C _6-10 aryl, -S (=O) ₂-C _6-10 aryl, -C (=O) -C _1-5 heteroaryl or -S (=O) ₂-C _1-5 heteroaryl;

wherein Y is optionally substituted with 1, 2, 3, 4, 5 or 6 Y ^a; each Y ^a is independently fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, C _1-3 alkyl, halo C _1-3 alkyl, C _2-3 alkenyl, halo C _2-3 alkenyl, C _2-3 alkynyl, halo C _2-3 alkynyl, C _1-3 alkoxy, C _1-3 alkylamino, C _1-3 alkylthio, C _3-6 cycloalkyl, C _2-6heterocyclyl, C _6-10 aryl or C _1-5 heteroaryl.

In still other embodiments, Y is -CH ₃, -CH ₂CH ₃, -CH ₂CH ₂CH ₃, -CH (CH ₃) ₂, -CH ₂CH (CH ₃) ₂, -C (CH ₃) ₃, -CH ₂CHF ₂, -CH ₂CF ₃, -CH ₂CF ₂CHF ₂, -CH ₂CH=CH ₂, -CH ₂-C≡CH, -C (=O) CH ₃, -CH ₂OCH ₃, -CH ₂OCH ₂CH ₃, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2, 4-difluorophenyl, benzyl, 2-chlorobenyl, 3-chlorobenyl, 4-chlorobenyl, benzoyl or benzenesulfonyl; or

Y is one of the following sub-formulae:

In some embodiments, provided herein is a compound having Formula (II) or a stereoisomer, an N-oxide or a salt thereof:

wherein X is fluorine, chlorine or bromine;

each of R ¹, R ², R ³, R ⁴, n, R ⁵, R ⁶, R ⁸, R ⁹, R ¹⁰, R ¹¹ and R ¹² is as defined herein.

wherein X is fluorine, chlorine or bromine;

each of R ¹, R ², R ³, R ⁴, n, R ⁵, R ⁶, R ⁸, R ⁹ and R ¹³ is as defined herein.

In some embodiments, provided herein is a compound having Formula (II-2) or a stereoisomer, an N-oxide or a salt thereof:

wherein X is fluorine, chlorine or bromine;

each of R ¹, R ², R ³, R ⁴, n, R ⁵, R ⁶, R ⁸, R ⁹, R ¹⁴, R ¹⁵ and R ¹⁶ is as defined herein.

In some embodiments, provided herein is a compound having Formula (II-3) or a stereoisomer, an N-oxide or a salt thereof:

wherein X is fluorine, chlorine or bromine;

each of R ¹, R ², R ³, R ⁴, n, R ⁵, R ⁶, R ⁸, R ⁹ and Ay1 is as defined herein.

In some embodiments, provided herein is a compound having Formula (II-4) or a stereoisomer, an N-oxide or a salt thereof:

wherein X is fluorine, chlorine or bromine;

each of R ¹, R ², R ³, R ⁴, n, R ⁵, R ⁶ and Ay2 is as defined herein.

wherein X is fluorine, chlorine or bromine;

each of R ¹, R ², R ³, R ⁴, n, R ⁵ and R ⁶ is as defined herein.

In some embodiments, provided herein is a compound having Formula (III-1) or a stereoisomer, an N-oxide or a salt thereof:

wherein each of R ¹, R ², R ³, R ⁴, n, R ⁵, R ⁶, R ⁸, R ⁹, R ¹⁰, R ¹¹ and R ¹² is as defined herein.

In some embodiments, provided herein is a compound having Formula (III-2) or a stereoisomer, an N-oxide or a salt thereof:

In one aspect, provided herein is a compound having Formula (IIa) or a stereoisomer, an N-oxide or a salt thereof,

wherein each of R ¹, R ², R ³, R ⁴, R ⁵, R ⁶, R ⁸, R ⁹, R ¹⁰, R ¹¹ and R ¹² is as defined herein.

wherein each of R ¹, R ², R ³, R ⁴, R ⁵, R ⁶, R ⁸, R ⁹ and R ¹³ is as defined herein.

In some embodiments, provided herein is a compound having Formula (IIa-3) or a stereoisomer, an N-oxide or a salt thereof:

wherein each of R ¹, R ², R ³, R ⁴, R ⁵, R ⁶, R ⁸, R ⁹, R ¹⁴, R ¹⁵ and R ¹⁶ is as defined herein.

In some embodiments, provided herein is a compound having Formula (IIa-4) or a stereoisomer, an N-oxide or a salt thereof:

In some embodiments, provided herein is a compound having Formula (IIa-5) or a stereoisomer, an N-oxide or a salt thereof:

wherein each of R ¹, R ², R ³, R ⁴, R ⁵, R ⁶, R ⁸, R ⁹ and Ay1 is as defined herein.

In some embodiments, provided herein is a compound having Formula (IIa-6) or a stereoisomer, an N-oxide or a salt thereof:

In some embodiments, provided herein is a compound having Formula (IIa-7) or a stereoisomer, an N-oxide or a salt thereof:

wherein each of R ¹, R ², R ³, R ⁴, R ⁵, R ⁶ and Ay2 is as defined herein.

In some embodiments, provided herein is a compound having Formula (IIa-8) or a stereoisomer, an N-oxide or a salt thereof:

In some embodiments, provided herein is a compound having Formula (IIa-9) or a stereoisomer, an N-oxide or a salt thereof:

In some embodiments, provided herein is a compound having Formula (IIa-10) or a stereoisomer, an N-oxide or a salt thereof:

In some embodiments, provided herein is a compound having Formula (IIa-11) or a stereoisomer, an N-oxide or a salt thereof:

In some embodiments, provided herein is a compound having Formula (IIa-12) or a stereoisomer, an N-oxide or a salt thereof:

In some embodiments, provided herein is a compound having Formula (IIa-13) or a stereoisomer, an N-oxide or a salt thereof:

In some embodiments, provided herein is a compound having Formula (IIa-14) or a stereoisomer, an N-oxide or a salt thereof:

In some embodiments, provided herein is a compound having Formula (IIa-15) or a stereoisomer, an N-oxide or a salt thereof:

In some embodiments, provided herein is a compound having Formula (IIa-16) or a stereoisomer, an N-oxide or a salt thereof:

wherein each of X, R ¹, R ², R ³, R ⁴, R ⁵ and R ⁶ is as defined herein.

In some embodiments, provided herein is a compound having Formula (IV) or a stereoisomer, an N-oxide or a salt thereof:

wherein,

Ay2 is optionally substituted C _10-14 aryl, optionally substituted C _1-9 heteroaryl, optionally substituted C _3-12 cycloalkyl, optionally substituted C _2-12 heterocyclyl, unsubstituted phenyl or substituted phenyl, wherein the substituted or optionally substituted groups described herein, the number of the substituents on the substituted or optionally substituted groups is 1, 2, 3, 4, 5 or 6; and the substituents may be the same or different; wherein the substitutents are fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, C _1-6 alkyl, halo C _1-6 alkyl, C _2-6 alkenyl, halo C _2-6 alkenyl, C _2-6 alkynyl, halo C _2-6 alkynyl, C _1-6 alkoxy, C _1-6 alkylamino, C _1-6 alkylthio, C _3-6 cycloalkyl, C _2-8 heterocyclyl, C _6-10 aryl or C _1-9 heteroaryl;

each of R ¹, R ², R ³, R ⁴, n, R ⁵ and R ⁶ is as defined herein;

with the proviso that when Ay2 is unsubstituted phenyl, R ⁵ and R ⁶ are hydrogen, n is 0, 1 or 2, R ³ and R ⁴ are hydrogen, and R ¹ is methyl, R ² is not methyl or chloromethyl; or, when Ay2 is unsubstituted phenyl, R ⁵ and R ⁶ are hydrogen, n is 0, 1 or 2, R ³ and R ⁴ are hydrogen, and R ² is methyl, R ¹ is not methyl or chloromethyl.

In some embodiments, each of R ¹ and R ² is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, C _1-6 alkyl, halo C _1-6 alkyl, C _3-6 cycloalkyl or C _3-6 cycloalkyl-C _1-6 alkyl; or, R ¹ and R ² together with the carbon atom to which they are attached, form a 3-to 8-membered ring.

In some embodiments, each of R ³ and R ⁴ is independently hydrogen, bromine, iodine, amino, nitro, hydroxy, carboxy, C _1-6 alkyl, C _3-6 cycloalkyl or C _3-6 cycloalkyl-C _1-6 alkyl; or, R ³ and R ⁴ together with the carbon atom to which they are attached, form a 3-to 8-membered ring.

In some embodiments, each of R ⁵ and R ⁶ is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl; or, R ⁵ and R ⁶ together with the carbon atom to which they are attached, form a 3-to 8-membered ring.

In some embodiments, each of R ⁸, R ⁹, R ¹⁰, R ¹¹ and R ¹² is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, C _1-6 alkyl, halo C _1-6 alkyl, C _2-6 alkenyl, halo C _2-6 alkenyl, C _2-6 alkynyl, halo C _2-6 alkynyl, C _1-6 alkoxy, C _1-6 alkylamino, C _1-6 alkylthio, C _3-6 cycloalkyl, C _2-8 heterocyclyl, C _6-10 aryl or C _1-9 heteroaryl.

In some embodiments, R ⁸ and R ⁹ together with the carbon atom to which they are attached, form an optionally substituted 3-to 10-membered ring; wherein the optionally substituted ring described herein, the number of the substituents on the optionally substituted ring is 1, 2, 3, 4, 5 or 6; and the substituents may be the same or different; wherein the substituents are fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, C _1-6 alkyl, halo C _1-6 alkyl, C _2-6 alkenyl, halo C _2-6 alkenyl, C _2-6 alkynyl, halo C _2-6 alkynyl, C _1-6 alkoxy, C _1-6 alkylamino, C _1-6 alkylthio, C _3-8 cycloalkyl, C _2-10 heterocyclyl, C _6-14 aryl or C _1-9 heteroaryl.

In some embodiments, R ⁸ and R ⁹ together with the carbon atom to which they are attached, form -C (=O) -;

In some embodiments, R ¹⁰, R ¹¹ and R ¹² together with the carbon atom to which they are attached, form -C≡CR ¹³ or -CR ¹⁴=CR ¹⁵R ¹⁶; wherein each of R ¹³, R ¹⁴, R ¹⁵ and R ¹⁶ is independently hydrogen, C _1-6 alkyl, halo C _1-6 alkyl, C _2-6 alkenyl, halo C _2-6 alkenyl, C _2-6 alkynyl or halo C _2-6 alkynyl.

In some embodiments, R ¹⁰, R ¹¹ and R ¹² together with the carbon atom to which they are attached, form optionally substituted C _6-14 aryl, optionally substituted C _1-9 heteroaryl, optionally substituted C _3-10 cycloalkyl or optionally substituted C _2-10 heterocyclyl (i.e.,

is

wherein Ay1 is optionally substituted C _6-14 aryl, optionally substituted C _1-9 heteroaryl, optionally substituted C _3-10 cycloalkyl or optionally substituted C _2-10heterocyclyl) , wherein the optionally substituted groups described herein, the number of the substituents on the optionally substituted groups is 1, 2, 3, 4, 5 or 6; and the substituents may be the same or different; wherein the substituents are fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, C _1-6 alkyl, halo C _1-6 alkyl, C _2-6 alkenyl, halo C _2-6 alkenyl, C _2-6 alkynyl, halo C _2-6 alkynyl, C _1-6 alkoxy, C _1-6 alkylamino, C _1-6 alkylthio, C _3-8 cycloalkyl, C _2-10 heterocyclyl, C _6-14 aryl or C _1-9 heteroaryl.

In some embodiments, -CR ⁸R ⁹-CR ¹⁰R ¹¹R ¹² is optionally substituted C _1-9 heteroaryl, optionally substituted C _3-10 cycloalkyl or optionally substituted C _2-10 heterocyclyl, unsubstituted phenyl or substituted phenyl (i.e.,

is

wherein Ay2 is optionally substituted C _10-14 aryl, optionally substituted C _1-9 heteroaryl, optionally substituted C _3-10 cycloalkyl, unsubstituted phenyl or substituted phenyl) , wherein the substituted or optionally substituted groups described herein, the number of the substituents on the substituted or optionally substituted groups is 1, 2, 3, 4, 5 or 6; and the substituents may be the same or different; wherein the substitutents are fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, C _1-6 alkyl, halo C _1-6 alkyl, C _2-6 alkenyl, halo C _2-6 alkenyl, C _2-6 alkynyl, halo C _2-6 alkynyl, C _1-6 alkoxy, C _1-6 alkylamino, C _1-6 alkylthio, C _3-8 cycloalkyl, C _2-10 heterocyclyl, C _6-14 aryl or C _1-9 heteroaryl.

In other embodiments, each of R ¹ and R ² is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, C _1-4 alkyl, halo C _1-4 alkyl, C _3-6 cycloalkyl or C _3-6 cycloalkyl-C _1-3 alkyl; or, R ¹ and R ² together with the carbon atom to which they are attached, form a 3-to 6-membered ring.

In other embodiments, each of R ³ and R ⁴ is independently hydrogen, bromine, iodine, amino, nitro, hydroxy, carboxy, C _1-3 alkyl, C _3-6 cycloalkyl or C _3-6cycloalkyl-C _1-3 alkyl; or, R ³ and R ⁴ together with the carbon atom to which they are attached, form a 3-to 6-membered ring.

In other embodiments, each of R ⁵ and R ⁶ is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, C _1-4 alkyl, C _2-4 alkenyl _, or C _2-4 alkynyl; or, R ⁵ and R ⁶ together with the carbon atom to which they are attached, form a 3-to 6-membered ring.

In other embodiments, each of R ³ and R ⁴ is independently hydrogen or bromine.

In other embodiments, each of R ⁵ and R ⁶ is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy or methyl.

wherein each of R ⁸, R ⁹, R ¹⁰, R ¹¹ and R ¹² is as defined herein.

wherein each of R ⁸, R ⁹, R ¹⁰, R ¹¹ and R ¹² is as defined herein.

In some embodiments, provided herein is a compound having Formula (IIIc) or a stereoisomer, an N-oxide or a salt thereof:

wherein each of R ⁸, R ⁹, R ¹⁰, R ¹¹ and R ¹² is as defined herein.

In some embodiments, provided herein is a compound having Formula (IIId) or a stereoisomer an N-oxide or a salt thereof:

wherein each of R ⁸, R ⁹, R ¹⁰, R ¹¹ and R ¹² is as defined herein.

In some embodiments, each of R ⁸, R ⁹, R ¹⁰, R ¹¹ and R ¹² is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, C _1-4 alkyl, halo C _1-4 alkyl, C _2-4 alkenyl, halo C _2-4 alkenyl, C _2-4 alkynyl, halo C _2-4 alkynyl, C _1-4 alkoxy, C _1-4 alkylamino, C _1-4 alkylthio, C _3-6 cycloalkyl, C _2-6 heterocyclyl, C _6-10 aryl or C _1-5 heteroaryl.

In some embodiments, R ⁸ and R ⁹ together with the carbon atom to which they are attached, form a optionally substituted 3-to 8-membered ring; wherein the optionally substituted ring described herein, the number of the substituents on the optionally substituted ring is 1, 2, 3, 4, 5 or 6; and the substituents may be the same or different; wherein the substituents are fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, C _1-6 alkyl, halo C _1-4 alkyl, C _2-4 alkenyl, halo C _2-4 alkenyl, C _2-4 alkynyl, halo C _2-4 alkynyl, C _1-4 alkoxy, C _1-4 alkylamino, C _1-4 alkylthio, C _3-6 cycloalkyl, C _2-6 heterocyclyl, C _6-10 aryl or C _1-5 heteroaryl.

In some embodiments, R ¹⁰, R ¹¹ and R ¹² together with the carbon atom to which they are attached, form -C≡CR ¹³ or -CR ¹⁴=CR ¹⁵R ¹⁶; wherein each of R ¹³, R ¹⁴, R ¹⁵ and R ¹⁶ is independently hydrogen, C _1-4 alkyl, halo C _1-4 alkyl, C _2-4 alkenyl, halo C _2-4 alkenyl, C _2-4 alkynyl or halo C _2-4 alkynyl.

In some embodiments, R ¹⁰, R ¹¹ and R ¹² together with the carbon atom to which they are attached, form optionally substituted C _6-10 aryl, optionally substituted C _1-6 heteroaryl, optionally substituted C _3-8 cycloalkyl or optionally substituted C _2-6 heterocyclyl (i.e.,

is

wherein Ay1 is optionally substituted C _6-10 aryl, optionally substituted C _1-6 heteroaryl, optionally substituted C _3-8 cycloalkyl or optionally substituted C _2-6 heterocyclyl) , wherein the optionally substituted groups described herein, the number of the substituents on the optionally substituted groups is 1, 2, 3, 4, 5 or 6; and the substituents may be the same or different; wherein the substitutents are fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, C _1-6 alkyl, halo C _1-4 alkyl, C _2-4 alkenyl, halo C _2-4 alkenyl, C _2-4 alkynyl, halo C _2-4 alkynyl, C _1-4 alkoxy, C _1-4 alkylamino, C _1-4 alkylthio, C _3-6 cycloalkyl, C _2-6 heterocyclyl, C _6-10 aryl or C _1-5 heteroaryl.

In some embodiments, -CR ⁸R ⁹-CR ¹⁰R ¹¹R ¹² is optionally substituted C _10-14 aryl, optionally substituted C _1-6 heteroaryl, optionally substituted C _3-8 cycloalkyl or optionally substituted C _2-6 heterocyclyl, unsubstituted phenyl or substituted phenyl (i.e.,

is

wherein Ay2 is optionally substituted C _10-14 aryl, optionally substituted C _1-6 heteroaryl, optionally substituted C _3-8 cycloalkyl, optionally substituted C _2-6 heterocyclyl, unsubstituted phenyl or substituted phenyl) , wherein the substituted or optionally substituted groups described above, the number of the substituents on the substituted or optionally substituted group is 1, 2, 3, 4, 5 or 6; and the substituents may be the same or different; wherein the substitutent is fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, C _1-6 alkyl, halo C _1-4 alkyl, C _2-4 alkenyl, halo C _2-4 alkenyl, C _2-4 alkynyl, halo C _2-4 alkynyl, C _1-4 alkoxy, C _1-4 alkylamino, C _1-4 alkylthio, C _3-6 cycloalkyl, C _2-6 heterocyclyl, C _6-10 aryl or C _1-5 heteroaryl.

each of R ⁸, R ⁹, R ¹⁰, R ¹¹ and R ¹² is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, -CH ₃, -CH ₂CH ₃, -CH ₂CH ₂CH ₃, -CH (CH ₃) ₂, -CH ₂F, -CHF ₂, -CH ₂Cl, -CH ₂Br, -CF ₃, -CH ₂CF ₃, -CH ₂CH ₂F, -CH ₂CH ₂Cl, -CH ₂CH ₂Br, -CH ₂CHF ₂, -CH ₂CH ₂CF ₃, -CH ₂CH ₂CH ₂F, -CH ₂CH ₂CH ₂Cl, -CH ₂CH ₂CH ₂Br, -CHFCH ₂CH ₃, -CHClCH ₂CH ₃, -CH=CH ₂, -CH ₂CH=CH ₂, CH ₃-CH=CH-, -C≡CH, -C≡CCH ₃, -CH ₂-C≡CH, -OCH ₃, -OCH ₂CH ₃, -OCH ₂CH ₂CH ₃, -OCH (CH ₃) ₂, -NHCH ₃, -N (CH ₃) ₂, -SCH ₃, -SCH ₂CH ₃, -SCH ₂CH ₂CH ₃, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or phenyl;

In other embodiments, R ⁸ and R ⁹ together with the carbon atom to which they are attached, form C _3-6 cycloalkyl.

In other embodiments, R ⁸ and R ⁹ together with the carbon atom to which they are attached, form -C (=O) -.

In other embodiments, R ¹⁰, R ¹¹ and R ¹² together with the carbon atom to which they are attached, form-C≡CH or -CH=CH ₂.

In other embodiments, R ¹⁰, R ¹¹ and R ¹² together with the carbon atom to which they are attached, form C _3-6 cycloalkyl, optionally halogen-substituted phenyl or C _2-6 heterocyclyl containing one oxygen atom.

In other embodiments, -CR ⁸R ⁹-CR ¹⁰R ¹¹R ¹² is C _3-6 cycloalkyl or halogen-substituted phenyl.

In still other embodiments, provided herein is a compound having Formula (IIIe) or a stereoisomer, an N-oxide or a salt thereof:

wherein,

each of R ⁵ and R ⁶ is independently hydrogen or fluorine;

X is fluroine or chlorine;

R ^m is hydrogen, C _1-3 alkyl or halo C _1-3 alkyl;

R ^v is hydrogen, C _1-3 alkyl or halo C _1-3 alkyl;

R ^w is C _1-3 alkyl or halo C _1-3 alkyl.

In still other embodiments, provided herein is a compound having Formula (IIIe) or a stereoisomer, an N-oxide or a salt thereof, wherein R ^m is hydrogen or methyl; R ^v is hydrogen or methyl; R ^w is methyl, isopropyl, difluoromethyl or tetrafluoromethyl.

In still other embodiments, provided herein is a compound having Formula (IIIf) or a stereoisomer, an N-oxide or a salt thereof:

wherein,

each of R ⁵ and R ⁶ is independently hydrogen or fluorine;

X is fluroine or chlorine;

R ^m is hydrogen, C _1-3 alkyl or halo C _1-3 alkyl;

R ^v is hydrogen, C _1-3 alkyl or halo C _1-3 alkyl;

R ^w is C _1-3 alkyl or halo C _1-3 alkyl.

In still other embodiments, provided herein is a compound having Formula (IIIf) or a stereoisomer, an N-oxide or a salt thereof, wherein R ^m is hydrogen or methyl; R ^v is hydrogen or methyl; R ^w is methyl, isopropyl, difluoromethyl or tetrafluoromethyl.

In still other embodiments, provided herein is a compound having Formula (IIIg) or a stereoisomer, an N-oxide or a salt thereof:

wherein X is chlorine.

In still other embodiments, provided herein is a compound having Formula (IIIh) or a stereoisomer, an N-oxide or a salt thereof:

wherein X is chlorine.

In some embodiments, provided herein is a compound having Formula (IVa) or a stereoisomer, an N-oxide or a salt thereof:

wherein Ay2 is as defined herein.

In some embodiments, provided herein is a compound having Formula (IVb) or a stereoisomer, an N-oxide or a salt thereof:

wherein Ay2 is as defined herein.

In some embodiments, Ay2 is optionally substituted C _10-14 aryl, optionally substituted C _1-5 heteroaryl, optionally substituted C _3-8 cycloalkyl, optionally substituted C _2-10 heterocyclyl or substituted phenyl, wherein the substituted or optionally substituted groups described herein, the number of the substituents on the substituted or optionally substituted groups is 1, 2, 3, 4, 5 or 6; and the substituents may be the same or different; wherein the substitutents are fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, C _1-4 alkyl, halo C _1-4 alkyl, C _2-4 alkenyl, halo C _2-4 alkenyl, C _2-4 alkynyl, halo C _2-4 alkynyl, C _1-4 alkoxy, C _1-4 alkylamino, C _1-4 alkylthio, C _3-6 cycloalkyl, C _2-6 heterocyclyl, C _6-10 aryl or C _1-5 heteroaryl.

In other embodiments, Ay2 is optionally substituted C _3-6 cycloalkyl, optionally substituted C _2-6 heterocyclyl or substituted phenyl; wherein substituted or optionally substituted groups described herein, the number of the substituents on the substituted or optionally substituted groups is 1, 2, 3, 4, 5 or 6; and the substituents may be the same or different; wherein the substituents are fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, difluoromethyl, trifluoromethyl, difluoromethoxy or trifluoromethoxy.

In some embodiments, provided herein is a compound having Formula (IVc) or a stereoisomer, an N-oxide or a salt thereof:

wherein Ay1 is as defined herein.

In some embodiments, provided herein is a compound having Formula (IVd) or a stereoisomer, an N-oxide or a salt thereof:

wherein Ay1 is as defined herein.

In some embodiments, Ay1 is optionally substituted C _6-10 aryl, optionally substituted C _1-6 heteroaryl, optionally substituted C _3-8 cycloalkyl or optionally substituted C _2-8 heterocyclyl, wherein the optionally substituted groups described herein, the number of the substituents on the optionally substituted groups is 1, 2, 3, 4, 5 or 6; and the substituents may be the same or different; wherein the substituents are fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, C _1-4 alkyl, halo C _1-4 alkyl, C _2-4 alkenyl, halo C _2-4 alkenyl, C _2-4 alkynyl, halo C _2-4 alkynyl, C _1-4 alkoxy, C _1-4 alkylamino, C _1-4 alkylthio, C _3-6 cycloalkyl, C _2-6 heterocyclyl, C _6-10 aryl or C _1-5 heteroaryl.

In other embodiments, Ay1 is optionally substituted phenyl, optionally substituted C _3-6 cycloalkyl or optionally substituted C _2-6 heterocyclyl; wherein the optionally substituted, the number of the substituents is 1, 2, 3, 4, 5 or 6; and the substituents may be the same or different; wherein the substituent is fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, difluoromethyl, trifluoromethyl, difluoromethoxy or trifluoromethoxy.

In other embodiments, Ay1 is C _3-6 cycloalkyl, optionally halogen-substituted phenyl or C _2-6 heterocyclyl containing one oxygen atom.

In some embodiments, provided herein is a compound having one of the following structures or a stereoisomer, an N-oxide or a salt thereof:

In another aspect, the invention provides a composition comprising the compound disclosed herein, or a stereoisomer, an N-oxide or a salt thereof.

In some embodiments, the composition further comprises at least one pesticidally acceptable adjuvant.

In other embodiments, the composition disclosed herein is a herbicidal composition.

In some embodiments, the invention provides the compound or the use of the composition comprising the compound described herein for controlling unwanted plants.

In some embodiments, the useful plant comprises soybean, peanut and sunflower.

In another aspect, the invention provides a method for controlling unwanted plants comprising applying an effective amount of a compound of the invention to a plant, a plant seed, soil in which or on which the plant grows, or a cultivation area.

The compound provided herein is a novel compound which is more effective for weeds, lower in cost, less toxic, and safe to the environment.

THE COMPOSITION AND PREPARATIONS OF THE COMPOUND OF THE INVENTION

The compound of the present invention is generally useful as herbicidal active ingredient in composition or formulation, wherein the composition or formulation has at least one adjuvant selected from surfactant, solid diluent and liquid diluent, etc, all of which meeting the requirements for the use of pesticides are within the scope of the invention. The formulation or composition ingredients are selected to be consistent with the physical properties of the active ingredients, mode of application and environmental factors such as soil type, moisture and temperature.

Useful formulations include both liquid and solid compositions Liquid compositions include solutions (including emulsifiable concentrates) , suspensions, emulsions (including microemulsions and/or suspoemulsions) and the like, which optionally can be thickened into gels. The general types of aqueous liquid compositions are soluble concentrate, suspension concentrate, capsule suspension, concentrated emulsion, microemulsion and suspo-emulsion. The general types of nonaqueous liquid compositions are emulsifiable concentrate, microemulsifiable concentrate, dispersible concentrate and oil dispersion.

The general types of solid compositions are dusts, powders, granules, pellets, prills, pastilles, tablets, filled films (including seed coatings) and the like, which can be water-dispersible ( "wettable" ) or water-soluble. Films and coatings formed from film-forming solutions or flowable suspensions are particularly useful for seed treatment. Active ingredient can be (micro) encapsulated and further formed into a suspension or solid formulation; alternatively the entire formulation of active ingredient can be encapsulated (or "overcoated" ) . Encapsulation can control or delay the release of active ingredients. An emulsifiable granule combines the advantages of both an emulsifiable concentrate formulation and a dry granular formulation. High-strength compositions are primarily used as intermediates for further formulation.

Sprayable formulations are typically extended in a suitable medium before spraying. Such liquid and solid formulations are formulated to be readily diluted in the spray medium, usually water. Spray volumes can range from about one to several thousand liters per hectare, but more typically are in the range from about ten to several hundred liters per hectare. Sprayable formulations can be tank mixed with water or another suitable medium for foliar treatment by aerial or ground application, or for application to the growing medium of the plant. Liquid and dry formulations can be metered directly into drip irrigation systems or metered into the furrow during planting.

The formulations will typically contain effective amounts of active ingredient, diluent and surfactant within the following approximate ranges which add up to 100 percent by weight.

Solid diluents include, for example, clays such as bentonite, montmorillonite, attapulgite and kaolin, gypsum, cellulose, titanium dioxide, zinc oxide, starch, dextrin, sugars (e.g., lactose, sucrose) , silica, talc, mica, diatomaceous earth, urea, calcium carbonate, sodium carbonate and bicarbonate, and sodium sulfate. Typical solid diluents are described in Watkins et al., Handbook of Insecticide Dust Diluents and Carriers, 2nd Ed., Dorland Books, Caldwell, New Jersey.

Liquid diluents include, for example, water, N, N-dimethylalkanamides (e.g., N, N-dimethylformamide) , limonene, dimethyl sulfoxide, N-alkylpyrrolidones (e.g., N-methylpyrrolidinone) , ethylene glycol, triethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, propylene carbonate, butylene carbonate, paraffins (e.g., white mineral oils, normal paraffins, isoparaffins) , alkylbenzenes, alkylnaphthalenes, glycerine, glycerol triacetate, sorbitol, triacetin, aromatic hydrocarbons, dearomatized aliphatics, alkylbenzenes, alkylnaphthalenes, ketones such as cyclohexanone, 2-heptanone, isophorone and 4-hydroxy-4-methyl-2-pentanone, acetates such as isoamyl acetate, hexyl acetate, heptyl acetate, octyl acetate, nonyl acetate, tridecyl acetate and isobornyl acetate, other esters such as alkylated lactate esters, dibasic esters and γ-butyrolactone, and alcohols, which can be linear, branched, saturated or unsaturated, such as methanol, ethanol, n-propanol, isopropyl alcohol, n-butanol, isobutanol, n-hexanol, 2-ethylhexanol, n-octanol, decanol, isodecanol, isooctadecanol, cetanol, laurinol, tridecanol, oleyl alcohol, cyclohexanol, tetrahydrofurfuryl alcohol, diacetone alcohol and benzyl alcohol. Liquid diluents also include glycerol esters of saturated and unsaturated fatty acids (typically C6-C22) such as plant seed and fruit oils (e.g., oils of olive, castor, linseed, sesame, corn (maize) , peanut, sunflower, grapeseed, safflower, cottonseed, soybean, rapeseed, coconut and palm kernel) , animal-sourced fats (e.g., beef tallow, pork tallow, lard, cod liver oil, fish oil) , and mixtures thereof. Liquid diluents also include alkylated fatty acids (e.g., methylated, ethylated, butylated) wherein the fatty acids may be obtained by hydrolysis of glycerol esters from plant and animal sources, and can be purified by distillation. Typical liquid diluents are described in Marsden, Solvents Guide, 2nd Ed., Interscience, New York, 1950.

The solid and liquid compositions of the present invention often include one or more surfactants. When added to a liquid, surfactants (also known as “surface-active agents” ) generally modify, most often reduce, the surface tension of the liquid. Depending on the nature of the hydrophilic and lipophilic groups in a surfactant molecule, surfactants can be useful as wetting agents, dispersants, emulsifiers or defoaming agents.

Surfactants can be classified as nonionic, anionic or cationic. Nonionic surfactants useful for the present compositions include, but are not limited to: alcohol alkoxylates such as alcohol alkoxylates based on natural and synthetic alcohols (which may be branched or linear) and prepared from the alcohols and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof; amine ethoxylates, alkanolamides and ethoxylated alkanolamides; alkoxylated triglycerides such as ethoxylated soybean, castor and rapeseed oils; alkylphenol alkoxylates such as octylphenol ethoxylates, nonylphenol ethoxylates, dinonyl phenol ethoxylates and dodecyl phenol ethoxylates (prepared from the phenols and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof) ; block polymers prepared from ethylene oxide or propylene oxide and reverse block polymers where the terminal blocks are prepared from propylene oxide; ethoxylated fatty acids; ethoxylated fatty esters and oils; ethoxylated methyl esters; ethoxylated tristyrylphenol (including those prepared from ethylene oxide, propylene oxide, butylene oxide or mixtures thereof) ; fatty acid esters, glycerol esters, lanolin-based derivatives, polyethoxylate esters such as polyethoxylated sorbitan fatty acid esters, polyethoxylated sorbitol fatty acid esters and polyethoxylated glycerol fatty acid esters; other sorbitan derivatives such as sorbitan esters; polymeric surfactants such as random copolymers, block copolymers, alkyd PEG (polyethylene glycol) resins, graft or comb polymers and star polymers; polyethylene glycols (PEG) ; polyethylene glycol fatty acid esters; silicone-based surfactants; and sugar-derivatives such as sucrose esters, alkyl polyglycosides and alkyl polysaccharides.

Useful anionic surfactants include, but are not limited to: alkylaryl sulfonic acids and their salts; carboxylated alcohol or alkylphenol ethoxylates; diphenyl sulfonate derivatives; lignin and lignin derivatives such as lignosulfonates; maleic or succinic acids or their anhydrides; olefin sulfonates; phosphate esters such as phosphate esters of alcohol alkoxylates, phosphate esters of alkylphenol alkoxylates and phosphate esters of styryl phenol ethoxylates; protein-based surfactants; sarcosine derivatives; styryl phenol ether sulfate; sulfates and sulfonates of oils and fatty acids; sulfates and sulfonates of ethoxylated alkylphenols; sulfates of alcohols; sulfates of ethoxylated alcohols; sulfonates of amines and amides such as N, N-alkyltaurates; sulfonates of benzene, cumene, toluene, xylene, and dodecyl and tridecylbenzenes; sulfonates of condensed naphthalenes; sulfonates of naphthalene and alkyl naphthalene; sulfonates of fractionated petroleum; sulfosuccinamates; and sulfosuccinates and their derivatives such as dialkyl sulfosuccinate salts.

Useful cationic surfactants include, but are not limited to: amides and ethoxylated amides; amines such as N-alkyl propanediamines, tripropylenetriamines and dipropylenetetramines, and ethoxylated amines, ethoxylated diamines and propoxylated amines (prepared from the amines and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof) ; amine salts such as amine acetates and diamine salts; quaternary ammonium salts such as quaternary salts, ethoxylated quaternary salts and diquaternary salts; and amine oxides such as alkyldimethylamine oxides and bis- (2-hydroxyethyl) -alkylamine oxides.

Also useful for the present compositions (i.e., final mixtures) are mixtures of nonionic and anionic surfactants or mixtures of nonionic and cationic surfactants. Nonionic, anionic and cationic surfactants and their recommended uses are disclosed in a variety of published references including McCutcheon's Emulsifiers and Detergents, annual American and International Editions published by McCutcheon's Division, The Manufacturing Confectioner Publishing Co.; Sisely and Wood, Encyclopedia of Surface Active Agents, Chemical Publ. Co., Inc., New York, 1964; and A. S. Davidson and B. Milwidsky, Synthetic Detergents, Seventh Edition, John Wiley and Sons, New York, 1987.

Compositions of this invention may also contain formulation auxiliaries and additives, known to those skilled in the art as formulation aids (some of which may be considered to also function as solid diluents, liquid diluents or surfactants) . Such formulation auxiliaries and additives may control: pH (buffers) , foaming during processing (antifoams such polyorganosiloxanes) , sedimentation of active ingredients (suspending agents) , viscosity (thixotropic thickeners) , in-container microbial growth (antimicrobials) , product freezing (antifreezes) , color (dyes/pigment dispersions) , wash-off (film formers or stickers) , evaporation (evaporation retardants) , and other formulation attributes. Film formers include, for example, polyvinyl acetates, polyvinyl acetate copolymers, polyvinylpyrrolidone-vinyl acetate copolymer, polyvinyl alcohols, polyvinyl alcohol copolymers and waxes. Examples of formulation auxiliaries and additives include those listed in McCutcheon 's Volume 2: Functional Materials, annual International and North American editions published by McCutcheon's Division, The Manufacturing Confectioner Publishing Co.; and PCT Publication WO 03/024222.

The herbicide active ingredients are typically incorporated into the present compositions by dissolving the active ingredient in a solvent or by grinding in a liquid or dry diluent. Solutions, including emulsifiable concentrates, can be prepared by simply mixing the ingredients. If the solvent of a liquid composition intended for use as an emulsifiable concentrate is water-immiscible, an emulsifier is typically added to emulsify the active-containing solvent upon dilution with water. Active ingredient slurries, with particle diameters of up to 2,000 μm can be wet milled using media mills to obtain particles with average diameters below 3 μm. Aqueous slurries can be made into finished suspension concentrates (see, for example, U.S. 3,060,084) or further processed by spray drying to form water-dispersible granules. Dry formulations usually require dry milling processes, which produce average particle diameters in the 2 to 10 μm range. Dusts and powders can be prepared by blending and usually grinding (such as with a hammer mill or fluid-energy mill) . Granules and pellets can be prepared by spraying the active material upon preformed granular carriers or by agglomeration techniques. See Browning, "Agglomeration" , Chemical Engineering, December 4, 1967, pp 147-48, Perry's Chemical Engineer 's Handbook, 4th Ed., McGraw-Hill, New York, 1963, pages 8-57 and following, and WO 91/13546. Pellets can be prepared as described in U.S. 4,172,714. Water-dispersible and water-soluble granules can be prepared as taught in U.S. 4,144,050, U.S. 3,920,442 and DE 3,246,493. Tablets can be prepared as taught in U.S. 5,180,587, U.S. 5,232,701 and U.S. 5,208,030. Films can be prepared as taught in GB 2,095,558 and U.S. 3,299,566.

For further information regarding the art of formulation, see T. S. Woods, “The Formulator’s Toolbox-Product Forms for Modern Agriculture” , Pesticide Chemistry and Bioscience, The Food-Environment Challenge, T. Brooks andT. R. Roberts Eds., Proceedings of the 9th International Congress on Pesticide Chemistry, The Royal Society of Chemistry, Cambridge, 1999, pp 120-133. See also U.S. 3,235,361, Col. 6, line 16 through Col. 7, line 19 and Examples 10-41; U.S. 3,309,192, Col. 5, line 43 through Col. 7, line 62 and Examples 8, 12, 15, 39, 41, 52, 53, 58, 132, 138-140, 162-164, 166, 167 and 169-182; U.S. 2,891,855, Col. 3, line 66 through Col. 5, line 17 and Examples 1-4; Klingman, Weed Control as a Science, John Wiley and Sons, Inc., New York, 1961, pp 81-96; Hance et al., Weed Control Handbook, 8th Ed., Blackwell Scientific Publications, Oxford, 1989; and Developments in formulation technology, PJB Publications, Richmond, UK, 2000.

USES OF COMPOUNDS OF THE INVENTION

The herbicide of the present invention can be used by spraying to a plant, applying it to soil, or applying it to surface of water. The amount of the active component is appropriately determined to meet the application purpose. The content of the active component is appropriately determined according to the purpose.

The amount of the compound of the invention depends on the kind of the compound to be used, the target weed, the tendency of the weed to appear, the environmental conditions, the type of the herbicide, and the like. When the form of the herbicide itself of the present invention is used, for example, in the form of a powder or granules, it is suitably used in an amount of from 1 g to 50 kg, preferably from 10 g to 10 kg per hectare, of the active ingredient. When the herbicide of the present invention is used in the form of a liquid, for example, in the form of an emulsifiable concentrate, a wettable powder or a flowable preparation, it is suitably used in an amount of from 0.1 to 50,000 ppm, preferably from 10 to 10,000 ppm.

The invention provides a method of controlling weeds in crops of useful plants, comprising applying to said weeds or to the locus of said weeds, or to said useful crop plants or to the locus of said useful crop plants, a compound or a composition of the invention.

The present invention also provides a method of selectively controlling grass and/or weeds in crops of useful plants comprising applying a herbicidally effective amount of compound having Formula (I) , (Ia) , (II) , (II-1) , (II-2) , (II-3) , (II-4) , (II-5) , (III-1) , (III-2) , (IIa) , (IIb) , (IIc) , (IId) , (IIa-1) , (IIa-2) , (IIa-3) , (IIa-4) , (IIa-5) , (IIa-6) , (IIa-7) , (IIa-8) , (IIa-9) , (IIa-10) , (IIa-11) , (IIa-12) , (IIa-13) , (IIa-14) , (IIa-15) , (IIa-16) , (IIa-17) , (IIa-18) , (IIIa) , (IIIb) , (IIIc) , (IIId) , (IIIe) , (IIIf) , (IIIg) , (IIIh) , (IV) , (IVa) , (IVb) , (IVc) or (IVd) , or a stereoisomer, an N-oxide or a salt thereof to a useful plant or a locus thereof or to a cultivation area.

The term “herbicide” as used herein denotes a compound which controls or modifies the growth of plants. The term “herbicidally effective amount” indicates the quantity of such a compound or combination of such compounds which is capable of producing a controlling or modifying effect on the growth of plants. Controlling or modifying effects include all deviation from natural development, for example: killing, retardation, leaf burn, albinism, dwarfing and the like. The term “plants” refers to all physical parts of a plant, including seeds, seedlings, saplings, roots, tubers, stems, stalks, foliage and fruits. The term “locus” is intended to include soil, seeds, and seedlings, as well as established vegetation and includes not only areas where weeds may already be growing, but also areas where weeds have yet to emerge, and also to areas under cultivation with respect to crops of useful plants. “Areas under cultivation” include land on which the crop plants are already growing and land intended for cultivation with such crop plants. The term “weeds” as used herein means any undesired plant, and thus includes not only agronomically important weeds as described below, but also volunteer crop plants.

Crops of useful plants in which the composition according to the invention can be used include, but are not limited to, perennial crops, such as citrus fruit, grapevines, nuts, oil palms, olives, pome fruit, stone fruit and rubber, and annual arable crops, such as cereals, for example barley and wheat, cotton, oilseed rape, maize, rice, soy beans, sugar beet, sugar cane, sunflowers, ornamentals, switchgrass, turf and vegetables, especially cereals, maize and soy beans.

The grasses and weeds to be controlled may be both monocotyledonous species, for example Agrostis, Alopecurus, Avena, Brachiaria, Bromus, Cenchrus, Cyperus, Digitaria, Echinochloa, Eriochloa, Lolium, Monochoria, Panicum, Poa, Rottboellia, Sagittaria, Scirpus, Setaria, Sida and Sorghum, and dicotyledonous species, for example Abutilon, Amaranthus, Chenopodium, Chrysanthemum, Euphorbia, Galium, Ipomoea, Kochia, Nasturtium, Polygonum, Sida, Sinapis, Solanum, Stellaria, Veronica, Viola and Xanthium.

Compounds of this invention may show tolerance to important agronomic crops including, but is not limited to, alfalfa, barley, cotton, wheat, rape, sugar beets, corn (maize) , sorghum, soybeans, rice, oats, peanuts, vegetables, tomato, potato, perennial plantation crops including coffee, cocoa, oil palm, rubber, sugarcane, citrus, grapes, fruit trees, nut trees, banana, plantain, pineapple, hops, tea and forests such as eucalyptus and conifers (e.g., loblolly pine) , and turf species (e.g., Kentucky bluegrass, St. Augustine grass, Kentucky fescue and Bermuda grass) .

If desired, the compound of Formula (I) , (Ia) , (II) , (II-1) , (II-2) , (II-3) , (II-4) , (II-5) , (III-1) , (III-2) , (IIa) , (IIb) , (IIc) , (IId) , (IIa-1) , (IIa-2) , (IIa-3) , (IIa-4) , (IIa-5) , (IIa-6) , (IIa-7) , (IIa-8) , (IIa-9) , (IIa-10) , (IIa-11) , (IIa-12) , (IIa-13) , (IIa-14) , (IIa-15) , (IIa-16) , (IIa-17) , (IIa-18) , (IIIa) , (IIIb) , (IIIc) , (IIId) , (IIIe) , (IIIf) , (IIIg) , (IIIh) , (IV) , (IVa) , (IVb) , (IVc) or (IVd) , or a stereoisomer, an N-oxide or a salt thereof, may also be combined with other active ingredients such as other herbicides and/or insecticides and/or acaricides and /or nematicides and /or molluscicides and/or fungicides and /or plant growth regulators for use. These mixtures, as well as the use of these mixtures to control the growth of weeds and/or undesirable plants, form further aspects of the invention. For the avoidance of doubt, the mixture of the present invention also includes mixtures of two or more different compounds having Formula (I) , (Ia) , (II) , (II-1) , (II-2) , (II-3) , (II-4) , (II-5) , (III-1) , (III-2) , (IIa) , (IIb) , (IIc) , (IId) , (IIa-1) , (IIa-2) , (IIa-3) , (IIa-4) , (IIa-5) , (IIa-6) , (IIa-7) , (IIa-8) , (IIa-9) , (IIa-10) , (IIa-11) , (IIa-12) , (IIa-13) , (IIa-14) , (IIa-15) , (IIa-16) , (IIa-17) , (IIa-18) , (IIIa) , (IIIb) , (IIIc) , (IIId) , (IIIe) , (IIIf) , (IIIg) , (IIIh) , (IV) , (IVa) , (IVb) , (IVc) or (IVd) , or a stereoisomer, an N-oxide or a salt thereof. In particular, the present invention also relates to a composition disclosed herein comprising at least one additional herbicide in addition to the compound having Formula (I) , (Ia) , (II) , (II-1) , (II-2) , (II-3) , (II-4) , (II-5) , (III-1) , (III-2) , (IIa) , (IIb) , (IIc) , (IId) , (IIa-1) , (IIa-2) , (IIa-3) , (IIa-4) , (IIa-5) , (IIa-6) , (IIa-7) , (IIa-8) , (IIa-9) , (IIa-10) , (IIa-11) , (IIa-12) , (IIa-13) , (IIa-14) , (IIa-15) , (IIa-16) , (IIa-17) , (IIa-18) , (IIIa) , (IIIb) , (IIIc) , (IIId) , (IIIe) , (IIIf) , (IIIg) , (IIIh) , (IV) , (IVa) , (IVb) , (IVc) or (IVd) , or a stereoisomer, an N-oxide or a salt thereof.

GENERAL SYNTHETIC PROCEDURES

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. Generally, the compounds disclosed herein may be prepared by methods described herein, except where further noted. The starting materials, reagents and the like used in the preparation of the compounds of the invention are all commercially available or can be prepared by conventional methods in the art.

¹H NMR spectra were recorded by a Bruker Avance 400 MHz spectrometer or Bruker Avance 600 MHz spectrometer, using CDC1 ₃, d ⁶-DMSO, CD ₃OD or d ⁶-acetone (reported in ppm) as solvent, and using TMS (0 ppm) or chloroform (7.26 ppm) as the reference standard. When peak multiplicities were reported, the following abbreviations were used: s (singlet) , d (doublet) , t (triplet) , q (quartet) , m (multiplet) , br (broadened) , dd (doublet of doublets) , and dt (doublet of triplets) . Coupling constants, when given, were reported in Hertz (Hz) .

The mass spectrometric analysis method used in the present invention was: using Agilent 1260 HPLC; Agilent 6120 ESI.

Phase A: water (containing 0.1%formic acid) ; phase B: acetonitrile (containing 0.1% formic acid) .

Gradient elution: 0-3 min, 5-100%B; 3-6 min, 100%B.

Flow rate: 0.6 mL/min.

Detection wavelength: 254 nm.

MS parameters: ESI positive scanning, collision induced dissociation: 70V.

Dry nitrogen: 12 L/min, atomizing gas pressure: 40 psi, gas temperature: 350 ℃.

An appropriate amount of sample was taken and dissolved in 0.5 mL of methanol to give a sample solution, and the given ample solution was injected. A full scan MS in positive ESI mode was performed to obtain the reading of quasi-molecular ion peak [M+H] ⁺.

The following abbreviations are used throughout the present invention:

Petroleum ether: PE

DMF: N, N-dimethylformamide, dimethylformamide

EtOAc: ethyl acetate

HBr: hydrogen bromide

K ₂CO ₃: potassium carbonate

m-CPBA: metachloroperbenzoic acid

NFSI: N-fluorobenzenesulfonimide

THF: tetrahydrofuran

TLC: thin layer chromatography

The following synthetic schemes and examples 1-16 are provided to further illustrate the contents of the present invention.

Scheme 1

The compound having Formula (5a) can be prepared according to the procedure described in Scheme 1, wherein R ^c is C _2-10 alkyl, haloalkyl or cycloalkyl. The compound having Formula (a’) can react with thiourea in HBr to give a compound having Formula (b’) ; ethyl difluoroacetoacetate can first react with hydrazine hydrate, then the obtained product can react with phosphorus oxychloride to give an intermediate, and the intermediate can react with R ^c-I to give a compound having Formula (1a) and a compound having Formula (1b) ; the compound having Formula (1a) can undergo reduction reaction to give the compound having Formula (2a) ; the compound having Formula (2a) can react with bromohydrocarbon (e.g., carbontetrabromide) to give a compound having Formula (3a) ; the compound having Formula (3a) with the compound having Formula (b’) can undergo condensation reaction under a base condition (such as K ₂CO ₃, etc. ) to give a compound having Formula (4a) ; the compound having Formula (4a) can further undergo oxidization to give compound having Formula (5a) .

Scheme 2

The compound having Formula (5b) can be prepared according to the procedure described in Scheme 1, wherein R ^c is C _2-10 alkyl, haloalkyl or cycloalkyl. The compound having Formula (1b) can undergo reduction reaction to give a compound having Formula (2b) ; the compound having Formula (2b) can react with a bromo-hydrocarbon (such as carbon tetrabromide) to give a compound having Formula (3b) ; The compound having Formula (3b) with a compound having Formula (b’) can undergo condensation reaction under a base condition (such as K ₂CO ₃, etc. ) to give a compound having Formula (4b) ; the compound having Formula (4b) can further undergo oxidization to give a compound having Formula (5b) .

Examples

Example 1: 3- ( ( (5-chloro-3- (difluoromethyl) -1-ethyl-1H-pyrazol-4-yl) methyl) sulfonyl) -5, 5-dimethyl-4, 5-dihydroisoxazole

Step 1: synthesis of 5, 5-dimethyl-4, 5-dihydroisoxazol-3-yl isothiourea hydrobromide

Thiourea (6 g, 79 mmol) was dissolved in acetonitrile (65 mL) at room temperature. To the solution was added dropwise hydrobromic acid (48%, 10 mL) , and the mixture was stirred for 1 h. To the mixture was added dropwise 3-chloro-5, 5-dimethyl-4, 5-dihydroisoxazole (12.6 g, 95 mmol) . The mixture was heated to 40 ℃ and stirred overnight. The solvent in the mixture was evaporated under pressure, and the obtained solid was recrystallized from ethyl acetate to give a white crystaline (19.2 g) , yield: 96.0%.

Step 2: synthesis of 5-chloro-3- (difluoromethyl) -1-ethyl-1H-pyrazol-4-carbaldehyde and 3-chloro-5- (difluoromethyl) -1-ethyl-1H-pyrazol-4-carbaldehyde

Ethyl difluoroacetoacetate (83.06 g, 0.5 mol) was dissolved in anhydrous ethanol (200 mL) , and the obtain mixture was stirred at 0 ℃, then hydrazine hydrate (37.50 g, 0.75 mol) was added slowly into the mixture. After addition, the mixture was stirred at room temperature for 4 h, then heated to 80 ℃ and stirred overnight, then the reaction was stopped. Ethanol was removed, and the residue mixture was washed with water (300 mL) , and then extracted with ethyl acetate (150 mL) three times. The combined organic layers were concentrated in vacuo to remove the solvent and give a light yellow solid.

DMF (38.01 g, 0.52 mol) was stirred at 0 ℃, then phosphorus oxychloride (239.20 g, 1.56 mol) was added slowly into DMF. After addition, the mixture was warmed to room temperature and stirred, then to the mixture was added the previously obtained light yellow solid. The above mixture was heated to 110 ℃ and refluxed overnight. After the reaction was completed, the reaction mixture was washed with water (500 mL) , and extracted with ethyl acetate (150 mL) three times. The combined organic layers was concentrated in vacuo to give a reddish brown solid.

The above reddish brown solid and potassium carbonate (57.96 g, 0.42 mol) were dissolved in DMF (100 mL) , and the mixture was stirred at room temperature, then iodoethane (35.78 g, 0.25 mol) was added into the above mixture. After addition, the mixture was heated to 80 ℃ and stirred for 24 h. After the reaction was completed, the mixture was washed with water (200 mL) , and extracted with ethyl acetate (100 mL) three times. The combined organic layers was concentrated in vacuo to remove the solvent, and the residue was purified by cholumn chromatography (eluent: Petroleum ether/EtOAc (v/v) = 10/1) to give colorless transparent liquids 5-chloro-3- (difluoromethyl) -1-ethyl-1H-pyrazol-4-carbaldehyde (15.69 g, yeild: 15.0%) and 3-chloro-5- (difluoromethyl) -1-ethyl-1H-pyrazol-4-carbaldehyde (15.92 g, yeild: 15.3%) .

5-chloro-3- (difluoromethyl) -1-ethyl-1H-pyrazol-4-carbaldehyde: MS-ESI: m/z 209.0 [M+H] ⁺; ¹H NMR (400 MHz, CDCl ₃) δ 9.89 (s, 1H) , 7.41 (t, J = 52.5 Hz, 1H) , 4.36 (q, J = 7.2 Hz, 2H) , 1.52 (t, J = 7.2 Hz, 3H) ; ¹⁹F NMR (376 MHz, CDCl ₃) δ -115.94 (s) , -116.08 (s) ;

3-chloro-5- (difluoromethyl) -1-ethyl-1H-pyrazol-4-carbaldehyde: MS-ESI: m/z 209.0 [M+H] ⁺; ¹H NMR (400 MHz, CDCl ₃) δ 9.97 (s, 1H) , 6.90 (t, J = 53.6 Hz, 1H) , 4.27 (q, J = 7.3 Hz, 2H) , 1.50 (t, J = 7.3 Hz, 3H) ; ¹⁹F NMR (376 MHz, CDCl ₃) δ -114.04 (s) , -114.18 (s) .

Step 3: synthesis of (5-chloro-3- (difluoromethyl) -1-ethyl-1H-pyrazol-4-yl) methanol

5-Chloro-3- (difluoromethyl) -1-ethyl-1H-pyrazol-4-carbaldehyde (6.0 g, 28.8 mmol) was dissolved in anhydrous methanol (50 mL) and the mixture was stirred at 0 ℃, then sodium borohydride (1.30 g, 34.5 mmol) was added in portions to the mixture. After addition, the resulting mixture was warmed to room temperature and stirred for 4 h. After the reaction was completed, methanol was removed, and the residue was washed with water (50 mL) , then extracted with ethyl acetate (50 mL) three times. The combined organic layers were concentrated in vacuo to remove the solvent and give the crude product as colorless liquid (5.50 g, yield: 90.7%) .

MS-ESI: m/z 211.0 [M+H] ⁺.

Step 4: synthesis of 4- (bromomethyl) -5-chloro-3- (difluoromethyl) -1-ethyl-1H-pyrazole

(5-Chloro-3- (difluoromethyl) -1-ethyl-1H-pyrazol-4-yl) methanol (6.00 g, 28.5 mmol) and triphenylphosphine (14.95 g, 57.0 mmol) were dissolved in acetonitrile (60 mL) , and the mixture was stirred at 0 ℃, then a solution of carbon tetrabromide (18.9 g, 57.0 mmol) in acetonitrile (20 mL) was added in portions to the mixture while controlling the temperature below 5 ℃. After addition, the resulting mixture was warmed to room temperature and stirred for 3.5 h. After the reaction was completed, acetonitrile was removed, and the residue was washed with water (300 mL) , then extracted with ethyl acetate (100 mL) three times. The combined organic layers were concentrated in vacuo to remove the solvent, and the residue was purified by cholumn chromatography (eluent: Petroleum ether/EtOAc (v/v) = 10/1) to give the crude product as colorless liquid (7.50 g, yield: 96.3%) .

MS-ESI: m/z 274.9 [M+H] ⁺.

Step 5: synthesis of 3- ( ( (5-chloro-3- (difluoromethyl) -1-ethyl-1H-pyrazol-4-yl) methyl) thio) -5, 5-dimethyl-4, 5-dihydroisoxazole

4- (Bromomethyl) -5-chloro-3- (difluoromethyl) -1-ethyl-1H-pyrazole (7.50 g, 27.4 mmol) and 5, 5-dimethyl-4, 5-dihydroisoxazol-3-yl isothiourea hydrobromide (8.36 g, 32.9 mmol) was dissolved in acetonitrile (100 mL) . The mixture was stirred at room temperature for 10 min, then potassium carbonate (15.12 g, 109.6 mmol) was added into the mixture. The resulting mixture was stirred for 12 h, then stopped. To the reaction mixture was added water (300 mL) with stirring. The mixture was extracted with ethyl acetate (100 mL) three times. The combined organic layers were concentrated in vacuo to remove the solvent and give the crude product as yellow liquid (7.00 g) , yield: 79.0%.

MS-ESI: m/z 324.0 [M+H] ⁺.

Step 6: synthesis of 3- ( ( (5-chloro-3- (difluoromethyl) -1-ethyl-1H-pyrazol-4-yl) methyl) sulfonyl) -5, 5-dimethyl-4, 5-dihydroisoxazole

3- ( ( (5-Chloro-3- (difluoromethyl) -1-ethyl-1H-pyrazol-4-yl) methyl) thio) -5, 5-dimethyl-4, 5 -dihydroisoxazole (7.00 g, 21.6 mmol) was dissolved in dichloromethane (100 mL) . The mixture was stirred at room temperature, then to the reaction mixture was added 85%m-CPBA (8.78 g, 43.2 mmol) . The mixture was stirred and reacted for 5 h, and then the reaction was stopped. The reaction mixture was washed with saturated aqueous sodium hydrogen sulfite (200 mL) and saturated aqueous sodium bicarbonate (200 mL) in turn, then extracted with dichloromethane (200 mL) . The combined organic layers dried over anhydrous sodium sufate, and then concentrated in vacuo to remove the solvent. The residue was purified by column chromatography (eluent: petroleum ether/EtOAc (v/v) = 5/1) to give a white solid (5.45 g) , yield: 71.0%.

MS-ESI: m/z 356.0 [M+H] ⁺;

¹H NMR (400 MHz, CDCl ₃) δ 6.82 (t, J = 54.8 Hz, 1H) , 4.62 (s, 2H) , 4.26 (q, J = 7.3 Hz, 2H) , 3.09 (s, 2H) , 1.52 (s, 6H) , 1.49 (t, J = 7.3 Hz, 3H) .

Example 2: 3- ( ( (3-chloro-5- (difluoromethyl) -1-ethyl-1H-pyrazol-4-yl) methyl) sulfonyl) -5, 5-dimethyl-4, 5-dihydroisoxazole

Step 1: synthesis of (3-chloro-5- (difluoromethyl) -1-ethyl-1H-pyrazol-4-yl) methanol

3-Chloro-5- (difluoromethyl) -1-ethyl-1H-pyrazol-4-carbaldehyde (6.3 g, 30.2 mmol) was dissolved in anhydrous methanol (50 mL) and the mixture was stirred at 0 ℃, then sodium borohydride (1.36 g, 36.2 mmol) was added in portions to the mixture. After addition, the resulting mixture was warmed to room temperature and stirred for 4 h. After the reaction was completed, methanol was removed, and the residue was washed with water (50 mL) , then extracted with ethyl acetate (50 mL) three times. The combined organic layers were concentrated in vacuo to remove the solvent and give the crude product as colorless liquid (6.00 g, yield: 94.3%) .

MS-ESI: m/z 211.0 [M+H] ⁺.

Step 2: synthesis of 4- (bromomethyl) -3-chloro-5- (difluoromethyl) -1-ethyl-1H-pyrazole

(3-Chloro-5- (difluoromethyl) -1-ethyl-1H-pyrazol-4-yl) methanol (6.00 g, 28.5 mmol) and triphenylphosphine (14.95 g, 57.0 mmol) were dissolved in acetonitrile (60 mL) , and the mixture was stirred at 0 ℃, then a solution of carbon tetrabromide (18.9 g, 57.0 mmol) in acetonitrile (20 mL) was added slowly into the mixture while controlling the temperature below 5 ℃. After addition, the resulting mixture was warmed to room temperature and stirred for 3.5 h. After the reaction was completed, acetonitrile was removed, and the residue was washed with water (300 mL) , then extracted with ethyl acetate (100 mL) three times. The combined organic layers were concentrated in vacuo to remove the solvent, and the residue was purified by cholumn chromatography (eluent: Petroleum ether/EtOAc (v/v) = 10/1) to give the crude product as colorless liquid (7.50 g, yield: 96.3%) .

MS-ESI: m/z 274.9 [M+H] ⁺.

Step 3: 3- ( ( (3-chloro-5- (difluoromethyl) -1-ethyl-1H-pyrazol-4-yl) methyl) thio) -5, 5-dimethyl -4, 5-dihydroisoxazole

4- (Bromomethyl) -3-chloro-5- (difluoromethyl) -1-ethyl-1H-pyrazole (7.50 g, 27.4 mmol) and 5, 5-dimethyl-4, 5-dihydroisoxazol-3-yl isothiourea hydrobromide (8.36 g, 32.9 mmol) were dissolved in acetonitrile (100 mL) . The mixture was stirred at room temperature for 10 min, then potassium carbonate (15.12 g, 109.6 mmol) was added into the mixture. The resulting mixture was stirred for 12 h, then stopped. Acetonitrile in the reaction mixture was removed, and the residue was washed with water (300 mL) , and then extracted with ethyl acetate (100 mL) three times. The combined organic layers were concentrated in vacuo to remove the solvent and give the crude product as yellow liquid (7.0 g) , yield: 79.0%.

MS-ESI: m/z 324.0 [M+H] ⁺.

Step 4: 3- ( ( (3-chloro-5- (difluoromethyl) -1-ethyl-1H-pyrazol-4-yl) methyl) sulfonyl) -5, 5-dimethyl-4, 5-dihydroisoxazole

3- ( ( (3-Chloro-5- (difluoromethyl) -1-ethyl-1H-pyrazol-4-yl) methyl) thio) -5, 5-dimethyl-4, 5 -dihydroisoxazole (7.00 g, 21.6 mmol) was dissolved in dichloromethane (100 mL) . The mixture was stirred at room temperature, then to the reaction mixture was added 85%m-CPBA (8.78 g, 43.2 mmol) . The mixture reacted for 5 h and then the reaction was stopped. The reaction mixture was washed with saturated aqueous sodium hydrogen sulfite (200 mL) and saturated aqueous sodium bicarbonate (200 mL) in turn, then extracted with dichloromethane (200 mL) . The organic layer was dried over anhydrous sodium sufate, and then concentrated in vacuo to remove the solvent. The residue was purified by column chromatography (eluent: petroleum ether/EtOAc (v/v) = 5/1) to give a white solid (5.40 g) , yield: 70.3%.

MS-ESI: m/z 356.1 [M+H] ⁺;

¹H NMR (400 MHz, CDCl ₃) δ 6.89 (t, J = 52.3 Hz, 1H) , 4.55 (s, 2H) , 4.31 (q, J = 7.2 Hz, 2H) , 3.02 (s, 2H) , 1.49 (s, 9H) .

Example 3: 3- ( ( (5-chloro-3- (difluoromethyl) -1-isopropyl-1H-pyrazol-4-yl) methyl) sulfonyl) -5, 5-dimethyl-4, 5-dihydroisoxazole

Step 1: synthesis of 5-chloro-3- (difluoromethyl) -1-isopropyl-1H-pyrazol-4-carbaldehyde and 3-chloro-5- (difluoromethyl) -1-isopropyl-1H-pyrazol-4-carbaldehyde

DMF (38.01 g, 0.52 mol) was stirred at 0 ℃, then phosphorus oxychloride (239.20 g, 1.56 mol) was added slowly into DMF. After addition, the mixture was warmed to room temperature and stirred, then to the mixture was added the previously obtained light yellow solid. The above mixture was heated to 110 ℃ and refluxed overnight. After the reaction was completed, the reaction mixture was washed with water (500 mL) , and extracted with ethyl acetate (150 mL) three times. The combined organic layers were concentrated in vacuo to give a reddish brown solid.

The above reddish brown solid and potassium carbonate (57.96 g, 0.42 mol) were dissolved in DMF (100 mL) , and the mixture was stirred at room temperature, then 2-iodopropane (42.50 g, 0.25 mol) was added into the above mixture. After addition, the mixture was heated to 80 ℃ and stirred for 24 h. After the reaction was completed, the mixture was washed with water (200 mL) , and extracted with ethyl acetate (100 mL) three times. The combined organic layers were concentrated in vacuo to remove the solvent, and the residue was purified by cholumn chromatography (eluent: Petroleum ether/EtOAc (v/v) = 10/1) to give colorless transparent liquids 5-chloro-3- (difluoromethyl) -1-isopropyl-1H-pyrazol -4-carbaldehyde (27.8 g, yield: 25.0%) and 3-chloro-5- (difluoromethyl) -1-isopropyl -1H-pyrazol-4-carbaldehyde (28.16 g, yield: 25.3%) .

5-chloro-3- (difluoromethyl) -1-isopropyl-1H-pyrazol-4-carbaldehyde: MS-ESI: m/z 223.1 [M+H] ⁺; ¹H NMR (400 MHz, CDCl ₃) δ 9.89 (s, 1H) , 7.44 (t, J = 52.5 Hz, 1H) , 4.86 (hept, J = 6.6 Hz, 1H) , 1.54 (d, J = 6.6 Hz, 6H) ; ¹⁹F NMR (376 MHz, CDCl ₃) δ -115.54 (s) , -115.68 (s) ;

3-chloro-5- (difluoromethyl) -1-isopropyl-1H-pyrazol-4-carbaldehyde: MS-ESI: m/z 223.1 [M+H] ⁺; ¹H NMR (400 MHz, CDCl ₃) δ 9.99 (s, 1H) , 6.88 (t, J = 53.6 Hz, 1H) , 4.79 (hept, J = 6.6 Hz, 1H) , 1.53 (d, J = 6.7 Hz, 6H) ; ¹⁹F NMR (376 MHz, CDCl ₃) δ -113.49 (s) , -113.64 (s) .

Step 2: synthesis of (5-chloro-3- (difluoromethyl) -1-isopropyl-1H-pyrazol-4-yl) methanol

5-Chloro-3- (difluoromethyl) -1-isopryl-1H-pyrazol-4-carbaldehyde (2.25 g, 10.1 mmol) was dissolved in anhydrous methanol (20 mL) and the mixture was stirred at 0 ℃, then sodium borohydride (0.45 g, 12.1 mmol) was added in portions to the mixture. After addition, the resulting mixture was warmed to room temperature and stirred for 4 h. After the reaction was completed, methanol was removed, and the residue was washed with water (50 mL) , then extracted with ethyl acetate (50 mL) three times. The combined organic layers were concentrated in vacuo to remove the solvent and give the crude product as colorless liquid (2.00 g, yield: 88.5%) .

MS-ESI: m/z 225.1 [M+H] ⁺.

Step 3: synthesis of 4- (bromomethyl) -5-chloro-3- (difluoromethyl) -1-isopropyl-1H-pyrazole

(5-Chloro-3- (difluoromethyl) -1-isopropyl-1H-pyrazol-4-yl) methanol (2.00 g, 8.9 mmol) and triphenylphosphine (4.67 g, 17.8 mmol) were dissolved in acetonitrile (20 mL) , and the mixture was stirred at 0 ℃, then a solution of carbon tetrabromide (5.90 g, 17.8 mmol) in acetonitrile (10 mL) was added in portions to the mixture while controlling the temperature below 5 ℃. After addition, the resulting mixture was warmed to room temperature and stirred for 3.5 h. After the reaction was completed, acetonitrile was removed, and the residue was washed with water (100 mL) , then extracted with ethyl acetate (50 mL) three times. The combined organic layers were concentrated in vacuo to remove the solvent, and the residue was purified by cholumn chromatography (eluent: Petroleum ether/EtOAc (v/v) = 10/1) to give the crude product as colorless liquid (2.20 g, yield: 86.3%) .

MS-ESI: m/z 288.9 [M+H] ⁺.

Step 4: 3- ( ( (5-chloro-3- (difluoromethyl) -1-isopropyl-1H-pyrazol-4-yl) methyl) thio) -5, 5-dimethyl-4, 5-dihydroisoxazole

4- (Bromomethyl) -5-chloro-3- (difluoromethyl) -1-isopropyl-1H-pyrazole (2.20 g, 7.6 mmol) and 5, 5-dimethyl-4, 5-dihydroisoxazol-3-yl isothiourea hydrobromide (2.33 g, 9.2 mmol) were dissolved in acetonitrile (30 mL) . The mixture was stirred at room temperature for 10 min, then potassium carbonate (4.20 g, 30.4 mmol) was added into the mixture. The resulting mixture was stirred for 12 h, then stopped. Acetonitrile was removed and the residue was washed with water (100 mL) . The mixture was extracted with ethyl acetate (30 mL) three times. The combined organic layers were concentrated in vacuo to remove the solvent and give the crude product as yellow liquid (2.48 g) , yield: 96.5%.

MS-ESI: m/z 338.1 [M+H] ⁺.

Step 5: 3- ( ( (5-chloro-3- (difluoromethyl) -1-isopropyl-1H-pyrazol-4-yl) methyl) sulfonyl) -5, 5 -dimethyl-4, 5-dihydroisoxazole

3- ( ( (5-Chloro-3- (difluoromethyl) -1-isopropyl-1H-pyrazol-4-yl) methyl) thio) -5, 5-dimethyl-4, 5-dihydroisoxazole (2.78 g, 8.2 mmol) was dissolved in dichloromethane (50 mL) . The mixture was stirred at room temperature, then to the reaction mixture was added 85%m-CPBA (3.34 g, 16.4 mmol) . The mixture reacted for 5 h and then the reaction was stopped. The reaction mixture was washed with saturated aqueous sodium hydrogen sulfite (100 mL) and saturated aqueous sodium bicarbonate (100 mL) in turn, then extracted with dichloromethane (50 mL) . The combined organic layers were dried over anhydrous sodium sufate, and then concentrated in vacuo to remove the solvent. The residue was purified by column chromatography (eluent: petroleum ether/EtOAc (v/v) = 5/1) to give a white solid (2.30 g) , yield: 84.8%.

MS-ESI: m/z 370.1 [M+H] ⁺;

¹H NMR (400 MHz, CDCl ₃) δ 6.79 (t, J = 54.7 Hz, 1H) , 4.73 (dt, J = 13.3, 6.6 Hz, 1H) , 4.62 (s, 2H) , 3.07 (s, 2H) , 1.50 (t, J = 3.3 Hz, 12H) .

Example 4: 3- ( ( (3-chloro-5- (difluoromethyl) -1-isopropyl-1H-pyrazol-4-yl) methyl) sulfonyl) -5, 5-dimethyl-4, 5-dihydroisoxazole

Step 1: synthesis of (3-chloro-5- (difluoromethyl) -1-isopropyl-1H-pyrazol-4-yl) methanol

3-Chloro-5- (difluoromethyl) -1-isopropyl-1H-pyrazol-4-carbaldehyde (1.60 g, 7.2 mmol) was dissolved in anhydrous methanol (20 mL) and the mixture was stirred at 0 ℃, then sodium borohydride (0.32 g, 8.6 mmol) was added in portions to the mixture. After addition, the resulting mixture was warmed to room temperature and stirred for 4 h. After the reaction was completed, methanol was removed, and the residue was washed with water (50 mL) , then extracted with ethyl acetate (50 mL) three times. The combined organic layers were concentrated in vacuo to remove the solvent and give the crude product as colorless liquid (1.55 g, yield: 95.8%) .

MS-ESI: m/z 225.1 [M+H] ⁺.

Step 2: synthesis of 4- (bromomethyl) -3-chloro-5- (difluoromethyl) -1-isopropyl-1H-pyrazole

(3-Chloro-5- (difluoromethyl) -1-isopropyl-1H-pyrazol-4-yl) methanol (1.55 g, 6.9 mmol) and triphenylphosphine (3.62 g, 13.8 mmol) were dissolved in acetonitrile (20 mL) , and the mixture was stirred at 0 ℃, then a solution of carbon tetrabromide (4.58 g, 13.8 mmol) in acetonitrile (10 mL) was added sl to the mixture while controlling the temperature below 5 ℃. After addition, the resulting mixture was warmed to room temperature and stirred for 3.5 h. After the reaction was completed, acetonitrile was removed, and the residue was washed with water (100 mL) , then extracted with ethyl acetate (50 mL) three times. The combined organic layers were concentrated in vacuo to remove the solvent, and the residue was purified by cholumn chromatography (eluent: Petroleum ether/EtOAc (v/v) = 10/1) to give the crude product as colorless liquid (1.46 g, yield: 74.0%) .

MS-ESI: m/z 288.9 [M+H] ⁺.

Step 3: 3- ( ( (3-chloro-5- (difluoromethyl) -1-isopropyl-1H-pyrazol-4-yl) methyl) thio) -5, 5-dimethyl-4, 5-dihydroisoxazole

4- (Bromomethyl) -3-chloro-5- (difluoromethyl) -1-isopropyl-1H-pyrazole (1.46 g, 5.1 mmol) and 5, 5-dimethyl-4, 5-dihydroisoxazol-3-yl isothiourea hydrobromide (1.55 g, 6.1 mmol) was dissolved in acetonitrile (30 mL) . The mixture was stirred at room temperature for 10 min, then potassium carbonate (2.82 g, 20.4 mmol) was added into the mixture. The resulting mixture was stirred for 12 h, then stopped. Acetonitrile was removed from the reaction mixture, and the residue was washed with water (100 mL) , extracted with ethyl acetate (30 mL) three times. The combined organic layers were concentrated in vacuo to remove the solvent and give the crude product as yellow liquid (1.65 g) , yield: 96.0%.

MS-ESI: m/z 338.1 [M+H] ⁺.

Step 4: 3- ( ( (3-chloro-5- (difluoromethyl) -1-isopropyl-1H-pyrazol-4-yl) methyl) sulfonyl) -5, 5-dimethyl-4, 5-dihydroisoxazole

3- ( ( (3-Chloro-5- (difluoromethyl) -1-isopropyl-1H-pyrazol-4-yl) methyl) thio) -5, 5-dimethyl-4, 5-dihydroisoxazole (1.64 g, 4.85 mmol) was dissolved in dichloromethane (30 mL) . The mixture was stirred at room temperature, then to the reaction mixture was added 85%m-CPBA (1.97 g, 9.7 mmol) . The mixture reacted for 5 h and then the reaction was stopped. The reaction mixture was washed with saturated aqueous sodium hydrogen sulfite (100 mL) and saturated aqueous sodium bicarbonate (100 mL) in turn, then extracted with dichloromethane (50 mL) . The combined organic layers were dried over anhydrous sodium sulfate, and then concentrated in vacuo to remove the solvent. The residue was purified by column chromatography (eluent: petroleum ether/EtOAc (v/v) = 5/1) to give a white solid (1.30 g) , yield: 72.6%.

MS-ESI: m/z 370.1 [M+H] ⁺;

¹H NMR (400 MHz, CDCl ₃) δ 6.87 (t, J = 52.2 Hz, 1H) , 4.77 (dt, J = 13.2, 6.5 Hz, 1H) , 4.54 (s, 2H) , 3.00 (s, 2H) , 1.52 (d, J = 6.6 Hz, 6H) , 1.48 (s, 6H) .

Example 5: 3- ( ( (5-chloro-1- (2, 2-difluoroethyl) -3- (difluoromethyl) -1H-pyrazol-4-yl) methyl) sulfonyl) -5, 5-dimethyl-4, 5-dihydroisoxazole

Step 1: synthesis of 5-chloro-1- (2, 2-difluoroethyl) -3- (difluoromethyl) -1H-pyrazol-4 -carbaldehyde and 3-chloro-1- (2, 2-difluoroethyl) -5- (difluoromethyl) -1H-pyrazol -4-carbaldehyde

Ethyl difluoroacetoacetate (83.06 g, 0.50 mol) was dissolved in anhydrous ethanol (200 mL) , and the obtain mixture was stirred at 0 ℃, then hydrazine hydrate (37.50 g, 0.75 mol) was added slowly into the mixture. After addition, the mixture was stirred at room temperature for 4 h, then heated to 80 ℃ and stirred overnight, then the reaction was stopped. Ethanol was removed, and the residue mixture was washed with water (300 mL) , and then extracted with ethyl acetate (150 mL) three times. The combined organic layers were concentrated in vacuo to remove the solvent and give a light yellow solid.

The above reddish brown solid and potassium carbonate (57.96 g, 0.42 mol) were dissolved in DMF (100 mL) , and the mixture was stirred at room temperature, then 1, 1-difluoro-2-iodoethane (48.00 g, 0.25 mol) was added into the above mixture. After addition, the mixture was heated to 80 ℃ and stirred for 24 h. After the reaction was completed, the mixture was washed with water (200 mL) , and extracted with ethyl acetate (100 mL) three times. The combined organic layers were concentrated in vacuo to remove the solvent, and the residue was purified by cholumn chromatography (eluent: Petroleum ether/EtOAc (v/v) = 10/1) to give colorless transparent liquids 5-chloro-1- (2, 2-difluoroethyl) -3- (difluoromethyl) -1H-pyrazol -4-carbaldehyde (20.03 g, yield: 16.4%) and 3-chloro-1- (2, 2-difluoroethyl) -5- (difluoromethyl) -1H-pyrazol-4-carbaldehyde (19.93 g, yield: 16.3%) .

5-chloro-1- (2, 2-difluoroethyl) -3- (difluoromethyl) -1H-pyrazol-4-carbaldehyde: MS-ESI: m/z 245.0 [M+H] ⁺; ¹H NMR (400 MHz, CDCl ₃) δ 9.92 (s, 1H) , 7.42 (t, J = 52.3 Hz, 1H) , 6.23 (tt, J = 55.0, 4.4 Hz, 1H) , 4.65 (td, J = 12.3, 4.4 Hz, 2H) ; ¹⁹F NMR (376 MHz, CDCl ₃) δ -114.83 (t, J = 3.6 Hz) , -114.96 (t, J = 3.5 Hz) , -122.48 (tt, J = 12.2, 3.6 Hz) , -122.63 (tt, J = 12.2, 3.6 Hz) ;

3-chloro-1- (2, 2-difluoroethyl) -5- (difluoromethyl) -1H-pyrazol-4-carbaldehyde: MS-ESI: m/z 245.0 [M+H] ⁺; ¹H NMR (400 MHz, CDCl ₃) δ 9.92 (s, 1H) , 7.42 (t, J = 52.3 Hz, 1H) , 6.22 (tt, J = 55.0, 4.4 Hz, 1H) , 4.65 (td, J = 12.3, 4.4 Hz, 2H) ; ¹⁹F NMR (376 MHz, CDCl ₃) δ -114.80 (t, J = 3.6 Hz) , -114.94 (t, J = 3.5 Hz) , -122.46 (tt, J = 12.2, 3.6 Hz) , -122.60 (tt, J = 12.2, 3.6 Hz) .

Step 2: synthesis of (5-chloro-1- (2, 2-difluoroethyl) -3- (difluoromethyl) -1H-pyrazol-4-yl) methanol

5-Chloro-1- (2, 2-difluoroethyl) -3- (difluoromethyl) -1H-pyrazol-4-carbaldehyde (0.61 g, 2.5 mmol) was dissolved in anhydrous methanol (20 mL) and the mixture was stirred at 0 ℃, then sodium borohydride (0.11 g, 3.0 mmol) was added in portions to the mixture. After addition, the resulting mixture was warmed to room temperature and stirred for 4 h. After the reaction was completed, methanol was removed, and the residue was washed with water (50 mL) , then extracted with ethyl acetate (50 mL) for three times. The combined organic layers were concentrated in vacuo to remove the solvent and give the crude product as colorless liquid (0.60 g, yield: 96.8%) .

MS-ESI: m/z 247.1 [M+H] ⁺.

Step 3: synthesis of 4- (bromomethyl) -5-chloro-1- (2, 2-difluoroethyl) -3- (difluoromethyl) -1H-pyrazol-4-yl) methanol

(5-Chloro-1- (2, 2-difluoroethyl) -3- (difluoromethyl) -1H-pyrazol-4-yl) methanol (0.60 g, 2.4 mmol) and triphenylphosphine (1.26 g, 4.8 mmol) were dissolved in acetonitrile (20 mL) , and the mixture was stirred at 0 ℃, then a solution of carbon tetrabromide (1.60 g, 4.8 mmol) in acetonitrile (10 mL) was added in portions to the mixture while controlling the temperature below 5 ℃. After addition, the resulting mixture was warmed to room temperature and stirred for 3.5 h. After the reaction was completed, acetonitrile was removed, and the residue was washed with water (100 mL) , then extracted with ethyl acetate (50 mL) three times. The combined organic layers were concentrated in vacuo to remove the solvent, and the residue was purified by cholumn chromatography (eluent: Petroleum ether/EtOAc (v/v) = 10/1) to give the crude product as colorless liquid (0.70 g, yield: 94.6%) .

MS-ESI: m/z 310.9 [M+H] ⁺.

Step 4: synthesis of 3- ( ( (5-chloro-1- (2, 2-difluoroethyl) -3- (difluoromethyl) -1H-pyrazol-4-yl) methyl) thio) -5, 5-dimethyl-4, 5-dihydroisoxazole

4- (Bromomethyl) -5-chloro-1- (2, 2-difluoroethyl) -3- (difluoromethyl) -1H-pyrazole (0.70 g, 2.3 mmol) and 5, 5-dimethyl-4, 5-dihydroisoxazol-3-yl isothiourea hydrobromide (0.70 g, 2.76 mmol) were dissolved in acetonitrile (30 mL) . The mixture was stirred at room temperature for 10 min, then potassium carbonate (1.27 g, 9.2 mmol) was added into the mixture. The resulting mixture was stirred for 12 h, then stopped. Acetonitrile was removed from the reaction mixture, and the residue was washed with water (100 mL) , extracted with ethyl acetate (30 mL) three times. The combined organic layers were concentrated in vacuo to remove the solvent and give the crude product as yellow liquid (0.79 g) , yield: 95.2%.

MS-ESI: m/z 360.1 [M+H] ⁺.

Step 5: synthesis of 3- ( ( (5-chloro-1- (2, 2-difluoroethyl) -3- (difluoromethyl) -1H-pyrazol -4-yl) methyl) sulfonyl) -5, 5-dimethyl-4, 5-dihydroisoxazole

3- ( ( (5-Chloro-1- (2, 2-difluoroethyl) -3- (difluoromethyl) -1H-pyrazol-4-yl) methyl) thio) -5, 5 -dimethyl-4, 5-dihydroisoxazole (0.79 g, 2.2 mmol) was dissolved in dichloromethane (30 mL) . The mixture was stirred at room temperature, then to the reaction mixture was added 85%m-CPBA (0.89 g, 4.4 mmol) . The mixture reacted for 5 h and then the reaction was stopped. The reaction mixture was washed with saturated aqueous sodium hydrogen sulfite (50 mL) and saturated aqueous sodium bicarbonate (50 mL) in turn, then extracted with dichloromethane (50 mL) . The combined organic layers were dried over anhydrous sodium sulfate, and then concentrated in vacuo to remove the solvent. The residue was purified by column chromatography (eluent: petroleum ether/EtOAc (v/v) = 5/1) to give a white solid (0.72 g) , yield: 83.7%.

MS-ESI: m/z 392.0 [M+H] ⁺;

¹H NMR (400 MHz, CDCl ₃) δ 6.83 (t, J = 54.6 Hz, 1H) , 6.35 –5.94 (m, 1H) , 4.62 (s, 2H) , 4.60 –4.50 (m, 2H) , 3.07 (s, 2H) , 1.50 (s, 6H) .

Example 6: 3- ( ( (3-chloro-1- (2, 2-difluoroethyl) -5- (difluoromethyl) -1H-pyrazol-4-yl) methyl) sulfonyl) -5, 5-dimethyl-4, 5-dihydroisoxazole

Step 1: synthesis of (3-chloro-1- (2, 2-difluoroethyl) -5- (difluoromethyl) -1H-pyrazol-4-yl) methanol

3-Chloro-1- (2, 2-difluoroethyl) -5- (difluoromethyl) -1H-pyrazol-4-carbaldehyde (0.60 g, 2.45 mmol) was dissolved in anhydrous methanol (20 mL) and the mixture was stirred at 0 ℃, then sodium borohydride (0.11 g, 2.94 mmol) was added in portions into the mixture. After addition, the resulting mixture was warmed to room temperature and stirred for 4 h. After the reaction was completed, methanol was removed, and the residue was washed with water (50 mL) , then extracted with ethyl acetate (50 mL) for three times. The combined organic layers were concentrated in vacuo to remove the solvent and give the crude product as colorless liquid (0.55 g, yield: 91.7%) .

MS-ESI: m/z 247.1 [M+H] ⁺.

Step 2: synthesis of 4- (bromomethyl) -3-chloro-1- (2, 2-difluoroethyl) -5- (difluoromethyl) -1H-pyrazol-4-yl) methanol

(3-Chloro-1- (2, 2-difluoroethyl) -5- (difluoromethyl) -1H-pyrazol-4-yl) methanol (0.55 g, 2.2 mmol) and triphenylphosphine (1.15 g, 4.4 mmol) were dissolved in acetonitrile (20 mL) , and the mixture was stirred at 0 ℃, then a solution of carbon tetrabromide (1.46 g, 4.4 mmol) in acetonitrile (10 mL) was added dropwise slowly into the mixture while controlling the temperature below 5 ℃. After addition, the resulting mixture was warmed to room temperature and stirred for 3.5 h. After the reaction was completed, acetonitrile was removed, and the residue was washed with water (100 mL) , then extracted with ethyl acetate (50 mL) three times. The combined organic layers were concentrated in vacuo to remove the solvent, and the residue was purified by cholumn chromatography (eluent: Petroleum ether/EtOAc (v/v) = 10/1) to give the crude product as colorless liquid (0.71 g, yield: 95.1%) .

MS-ESI: m/z 310.9 [M+H] ⁺.

Step 3: synthesis of 3- ( ( (3-chloro-1- (2, 2-difluoroethyl) -5- (difluoromethyl) -1H-pyrazol-4-yl) methyl) thio) -5, 5-dimethyl-4, 5-dihydroisoxazole

4- (Bromomethyl) -3-chloro-1- (2, 2-difluoroethyl) -5- (difluoromethyl) -1H-pyrazole (0.58 g, 1.87 mmol) and 5, 5-dimethyl-4, 5-dihydroisoxazol-3-yl isothiourea hydrobromide (0.56 g, 2.2 mmol) were dissolved in acetonitrile (30 mL) . The mixture was stirred at room temperature for 10 min, then potassium carbonate (1.03 g, 7.48 mmol) was added into the mixture. The resulting mixture was stirred for 12 h, then stopped. Acetonitrile was removed and the residue was washed with water (100 mL) . The mixture was extracted with ethyl acetate (30 mL) three times. The combined organic layers were concentrated in vacuo to remove the solvent and give the crude product as yellow liquid (0.77 g) , yield: 93.2%.

MS-ESI: m/z 360.1 [M+H] ⁺.

Step 4: synthesis of 3- ( ( (3-chloro-1- (2, 2-difluoroethyl) -5- (difluoromethyl) -1H-pyrazol-4-yl) methyl) sulfonyl) -5, 5-dimethyl-4, 5-dihydroisoxazole

3- ( ( (3-Chloro-1- (2, 2-difluoroethyl) -5- (difluoromethyl) -1H-pyrazol-4-yl) methyl) thio) -5, 5 -dimethyl-4, 5-dihydroisoxazole (0.77 g, 2.1 mmol) was dissolved in dichloromethane (30 mL) . The mixture was stirred at room temperature, then to the reaction mixture was added 85%m-CPBA (0.87 g, 4.2 mmol) . The mixture reacted for 5 h and then the reaction was stopped. The reaction mixture was washed with saturated aqueous sodium hydrogen sulfite (50 mL) and saturated aqueous sodium bicarbonate (50 mL) in turn, then extracted with dichloromethane (50 mL) . The combined organic layers were dried over anhydrous sodium sulfate, and then concentrated in vacuo to remove the solvent. The residue was purified by column chromatography (eluent: petroleum ether/EtOAc (v/v) = 5/1) to give a white solid (0.70 g) , yield: 85.4%.

MS-ESI: m/z 392.0 [M+H] ⁺;

¹H NMR (400 MHz, CDCl ₃) δ 6.96 (t, J = 52.4 Hz, 1H) , 6.18 (tt, J = 55.1, 4.3 Hz, 1H) , 4.63 (dd, J = 12.6, 4.3 Hz, 2H) , 4.58 (s, 2H) , 3.02 (s, 2H) , 1.49 (s, 6H) .

Example 7: synthesis of 3- ( (1- (3-chloro-5- (difluoromethyl) -1-isopropyl-1H-pyrazol-4-yl) ethyl) sulfonyl) -5, 5-dimethyl-4, 5-dihydroisoxazole

3- ( ( (3-Chloro-5- (difluoromethyl) -1-isoproyl-1H-pyrazol-4-yl) methyl) sulfonyl) -5, 5-dime thyl-4, 5-dihydroisoxazole (0.63 g, 1.70 mmol) and potassium carbonate (0.47 g, 3.4 mmol) were dissolved in DMF (10 mL) , and the mixture was stirred at room temperature. To the mixture was added dropwise iodomethane (0.29 g, 2.0 mmol) , and the resulting mixture was stirred at room temperature. After the reaction monitored by TLC was completed, the reaction mixture was washed with water (100 mL) and extracted with ethyl acetate (30 mL) three times. The combined oragnic layers were concentrated in vacuo to remove the solvent. The residue was purified by the column chromatography (eluent: Petroleum ether/EtOAc (v/v) = 5/1) to give yellow oil (0.23 g) , yeild: 35.3%.

MS-ESI: m/z 384.1 [M+H] ⁺;

¹H NMR (400 MHz, DMSO-d ₆) δ 7.33 (t, J = 50.6 Hz, 1H) , 5.03 (s, 1H) , 4.78 (dt, J = 12.9, 6.4 Hz, 1H) , 3.07 (d, J = 17.5 Hz, 2H) , 1.77 (d, J = 7.2 Hz, 3H) , 1.47 –1.32 (m, 12H) .

Example 8: 3- ( (1- (3-chloro-1- (2, 2-difluoroethyl) -5- (difluoromethyl) -1H-pyrazol-4-yl) ethyl) sulfonyl) -5, 5-dimethyl-4, 5-dihydroisoxazole

3- ( ( (3-Chloro-1- (2, 2-difluoroethyl) -5- (difluoromethyl) -1H-pyrazol-4-yl) methyl) sulfonyl ) -5, 5-dimethyl-4, 5-dihydroisoxazole (0.48 g, 1.2 mmol) and potassium carbonate (0.33 g, 2.4 mmol) were dissolved in DMF (10 mL) , and the mixture was stirred at room temperature. To the mixture was added dropwise iodomethane (0.21 g, 1.5 mmol) , and the resulting mixture was stirred at room temperature. After the reaction monitored by TLC was completed, the reaction mixture was washed with water (100 mL) and extracted with ethyl acetate (30 mL) three times. The combined oragnic layers were concentrated in vacuo to remove the solvent. The residue was purified by the column chromatography (eluent: Petroleum ether/EtOAc (v/v) = 5/1) to give a yellow solid (0.18 g) , yeild: 37.0%.

MS-ESI: m/z 406.1 [M+H] ⁺;

¹H NMR (400 MHz, CDCl ₃) δ 7.12 (d, J = 51.6 Hz, 1H) , 6.19 (tt, J = 55.3, 4.4 Hz, 1H) , 4.75 (q, J = 7.4 Hz, 1H) , 4.63 (td, J = 12.4, 4.4 Hz, 2H) , 2.84 (dd, J = 150.7, 17.4 Hz, 2H) , 1.85 (d, J = 7.4 Hz, 3H) , 1.42 (d, J = 31.5 Hz, 6H) .

Example 9: 3- ( ( (5-fluoro-3- (difluoromethyl) -1-ethyl-1H-pyrazol-4-yl) methyl) sulfonyl) -5, 5-dimethyl-4, 5-dihydroisoxazole

Step 1: synthesis of 3- (difluoromethyl) -1-ethyl-5-fluoro-1H-pyrazol-4-carbaldehyde

5-Chloro-3- (difluoromethyl) -1-ethyl-1H-pyrazol-4-carbaldehyde (0.74 g, 3.5 mmol) and anhydrous potassium fluoride (0.51 g, 8.8 mmol) were dissolved in dry DMF (50 mL) , then the mixture was heated to 150 ℃ and stirred for 12 h. After the reaction was completed, the mixture was washed with water (100 mL) , then extracted with ethyl acetate (100 mL) three times. The combined organic layers were concentrated in vacuo to remove the solvent and give the crude product. The crude product was purified by column chromatography (eluent: Petroleum ether/EtOAc (v/v) = 15/1) to give colorless liquid (0.30 g, yield: 44.8%) .

MS-ESI: m/z 193.1 [M+H] ⁺.

Step 2: synthesis of (5-fluoro-3- (difluoromethyl) -1-ethyl-1H-pyrazol-4-yl) methanol

5-Fluoro-3- (difluoromethyl) -1-ethyl-1H-pyrazol-4-carbaldehyde (0.30 g, 1.6 mmol) was dissolved in anhydrous methanol (20 mL) and the mixture was stirred at 0 ℃, then sodium borohydride (0.15 g, 3.9 mmol) was added in portions to the mixture. After addition, the resulting mixture was warmed to room temperature and stirred for 4 h. After the reaction was completed, methanol was removed, and the residue was washed with water (50 mL) , then extracted with ethyl acetate (50 mL) three times. The combined organic layers were concentrated in vacuo to remove the solvent and give light yellow liquid (0.24 g, yield: 77.4%) .

MS-ESI: m/z 195.1 [M+H] ⁺.

Step 3: synthesis of 4- (bromomethyl) -5-fluoro-3- (difluoromethyl) -1-ethyl-1H-pyrazole

(5-Fluoro-3- (difluoromethyl) -1-ethyl-1H-pyrazol-4-yl) methanol (0.24 g, 1.2mmol) and triphenylphosphine (0.65 g, 2.4 mmol) were dissolved in acetonitrile (20 mL) , and the mixture was stirred at 0 ℃, then a solution of carbon tetrabromide (0.82 g, 2.4 mmol) in acetonitrile (5 mL) was added dropwise slowly into the mixture while controlling the temperature below 5 ℃. After addition, the resulting mixture was warmed to room temperature and stirred for 3.5 h. After the reaction was completed, acetonitrile was removed, and the residue was washed with water (100 mL) , then extracted with ethyl acetate (50 mL) three times. The combined organic layers were concentrated in vacuo to remove the solvent, and the residue was purified by cholumn chromatography (eluent: Petroleum ether/EtOAc (v/v) = 15/1) to give light yellow liquid (0.20 g, yield: 64.9%) .

MS-ESI: m/z 257.0 [M+H] ⁺.

Step 4: 3- ( ( (5-fluoro-3- (difluoromethyl) -1-ethyl-1H-pyrazol-4-yl) methyl) thio) -5, 5 -dimethyl-4, 5-dihydroisoxazole

4- (Bromomethyl) -5-fluoro-3- (difluoromethyl) -1-ethyl-1H-pyrazole (0.20 g, 0.8 mmol) and 5, 5-dimethyl-4, 5-dihydroisoxazol-3-yl isothiourea hydrobromide (0.24 g, 0.9 mmol) were dissolved in acetonitrile (20 mL) . The mixture was stirred at room temperature for 10 min, then potassium carbonate (0.43 g, 3.1 mmol) was added into the mixture. The resulting mixture was stirred for 12 h, then stopped. The acetonitrile was removed and the residue was washed with water (100 mL) , extracted with ethyl acetate (50 mL) three times. The combined organic layers were concentrated in vacuo to remove the solvent and give yellow liquid (0.21 g) , yield: 87.5%.

MS-ESI: m/z 308.1 [M+H] ⁺.

Step 5: synthesis of 3- ( ( (5-fluoro-3- (difluoromethyl) -1-ethyl-1H-pyrazol-4-yl) methyl) sulfonyl) -5, 5-dimethyl-4, 5-dihydroisoxazole

3- ( ( (5-Fluoro-3- (difluoromethyl) -1-ethyl-1H-pyrazol-4-yl) methyl) thio) -5, 5-dimethyl-4, 5 -dihydroisoxazole (0.21 g, 0.7 mmol) was dissolved in dichloromethane (30 mL) . The mixture was stirred at room temperature, then to the reaction mixture was added 85%m-CPBA (0.28 g, 1.4 mmol) . The mixture reacted for 5 h and then the reaction was stopped. The reaction mixture was washed with saturated aqueous sodium hydrogen sulfite (50 mL) and saturated aqueous sodium bicarbonate (50 mL) , then extracted with dichloromethane (50 mL) . The combined organic layers were dried over anhydrous sodium sulfate, and then concentrated in vacuo to remove the solvent. The residue was purified by column chromatography (eluent: petroleum ether/EtOAc (v/v) = 5/1) to give a yellow solid (0.10 g) , yield: 43.5%.

MS-ESI: m/z 340.1 [M+H] ⁺;

¹H NMR (400 MHz, CDCl ₃) δ 6.70 (t, J = 54.6 Hz, 1H) , 4.54 (s, 2H) , 4.12 (q, J = 7.2 Hz, 2H) , 3.08 (s, 2H) , 1.58 –1.41 (m, 9H) .

Example 10: 3- ( ( (5-chloro-3- (difluoromethyl) -1- (prop-2-yn-1-yl) -1H-pyrazol-4-yl) methyl) sulfonyl) -5, 5-dimethyl-4, 5-dihydroisoxazole

Step 1: synthesis of 5-chloro-3- (difluoromethyl) -1- (prop-2-yn-1-yl) -1H-pyrazol-4-carbaldehyde

Ethyl difluoroacetoacetate (83.06 g, 0.5 mol) was dissolved in anhydrous ethanol (200 mL) , and the obtain mixture was stirred at 0 ℃, then hydrazine hydrate (37.50 g, 0.75 mol) was added slowly into the mixture. After addition, the mixture was stirred at room temperature for 4 h, then heated to 80 ℃ and stirred overnight, then the reaction was stopped. Ethanol was removed, and the residue was washed with water (300 mL) , and then extracted with ethyl acetate (150 mL) three times. The combined organic layers were concentrated in vacuo to remove the solvent and give a light yellow solid.

The above reddish brown solid (1 g, 1.85 mmol) and potassium carbonate (2.3 g, 16.6 mmol) were dissolved in DMF (15 mL) , and the mixture was stirred at room temperature, then 3-bromopropyne (1.1 g, 9.1 mmol) was added into the above mixture. After addition, the mixture was and stirred at room temperature for 24 h. After the reaction was completed, the mixture was washed with water (20 mL) , and extracted with ethyl acetate (40 mL) three times. The organic layer was concentrated in vacuo to remove the solvent, and the residue was purified by cholumn chromatography (eluent: Petroleum ether/EtOAc (v/v) = 10/1) to give colorless transparent liquid 5-chloro-3- (difluoromethyl) -1- (prop-2-yn-1-yl) -1H-pyrazol-4-carbaldehyde (0.83 g, yield: 46%) ; and colorless transparent liquid 3-chloro-5- (difluoromethyl) -1- (prop-2-yn-1-yl) -1H-pyrazol-4-carbaldehyde (0.65 g, yield: 36.0%) .

5-chloro-3- (difluoromethyl) -1- (prop-2-yn-1-yl) -1H-pyrazol-4-carbaldehyde: MS-ESI: m/z 219.0 [M+H] ⁺; ¹H NMR (400 MHz, CDCl ₃) δ 9.91 (s, 1H) , 7.40 (t, J = 53.5 Hz, 1H) , 5.09 (d, J = 2.4 Hz, 2H) , 2.52 (t, J = 2.5 Hz, 1H) ; ¹⁹F NMR (376 MHz, CDCl ₃) δ -115.59 (s) , -115.73 (s) ;

3-chloro-5- (difluoromethyl) -1- (prop-2-yn-1-yl) -1H-pyrazol-4-carbaldehyde: MS-ESI: m/z 219.0 [M+H] ⁺; ¹H NMR (400 MHz, CDCl ₃) δ 9.99 (s, 1H) , 6.90 (t, J = 53.5 Hz, 1H) , 5.01 (d, J = 2.4 Hz, 2H) , 2.51 (t, J = 2.5 Hz, 1H) ; ¹⁹F NMR (376 MHz, CDCl ₃) δ -113.99 (s) , -114.13 (s) .

Step 2: synthesis of (5-chloro-3- (difluoromethyl) -1- (prop-2-yn-1-yl) -1H-pyrazol-4-yl) methanol

5-Chloro-3- (difluoromethyl) -1- (prop-2-yn-1-yl) -1H-pyrazol-4-carbaldehyde (0.83 g, 3.80 mmol) was dissolved in anhydrous methanol (15 mL) and the mixture was stirred at 0 ℃, then sodium borohydride (0.29 g, 7.6 mmol) was added in portions into the mixture. After addition, the resulting mixture was warmed to room temperature and stirred for 4 h. After the reaction was completed, methanol was removed, and the residue was washed with water (20 mL) , then extracted with ethyl acetate (20 mL) three times. The combined organic layers were concentrated in vacuo to remove the solvent and give the crude product as light yellow liquid (0.68 g, yield: 82.0%) .

MS-ESI: m/z 221.0 [M+H] ⁺.

Step 3: synthesis of 4- (bromomethyl) -5-chloro-3- (difluoromethyl) -1- (prop-2-yn-1-yl) -1H-pyrazole

(5-Chloro-3- (difluoromethyl) -1- (prop-2-yn-1-yl) -1H-pyrazol-4-yl) methanol (0.68 g, 3.08 mmol) was dissolved in dicloromethane (20 mL) , and the mixture was stirred at 0 ℃, then a solution of phosphorus tribromide (1.0 g, 3.70 mmol) in dicloromethane (10 mL) was added slowly into the mixture while controlling the temperature below 5 ℃. After addition, the resulting mixture was warmed to room temperature and stirred for 3.5 h. After the reaction was completed, the reaction was quenched with with ice-water (30 mL) , then the resulting mixture was extracted with ethyl acetate (40 mL) three times. The combined organic layers were concentrated in vacuo to remove the solvent, and the residue was purified by cholumn chromatography (eluent: Petroleum ether/EtOAc (v/v) = 10/1) to give the crude product as colorless liquid (0.54 g, yield: 65.5%) .

MS-ESI: m/z 282.9 [M+H] ⁺.

Step 4: synthesis of 3- ( ( (5-chloro-3- (difluoromethyl) -1- (prop-2-yn-1-yl) -1H-pyrazol-4-yl) methyl) thio) -5, 5-dimethyl-4, 5-dihydroisoxazole

4- (Bromomethyl) -5-chloro-3- (difluoromethyl) -1- (prop-2-yn-1-yl) -1H-pyrazole (0.54 g, 1.90 mmol) and 5, 5-dimethyl-4, 5-dihydroisoxazol-3-yl isothiourea hydrobromide (0.58 g, 2.28 mmol) were dissolved in acetonitrile (20 mL) . The mixture was stirred at room temperature for 10 min, then potassium carbonate (1.05 g, 7.60 mmol) was added into the mixture. The resulting mixture was stirred for 12 h, then stopped. Acetonitrile was removed from the reaction mixture, and the residue was washed with water (20 mL) , extracted with ethyl acetate (50 mL) three times. The combined organic layers were concentrated in vacuo to remove the solvent and give yellow liquid (0.62 g) , yield: 97.0%.

MS-ESI: m/z 334.0 [M+H] ⁺.

Step 5: synthesis of 3- ( ( (5-chloro-3- (difluoromethyl) -1- (prop-2-yn-1-yl) -1H-pyrazol-4-yl) methyl) sulfonyl) -5, 5-dimethyl-4, 5-dihydroisoxazole

3- ( ( (5-Chloro-3- (difluoromethyl) -1- (prop-2-yn-1-yl) -1H-pyrazol-4-yl) methyl) thio) -5, 5 -dimethyl-4, 5-dihydroisoxazole (0.62 g, 1.85 mmol) was dissolved in dichloromethane (20 mL) . The mixture was stirred at room temperature, then to the reaction mixture was added 85%m-CPBA (0.94 g, 4.63 mmol) . The mixture reacted for 5 h and then the reaction was stopped. The reaction mixture was washed with saturated aqueous sodium hydrogen sulfite (20 mL) and saturated aqueous sodium bicarbonate (20 mL) in turn, then extracted with dichloromethane (30 mL) . The combined organic layers were dried over anhydrous sodium sulfate, and then concentrated in vacuo to remove the solvent. The residue was purified by column chromatography (eluent: petroleum ether/EtOAc (v/v) = 5/1) to give colorless liquid (0.43 g) , yield: 70.2%.

MS-ESI: m/z 366.4 [M+H] ⁺;

¹H NMR (400 MHz, CDCl ₃) δ 6.82 (t, J = 54.6 Hz, 1H) , 4.99 (d, J = 2.2 Hz, 2H) , 4.62 (s, 2H) , 3.07 (s, 2H) , 2.47 (d, J = 2.2 Hz, 1H) , 1.50 (s, 6H) .

Example 11: 3- ( ( (3-chloro-5- (difluoromethyl) -1- (prop-2-yn-1-yl) -1H-pyrazol-4-yl) methyl) sulfonyl) -5, 5-dimethyl-4, 5-dihydroisoxazole

Step 1: synthesis of (3-chloro-5- (difluoromethyl) -1- (prop-2-yn-1-yl) -1H-pyrazol-4-yl) methanol

3-Chloro-5- (difluoromethyl) -1- (prop-2-yn-1-yl) -1H-pyrazol-4-carbaldehyde (0.65 g, 2.95 mmol) was dissolved in anhydrous methanol (20 mL) and the mixture was stirred at 0 ℃, then sodium borohydride (0.23 g, 5.90 mmol) was added in portions to the mixture. After addition, the resulting mixture was warmed to room temperature and stirred for 4 h. After the reaction was completed, methanol was removed, and the residue was washed with water (30 mL) , then extracted with ethyl acetate (30 mL) three times. The combined organic layers were concentrated in vacuo to remove the solvent and give the crude product as a light yellow solid (0.70 g, yield: 98%) .

MS-ESI: m/z 221.0 [M+H] ⁺.

Step 2: synthesis of 4- (bromomethyl) -3-chloro-5- (difluoromethyl) -1- (prop-2-yn-1-yl) -1H-pyrazole

(3-Chloro-5- (difluoromethyl) -1- (prop-2-yn-1-yl) -1H-pyrazol-4-yl) methanol (0.64 g, 2.90 mmol) was dissolved in dicloromethane (30 mL) , and the mixture was stirred at 0 ℃, then a solution of phosphorus tribromide (0.95 g, 3.48 mmol) in dicloromethane (15 mL) was added slowly into the mixture while controlling the temperature below 5 ℃. After addition, the resulting mixture was warmed to room temperature and stirred for 3.5 h. After the reaction was completed, the reaction was quenched with ice-water (40 mL) , then the resulting mixture was extracted with ethyl acetate (40 mL) three times. The combined organic layers were concentrated in vacuo to remove the solvent, and the residue was purified by cholumn chromatography (eluent: Petroleum ether/EtOAc (v/v) = 10/1) to give a light yellow solid (0.50 g, yield: 65.0%) .

MS-ESI: m/z 283.9 [M+H] ⁺.

Step 3: synthesis of 3- ( ( (3-chloro-5- (difluoromethyl) -1- (prop-2-yn-1-yl) -1H-pyrazol-4-yl) methyl) thio) -5, 5-dimethyl-4, 5-dihydroisoxazole

4- (Bromomethyl) -3-chloro-5- (difluoromethyl) -1- (prop-2-yn-1-yl) -1H-pyrazole (0.50 g, 1.76 mmol) and 5, 5-dimethyl-4, 5-dihydroisoxazol-3-yl isothiourea hydrobromide (0.97 g, 7.04 mmol) were dissolved in acetonitrile (30 mL) . The mixture was stirred at room temperature for 10 min, then potassium carbonate (0.52 g, 2.04 mmol) was added into the mixture. The resulting mixture was stirred for 12 h, then stopped. Acetonitrile was removed, and the residue was washed with water (40 mL) , extracted with ethyl acetate (50 mL) three times. The combined organic layers were concentrated in vacuo to remove the solvent and give the crude product as a tawny solid (0.55 g) , yield: 93.0%.

MS-ESI: m/z 334.0 [M+H] ⁺.

Step 4: synthesis of 3- ( ( (3-chloro-5- (difluoromethyl) -1- (prop-2-yn-1-yl) -1H-pyrazol-4-yl) methyl) sulfonyl) -5, 5-dimethyl-4, 5-dihydroisoxazole

3- ( ( (3-Chloro-5- (difluoromethyl) -1- (prop-2-yn-1-yl) -1H-pyrazol-4-yl) methyl) thio) -5, 5 -dimethyl-4, 5-dihydroisoxazole (0.55 g, 1.65 mmol) was dissolved in dichloromethane (40 mL) . The mixture was stirred at room temperature, then to the reaction mixture was added 85%m-CPBA (75%, 0.88 g, 3.80 mmol) . The mixture reacted for 5 h and then the reaction was stopped. The reaction mixture was washed with saturated aqueous sodium hydrogen sulfite (20 mL) and saturated aqueous sodium bicarbonate (20 mL) , then extracted with dichloromethane (50 mL) . The combined organic layers were dried over anhydrous sodium sufate, and then concentrated in vacuo to remove the solvent. The residue was purified by column chromatography (eluent: petroleum ether/EtOAc (v/v) = 6/1) to give a white solid (0.30 g) , yield: 51.3%.

MS-ESI: m/z 366.0 [M+H] ⁺;

¹H NMR (400 MHz, CDCl ₃) δ 6.99 (t, J = 52.7 Hz, 1H) , 5.05 (d, J = 2.4 Hz, 2H) , 4.58 (s, 2H) , 3.03 (s, 2H) , 2.50 (t, J = 2.4 Hz, 1H) , 1.50 (s, 6H) .

Example 12: 3- ( ( (3-chloro-5- (difluoromethyl) -1-ethyl-1H-pyrazol-4-yl) difluoromethyl) sulfonyl) -5, 5-dimethyl-4, 5-dihydroisoxazole

3- ( ( (3-Chloro-5- (difluoromethyl) -1-ethyl-1H-pyrazol-4-yl) methyl) sulfonyl) -5, 5 -dimethyl-4, 5-dihydroisoxazole (1.42 g, 4 mmol) was dissolved in anhydrous THF (20 mL) in a three-neck flask, and the mixture was stirred at -78 ℃. To the above mixture was added dropwise a solution of sodium bis (trimethylsilyl) amide in tetrahydrofuran (1 M, 7.2 mL) . After addition, the mixture was stirred for further 10 min. To the mixture was added NFSI (2.52 g, 8 mmol) , and the resulting mixture was stirred for 20 min. After the reaction was completed, to the reaction mixture was added saturated aqueous ammonium chloride (20 mL) to quench the reaction. The resulting mixture was washed with water (100 mL) and extracted with ethyl acetate (100 mL) three times. The combined oragnic layers were dried over anhydrous magnesium sulfate, and the solvent was removed. The residue was purified by the column chromatography (eluent: Petroleum ether/EtOAc (v/v) = 10/1) to give a light yellow solid (0.80 g) , yeild: 51.3%.

MS-ESI: m/z 392.0 [M+H] ⁺;

¹H NMR (400 MHz, CDCl ₃) δ 6.86 (t, J = 51.6 Hz, 1H) , 4.39 (q, J = 7.2 Hz, 2H) , 3.17 (s, 2H) , 1.56 (s, 6H) , 1.53 (d, J = 7.2 Hz, 3H) .

Example 13: 3- ( ( (3-chloro-5- (difluoromethyl) -1-methyl-1H-pyrazol-4-yl) methyl) sulfonyl) -5-ethyl-5-methyl-4, 5-dihydroisoxazole

Step 1: synthesis of 5-ethyl-5-methyl-3- (methylsulfonyl) -4, 5-dihydroisoxazole

3-Chloro-5-ethyl-5-methyl-4, 5-dihydroisoxazole (10.00 g, 67.80 mmol) was weighed in a three-neck flask and dissolved in DMF (50 mL) , then the mixture was stirred at 0 ℃. To the mixture was added dropwise aqueous sodium thiomethoxide (20%, 28.50 g, 81.30 mmol) . After addition, the mixture was stirred at room temperature for 12 h. After the reaction was completed, to the reaction mixture was added water (100 mL) , and the resulting mixture was stirred. The mixture was extracted with ethyl acetate (50 mL) three times, and the combined organic layers were dried over anhydrous sodium sulfate, filtered. The filtrate was dried by rotary evaporation to give a yellow liquid: 5-ethyl-5-methyl-3- (methylthio) -4, 5-dihydroisoxazole (10.00 g, yield: 92.7%) .

MS-ESI: m/z 160.3 [M+H] ⁺.

5-Ethyl-5-methyl-3- (methylthio) -4, 5-dihydroisoxazole (10.00 g, 62.80 mmol) was dissolved in dichloromethane (100 mL) . The mixture was stirred at room temperature, then to the reaction mixture was added 85%m-CPBA (25.50 g, 125.60 mmol) . The mixture reacted for 5 h and then the reaction was stopped. The reaction mixture was filtered, and the filtrate was washed with saturated aqueous sodium hydrogen sulfite (100 mL) and saturated aqueous sodium bicarbonate (100 mL) , then extracted with dichloromethane (100 mL) . The combined organic layers were dried over anhydrous sodium sufate, and then concentrated in vacuo to remove the solvent. The residue was purified by column chromatography (eluent: petroleum ether/EtOAc (v/v) = 5/1) to give a yellow solid (8.00 g) , yield: 66.6%.

MS-ESI: m/z 192.3 [M+H] ⁺.

Step 2: synthesis of 5-chloro-3- (difluoromethyl) -1-methyl-1H-pyrazol-4-carbaldehyde and 3-chloro-5- (difluoromethyl) -1-methyl-1H-pyrazol-4-carbaldehyde

Ethyl difluoroacetoacetate (5.00 g, 30.1 mmol) was dissolved in anhydrous ethanol (100 mL) , and the obtained mixture was stirred at 0 ℃, then hydrazine hydrate (1.45 g, 45.2 mmol) was added slowly into the mixture. After addition, the mixture was stirred at room temperature for 4 h, then heated to 80 ℃ and stirred overnight, then the reaction was stopped. Ethanol was removed, and the residue was washed with water (50 mL) , and then extracted with ethyl acetate (50 mL) three times. The combined organic layers were concentrated in vacuo to remove the solvent and give the product as a light yellow solid.

DMF (2.20 g, 30.1 mmol) was stirred at 0 ℃, then phosphorus oxychloride (13.8 g, 90.3 mmol) was added slowly into DMF. After addition, the mixture was warmed to room temperature and stirred, then to the mixture was added the previously obtained light yellow solid. The above mixture was heated to 110 ℃ and refluxed overnight. After the reaction was completed, the reaction mixture was washed with water (50 mL) , and extracted with ethyl acetate (50 mL) three times. The combined organic layers were concentrated in vacuo to remove the solvent and give the product as a reddish brown solid.

The above reddish brown solid and potassium carbonate (4.16 g, 30.1 mmol) were dissolved in DMF (50 mL) , and the mixture was stirred at room temperature, then iodomethane (2.14 g, 15.1 mmol) was added into the above mixture. After addition, the mixture was heated to 80 ℃ and stirred for 12 h. After the reaction was completed, the mixture was washed with water (50 mL) , and extracted with ethyl acetate (50 mL) three times. The combined organic layers were concentrated in vacuo to remove the solvent, and the residue was purified by cholumn chromatography (eluent: Petroleum ether/EtOAc (v/v) = 10/1) to give colorless transparent liquids 5-chloro-3- (difluoromethyl) -1-methyl-1H-pyrazol-4-carbaldehyde (1.00 g, yield: 17.1%) and 3-chloro-5- (difluoromethyl) -1-methyl-1H-pyrazol-4-carbaldehyde (0.96 g, yield: 16.4%) .

5-chloro-3- (difluoromethyl) -1-methyl-1H-pyrazol-4-carbaldehyde: MS-ESI: m/z 195.6 [M+H] ⁺; ¹H NMR (400 MHz, CDCl ₃) δ 9.96 (s, 1H) , 6.90 (t, J = 53.6 Hz, 1H) , 3.93 (s, 3H) ; ¹⁹F NMR (376 MHz, CDCl ₃) δ -114.16 (s) , -114.30 (s) ;

3-chloro-5- (difluoromethyl) -1-methyl-1H-pyrazol-4-carbaldehyde: MS-ESI: m/z 195.6 [M+H] ⁺; ¹H NMR (400 MHz, CDCl ₃) δ 9.89 (s, 1H) , 7.38 (t, J = 52.4 Hz, 1H) , 4.06 (s, 3H) ; ¹⁹F NMR (376 MHz, CDCl ₃) δ -116.74 (s) , -116.88 (s) .

Step 3: synthesis of (3-chloro-5- (difluoromethyl) -1-methyl-1H-pyrazol-4-yl) methanol

3-Chloro-5- (difluoromethyl) -1-methyl-1H-pyrazol-4-carbaldehyde (1.00 g, 5.14 mmol) was dissolved in anhydrous methanol (20 mL) and the mixture was stirred at 0 ℃ , then sodium borohydride (389 mg, 10.3 mmol) was added in portions into the mixture. After addition, the resulting mixture was warmed to room temperature and stirred for 4 h. After the reaction was completed, methanol was removed, and the residue was washed with water (20 mL) , then extracted with ethyl acetate (20 mL) three times. The combined organic layers were concentrated in vacuo to remove the solvent and give the crude product as colorless oil (1.00 g, yield: 99.0%) .

MS-ESI: m/z 197.6 [M+H] ⁺.

Step 4: synthesis of 4- (bromomethyl) -3-chloro-5- (difluoromethyl) -1-methyl-1H-pyrazole

(3-Chloro-5- (difluoromethyl) -1-methyl-1H-pyrazol-4-yl) methanol (1.00 g, 5.09 mmol) was dissolved in DCM (20 mL) and the mixture was stirred at 0 ℃ , then phosphorus tribromide (1.38 g, 5.09 mmol) was added dropwise into the mixture. After addition, the resulting mixture was warmed to room temperature and stirred for 3.5 h. After the reaction was completed, the mixture was washed with water (20 mL) , then extracted with dichloromethane (20 mL) two times. The combined organic layers were concentrated in vacuo to remove the solvent and give the crude product as yellow liquid (1.00 g, yield: 75.8%) .

MS-ESI: m/z 260.5 [M+H] ⁺.

Step 5: synthesis of 3- ( ( (3-chloro-5- (difluoromethyl) -1-methyl-1H-pyrazol-4-yl) methyl) thio) -5-ethyl-5-methyl-4, 5-dihydroisoxazole

4- (Bromomethyl) -3-chloro-5- (difluoromethyl) -1-methyl-1H-pyrazole (0.50 g, 1.93 mmol) was dissolved in methanol (30 mL) . The mixture was stirred at room temperature, then thiourea (147 mg, 1.93 mmol) was added into the mixture, and the resulting mixture was stirred for 2 hours. To the above mixture were added potassium carbonate (533 mg, 3.85 mmol) and 5-ethyl-5-methyl-3- (methylsulfonyl) -4, 5-dihydroisoxazole (368 mg, 1.93 mmol) . The resulting mixture was heated to 75 ℃ and stirred for 12 hours, then stopped. Methanol was removed from the reaction mixture, and then the residue was washed with water (30 mL) , extracted with ethyl acetate (20 mL) three times. The combined organic layers were concentrated in vacuo to remove the solvent and the residue was purified by cholumn chromatography (eluent: Petroleum ether/EtOAc (v/v) = 10/1) to give yellow liquid (0.40 g, yield: 64.1%) .

MS-ESI: m/z 324.8 [M+H] ⁺.

Step 6: synthesis of 3- ( ( (3-chloro-5- (difluoromethyl) -1-methyl-1H-pyrazol-4-yl) methyl) sulfonyl) -5-ethyl-5-methyl-4, 5-dihydroisoxazole

3- ( ( (3-Chloro-5- (difluoromethyl) -1-methyl-1H-pyrazol-4-yl) methyl) thio) -5-ethyl-5-methyl-4, 5-dihydroisoxazole (0.40 g, 1.24 mmol) was dissolved in dichloromethane (10 mL) . The mixture was stirred at room temperature, then to the reaction mixture was added 85%m-CPBA (503 mg, 2.48 mmol) . The mixture reacted for 12 h and then the reaction was stopped. The reaction mixture was washed with saturated aqueous sodium hydrogen sulfite (20 mL) and saturated aqueous sodium bicarbonate (20 mL) in turn, then extracted with dichloromethane (20 mL) two times. The combined organic layers were dried over anhydrous sodium sufate, and then concentrated in vacuo to remove the solvent. The residue was purified by column chromatography (eluent: petroleum ether/EtOAc (v/v) = 5/1) to give a white solid (0.30 g) , yield: 68.3%.

MS-ESI: m/z 356.8 [M+H] ⁺;

¹H NMR (400 MHz, CDCl ₃) δ 6.90 (t, J = 52.3 Hz, 1H) , 4.55 (s, 2H) , 4.01 (s, 3H) , 3.01 (dd, J = 63.4, 17.3 Hz, 2H) , 1.76 (q, J = 7.4 Hz, 2H) , 1.45 (s, 3H) , 0.95 (t, J = 7.4 Hz, 3H) .

Example 14: 3- ( ( (5-chloro-3- (difluoromethyl) -1-methyl-1H-pyrazol-4-yl) methyl) sulfonyl) -5-ethyl-5-methyl-4, 5-dihydroisoxazole

Step 1: synthesis of (5-chloro-3- (difluoromethyl) -1-methyl-1H-pyrazol-4-yl) methanol

5-Chloro-3- (difluoromethyl) -1-methyl-1H-pyrazol-4-carbaldehyde (1.00 g, 5.14 mmol) was dissolved in anhydrous methanol (20 mL) and the mixture was stirred at 0 ℃, then sodium borohydride (389 mg, 10.3 mmol) was added in portions into the mixture. After addition, the resulting mixture was warmed to room temperature and stirred for 4 h. After the reaction was completed, methanol was removed, and the residue was washed with water (20 mL) , extracted with ethyl acetate (20 mL) three times. The combined organic layers were concentrated in vacuo to remove the solvent and give the crude product as colorless liquid (1.00 g, yield: 99.0%) .

MS-ESI: m/z 197.6 [M+H] ⁺.

Step 2: synthesis of 4- (bromomethyl) -5-chloro-3- (difluoromethyl) -1-methyl-1H-pyrazole

(5-Chloro-3- (difluoromethyl) -1-methyl-1H-pyrazol-4-yl) methanol (1.00 g, 5.09 mmol) was dissolved in DCM (20 mL) and the mixture was stirred at 0 ℃ , then phosphorus tribromide (1.38 g, 5.09 mmol) was added dropwise into the mixture. After addition, the resulting mixture was warmed to room temperature and stirred for 3.5 h. After the reaction was completed, the mixture was washed with water (20 mL) , extracted with dichloromethane (20 mL) two times. The combined organic layers were concentrated in vacuo to remove the solvent and give the crude product as yellow liquid (1.00 g, yield: 75.8%) .

MS-ESI: m/z 260.5 [M+H] ⁺.

Step 3: synthesis of 3- ( ( (5-chloro-3- (difluoromethyl) -1-methyl-1H-pyrazol-4-yl) methyl) thio) -5-ethyl-5-methyl-4, 5-dihydroisoxazole

4- (Bromomethyl) -5-chloro-3- (difluoromethyl) -1-methyl-1H-pyrazole (0.50 g, 1.93 mmol) was dissolved in methanol (30 mL) . The mixture was stirred at room temperature, then thiourea (147 mg, 1.93 mmol) was added into the mixture, and the resulting mixture was stirred for 2 hours. To the above mixture were added potassium carbonate (533 mg, 3.85 mmol) and 5-ethyl-5-methyl-3- (methylsulfonyl) -4, 5-dihydroisoxazole (368 mg, 1.93 mmol) . The resulting mixture was heated to 75 ℃ and stirred for 12 hours, then stopped. Methanol was removed from the reaction mixture, and then the residue was washed with water (30 mL) , extracted with ethyl acetate (20 mL) three times. The combined organic layers were concentrated in vacuo to remove the solvent and the residue was purified by cholumn chromatography (eluent: Petroleum ether/EtOAc (v/v) = 10/1) to give yellow liquid (0.40 g, yield: 64.1%) .

MS-ESI: m/z 324.8 [M+H] ⁺.

Step 4: synthesis of 3- ( ( (5-chloro-3- (difluoromethyl) -1-methyl-1H-pyrazol-4-yl) methyl) sulfonyl) -5-ethyl-5-methyl-4, 5-dihydroisoxazole

3- ( ( (5-Chloro-3- (difluoromethyl) -1-methyl-1H-pyrazol-4-yl) methyl) thio) -5-ethyl-5-methyl-4, 5-dihydroisoxazole (0.40 g, 1.24 mmol) was dissolved in dichloromethane (10 mL) . The mixture was stirred at room temperature, then to the reaction mixture was added 85%m-CPBA (503 mg, 2.48 mmol) . The mixture reacted for 12 h and then the reaction was stopped. The reaction mixture was washed with saturated aqueous sodium hydrogen sulfite (20 mL) and saturated aqueous sodium bicarbonate (20 mL) in turn, then extracted with dichloromethane (20 mL) two times. The combined organic layers were dried over anhydrous sodium sufate, and then concentrated in vacuo to remove the solvent. The residue was purified by column chromatography (eluent: petroleum ether/EtOAc (v/v) = 5/1) to give white solid (0.32 g) , yield: 72.8%.

MS-ESI: m/z 356.8 [M+H] ⁺;

Example 15: 3- ( ( (5-chloro-3- (difluoromethyl) -1-ethyl-1H-pyrazol-4-yl) fluoromethyl) sulfonyl) -5, 5-dimethyl-4, 5-dihydroisoxazole

Example 16: 3- ( ( (5-chloro-3- (difluoromethyl) -1-ethyl-1H-pyrazol-4-yl) difluoromethyl) sulfonyl) -5, 5-dimethyl-4, 5-dihydroisoxazole

The prepration methods of compounds of example 15 and example 16 were as follows:

3- ( ( (5-Chloro-3- (difluoromethyl) -1-ethyl-1H-pyrazol-4-yl) methyl) sulfonyl) -5, 5-dimethyl-4, 5-dihydroisoxazole (1.07 g, 3 mmol) was dissolved in anhydrous THF (20 mL) , and the mixture was stirred at -78 ℃. To the mixture was added dropwise a solution of sodium bis(trimethylsilyl) amide in THF (1 M, 5.4 mL) . After addition, the mixture was stirred for 10 min, then NFSI (1.14 g, 3.6 mmol) was added, and the reaction was mornitored by TLC. After the reaction was completed, to the reaction mixture was added saturated aqueoues ammonium chloride (20 mL) to quench the reaction. The resulting mixture was washed with water (100 mL) , then extracted with ethyl acetate (50 mL) three times, dired over anhydrous sodium sulfate, and the solvent was removed to give yellow liquid product, which was further purified by column chromatography (eluent: petroleum ether/EtOAc (v/v) = 10/1) to give 3- ( ( (5-chloro-3- (difluoromethyl) -1-ethyl-1H-pyrazol-4-yl) fluoromethyl) sulfonyl) -5, 5-dimethyl -4, 5-dihydroisoxazole as a white solid (150 mg, 13.6%) and 3- ( ( (5-chloro-3- (difluoromethyl) -1-ethyl-1H-pyrazol-4-yl) difluoromethyl) sulfonyl) -5, 5-dimethyl-4, 5-dihydroisoxazole as a white solid (100 mg, 8.5%) .

3- ( ( (5-chloro-3- (difluoromethyl) -1-ethyl-1H-pyrazol-4-yl) fluoromethyl) sulfonyl) -5, 5-dimethyl-4, 5-dihydroisoxazole: MS-ESI: m/z 374.0 [M+H] ⁺;

¹H NMR (400 MHz, CDCl ₃) δ 6.83 (t, J = 53.8 Hz, 1H) , 6.53 (d, J = 44.6 Hz, 1H) , 4.28 (q, J = 7.3 Hz, 2H) , 3.18 (d, J = 2.7 Hz, 2H) , 1.54 (s, 6H) , 1.49 (t, J = 7.3 Hz, 3H) ;

3- ( ( (5-chloro-3- (difluoromethyl) -1-ethyl-1H-pyrazol-4-yl) difluoromethyl) sulfonyl) -5, 5-dimethyl-4, 5-dihydroisoxazole: MS-ESI: m/z 392.0 [M+H] ⁺;

¹H NMR (400 MHz, CDCl ₃) δ 6.75 (t, J = 53.4 Hz, 1H) , 4.32 –4.27 (m, 2H) , 3.18 (s, 2H) , 1.56 (s, 6H) , 1.51 (t, J = 7.3 Hz, 3H) .

Biological examples

Preparation of compound: A certain amount of the active compound was weighed on an analytical balance (0.0001 g) , dissolved in DMF containing 1wt%Tween-80 emulsifier to prepare a 1.0 wt%mother liquor, and then the mother liquid was diluted with distilled water for use.

Test method: potted plant method, the target of the test was piemarker, amaranthus retroflexus, eclipta prostrata, crabgrass, barnyard grass and green bristlegrass. A flower pot with an inner diameter of 7.5 cm was taken, and compound soil (garden soil: seedling substrate, 1: 2, v/v) was filled to 3/4 of the flower pot, then the above six weed targets (bud rate ≥85%) were sown directly with covering soil 0.2 cm. Water was added to keep the soil moist for 24 hours for use. Each compound placed in an automatic spray tower (model: 3WPSH-700E) was applied to the weed targets at doses of 150 g ai/ha, 75 g ai/ha and 37.5 g ai/ha, respectively. After the liquid on the soil surface was dried, the weed targets in the flower pot were transferred to a greenhouse for culture, and 25 days later, the activity of each compound against weed was investigated (%) ; wherein “0” denotes weed had no injury or was in normal growth process, “100” denotes weed had no emergence or at least part of the weed on the above groud was completely dead.

The test results were shown in Table A and Table B.

Table A The pre-emergence herbicidal activity of compound of the invention at a dose of 150 g a.i. /ha

The results in Table A show that the herbicidal activity of the compound of the present invention against piemarker, amaranthus retroflexus, eclipta prostrata, crabgrass, barnyard grass and/or green bristlegrass at a dose of 150 g ai/ha is superior to that of Pyroxasulfone.

Table B The pre-emergence herbicidal activity of compound of the invention at doses of 75 g a.i. /ha and 37.5 g a.i. /ha respectively

The results in Table B show that the compounds of the present invention have excellent control effects on grass weeds such as crab grass, barnyard grass and green bristlegrass at a lower dose, and aslo have good control effects on broadleaf weeds such as piemarker, amaranthus retroflexus and eclipta prostrate at the same time. The compounds of the present invention can also control broadleaf weeds while controlling grass weeds.

Crop safety test

Test method: potted plant method, the test targets were soybean, peanut, cotton, oilseed rape, sunflower, corn, wheat and rice. A flower pot with an inner diameter of 7.5 cm was taken, and compound soil (garden soil: seedling substrate, 1: 2, v/v) was filled to 3/4 of the flower pot, then the above eight weed targets (bud rate ≥85%) were sown directly with covering soil 0.2 cm. Water was added to keep the soil moist for 24 hours for use. Each compound placed in an automatic spray tower (model: 3WPSH-700E) was applied to the weed targets at a specified dose. After the liquid on the soil surface was dried, the weed targets in the flower pot were transferred to a greenhouse for culture, and 25 days later, the phytotoxicity of each compound to crops was investigated (%) ; wherein “0” denotes crop had no injury or was in normal growth process, “100” denotes crop had no emergence or at least part of the crop on the above groud was completely dead.

The test results were shown in Table C.

Table C Crop safety of the compounds of the invention

The results in Table C show that the compounds of the present invention are very safe for soybeans, peanuts and sunflowers at doses of 150 g a.i. /hm ², 300 g a.i. /hm ² and 600 g a.i. /hm ².

In addition, the compounds of the invention are very safe for cottons, oilseed rapes, corns, wheat and rice. For example, compounds of example 1, example 2, example 3 and example 4 of the invention have no injury to oilseed rapes at a dose of 150 g a.i. /hm ². Compounds of of example 1, example 2, example 3 and example 4 of the invention have injury of less than 20 to cottons at a dose of 150 g a.i. /hm ². Compounds of of example 2, example 3 and example 4 of the invention have injury of less than 20 to wheat at a dose of 150 g a.i. /hm ².

The compounds of the invention have good control effects on broadleaf weeds (such aspiemarker, amaranthus retroflexus, eclipta prostrata) and grass weeds (such as crab grass, barnyard grass and green bristlegrass) ; and control effects on weeds of the compounds of the invention are superior to that of commercially available herbicide Pyroxasulfone and the structurally similar isoxazoline compounds. The compound of the invention is safe for crops such as soybean, peanut, sunflower, oilseed rape, cotton and wheat, etc., and has excellent application prospects.

Claims

A compound having Formula (Ia) or a stereoisomer, an N-oxide or a salt thereof,

wherein,

each of R ¹ and R ² is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, alkyl, haloalkyl, cycloalkyl or cycloalkylalkyl; or, R ¹ and R ² together with the carbon atom to which they are attached, form a 3-to 12-membered ring;

each of R ³ and R ⁴ is independently hydrogen, bromine, iodine, amino, nitro, hydroxy, carboxy, alkyl, cycloalkyl or cycloalkylalkyl; or, R ³ and R ⁴ together with the carbon atom to which they are attached, form a 3-to 12-membered ring;

n is 0, 1 or 2;

each of R ⁵ and R ⁶ is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, alkyl, alkenyl or alkynyl; or, R ⁵ and R ⁶ together with the carbon atom to which they are attached, form a 3-to 12-membered ring;

X is fluorine, chlorine or bromine;

Y is alkyl, haloalkyl, alkoxyalkyl, alkylaminoalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, -C (=O) -alkyl, -S (=O) ₂-alkyl, -C (=O) -cycloalkyl, -S (=O) ₂-cycloalkyl, -C (=O) -heterocyclyl, -S (=O) ₂-heterocyclyl, -C (=O) -aryl, -S (=O) ₂-aryl, -C (=O) -heteroaryl or -S (=O) ₂-heteroaryl;

Wherein Y is optionally substituted with 1, 2, 3, 4, 5 or 6 substituents selected from Y ^a; and each Y ^a is independently fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkoxy, alkylamino, alkylthio, cycloalkyl, heterocyclyl, aryl or heteroaryl;

with the proviso that:

(1) when Y is methyl, X is chlorine, R ⁵ and R ⁶ are hydrogen, n is 0, 1 or 2, R ³ and R ⁴ are hydrogen, and R ¹ is methyl, R ² is not methyl or chloromethyl;

(2) when Y is methyl, X is chlorine, R ⁵ and R ⁶ are hydrogen, n is 0, 1 or 2, R ³ and R ⁴ are hydrogen, and R ² is methyl, R ¹ is not methyl or chloromethyl;

(3) when Y is unsubstituted phenyl, X is chlorine, R ⁵ and R ⁶ are hydrogen, n is 0, 1 or 2, R ³ and R ⁴ are hydrogen, and R ¹ is methyl, R ² is not methyl or chloromethyl;

(4) when Y is unsubstituted phenyl, X is chlorine, R ⁵ and R ⁶ are hydrogen, n is 0, 1 or 2, R ³ and R ⁴ are hydrogen, and R ² is methyl, R ¹ is not methyl or chloromethyl;

(5) when Y is ethyl or isopropyl, X is chlorine on the 5 position of pyrazole ring, R ⁵ and R ⁶ are hydrogen, n is 0 or 2, R ³ and R ⁴ are hydrogen, and R ¹ is methyl, R ² is not chloromethyl; or

(6) when Y is ethyl or isopropyl, X is chlorine on the 5 position of pyrazole ring, R ⁵ and R ⁶ are hydrogen, n is 0 or 2, R ³ and R ⁴ are hydrogen, and R ² is methyl, R ¹ is not chloromethyl.
The compound of claim 1 having Formula (II) or a stereoisomer, an N-oxide or a salt thereof,

wherein:

X is fluorine, chlorine or bromine;

each of R ¹ and R ² is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, alkyl, haloalkyl, cycloalkyl or cycloalkylalkyl; or, R ¹ and R ² together with the carbon atom to which they are attached, form a 3-to 12-membered ring;

each of R ³ and R ⁴ is independently hydrogen, bromine, iodine, amino, nitro, hydroxy, carboxy, alkyl, cycloalkyl or cycloalkylalkyl; or, R ³ and R ⁴ together with the carbon atom to which they are attached, form a 3-to 12-membered ring;

each of R ⁵ and R ⁶ is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, alkyl, alkenyl or alkynyl; or, R ⁵ and R ⁶ together with the carbon atom to which they are attached, form a 3-to 12-membered ring;

n is 0, 1 or 2;

each of R ⁸, R ⁹, R ¹⁰, R ¹¹ and R ¹² is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkoxy, alkylamino, alkylthio, cycloalkyl, heterocyclyl, aryl or heteroaryl;

or, R ⁸ and R ⁹ together with the carbon atom to which they are attached, form a 3 to 12-membered ring;

or, R ⁸ and R ⁹ together with the carbon atom to which they are attached, form -C (=O) -;

or, R ¹⁰, R ¹¹ and R ¹² together with the carbon atom to which they are attached, form -C≡CR ¹³or -CR ¹⁴=CR ¹⁵R ¹⁶; wherein each of R ¹³, R ¹⁴, R ¹⁵ and R ¹⁶ is independently hydrogen, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl or haloalkynyl;

or, R ¹⁰, R ¹¹ and R ¹² together with the carbon atom to which they are attached, form optionally substituted C _6-14 aryl, optionally substituted C ₁- ₉ heteroaryl, optionally substituted C _3-12 cycloalkyl or optionally substituted C _2-12 heterocyclyl;

or -CR ⁸R ⁹-CR ¹⁰R ¹¹R ¹² is optionally substituted C _10-14 aryl, optionally substituted C _1-9 heteroaryl, optionally substituted C _3-12 cycloalkyl, optionally substituted C _2-12 heterocyclyl, unsubstituted phenyl or substituted phenyl;

wherein the substituted or optionally substituted groups described above, the number of the substituents on the substituted or optionally substituted groups is 1, 2, 3, 4, 5 or 6; and the substituents may be the same or different; wherein the substituents are fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkoxy, alkylamino, alkylthio, cycloalkyl, heterocyclyl, aryl or heteroaryl;

with the proviso that:

(a) when -CR ⁸R ⁹-CR ¹⁰R ¹¹R ¹² is unsubstituted phenyl, X is chlorine, R ⁵ and R ⁶ are hydrogen, n is 0, 1 or 2, R ³ and R ⁴ are hydrogen, and R ¹ is methyl, R ² is not methyl or chloromethyl;

(b) when -CR ⁸R ⁹-CR ¹⁰R ¹¹R ¹² is unsubstituted phenyl, X is chlorine, R ⁵ and R ⁶ are hydrogen, n is 0, 1 or 2, R ³ and R ⁴ are hydrogen, and R ² is methyl, R ¹ is not methyl or chloromethyl;

(c) when -CR ⁸R ⁹-CR ¹⁰R ¹¹R ¹² is ethyl or isopropyl, X is chlorine on the 5 position of pyrazole ring, R ⁵ and R ⁶ are hydrogen, n is 0 or 2, R ³ and R ⁴ are hydrogen, and R ¹ is methyl, R ² is not chloromethyl; or

(d) when -CR ⁸R ⁹-CR ¹⁰R ¹¹R ¹² is ethyl or isopropyl, X is chlorine on the 5 position of pyrazole ring, R ⁵ and R ⁶ are hydrogen, n is 0 or 2, R ³ and R ⁴ are hydrogen, and R ² is methyl, R ¹ is not chloromethyl.
The compound of claim 1 or 2 having Formula (IIa) or a stereoisomer, an N-oxide or a salt thereof, or having Formula (IIb) or a stereoisomer, an N-oxide or a salt thereof:
The compound of claim 1 or 2 having Formula (IIc) or a stereoisomer, an N-oxide or a salt thereof, or having Formula (IId) or a stereoisomer, an N-oxide or a salt thereof:
The compound of any one of claims 1 to 4, wherein

each of R ¹ and R ² is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, C _1-6 alkyl, halo C _1-6 alkyl, C _3-6 cycloalkyl or C _3-6 cycloalkyl-C _1-6 alkyl; or, R ¹ and R ² together with the carbon atom to which they are attached, form a 3-to 8-membered ring;

each of R ³ and R ⁴ is independently hydrogen, bromine, iodine, amino, nitro, hydroxy, carboxy, C _1-6 alkyl, C _3-6 cycloalkyl or C _3-6 cycloalkyl-C _1-6 alkyl; or, R ³ and R ⁴ together with the carbon atom to which they are attached, form a 3-to 8-membered ring;

each of R ⁵ and R ⁶ is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl; or, R ⁵ and R ⁶ together with the carbon atom to which they are attached, form a 3-to 8-membered ring.
The compound of any one of claims 2 to 5, wherein

each of R ⁸, R ⁹, R ¹⁰, R ¹¹ and R ¹² is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, C _1-6 alkyl, halo C _1-6 alkyl, C _2-6 alkenyl, halo C _2-6 alkenyl, C _2-6 alkynyl, halo C _2-6 alkynyl, C _1-6 alkoxy, C _1-6 alkylamino, C _1-6 alkylthio, C _3-6 cycloalkyl, C _2-8 heterocyclyl, C _6-10 aryl or C _1-9 heteroaryl;

or, R ⁸ and R ⁹ together with the carbon atom to which they are attached, form a 3 to 10-membered ring;

or, R ⁸ and R ⁹ together with the carbon atom to which they are attached, form -C (=O) -;

or, R ¹⁰, R ¹¹ and R ¹² together with the carbon atom to which they are attached, form -C≡CR ¹³or -CR ¹⁴=CR ¹⁵R ¹⁶; wherein each of R ¹³, R ¹⁴, R ¹⁵ and R ¹⁶ is independently hydrogen, C _1-6 alkyl, halo C _1-6 alkyl, C _2-6 alkenyl, halo C _2-6 alkenyl, C _2-6 alkynyl or halo C _2-6 alkynyl;

or, R ¹⁰, R ¹¹ and R ¹² together with the carbon atom to which they are attached, form optionally substituted C _6-14 aryl, optionally substituted C _1-9 heteroaryl, optionally substituted C _3-10 cycloalkyl or optionally substituted C _2-10 heterocyclyl;

or -CR ⁸R ⁹-CR ¹⁰R ¹¹R ¹² is optionally substituted C _10-14 aryl, optionally substituted C _1-9 heteroaryl, optionally substituted C _3-10 cycloalkyl, optionally substituted C _2-10 heterocyclyl, unsubstituted phenyl or substituted phenyl;

wherein the substituted or optionally substituted groups described above , the number of the substituents on the substituted or optionally substituted groups is 1, 2, 3, 4, 5 or 6; and the substituents may be the same or different; wherein the substituents are fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, C _1-6 alkyl, halo C _1-6 alkyl, C _2-6 alkenyl, halo C _2-6 alkenyl, C _2-6 alkynyl, halo C _2-6 alkynyl, C _1-6 alkoxy, C _1-6 alkylamino, C _1-6 alkylthio, C _3-8 cycloalkyl, C _2-10 heterocyclyl, C _6-14 aryl or C _1-9 heteroaryl.
The compound of claim 1 or 2 having Formula (II-1) or a stereoisomer, an N-oxide or a salt thereof,

wherein,

each of R ¹ and R ² is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, alkyl, haloalkyl, cycloalkyl or cycloalkylalkyl; or, R ¹ and R ² together with the carbon atom to which they are attached, form a 3-to 12-membered ring;

each of R ³ and R ⁴ is independently hydrogen, bromine, iodine, amino, nitro, hydroxy, carboxy, alkyl, cycloalkyl or cycloalkylalkyl; or, R ³ and R ⁴ together with the carbon atom to which they are attached, form a 3-to 12-membered ring;

n is 0, 1 or 2;

each of R ⁵ and R ⁶ is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, alkyl, alkenyl or alkynyl; or, R ⁵ and R ⁶ together with the carbon atom to which they are attached, form a 3-to 12-membered ring;

X is fluorine, chlorine or bromine;

each of R ⁸ and R ⁹ is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkoxy, alkylamino, alkylthio, cycloalkyl, heterocyclyl, aryl or heteroaryl;

R ¹³ is hydrogen, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl or haloalkynyl.
The compound of claim 7 having Formula (IIa-1) or a stereoisomer, an N-oxide or a salt thereof, or having Formula (IIa-2) or a stereoisomer, an N-oxide or a salt thereof:

wherein,

each of R ¹ and R ² is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, C _1-6 alkyl, halo C _1-6 alkyl, C _3-6 cycloalkyl or C _3-6 cycloalkyl-C _1-6 alkyl; or, R ¹ and R ² together with the carbon atom to which they are attached, form a 3-to 8-membered ring;

each of R ³ and R ⁴ is independently hydrogen, bromine, iodine, amino, nitro, hydroxy, carboxy, C _1-6 alkyl, C _3-6 cycloalkyl or C _3-6 cycloalkyl-C _1-6 alkyl; or, R ³ and R ⁴ together with the carbon atom to which they are attached, form a 3-to 8-membered ring;

each of R ⁵ and R ⁶ is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, C _1-6 alkyl, C _2-6 alkenyl, or C _2-6 alkynyl; or, R ⁵ and R ⁶ together with the carbon atom to which they are attached, form a 3-to 8-membered ring;

each of R ⁸ and R ⁹ is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, C _1-6 alkyl, halo C _1-6 alkyl, C _2-6 alkenyl, halo C _2-6 alkenyl, C _2-6 alkynyl, halo C _2-6 alkynyl, C _1-6 alkoxy, C _1-6 alkylamino, C _1-6 alkylthio, C _3-6 cycloalkyl, C _2-8 heterocyclyl, C _6-10 aryl or C _1-9 heteroaryl;

R ¹³ is hydrogen, C _1-6 alkyl, halo C _1-6 alkyl, C _2-6 alkenyl, halo C _2-6 alkenyl, C _2-6 alkynyl or halo C _2-6 alkynyl.
The compound of claim 1 having Formula (II-5) or a stereoisomer, an N-oxide or a salt thereof,

wherein,

each of R ¹ and R ² is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, alkyl, haloalkyl, cycloalkyl or cycloalkylalkyl; or, R ¹ and R ² together with the carbon atom to which they are attached, form a 3-to 12-membered ring;

each of R ³ and R ⁴ is independently hydrogen, bromine, iodine, amino, nitro, hydroxy, carboxy, alkyl, cycloalkyl or cycloalkylalkyl; or, R ³ and R ⁴ together with the carbon atom to which they are attached, form a 3-to 12-membered ring;

n is 0, 1 or 2;

each of R ⁵ and R ⁶ is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, alkyl, alkenyl or alkynyl; or, R ⁵ and R ⁶ together with the carbon atom to which they are attached, form a 3-to 12-membered ring;

X is fluorine, chlorine or bromine;

with the proviso that:

(i) when X is chlorine, R ⁵ and R ⁶ are hydrogen, n is 0, 1 or 2, and R ³ and R ⁴ are hydrogen, R ¹and R ² cannot be both methyl at the same time;

(ii) when X is chlorine on the 5 position of pyrazole ring, R ⁵ and R ⁶ are hydrogen, n is 0, 1 or 2, R ³ and R ⁴ are hydrogen, and R ² is methyl, R ¹ is not chloromethyl; or

(iii) when X is chlorine on the 5 position of parazole ring, R ⁵ and R ⁶ are hydrogen, n is 0, 1 or 2, R ³ and R ⁴ are hydrogen, and R ¹ is methyl, R ² is not chloromethyl.
The compound of claim 9 having Formula (IIa-17) or a stereoisomer, an N-oxide or a salt thereof, or having Formula (IIa-18) or a stereoisomer, an N-oxide or a salt thereof:

wherein,

each of R ¹ and R ² is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, C _1-6 alkyl, halo C _1-6 alkyl, C _3-6 cycloalkyl or C _3-6 cycloalkyl-C _1-6 alkyl; or, R ¹ and R ² together with the carbon atom to which they are attached, form a 3-to 8-membered ring;

each of R ³ and R ⁴ is independently hydrogen, bromine, iodine, amino, nitro, hydroxy, carboxy, C _1-6 alkyl, C _3-6 cycloalkyl or C _3-6 cycloalkyl-C _1-6 alkyl; or, R ³ and R ⁴ together with the carbon atom to which they are attached, form a 3-to 8-membered ring;

each of R ⁵ and R ⁶ is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl; or, R ⁵ and R ⁶ together with the carbon atom to which they are attached, form a 3-to 8-membered ring;

X is fluorine, chlorine or bromine;

with the proviso that:

(1) when X is chlorine, R ⁵ and R ⁶ are hydrogen, and R ³ and R ⁴ are hydrogen, R ¹and R ² can not be both methyl at the same time;

(2) when X is chlorine on the 5 position of pyrazole ring, R ⁵ and R ⁶ are hydrogen, R ³ and R ⁴ are hydrogen, and R ² is methyl, R ¹ is not chloromethyl; or

(3) when X is chlorine on the 5 position of pyrazole ring, R ⁵ and R ⁶ are hydrogen, R ³ and R ⁴ are hydrogen, and R ¹ is methyl, R ² is not chloromethyl.
The compound of any one of claims 1 to 10, wherein

each of R ¹ and R ² is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, C _1-4 alkyl, halo C _1-4 alkyl, C _3-6 cycloalkyl or C _3-6 cycloalkyl-C _1-3 alkyl; or, R ¹ and R ² together with the carbon atom to which they are attached, form a 3-to 6-membered ring;

each of R ³ and R ⁴ is independently hydrogen, bromine, iodine, amino, nitro, hydroxy, carboxy, C _1-3 alkyl, C _3-6 cycloalkyl or C _3-6cycloalkyl-C _1-3 alkyl; or, R ³ and R ⁴ together with the carbon atom to which they are attached, form a 3-to 6-membered ring;

each of R ⁵ and R ⁶ is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, C _1-4 alkyl, C _2-4 alkenyl or C _2-4 alkynyl; or, R ⁵ and R ⁶ together with the carbon atom to which they are attached, form a 3-to 6-membered ring.
The compound of claims 1 to 11, wherein

each of R ¹ and R ² is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, methyl, ethyl, n-propyl, isopropyl, -CH ₂F, -CH ₂Cl, -CH ₂Br or -CF ₃;

each of R ³ and R ⁴ is independently hydrogen or bromine;

each of R ⁵ and R ⁶ is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy or methyl.
The compound of any one of claims 1 to 3 or claim 6 having Formula (IIIa) or a stereoisomer, an N-oxide or a salt thereof,
The compound of any one of claims 1 to 3 or claim 6 having Formula (IIIb) or a stereoisomer, an N-oxide or a salt thereof:
The compound of any one of claims 1 to 2 or claim 4 or claim 6 having Formula (IIIc) or a stereoisomer, an N-oxide or a salt thereof:
The compound of any one of claims 1 to 2 or claim 4 or claim 6 having Formula (IIId) or a stereoisomer, an N-oxide or a salt thereof:
The compound of claim 6 or any one of claims 13 to 16, wherein

each of R ⁸, R ⁹, R ¹⁰, R ¹¹ and R ¹² is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, C _1-4 alkyl, halo C _1-4 alkyl, C _2-4 alkenyl, halo C _2-4 alkenyl, C _2-4 alkynyl, halo C _2-4 alkynyl, C _1-4 alkoxy, C _1-4 alkylamino, C _1-4 alkylthio, C _3-6 cycloalkyl, C _2-6 heterocyclyl, C _6-10 aryl or C _1-5 heteroaryl;

or, R ⁸ and R ⁹ together with the carbon atom to which they are attached, form a 3 to 8-membered ring;

or, R ⁸ and R ⁹ together with the carbon atom to which they are attached, form -C (=O) -;

or, R ¹⁰, R ¹¹ and R ¹² together with the carbon atom to which they are attached, form -C≡CR ¹³or -CR ¹⁴=CR ¹⁵R ¹⁶; wherein each of R ¹³, R ¹⁴, R ¹⁵ and R ¹⁶ is independently hydrogen, C _1-4 alkyl, halo C _1-4 alkyl, C _2-4 alkenyl, halo C _2-4 alkenyl, C _2-4 alkynyl or halo C _2-4 alkynyl;

or, R ¹⁰, R ¹¹ and R ¹² together with the carbon atom to which they are attached, form optionally substituted C _6-10 aryl, optionally substituted C _1-6 heteroaryl, optionally substituted C _3-8 cycloalkyl or optionally substituted C _2-6 heterocyclyl;

or -CR ⁸R ⁹-CR ¹⁰R ¹¹R ¹² is optionally substituted C _10-14 aryl, optionally substituted C _1-6 heteroaryl, optionally substituted C _3-8 cycloalkyl, optionally substituted C _2-6 heterocyclyl, unsubstituted phenyl or substituted phenyl;

wherein the substituted or optionally substituted groups described above, the number of the substituents on the substituted or optionally substituted groups is 1, 2, 3, 4, 5 or 6; and the substituents may be the same or different; wherein the substituents are hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, C _1-6 alkyl, halo C _1-4 alkyl, C _2-4 alkenyl, halo C _2-4 alkenyl, C _2-4 alkynyl, halo C _2-4 alkynyl, C _1-4 alkoxy, C _1-4 alkylamino, C _1-4 alkylthio, C _3-6 cycloalkyl, C _2-6 heterocyclyl, C _6-10 aryl or C _1-5 heteroaryl.
The compound of claim 6 or claims 13 to 17, wherein

each of R ⁸, R ⁹, R ¹⁰, R ¹¹ and R ¹² is independently hydrogen, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, hydroxy, carboxy, -CH ₃, -CH ₂CH ₃, -CH ₂CH ₂CH ₃, -CH (CH ₃) ₂, -CH ₂F, -CHF ₂, -CH ₂Cl, -CH ₂Br, -CF ₃, -CH ₂CF ₃, -CH ₂CH ₂F, -CH ₂CH ₂Cl, -CH ₂CH ₂Br, -CH ₂CHF ₂, -CH ₂CH ₂CF ₃, -CH ₂CH ₂CH ₂F, -CH ₂CH ₂CH ₂Cl, -CH ₂CH ₂CH ₂Br, -CHFCH ₂CH ₃, -CHClCH ₂CH ₃, -CH=CH ₂, -CH ₂CH=CH ₂, CH ₃-CH=CH-, -C≡CH, -C≡CCH ₃, -CH ₂-C≡CH, -OCH ₃, -OCH ₂CH ₃, -OCH ₂CH ₂CH ₃, -OCH (CH ₃) ₂, -NHCH ₃, -N (CH ₃) ₂, -SCH ₃, -SCH ₂CH ₃, -SCH ₂CH ₂CH ₃, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or phenyl;

or, R ⁸ and R ⁹ together with the carbon atom to which they are attached, form C _3-6 cycloalkyl;

or, R ⁸ and R ⁹ together with the carbon atom to which they are attached, form -C (=O) -;

or, R ¹⁰, R ¹¹ and R ¹² together with the carbon atom to which they are attached, form -C≡CH or -CH=CH ₂;

or, R ¹⁰, R ¹¹ and R ¹² together with the carbon atom to which they are attached, form C _3-6 cycloalkyl, optionally halogen-substituted phenyl or C _2-6 heterocyclyl containing one oxygen atom;

or -CR ⁸R ⁹-CR ¹⁰R ¹¹R ¹² is C _3-6 cycloalkyl or halogen-substituted phenyl.
The compound of claim 1 or 2 having Formula (IIIe) or a stereoisomer, an N-oxide or a salt thereof,

wherein,

each of R ⁵ and R ⁶ is independently hydrogen or fluorine;

X is fluorine or chlorine;

R ^m is hydrogen, C _1-3 alkyl or halo C _1-3 alkyl;

R ^v is hydrogen, C _1-3 alkyl or halo C _1-3 alkyl;

R ^w is C _1-3 alkyl or halo C _1-3 alkyl.
The compound of claim 19, wherein,

R ^m is hydrogen or methyl;

R ^v is hydrogen or methyl;

R ^w is methyl, isopropyl, difluoromethyl or tetrafluoroethyl.
The compound of claim 1 or 2 having Formula (IIIf) or a stereoisomer, an N-oxide or a salt thereof:

wherein,

each of R ⁵ and R ⁶ is independently hydrogen or fluorine;

X is fluorine or chlorine;

R ^m is hydrogen, C _1-3 alkyl or halo C _1-3 alkyl;

R ^v is hydrogen, C _1-3 alkyl or halo C _1-3 alkyl;

R ^w is C _1-3 alkyl or halo C _1-3 alkyl.
The compound of claim 21, wherein,

R ^m is hydrogen or methyl;

R ^v is hydrogen or methyl;

R ^w is methyl, isopropyl, difluoromethyl or tetrafluoroethyl.
A compound of claim 1 or 2 having Formula (IIIg) or a stereoisomer, an N-oxide or a salt thereof:

wherein X is fluroine or chlorine.
A compound of claim 1 having Formula (IIIh) or a stereoisomer, an N-oxide or a salt thereof:

wherein X is fluorine, chlorine or bromine.
The compound of any one of claims 1 to 24 having one of the following structures or a stereoisomer, an N-oxide or a salt thereof,
A herbicidal composition comprising the compound of any one of claims 1 to 25, or a stereoisomer, an N-oxide or a salt thereof as active component.
Use of the compound of any one of claims 1 to 25 or the herbicidal composition of claim 26 in agriculture for weed control.
A method for controlling the growth of weed in a growing field of useful plant comprising administering an effective amount of the compound of any one of claims 1 to 25 to the field before weed emergence.
The method of claim 28, wherein the weed comprises broadleaf weed and grass weed.
The method of claim 29, wherein the broadleaf weed comprises aspiemarker, amaranthus retroflexus and eclipta prostrata; and the grass weed comprises crab grass, barnyard grass and green bristlegrass.
The method of claim 28, wherein the useful plant comprises soybean, peanut and sunflower.