Aryl-substituted bicyclic compounds as herbicides
1. A compound of formula 1B
2. The compound of formula 1B according to claim 1, which is racemic.
3. A process for preparing a compound of formula 1C
Which comprises reducing a compound of formula 1B
The resulting amine is then cyclized in situ,
wherein the compound of formula 1B is prepared by reacting the compound of formula 1A with nitromethane
4. The process of claim 3, wherein the reduction of the compound of formula 1B is carried out in the presence of a nickel catalyst.
5. A process according to claim 3, wherein the reduction of the compound of formula 1B is carried out using sodium borohydride in the presence of nickel (II) chloride hexahydrate.
6. A compound which is 2-oxo-4- [4- (trifluoromethyl) phenyl ] -3-pyrrolidinecarboxylic acid methyl ester.
7. A process for preparing a compound of formula 3C
Which comprises reducing a compound of formula 3B
The resulting amine is then cyclized in situ.
8. The process of claim 7, wherein the reduction of the compound of formula 3B is carried out in the presence of a nickel catalyst.
9. The process of claim 7, wherein the reduction of the compound of formula 3B is performed with sodium borohydride in the presence of nickel (II) chloride hexahydrate.
10. The method of claim 7, wherein the compound of formula 3B is prepared by reacting 4-trifluoromethylbenzaldehyde with dimethyl malonate.
11. The method of claim 10, wherein the reaction is carried out in the presence of piperidine.
Background
Control of undesirable vegetation is extremely important in achieving high crop efficiency. Achieving selective control of weed growth, particularly in such useful crops as rice, soybean, sugarbeet, maize, potato, wheat, barley, tomato, and plantation crops, among others, is highly desirable. Uninhibited weed growth in such useful crops can cause significant reductions in yield and thereby result in increased consumer costs. Control of undesirable vegetation in non-crop areas is also important. For these purposes, many products are commercially available, but there is a continuing need for new compounds that are more effective, less costly, less toxic, environmentally safer, or have different sites of action.
Disclosure of Invention
The present invention is directed to compounds of formula 1 (including all stereoisomers), including N-oxides and salts thereof, agricultural compositions containing them, and their use as herbicides:
wherein
Q1Is a phenyl or benzyl ring or a naphthalene ring system, each ring or ring system optionally being selected up to 5 independently from R9Substituted with the substituent(s); or is a 5-to 6-membered fully unsaturated heterocyclic ring or is an 8-to 10-membered heteroaromatic bicyclic ring system, each ring or ring system containing ring members selected from carbon atoms and 1 to 4 heteroatoms independently selected from up to 2O, up to 2S and up to 4N atoms, wherein up to 3 carbon ring members are independently selected from C (═ O) and C (═ S), and the sulfur ring members are independently selected from S (═ O)u(＝NR8)vEach ring or ring system being optionally substituted with up to 5 substituents independently selected from R on carbon atom ring members9And said substituents on the ring members of the nitrogen atom are independently selected from R10；
Q2Is a benzene ring or a naphthalene ring system, each ring or ring system optionally being selected up to 5 independently from R11Substituted with the substituent(s); or a 5-to 6-membered fully unsaturated heterocyclic ring or an 8-to 10-membered heteroaromatic bicyclic ring system, each ring or ring system containing ring members selected from carbon atoms and 1 to 4 heteroatomsIndependently selected from up to 2O, up to 2S and up to 4N atoms, wherein up to 3 carbon ring members are independently selected from C (═ O) and C (═ S), and the sulfur ring members are independently selected from S (═ O)u(＝NR8)vEach ring or ring system being optionally substituted with up to 5 substituents independently selected from R on carbon atom ring members11And said substituents on the ring members of the nitrogen atom are independently selected from R12；
R1And R2Each independently is H, halogen, hydroxy or C1-C4An alkyl group;
y is O, S or NR15；
A is a saturated, partially unsaturated or fully unsaturated chain containing 2 to 4 atoms selected from up to 4 carbons, up to 1O, up to 1S and up to 2N atoms, wherein up to 2 carbon members are independently selected from C (═ O) and C (═ S) and the sulfur atom member is selected from S (═ O)u(＝NR8)v(ii) a Said chain being optionally substituted with up to 5 substituents independently selected from R on carbon3And on the nitrogen atom the substituents are independently selected from R4；
Each R3Independently halogen, cyano, hydroxy, -CO2H、C1-C4Alkyl radical, C1-C4Haloalkyl, C1-C4Alkoxy radical, C1-C4Alkylthio radical, C1-C4Haloalkoxy, C2-C4Alkoxyalkyl group, C2-C4Alkylcarbonyl group, C2-C4Alkoxycarbonyl group, C3-C6Cycloalkyl or C4-C6A cycloalkylalkyl group; or
Two R3Together with one or more of the carbon atoms to which they are bound form C3-C7A cycloalkyl ring;
each R4Independently of one another is cyano, C1-C4Alkyl radical, C1-C4Haloalkyl, C1-C4Alkoxy radical, C2-C4Alkylcarbonyl group, C2-C4Alkoxycarbonyl or C3-C6A cycloalkyl group;
j is-CR5R6-or-CR5R6-CR5aR6a-wherein the-CR5R6-the moiety is directly connected to N;
R5and R6Each independently of the others being H, halogen, hydroxy, C1-C4Alkyl or C1-C4An alkoxy group; or
R5And R6Together with the carbon atom to which they are bound form C3-C7A cycloalkyl ring;
R5aand R6aEach independently is H, halogen or C1-C4An alkyl group; or
R5aAnd R6aTogether with the carbon atom to which they are bound form C3-C7A cycloalkyl ring;
R7is H, hydroxy, amino, C1-C6Alkyl radical, C1-C6Haloalkyl, C2-C6Alkenyl radical, C3-C6Alkynyl, C2-C8Alkoxyalkyl group, C2-C8Haloalkoxyalkyl, C2-C8Alkylthio alkyl, C2-C8Alkylsulfinylalkyl radical, C2-C8Alkylsulfonylalkyl group, C2-C8Alkylcarbonyl group, C2-C8Halogenoalkylcarbonyl group, C4-C10Cycloalkyl carbonyl group, C2-C8Alkoxycarbonyl group, C2-C8Halogenoalkoxycarbonyl, C4-C10Cycloalkoxycarbonyl radical, C2-C8Alkylaminocarbonyl radical, C3-C10Dialkylaminocarbonyl group, C4-C10Cycloalkylaminocarbonyl group, C1-C6Alkoxy radical, C1-C6Alkylthio radical, C1-C6Haloalkylthio, C3-C8Cycloalkylthio radical, C1-C6Alkylsulfinyl radical, C1-C6Haloalkylsulfinyl radical, C3-C8Cycloalkyl sulfinyl radical, C1-C6Alkylsulfonyl radical, C1-C6Haloalkylsulfonyl group, C3-C8Cycloalkylsulfonyl radical, C1-C6Alkylaminosulfonyl radical, C2-C8Dialkylaminosulfonyl radical, C3-C10Trialkylsilyl or G1；
Each R8Independently of one another H, cyano, C2-C3Alkylcarbonyl or C2-C3A haloalkylcarbonyl group;
each R9Independently halogen, cyano, nitro, C1-C8Alkyl radical, C1-C4Cyanoalkyl, C1-C4Cyanoalkoxy group, C1-C8Haloalkyl, C1-C8Nitroalkyl, C2-C8Alkenyl radical, C2-C8Haloalkenyl, C2-C8Nitroalkenyl radical, C2-C8Alkynyl, C2-C8Halogenated alkynyl, C4-C10Cycloalkylalkyl radical, C4-C10Halocycloalkylalkyl radical, C5-C12Alkyl cycloalkyl alkyl, C5-C12Cycloalkylalkenyl radical, C5-C12Cycloalkyl alkynyl, C3-C8Cycloalkyl radical, C3-C8Halogenocycloalkyl, C4-C10Alkyl cycloalkyl radical, C6-C12Cycloalkyl, C3-C8Cycloalkenyl radical, C3-C8Halogenated cycloalkenyl radical, C2-C8Alkoxyalkyl group, C2-C8Haloalkoxyalkyl, C3-C8Haloalkoxyalkoxy group, C1-C4Hydroxyalkyl radical, C4-C10Cycloalkoxyalkyl radical, C3-C10Alkoxyalkoxyalkyl group, C2-C8Alkylthio alkyl, C2-C8Alkylsulfinylalkyl radical, C2-C8Alkyl sulfonic acidAcylalkyl, C2-C8Alkylaminoalkyl, C2-C8Haloalkyl aminoalkyl radical, C4-C10Cycloalkylaminoalkyl radical, C3-C10Dialkylaminoalkyl, -CHO, C2-C8Alkylcarbonyl group, C2-C8Halogenoalkylcarbonyl group, C4-C10Cycloalkyl-carbonyl, -C (═ O) OH, C2-C8Alkoxycarbonyl group, C2-C8Halogenoalkoxycarbonyl, C4-C10Cycloalkoxycarbonyl radical, C5-C12Cycloalkylalkoxycarbonyl, -C (═ O) NH2、C2-C8Alkylaminocarbonyl radical, C4-C10Cycloalkylaminocarbonyl group, C3-C10Dialkylaminocarbonyl group, C1-C8Alkoxy radical, C1-C8Haloalkoxy, C2-C8Alkoxyalkoxy radical, C2-C8Alkenyloxy radical, C2-C8Haloalkenyloxy, C2-C8Haloalkoxy, C3-C8Alkynyloxy, C3-C8Haloalkynyloxy, C3-C8Cycloalkoxy, C3-C8Halogenocycloalkoxy, C4-C10Cycloalkylalkoxy radical, C3-C10Alkylcarbonylalkoxy, C2-C8Alkylcarbonyloxy, C2-C8Halogenoalkylcarbonyloxy group, C4-C10Cycloalkyl carbonyloxy, C1-C8Alkylsulfonyloxy, C1-C8Haloalkylsulfonyloxy, C1-C8Alkylthio radical, C1-C8Haloalkylthio, C3-C8Cycloalkylthio radical, C1-C8Alkylsulfinyl radical, C1-C8Haloalkylsulfinyl radical, C1-C8Alkylsulfonyl radical, C1-C8Haloalkylsulfonyl group, C3-C8Cycloalkyl sulfonyl, carboxamido, C2-C8Alkylcarbonylamino, C2-C8HaloalkylcarbonylaminoBase, C2-C8Alkoxycarbonylamino group, C1-C6Alkylsulfonylamino group, C1-C6Haloalkylsulfonylamino, -SF5、-SCN、SO2NH2、C3-C12Trialkylsilyl group, C4-C12Trialkylsilylalkyl radical, C4-C12Trialkylsilylalkoxy or G2；
Each R11Independently halogen, cyano, nitro, C1-C8Alkyl radical, C1-C4Cyanoalkyl, C1-C4Cyanoalkoxy group, C1-C8Haloalkyl, C1-C8Nitroalkyl, C2-C8Alkenyl radical, C2-C8Haloalkenyl, C2-C8Nitroalkenyl radical, C2-C8Alkynyl, C2-C8Halogenated alkynyl, C4-C10Cycloalkylalkyl radical, C4-C10Halocycloalkylalkyl radical, C5-C12Alkyl cycloalkyl alkyl, C5-C12Cycloalkylalkenyl radical, C5-C12Cycloalkyl alkynyl, C3-C8Cycloalkyl radical, C3-C8Halogenocycloalkyl, C4-C10Alkyl cycloalkyl radical, C6-C12Cycloalkyl, C3-C8Cycloalkenyl radical, C3-C8Halogenated cycloalkenyl radical, C2-C8Alkoxyalkyl group, C2-C8Haloalkoxyalkyl, C3-C8Haloalkoxyalkoxy group, C1-C4Hydroxyalkyl radical, C4-C10Cycloalkoxyalkyl radical, C3-C10Alkoxyalkoxyalkyl group, C2-C8Alkylthio alkyl, C2-C8Alkylsulfinylalkyl radical, C2-C8Alkylsulfonylalkyl group, C2-C8Alkylaminoalkyl, C2-C8Haloalkyl aminoalkyl radical, C4-C10Cycloalkylaminoalkyl radical, C3-C10DialkylaminesArylalkyl, -CHO, C2-C8Alkylcarbonyl group, C2-C8Halogenoalkylcarbonyl group, C4-C10Cycloalkyl-carbonyl, -C (═ O) OH, C2-C8Alkoxycarbonyl group, C2-C8Halogenoalkoxycarbonyl, C4-C10Cycloalkoxycarbonyl radical, C5-C12Cycloalkylalkoxycarbonyl, -C (═ O) NH2、C2-C8Alkylaminocarbonyl radical, C4-C10Cycloalkylaminocarbonyl group, C3-C10Dialkylaminocarbonyl group, C1-C8Alkoxy radical, C1-C8Haloalkoxy, C2-C8Alkoxyalkoxy radical, C2-C8Alkenyloxy radical, C2-C8Haloalkenyloxy, C2-C8Haloalkoxy, C3-C8Alkynyloxy, C3-C8Haloalkynyloxy, C3-C8Cycloalkoxy, C3-C8Halogenocycloalkoxy, C4-C10Cycloalkylalkoxy radical, C3-C10Alkylcarbonylalkoxy, C2-C8Alkylcarbonyloxy, C2-C8Halogenoalkylcarbonyloxy group, C4-C10Cycloalkyl carbonyloxy, C1-C8Alkylsulfonyloxy, C1-C8Haloalkylsulfonyloxy, C1-C8Alkylthio radical, C1-C8Haloalkylthio, C3-C8Cycloalkylthio radical, C1-C8Alkylsulfinyl radical, C1-C8Haloalkylsulfinyl radical, C1-C8Alkylsulfonyl radical, C1-C8Haloalkylsulfonyl group, C3-C8Cycloalkyl sulfonyl, carboxamido, C2-C8Alkylcarbonylamino, C2-C8Haloalkylcarbonylamino, C2-C8Alkoxycarbonylamino group, C1-C6Alkylsulfonylamino group, C1-C6Haloalkylsulfonylamino, -SF5、-SCN、SO2NH2、C3-C12Trialkylsilyl group, C4-C12Trialkylsilylalkyl radical, C4-C12Trialkylsilylalkoxy or G3；
Each R10And R12Independently of one another is cyano, C1-C3Alkyl radical, C2-C3Alkenyl radical, C2-C3Alkynyl, C3-C6Cycloalkyl radical, C2-C3Alkoxyalkyl group, C1-C3Alkoxy radical, C2-C3Alkylcarbonyl group, C2-C3Alkoxycarbonyl group, C2-C3Alkylaminoalkyl or C3-C4A dialkylaminoalkyl group;
R15is H, cyano, C1-C4Alkyl radical, C1-C4Haloalkyl, - (C ═ O) CH3Or- (C ═ O) CF3；
Each G1Independently is phenyl, phenylmethyl (i.e. benzyl), pyridylmethyl, pyridyloxy, phenylcarbonyl (i.e. benzoyl), phenoxy, phenylethynyl, phenylsulfonyl, phenylcarbonyl (C)1-C4Alkyl groups); or is a 5-or 6-membered heteroaromatic ring, each optionally substituted with up to 5 substituents independently selected from R on the ring members13Substituted with the substituent(s);
each G2Independently is phenyl, phenylmethyl (i.e., benzyl), pyridylmethyl, phenylcarbonyl (i.e., benzoyl), phenylcarbonylalkyl, phenoxy, phenylethynyl, phenylsulfonyl, or pyridyloxy; or is a 5-or 6-membered heteroaromatic ring, each optionally substituted with up to 5 substituents independently selected from R on the ring members14Substituted with the substituent(s); or R is16ON＝CR17-、(R18)2C＝NO-、(R19)2NN＝CR17-、(R18)2C＝NNR20-、R21N＝CR17-、(R18)2C＝N-、R22ON＝CR17C(R23)2-or (R)18)2C＝NOC(R23)2-，Wherein the free key extending to the right indicates and Q1The connection point of (a);
each G3Independently is phenyl, phenylmethyl (i.e., benzyl), pyridylmethyl, phenylcarbonyl (i.e., benzoyl), phenylcarbonylalkyl, phenoxy, phenylethynyl, phenylsulfonyl, or pyridyloxy; or is a 5-or 6-membered heteroaromatic ring, each optionally substituted with up to 5 substituents independently selected from R on the ring members15Substituted with the substituent(s);
each R13、R14And R15Independently is halogen, cyano, hydroxy, amino, nitro, -CHO, -C (═ O) OH, -C (═ O) NH2、-SO2NH2、C1-C6Alkyl radical, C1-C6Haloalkyl, C2-C6Alkenyl radical, C2-C6Alkynyl, C2-C8Alkylcarbonyl group, C2-C8Halogenoalkylcarbonyl group, C2-C8Alkoxycarbonyl group, C4-C10Cycloalkoxycarbonyl radical, C5-C12Cycloalkyl alkoxycarbonyl, C2-C8Alkylaminocarbonyl radical, C3-C10Dialkylaminocarbonyl group, C1-C6Alkoxy radical, C1-C6Haloalkoxy, C2-C8Alkylcarbonyloxy, C1-C6Alkylthio radical, C1-C6Haloalkylthio, C1-C6Alkylsulfinyl radical, C1-C6Haloalkylsulfinyl radical, C1-C6Alkylsulfonyl radical, C1-C6Haloalkylsulfonyl group, C1-C6Alkylaminosulfonyl radical, C2-C8Dialkylaminosulfonyl radical, C3-C10Trialkylsilyl group, C1-C6Alkylamino radical, C2-C8Dialkylamino radical, C2-C8Alkylcarbonylamino or C1-C6An alkylsulfonylamino group;
each R16Independently is H, C1-C6Alkyl radical, C3-C8Cycloalkyl radical, C4-C8Cycloalkylalkyl radical, C1-C6Haloalkyl, C2-C6Alkenyl radical, C3-C6Alkynyl, C2-C8Alkoxyalkyl group, C2-C8Haloalkoxyalkyl, C2-C8Alkylthio alkyl, C2-C8Alkylsulfinylalkyl radical, C2-C8Alkylsulfonylalkyl group, C2-C8Alkylcarbonyl group, C2-C8Halogenoalkylcarbonyl group, C4-C10Cycloalkyl carbonyl group, C2-C8Alkoxycarbonyl group, C2-C8Halogenoalkoxycarbonyl, C4-C10Cycloalkoxycarbonyl radical, C2-C8Alkylaminocarbonyl radical, C3-C10Dialkylaminocarbonyl group, C4-C10Cycloalkylaminocarbonyl group, C1-C6Alkylsulfinyl radical, C1-C6Haloalkylsulfinyl radical, C3-C8Cycloalkyl sulfinyl radical, C1-C6Alkylsulfonyl radical, C1-C6Haloalkylsulfonyl group, C3-C8Cycloalkylsulfonyl radical, C1-C6Alkylaminosulfonyl radical, C2-C8Dialkylaminosulfonyl radical, C3-C10Trialkylsilyl or G1；
Each R17Independently is H, C1-C6Alkyl radical, C3-C8Cycloalkyl radical, C4-C8Cycloalkylalkyl radical, C1-C6Haloalkyl, C2-C6Alkenyl radical, C3-C6Alkynyl, C2-C8Alkoxyalkyl group, C2-C8Haloalkoxyalkyl, C2-C8Alkylthio alkyl, C2-C8Alkylsulfinylalkyl radical, C2-C8Alkylsulfonylalkyl group, C1-C6Alkoxy radical, C1-C6Alkylthio radical, C1-C6Haloalkylthio, C3-C8Cycloalkylthio radical, C3-C10Trialkylsilyl or G1；
Each R18Independently is H, hydroxy, C1-C6Alkyl radical, C3-C8Cycloalkyl radical, C4-C8Cycloalkylalkyl radical, C1-C6Haloalkyl, C2-C6Alkenyl radical, C3-C6Alkynyl, C2-C8Alkoxyalkyl group, C2-C8Haloalkoxyalkyl, C2-C8Alkylthio alkyl, C2-C8Alkylsulfinylalkyl radical, C2-C8Alkylsulfonylalkyl group, C2-C8Alkylcarbonyl group, C2-C8Halogenoalkylcarbonyl group, C4-C10Cycloalkyl carbonyl group, C2-C8Alkoxycarbonyl group, C2-C8Halogenoalkoxycarbonyl, C4-C10Cycloalkoxycarbonyl radical, C2-C8Alkylaminocarbonyl radical, C3-C10Dialkylaminocarbonyl group, C4-C10Cycloalkylaminocarbonyl group, C1-C6Alkoxy radical, C1-C6Alkylthio radical, C1-C6Haloalkylthio, C3-C8Cycloalkylthio radical, C1-C6Alkylsulfinyl radical, C1-C6Haloalkylsulfinyl radical, C3-C8Cycloalkyl sulfinyl radical, C1-C6Alkylsulfonyl radical, C1-C6Haloalkylsulfonyl group, C3-C8Cycloalkylsulfonyl radical, C1-C6Alkylaminosulfonyl radical, C2-C8Dialkylaminosulfonyl radical, C3-C10Trialkylsilyl or G1；
Each R19Independently is H, C1-C6Alkyl radical, C3-C8Cycloalkyl radical, C4-C8Cycloalkylalkyl radical, C1-C6Haloalkyl, C2-C6Alkenyl radical, C3-C6Alkynyl, C2-C8Alkoxyalkyl group, C2-C8Haloalkoxyalkyl, C2-C8Alkylthio alkyl, C2-C8Alkylsulfinylalkyl radical, C2-C8Alkylsulfonylalkyl group, C2-C8Alkylcarbonyl group, C2-C8Halogenoalkylcarbonyl group, C4-C10Cycloalkyl carbonyl group, C2-C8Alkoxycarbonyl group, C2-C8Halogenoalkoxycarbonyl, C4-C10Cycloalkoxycarbonyl radical, C2-C8Alkylaminocarbonyl radical, C3-C10Dialkylaminocarbonyl group, C4-C10Cycloalkylaminocarbonyl group, C1-C6Alkoxy radical, C1-C6Alkylsulfinyl radical, C1-C6Haloalkylsulfinyl radical, C3-C8Cycloalkyl sulfinyl radical, C1-C6Alkylsulfonyl radical, C1-C6Haloalkylsulfonyl group, C3-C8Cycloalkylsulfonyl radical, C1-C6Alkylaminosulfonyl radical, C2-C8Dialkylaminosulfonyl radical, C3-C10Trialkylsilyl or G1；
Each R20Independently is H, C1-C6Alkyl radical, C3-C8Cycloalkyl radical, C4-C8Cycloalkylalkyl radical, C1-C6Haloalkyl, C2-C6Alkenyl radical, C3-C6Alkynyl, C2-C8Alkoxyalkyl group, C2-C8Haloalkoxyalkyl, C2-C8Alkylthio alkyl, C2-C8Alkylsulfinylalkyl radical, C2-C8Alkylsulfonylalkyl group, C1-C6Alkoxy radical C3-C10Trialkylsilyl or G1；
Each R21Independently is H, hydroxy, amino, C1-C6Alkyl radical, C3-C8Cycloalkyl radical, C4-C8Cycloalkylalkyl radical, C1-C6Haloalkyl, C2-C6Alkenyl radical, C3-C6Alkynyl, C2-C8Alkoxyalkyl group, C2-C8Haloalkoxyalkyl, C2-C8Alkylthio alkyl, C2-C8Alkylsulfinylalkyl radical, C2-C8Alkylsulfonylalkyl group, C2-C8Alkylcarbonyl group, C2-C8Halogenoalkylcarbonyl group, C4-C10Cycloalkyl carbonyl group, C2-C8Alkoxycarbonyl group, C2-C8Halogenoalkoxycarbonyl, C4-C10Cycloalkoxycarbonyl radical, C2-C8Alkylaminocarbonyl radical, C3-C10Dialkylaminocarbonyl group, C4-C10Cycloalkylaminocarbonyl group, C1-C6Alkoxy radical, C1-C6Alkylsulfinyl radical, C1-C6Haloalkylsulfinyl radical, C3-C8Cycloalkyl sulfinyl radical, C1-C6Alkylsulfonyl radical, C1-C6Haloalkylsulfonyl group, C3-C8Cycloalkylsulfonyl radical, C1-C6Alkylaminosulfonyl radical, C2-C8Dialkylaminosulfonyl radical, C3-C10Trialkylsilyl or G1；
Each R22Independently is H, C1-C4Alkyl radical, C3-C8Cycloalkyl radical, C4-C8Cycloalkylalkyl radical, C1-C4Haloalkyl, C1-C4Alkoxy radical, C1-C4Haloalkoxy, C2-C4Alkoxyalkyl group, C2-C4Alkylcarbonyl group, C2-C4Alkoxycarbonyl or C3-C6A cycloalkyl group;
each R23Independently H, halogen, cyano, hydroxy, C1-C4Alkyl radical, C3-C8Cycloalkyl radical, C4-C8Cycloalkylalkyl radical, C1-C4Haloalkyl, C1-C4Alkoxy radical, C1-C4Haloalkoxy, C2-C4Alkoxyalkyl group, C2-C4Alkylcarbonyl group, C2-C4Alkoxycarbonyl or C3-C6A cycloalkyl group; and is
At S (═ O)u(＝NR8)vEach u and v is independently 0, 1 or 2, provided that the sum of u and v is 0, 1 or 2; and provided that the compound is different from the compound of the following formula 1, in which formula 1Q is1Is Ph (3-CF)3)；Q2Is Ph (2-F); r1Is H; r2Is H; y is O; a is-CH2CH2-; j is-CR5R6-；R5Is H; r6Is H; and R is7Is H.
More particularly, the present invention relates to a compound of formula 1 (including all stereoisomers), an N-oxide or a salt thereof. The present invention also relates to a herbicidal composition comprising a compound of the present invention (i.e., in a herbicidally effective amount) and at least one component selected from the group consisting of: surfactants, solid diluents and liquid diluents. The invention also relates to a method for controlling the growth of undesirable vegetation which comprises contacting the vegetation or its environment with a herbicidally effective amount of a compound of the invention (e.g., as a composition described herein).
The present invention also includes a herbicidal mixture comprising (a) a compound selected from formula 1, N-oxides, and salts thereof, and (b) at least one additional active ingredient selected from the salts of the compounds (b1) through (b16), and (b1) through (b16) as described below.
Detailed Description
As used herein, the terms "comprising," "including," "having," "containing," "characterized by," or any other variation thereof, are intended to cover a non-exclusive inclusion, subject to any limitation explicitly indicated. For example, a composition, mixture, process, or method that comprises a list of elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such composition, mixture, process, or method.
The conjunctive phrase "consisting of" excludes any unspecified elements, steps or components. If in the claims, such phrases are to be construed to mean that the claims are closed, including no material other than those recited, except for impurities normally associated therewith. When the phrase "consisting of" appears in a clause of the subject matter of the claims, rather than immediately preceding it, it is limited only to the elements mentioned in that clause; other elements are not excluded as a whole from the claims.
The conjunctive phrase "consisting essentially of" is used to define compositions or methods that include materials, steps, features, components, or elements in addition to those literally disclosed, provided that such additional materials, steps, features, components, or elements do not materially affect the basic and novel characteristics of the claimed invention. The term "consisting essentially of" is intermediate to "including" and "consisting of.
Where applicants have defined the invention, or a portion thereof, in open-ended terms such as "comprising," then it should be readily understood (unless otherwise indicated) that the specification should be interpreted to describe the invention also in terms of "consisting essentially of or" consisting of.
Furthermore, unless expressly stated to the contrary, "or" refers to an inclusive "or" and not to an exclusive "or". For example, condition a or B is satisfied by any one of: a is true (or present) and B is false (or not present), a is false (or not present) and B is true (or present), and both a and B are true (or present).
Also, the indefinite articles "a" and "an" preceding an element or component of the invention are intended to be nonrestrictive regarding the number of instances (i.e., occurrences) of the element or component. Thus, "a" or "an" should be understood to include one or at least one and the singular forms of an element or component also include the plural unless the number clearly dictates otherwise.
As referred to herein, the term "seedling" used alone or in combination of words refers to a young plant developed from the embryo of a seed.
As referred to herein, the term "broadleaf" used alone or in words such as "broadleaf weeds" refers to dicots or dicots, a term used to describe a class of angiosperms characterized by embryos having two cotyledons.
As used herein, the term "alkylating agent" refers to a compound in which a carbon-containing group is bonded through a carbon atom to a leaving group, such as a halide or sulfonate, which leaving group can be displaced by bonding of a nucleophile to the carbon atom. Unless otherwise indicated, the term "alkylating" does not limit the carbon-containing group to an alkyl group; the carbon-containing group in the alkylating agent includes the group consisting of9And R11) Various carbon-bonded substituent groups are specified. The term "directly linked" refers to "linked" or "bonded".
In the above recitations, the term "alkyl", used either alone or in compound words such as "alkylthio" or "haloalkyl", includes straight-chain or branched alkyl, such as methyl, ethyl, n-propyl, isopropyl, or the different butyl, pentyl, or hexyl isomers. "alkenyl" includes straight or branched chain alkenes such as ethenyl, 1-propenyl, 2-propenyl, and the different butenyl, pentenyl and hexenyl isomers. "alkenyl" also includes polyalkenes such as 1, 2-allenyl and 2, 4-hexadienyl. "alkynyl" includes straight or branched alkynes such as ethynyl, 1-propynyl, 2-propynyl, and the different butynyl, pentynyl and hexynyl isomers. "alkynyl" may also include moieties made up of multiple triple bonds, such as 2, 5-hexadiynyl.
"alkoxy" includes, for example, methoxy, ethoxy, n-propoxy, isopropoxy, and the different butoxy, pentoxy, and hexoxy isomers. "alkoxyalkyl" refers to an alkoxy substitution on an alkyl group. Examples of "alkoxyalkyl" include CH3OCH2、CH3OCH2CH2、CH3CH2OCH2、CH3CH2CH2CH2OCH2And CH3CH2OCH2CH2. "Alkoxyalkoxy" means an alkoxy substitution on an alkoxy group. "Alkoxyalkoxyalkyl" means an alkoxy substitution on the alkoxyalkyl moiety. "alkenyloxy" includes straight or branched alkenyloxy moieties. Examples of "alkenyloxy" include H2C＝CHCH2O、(CH3)2C＝CHCH2O、(CH3)CH＝CHCH2O、(CH3)CH＝C(CH3)CH2O and CH2＝CHCH2CH2And O. "alkynyloxy" includes straight or branched alkynyloxy moieties. Examples of "alkynyloxy" include HC ≡ CCH2O、CH3C≡CCH2O and CH3C≡CCH2CH2And O. "alkylthio" includes branched or straight chain alkylthio moieties such as methylthio, ethylthio, and the different propylthio, butylthio, pentylthio, and hexylthio isomers. "Alkylsulfinyl" includes the two enantiomers of alkylsulfinyl. Examples of "alkylsulfinyl" include CH3S(O)-、CH3CH2S(O)-、CH3CH2CH2S(O)-、(CH3)2CHS (O) -and the different butylsulfinyl, pentylsulfinyl and hexylsulfinyl isomers. Examples of "alkylsulfonyl" include CH3S(O)2-、CH3CH2S(O)2-、CH3CH2CH2S(O)2-、(CH3)2CHS(O)2-, and the different butylsulfonyl, pentylsulfonyl and hexylsulfonyl isomers. "alkylthioalkyl" refers to an alkylthio substitution on an alkyl group. Examples of "alkylthioalkyl" include CH3SCH2、CH3SCH2CH2、CH3CH2SCH2、CH3CH2CH2CH2SCH2And CH3CH2SCH2CH2. "cyanoalkyl" means an alkane substituted by one cyano groupAnd (4) a base. Examples of "cyanoalkyl" include NCCH2、NCCH2CH2And CH3CH(CN)CH2. "alkylamino", "dialkylamino", and the like are defined similarly to the above examples. The terms "alkylthioalkyl", "alkylsulfonylamino", "alkylsulfonyloxy", "alkylaminosulfonyl", "alkylsulfonylamino", "alkylaminoalkyl", "alkylsulfinylalkyl", "alkylsulfonylalkyl", "dialkylaminoalkyl" are likewise defined.
"cycloalkyl" includes, for example, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. The term "alkylcycloalkyl" denotes alkyl substitution on the cycloalkyl moiety and includes, for example, ethylcyclopropyl, isopropylcyclobutyl, 3-methylcyclopentyl and 4-methylcyclohexyl. The term "cycloalkylalkyl" denotes cycloalkyl substitution on the alkyl moiety. The term "cycloalkylalkenyl" denotes a cycloalkyl substitution on an alkenyl moiety. The term "cycloalkylalkynyl" denotes a cycloalkyl substitution on an alkynyl moiety. Examples of "cycloalkylalkyl" groups include cyclopropylmethyl, cyclopentylethyl, and other cycloalkyl moieties bonded to straight or branched chain alkyl groups. The term "cycloalkoxy" denotes a cycloalkyl group attached through an oxygen atom, such as cyclopentyloxy and cyclohexyloxy. "cycloalkylalkoxy" means a cycloalkylalkyl group attached through an oxygen atom attached to an alkyl chain. Examples of "cycloalkylalkoxy" groups include cyclopropylmethoxy, cyclopentylethoxy, and other cycloalkyl moieties bonded to straight or branched alkoxy groups. "cycloalkenyl" includes groups such as cyclopentenyl and cyclohexenyl as well as groups having more than one double bond, for example 1, 3-and 1, 4-cyclohexadienyl. The term "cycloalkylcycloalkyl" refers to a cycloalkyl substitution on a cycloalkyl moiety. The terms "cycloalkoxyalkyl", "alkylcycloalkylalkyl", "cycloalkylaminoalkyl", "cycloalkylthio", "cycloalkylsulfinyl", "cycloalkylsulfonyl" are defined identically.
The term "halogen", alone or in compound words such as "haloalkyl", or when used in describing words such as "alkyl substituted with halogen",including fluorine, chlorine, bromine or iodine. Further, when used in compound words such as "haloalkyl", or when used in describing words such as "alkyl substituted with halogen", the alkyl may be partially or fully substituted with halogen atoms (which may be the same or different). Examples of "haloalkyl" or "alkyl substituted with halo" include F3C、ClCH2、CF3CH2And CF3CCl2. The terms "halocycloalkyl", "halocycloalkoxy", "halocycloalkenyl", "halocycloalkylalkyl", "haloalkoxy", "haloalkylaminoalkyl", "haloalkylcarbonylamino", "haloalkylthio", "haloalkylsulfonylamino", "haloalkenyl", "haloalkynyl", "haloalkylcarbonyloxy", "haloalkylsulfonyloxy", "haloalkynyloxy", and the like are defined analogously to the term "haloalkyl". Examples of "haloalkoxy" include CF3O-、CCl3CH2O-、HCF2CH2CH2O-and CF3CH2O-is formed. Examples of "haloalkylthio" include CCl3S-、CF3S-、CCl3CH2S-and ClCH2CH2CH2S-. Examples of "haloalkylsulfinyl" include CF3S(O)-、CCl3S(O)-、CF3CH2S (O) -and CF3CF2S (O) -. Examples of "haloalkylsulfonyl" include CF3S(O)2-、CCl3S(O)2-、CF3CH2S(O)2And CF3CF2S(O)2-. Examples of "haloalkenyl" include (Cl)2C＝CHCH2And CF3CH2CH＝CHCH2-. Examples of "haloalkynyl" include HC ≡ CCHCl-, CF3C≡C-、CCl3C ≡ C-and FCH2C≡CCH2-. Examples of "haloalkoxyalkoxy" include CF3OCH2O-、ClCH2CH2OCH2CH2O-、Cl3CCH2OCH2O-and branched alkyl derivatives. Examples of "haloalkenyloxy" include (Cl)2C＝CHCH2O-and CF3CH2CH＝CHCH2O-is formed. Examples of "haloalkoxyalkyl" include CF3OCH2-、CCl3CH2OCH2-、HCF2CH2CH2OCH2And CF3CH2OCH2-。
"alkylcarbonyl" refers to a straight or branched chain alkyl moiety bonded to a C (═ O) moiety. Examples of "alkylcarbonyl" include CH3C(＝O)-、CH3CH2CH2C (═ O) -, and (CH)3)2CHC (═ O) -. Examples of "alkoxycarbonyl" include CH3OC(＝O)-、CH3CH2OC(＝O)-、CH3CH2CH2OC(＝O)-、(CH3)2CHOC (═ O) -, and the different butoxy-or pentoxycarbonyl isomers. The terms "alkylcarbonylalkyl", "alkylcarbonyloxy", "alkylcarbonylalkoxy", "alkylcarbonylamino", "alkoxycarbonylamino", "alkylaminocarbonyl", "dialkylaminosulfonyl", "cycloalkylcarbonyl", "cycloalkylalkoxycarbonyl", "cycloalkoxycarbonyl", "cycloalkylcarbonyloxy", "dialkylaminocarbonyl", "cycloalkylaminocarbonyl", "haloalkylcarbonyl" and "haloalkoxycarbonyl" are likewise defined. The term "hydroxyalkyl" refers to a hydroxyl group attached to an alkyl group. The term "cyanoalkyl" refers to a cyano group attached to an alkyl group. The term "cyanoalkoxy" refers to a cyano group attached to an alkoxy group. The term "nitroalkyl" refers to a nitro group attached to an alkyl group. The term "nitroalkenyl" refers to a nitro group attached to an alkenyl group.
The term "trialkylsilyl" refers to a silyl group substituted with three alkyl groups. The term "trialkylsilylalkyl" is intended to mean a trialkylsilyl group bonded through an alkyl group (e.g. -CH)2TMS). The term "trialkylsilyloxy" means a trialkylsilyl group bonded through an oxygen (e.g., -OTMS).
In takingThe total number of carbon atoms in the substituent groups being represented by "Ci-Cj"prefix" indicates where i and j are numbers from 1 to 12. E.g. C1-C4Alkylsulfonyl represents methylsulfonyl to butylsulfonyl; c2Alkoxyalkyl represents CH3OCH2-；C3Alkoxyalkyl denotes, for example, CH3CH(OCH3)-、CH3OCH2CH2-or CH3CH2OCH2-; and C4Alkoxyalkyl denotes various isomers of an alkyl group substituted with an alkoxy group containing a total of four carbon atoms, and examples include CH3CH2CH2OCH2-and CH3CH2OCH2CH2-。
When a compound is substituted with a substituent bearing a subscript (which indicates that the number of said substituents may exceed 1), said substituents (when they exceed 1) are independently selected from the group of defined substituents, e.g., S (═ O)u(＝NR8)vU and v are independently 0, 1 or 2). When the radical contains substituents which may be hydrogen, e.g. (R)5Or R6) When the substituent is hydrogen, it is recognized that this is equivalent to the group being unsubstituted. When the variable group is shown as optionally attached to one position, e.g. R9And R11Where n may be 0, hydrogen may be in the position even if not stated in the definition of the variable group. When one or more positions on a group are said to be "unsubstituted" or "unsubstituted," then a hydrogen atom is attached to occupy any free valence.
Unless otherwise indicated, a "ring" or "ring system" (e.g., substituent Q) as a component of formula 11And Q2Is heterocyclic). The term "ring system" denotes two or more fused rings. The terms "bicyclic ring system" and "fused bicyclic ring system" refer to a ring system consisting of two fused rings, wherein either of the two rings may be saturated, partially unsaturated, or fully unsaturated, unless otherwise specified. The term "fused heterobicyclic ring system" denotes a fused ring wherein at least one ring atom is not carbonThe bicyclic ring system of (1). The term "ring member" refers to an atom or other moiety (e.g., C (═ O), C (═ S), S (O), or S (O)) that forms the backbone of a ring or ring system2)。
The term "heterocyclic ring", "heterocyclic ring" or "heterocyclic ring system" denotes a ring or ring system wherein at least one of the atoms forming the ring backbone is not carbon (e.g. nitrogen, oxygen or sulfur). Typically, the heterocyclic ring contains no more than 4 nitrogens, no more than 2 oxygens and no more than 2 sulphurs. Unless otherwise indicated, the heterocyclic ring may be a saturated, partially unsaturated, or fully unsaturated ring. When a fully unsaturated heterocyclic ring satisfies the huckel rule, then the ring is also referred to as a "heteroaromatic ring" or an "aromatic heterocyclic ring". Unless otherwise indicated, the heterocyclic rings and ring systems may be attached through any available carbon or nitrogen via a hydrogen substituted on said carbon or nitrogen.
By "aromatic" is meant that each ring atom is substantially in the same plane and has a p-orbital perpendicular to the plane of the ring, and that (4n +2) pi electrons (where n is a positive integer) are associated with the ring to comply with the Huckel rule. The term "aromatic ring system" denotes a carbocyclic or heterocyclic ring system in which at least one ring of the ring system is aromatic. The term "aromatic heterocyclic ring system" denotes a heterocyclic ring system wherein at least one ring of the ring system is aromatic. The term "non-aromatic ring system" means a carbocyclic or heterocyclic ring system that may be fully saturated, as well as partially or fully unsaturated, provided that none of the rings in the ring system are aromatic.
The term "optionally substituted" in relation to a heterocycle refers to a group that is unsubstituted or has at least one non-hydrogen substituent that does not eliminate the biological activity possessed by the unsubstituted analog. As used herein, the following definitions will apply unless otherwise indicated. The term "optionally substituted" is used interchangeably with the phrase "substituted or unsubstituted" or with the term "(un) substituted". Unless otherwise indicated, an optionally substituted group may have a substituent at each substitutable position of the group, and each substitution is independent of the other.
As noted above, Q1Can be used forIs (especially) phenyl optionally substituted with one or more substituents selected from the group of substituents as defined in the summary of the invention. Examples of the phenyl group optionally substituted with one to five substituents are rings as shown in U-1 in example 1, wherein R isvIs as in the summary of the invention for Q1R as defined9And R isvIs as in the summary of the invention for Q2R as defined11And r is an integer from 0 to 5.
As noted above, Q1May be (especially) a 5-or 6-membered fully unsaturated heterocyclic ring (which may be saturated or unsaturated), optionally substituted by one or more substituents selected from the group of substituents as defined in the summary of the invention. Examples of the 5-or 6-membered unsaturated aromatic heterocyclic ring optionally substituted with one or more substituents include rings U-2 to U-61 shown in example 1, wherein R isvIs as in the summary of the invention for Q1Any substituent defined (i.e. R)9) And r is an integer from 0 to 5, limited by the number of available positions on each U group. Since U-29, U-30, U-36, U-37, U-38, U-39, U-40, U-41, U-42, and U-43 have only one position available, for these U groups R is limited to the integer 0 or 1, and R is 0 means that the U group is unsubstituted and hydrogen is present in the group consisting of (R-30, U-36, U-37, U-38, U-39, U-40, U-41, U-42, and U-43)v)rAt the indicated position.
Example 1
Examples of 5-or 6-membered saturated or non-aromatic unsaturated heterocyclic rings containing ring members selected from up to two O atoms and up to two S atoms and up to 4N atoms, and optionally substituted on the carbon atom ring members with up to 5 halogen atoms include those as shown in example 2Rings G-1 to G-35. It should be noted that when the attachment point on the G group is shown as floating, the G group may be attached to the remainder of formula 1 through any available carbon or nitrogen of the G group via replacement of a hydrogen atom. Corresponds to RvThe optional substituents of (a) may be attached to any available carbon or nitrogen by replacement of a hydrogen atom. For these G rings, r is typically an integer from 0 to 5, limited by the number of available positions on each G group.
It should be noted that when Q is1Or Q2Containing a ring selected from G-28 to G-35, G2Selected from O, S or N. It should be noted that when G is2When N, the nitrogen atom may be substituted by H or by a group corresponding to Q as in the summary of the invention1Or Q2R as definedvThe substituent(s) is substituted so that its valency is complete.
Example 2
As noted above, Q1May be (in particular) an 8-, 9-or 10-membered heteroaromatic bicyclic ring system, optionally substituted by one or more substituents selected from the group of substituents as defined in the summary of the invention (i.e. R)9And R11) And (4) substitution. Examples of 8-, 9-or 10-membered heteroaromatic bicyclic ring systems optionally substituted with one or more substituents include rings U-81 to U-123 shown in example 3, wherein R isvIs as in the summary of the invention for Q1Any substituent defined (i.e. R)8) And r is typically an integer from 0 to 5.
Example 3
Although R is shown in structures U-1 through U-123vGroups, it should be noted, however, that they need not be present because they are optional substituents. It should be noted that when R isvWhen attached to an atom, this is as if the atom was unsubstituted. The nitrogen atom to be substituted to fill its valence is substituted by H or RvAnd (4) substitution. It should be noted that when (R)v)rWhen the point of attachment to the U group is shown as floating, (R)v)rAny available carbon or nitrogen atom that can be attached to the U group. It should be noted that when the attachment point on the U group is shown as floating, the U group can be attached to the remainder of formula 1 through any available carbon or nitrogen of the U group via replacement of a hydrogen atom. It should be noted that some U groups can only be substituted by less than 4RvSubstituted (e.g., U-2 to U-5, U-7 to U-48, and U-52 to U-61).
Various synthetic methods are known in the art to enable the preparation of aromatic and non-aromatic heterocycles and ring systems; for an extensive review see eight volumes of Comprehensive Heterocyclic Chemistry [ integrated Heterocyclic Chemistry ], A.R.Katritzky and C.W.Rees master eds, Pergamon Press, Oxford [ Pegman Press, Oxford ], 1984 and twelve volumes of Comprehensive Heterocyclic Chemistry II [ integrated Heterocyclic Chemistry II ], A.R.Katritzky, C.W.Rees and E.F.V.Scriven master eds, Pegman Press, Oxford, 1996.
The compounds of the present invention may exist as one or more stereoisomers. The various stereoisomers include enantiomers, diastereomers, atropisomers and geometric isomers. Stereoisomers are isomers that are identical in composition but differ in the arrangement of their atoms in space, and include enantiomers, diastereomers, cis-trans isomers (also known as geometric isomers) and atropisomers. Atropisomers result from restricted rotation about a single bond, where the rotational barrier is high enough to allow separation of isomeric species. One skilled in the art will appreciate that one stereoisomer may be more active and/or may exhibit beneficial effects when enriched relative to one or more other stereoisomers, or when separated from one or more other stereoisomers. In addition, the skilled artisan knows how to isolate, enrich and/or selectively prepare the stereoisomers. The compounds of the present invention may exist as mixtures of stereoisomers, individual stereoisomers, or as optically active forms.
When enantiomerically enriched, one enantiomer is present in a greater amount than the other, and the degree of enrichment can be defined by the expression of an enantiomeric excess ("ee") defined as (2x-1) · 100%, where x is the molar fraction of the predominate enantiomer in the mixture (e.g., 20% ee corresponds to a 60:40 ratio of enantiomers).
Preferably, the compositions of the present invention have an enantiomeric excess of at least 50% of the more active isomer; more preferably at least 75% enantiomeric excess; still more preferably at least 90% enantiomeric excess; and most preferably at least a 94% enantiomeric excess. Of particular note are the enantiomerically pure examples of the more active isomers.
The compound of formula 1 may contain additional chiral centers. For example, substituents and other molecular constituents such as R2And R3May itself contain a chiral center. The present invention includes racemic mixtures as well as enriched and substantially pure stereoconfigurations at these additional chiral centers.
Due to surrounding amide bond (e.g., C (Y) N (Q) in formula 12)(R7) Limited rotation, the compounds of the invention may thus exist as one or more conformers. The present invention includes mixtures of conformers. In addition, the invention includes compounds enriched in one conformer relative to the other conformers.
The compounds of formula 1 typically exist in more than one form, and formula 1 thus includes all crystalline and non-crystalline forms of the compounds they represent. Non-crystalline forms include embodiments that are solids, such as waxes and gums, and embodiments that are liquids, such as solutions and melts. Crystalline forms include embodiments that represent substantially single crystal types and embodiments that represent mixtures of polymorphs (i.e., different crystalline types). The term "polymorph" refers to a particular crystalline form of a compound that can crystallize in different crystalline forms having different molecular arrangements and/or conformations in the crystal lattice. Although polymorphs can have the same chemical composition, they can also differ in composition due to the presence or absence of co-crystallized water or other molecules, which can be weakly or strongly bound within the crystal lattice. Polymorphs can differ in such chemical, physical, and biological properties as crystal shape, density, hardness, color, chemical stability, melting point, hygroscopicity, suspensibility, dissolution rate, and bioavailability. One skilled in the art will appreciate that a polymorph of a compound of formula 1 can exhibit beneficial effects (e.g., suitability for preparation of useful formulations, improved biological performance) relative to another polymorph or mixture of polymorphs of the same compound of formula 1. The preparation and isolation of specific polymorphs of the compound of formula 1 can be achieved by methods known to those skilled in the art, including, for example, crystallization using selected solvents and temperatures. For a comprehensive discussion of Polymorphism, see Polymorphism in the Pharmaceutical Industry, edited by r.hilfiker, Wiley-VCH, Weinheim (Weinheim), 2006.
Those skilled in the art will appreciate that not all nitrogen-containing heterocycles can form N-oxides because the nitrogen requires an available lone pair to oxidize to the oxide; those skilled in the art will recognize those nitrogen-containing heterocycles that can form N-oxides. Those skilled in the art will also recognize that tertiary amines are capable of forming N-oxides. Synthetic methods for preparing N-oxides of heterocycles and tertiary amines are well known to those skilled in the art and include the oxidation of heterocycles and tertiary amines using peroxy acids such as peracetic and m-chloroperoxybenzoic acid (MCPBA), hydrogen peroxide, alkyl hydroperoxides such as t-butyl hydroperoxide, sodium perborate, and dioxiranes such as dimethyldioxirane. These methods for preparing N-oxides have been widely described and reviewed in the literature, see for example: gilchrist, Comprehensive Organic Synthesis, Vol.7, pp.748-750, edited by S.V.Ley, Pegman Press; tisler and b.stanovnik, Comprehensive Heterocyclic Chemistry, volume 3, pages 18-20, editors a.j.boulton and a.mckillop, pegman press; M.R.Grimett and B.R.T.Keene, Advances in Heterocyclic Chemistry [ Advances in heterocycle Chemistry ], Vol.43, p.149-161, edited by A.R.Katritzky, Academic Press [ Academic Press ]; tisler and b.stanovnik, advanced in Heterocyclic Chemistry [ Advances in Heterocyclic Chemistry ], volume 9, page 285-; and g.w.h.cheeseman and e.s.g.werstink, heterocyclic chemistry evolution, vol 22, p 390-392, editions a.r.katritzky and a.j.boulton, academic press.
One skilled in the art recognizes that salts share the biological utility of non-salt forms, as salts of compounds are in equilibrium with their corresponding non-salt forms in the environment and under physiological conditions. Thus, a variety of salts of the compounds of formula 1 are useful for controlling undesirable vegetation (i.e., are agriculturally suitable). Salts of the compounds of formula 1 include acid-addition salts with inorganic or organic acids such as hydrobromic, hydrochloric, nitric, phosphoric, sulfuric, acetic, butyric, fumaric, lactic, maleic, malonic, oxalic, propionic, salicylic, tartaric, 4-toluenesulfonic or valeric. When the compound of formula 1 contains an acidic moiety such as a carboxylic acid or phenol, salts also include those formed with organic or inorganic bases such as pyridine, triethylamine or ammonia, or amides, hydrides, hydroxides or carbonates of sodium, potassium, lithium, calcium, magnesium or barium. Accordingly, the present invention includes a compound selected from formula 1, an N-oxide thereof, and an agriculturally suitable salt thereof.
Embodiments of the invention as described in the summary of the invention include (where formula 1 as used in the following embodiments includes N-oxides and salts thereof) the following:
example 1. compounds according to formula 1 (including all stereoisomers), N-oxides and salts thereof, agricultural compositions containing them, and their use as herbicides, as described in the summary of the invention.
Embodiment 2. the compound of embodiment 1, wherein Q1Is a phenyl or benzyl ring or a naphthalene ring system, each ring or ring system optionally being selected up to 5 independently from R9Substituted with the substituent(s); or is a 5-to 6-membered fully unsaturated heterocyclic ring, each ring or ring system containing ring members selected from carbon atoms and 1 to 4 heteroatoms independently selected from up to 2O, up to 2S and up to 4N atoms, wherein up to 3 carbon ring members are independently selected from C (═ O) and C (═ S) and the sulfur ring members are independently selected from S (═ O)u(＝NR8)vEach ring or ring system is optionally substituted with up to 5 substituents independently selected from R on carbon atom ring members9And said substituents on the ring members of the nitrogen atom are independently selected from R10。
Embodiment 3. the compound of embodiment 2, wherein Q1Is optionally selected from R by up to 59A benzene ring substituted with the substituent of (1); or is a 5-to 6-membered fully unsaturated heterocyclic ring, each ring containing ring members selected from carbon atoms and 1 to 4 heteroatoms independently selected from up to 2O, up to 2S and up to 4N atoms, wherein up to 3 carbon ring members are independently selected from C (═ O) and C (═ S), and the sulfur ring members are independently selected from S (═ O)u(＝NR8)vEach ring or ring system is optionally substituted with up to 5 substituents independently selected from R on carbon atom ring members9And said substituents on the ring members of the nitrogen atom are independently selected from R10。
Embodiment 4. the compound of embodiment 3, wherein Q1Is optionally selected from R by up to 59A benzene ring substituted with the substituent(s).
Embodiment 5. the compound of embodiment 4, wherein Q1Is selected from 1 to 3 independently from R9A benzene ring substituted with the substituent(s).
Example 6 exampleThe compound of embodiment 5, wherein Q1Is selected from 1 to 2 independently from R9A benzene ring substituted with the substituent(s).
Embodiment 7. the compound of embodiment 6, wherein Q1Is selected from R at the para (4-) position9The phenyl ring of the substituent (and optionally other substituents).
Example 8A compound of example 7, wherein when Q1Is selected from at least two R9When the phenyl ring is substituted with the substituent(s) of (c), then one substituent is in the para (4-) position (of the phenyl ring) and at least one other substituent is in the meta position.
Embodiment 9. the compound of any one of embodiments 1 to 3, wherein Q1Is a 5-to 6-membered fully unsaturated heterocyclic ring, each ring containing ring members selected from carbon atoms and 1 to 3 heteroatoms independently selected from up to 1O, up to 1S and up to 2N atoms, wherein up to 2 carbon ring members are independently selected from C (═ O) and C (═ S), and the sulfur ring members are independently selected from S (═ O)u(＝NR8)vEach ring optionally substituted with up to 5 substituents independently selected from R on carbon atom ring members9And said substituents on the ring members of the nitrogen atom are independently selected from R10。
Embodiment 10. the compound of embodiment 9, wherein Q2Is a benzene ring or a naphthalene ring system, each ring or ring system optionally being selected up to 5 independently from R11Substituted with the substituent(s); or is a 5-to 6-membered fully unsaturated heterocyclic ring, each ring containing ring members selected from carbon atoms and 1 to 4 heteroatoms independently selected from up to 1O, up to 1S and up to 2N atoms, wherein up to 2 carbon ring members are independently selected from C (═ O) and C (═ S), and the sulfur ring members are independently selected from S (═ O)u(＝NR8)vEach ring or ring system is optionally substituted with up to 5 substituents independently selected from R on carbon atom ring members11And said substituents on the ring members of the nitrogen atom are independently selected from R12。
Embodiment 11. the compound of embodiment 10, wherein Q2Is optionally selected from R by up to 511A benzene ring substituted with the substituent(s).
Embodiment 12. the compound of embodiment 11, wherein Q2Is optionally selected from R by up to 311A benzene ring substituted with the substituent(s).
Embodiment 13. the compound of embodiment 12, wherein Q2Is at the 3-position selected from R by 111A benzene ring substituted with the substituent(s).
Embodiment 14. the compound of embodiment 10, wherein Q2Is a 5-to 6-membered fully unsaturated heterocyclic ring, each ring containing ring members selected from carbon atoms and 1 to 4 heteroatoms independently selected from up to 1O, up to 1S and up to 2N atoms, wherein up to 2 carbon ring members are independently selected from C (═ O) and C (═ S), and the sulfur ring members are independently selected from S (═ O)u(＝NR8)vEach ring or ring system is optionally substituted with up to 5 substituents independently selected from R on carbon atom ring members11And said substituents on the ring members of the nitrogen atom are independently selected from R12。
Embodiment 15. the compound of any one of embodiments 1 to 14, wherein R1And R2Each independently is H, halogen or C1-C4An alkyl group.
Embodiment 16. the compound of embodiment 15, wherein R1And R2Each independently is H, Cl, or CH3。
An embodiment 17. the compound of embodiment 16, wherein R1And R2Each independently is H or Cl.
Embodiment 18. the compound of embodiment 17, wherein R1And R2Each is H.
Embodiment 19. the compound of any one of embodiments 1 to 16, wherein Y is O or S.
Embodiment 20. the compound of embodiment 19, wherein Y is O.
An embodiment 21. the compound of embodiment 19, wherein Y is S.
An embodiment 22. the compound of any one of embodiments 1 to 21, wherein a is a saturated, partially unsaturated, or fully unsaturated chain containing 2 to 4 atoms selected from up to 3 carbons, up to 1O, up to 1S, and up to 1N atom, wherein up to 2 carbon members are independently selected from C (═ O) and C (═ S) and the sulfur atom member is selected from S (═ O)u(＝NR8)v(ii) a Said chain being optionally substituted with up to 3 substituents independently selected from R on carbon3And on the nitrogen atom the substituents are independently selected from R4。
An embodiment 23. the compound of embodiment 22, wherein a is a saturated or partially unsaturated chain containing 2 to 4 atoms selected from up to 2 carbons and up to 1N atom, wherein up to 1 carbon member is independently selected from C (═ O) and C (═ S); said chain being optionally substituted with up to 2 substituents independently selected from R on carbon3And on the nitrogen atom the substituents are independently selected from R4。
An embodiment 24. the compound of embodiment 23, wherein a is a saturated or partially unsaturated chain containing 2 to 3 atoms selected from up to 2 carbons and up to 1N atom, wherein up to 1 carbon member is independently selected from C (═ O); said chain being optionally substituted with up to 1 substituent independently selected from R on carbon3And on the nitrogen atom the substituents are independently selected from R4。
Embodiment 25. the compound of embodiment 24, wherein A is-CH2CH2CH2-、-NCH2-、-C(＝O)CH2-or-CH ═ CH-, wherein the bond projecting to the left is linked to the nitrogen of the-N-J-moiety, and the bond projecting to the right is linked to the nitrogen of the-N ═ C- (or-N-CH-) moiety of formula 1.
Example 26. the compound of example 25, whichWherein A is-CH2CH2CH2-。
Example 27. the compound of example 25, wherein A is-NCH2-wherein the bond extending to the left is linked to the nitrogen of the-N-J-moiety and the bond extending to the right is linked to the nitrogen of the-N ═ C-moiety of formula 1.
An embodiment 28. the compound of embodiment 25 wherein a is-C (═ O) CH2-wherein the bond extending to the left is linked to the nitrogen of the-N-J-moiety and the bond extending to the right is linked to the nitrogen of the-N ═ C-moiety of formula 1.
An embodiment 29. the compound of embodiment 25 wherein a is-CH ═ CH-.
Embodiment 30. the compound of any one of embodiments 1 to 29, wherein each R3Independently halogen, cyano, hydroxy, -CO2H、C1-C4Alkyl radical, C1-C4Haloalkyl, C1-C4Alkoxy radical, C1-C4Alkylthio radical, C3-C6Cycloalkyl or C4-C6A cycloalkylalkyl group.
Embodiment 31. the compound of embodiment 30, wherein each R3Independently cyano, -CO2H、C1-C4Alkyl radical, C1-C4Haloalkyl, C1-C4Alkylthio or C4-C6A cycloalkylalkyl group.
Embodiment 32. the compound of embodiment 31, wherein each R3Independently cyano, -CO2H、C1-C4Alkyl or C1-C4A haloalkyl group.
Embodiment 33. the compound of embodiment 32, wherein each R3Independently cyano, -CO2H or C1-C4An alkyl group.
Example 34 Compounds of example 1, wherein two R3Together with one or more of the carbon atoms to which they are bound form C4A cycloalkyl ring.
Example 35 As in examples 1 to 34The compound of any one of, wherein each R4Independently is C1-C4Alkyl radical, C1-C4Haloalkyl or C3-C6A cycloalkyl group.
Embodiment 36. the compound of embodiment 35, wherein each R4Independently is C1-C4An alkyl group.
Embodiment 37. the compound of embodiment 36, wherein each R4Is CH3。
Embodiment 38. the compound of any one of embodiments 1 to 37, wherein J is-CR5R6-。
Embodiment 39. the compound of any one of embodiments 1 to 37, wherein J is-CR5R6-CR5aR6a-wherein the-CR5R6The moiety is directly connected to N.
Embodiment 40. the compound of embodiment 38, wherein J is-CH2-。
An embodiment 41. the compound of embodiment 39, wherein J is-CH2CH2-。
Embodiment 42. the compound of any one of embodiments 1 to 39, wherein R5And R6Each independently is H, halogen, hydroxy or CH3。
Embodiment 43A compound as described in embodiment 42, wherein R5And R6Each independently is H or halogen.
Embodiment 44. the compound of embodiment 43, wherein R5And R6Each is H.
Embodiment 45. the compound of any one of embodiments 1 to 39, wherein R5And R6Together with the carbon atom to which they are bound form C4A cycloalkyl ring.
Embodiment 46. the compound of any one of embodiments 1 to 39, wherein R5aAnd R6aEach independently is H or C1-C4An alkyl group.
Embodiment 47. the compound of any one of embodiments 1 to 46, whereinIn R7Is H, hydroxy, amino, C1-C6Alkyl radical, C1-C6Haloalkyl, C2-C6Alkenyl radical, C3-C6Alkynyl, C2-C8Alkoxyalkyl group, C2-C8Haloalkoxyalkyl, C2-C8Alkylthio alkyl, C2-C8Alkylsulfinylalkyl radical, C2-C8Alkylsulfonylalkyl group, C2-C8Alkylcarbonyl group, C2-C8Halogenoalkylcarbonyl group, C4-C10Cycloalkyl carbonyl group, C2-C8Alkoxycarbonyl group, C2-C8Halogenoalkoxycarbonyl, C4-C10Cycloalkoxycarbonyl radical, C2-C8Alkylaminocarbonyl radical, C3-C10Dialkylaminocarbonyl or C4-C10A cycloalkylaminocarbonyl group.
Embodiment 48. the compound of embodiment 47, wherein R7Is H, hydroxy, amino, C1-C6Alkyl radical, C1-C6Haloalkyl, C2-C6Alkenyl radical, C3-C6Alkynyl, C2-C8Alkoxyalkyl group, C2-C8Haloalkoxyalkyl or C2-C8An alkylthioalkyl group.
Embodiment 49. the compound of embodiment 48, wherein R7Is H, C1-C6Alkyl radical, C2-C6Alkenyl radical, C3-C6Alkynyl or C2-C8An alkoxyalkyl group.
Embodiment 50. the compound of embodiment 49, wherein R7Is H or C1-C6An alkyl group.
Embodiment 51. the compound of any one of embodiments 1 to 50, wherein each R8Independently is H, cyano or C2-C3An alkylcarbonyl group.
Example 52. the compound of example 51, wherein each R8Independently is H.
Embodiment 53. the compound of any one of embodiments 1 to 52, wherein each R9Independently halogen, cyano, nitro, C1-C8Alkyl radical, C1-C4Cyanoalkyl, C1-C4Cyanoalkoxy group, C1-C8Haloalkyl, C1-C8Nitroalkyl, C2-C8Alkenyl radical, C2-C8Haloalkenyl, C2-C8Nitroalkenyl radical, C2-C8Alkynyl, C2-C8Halogenated alkynyl, C4-C10Cycloalkylalkyl radical, C4-C10Halocycloalkylalkyl radical, C5-C12Alkyl cycloalkyl alkyl, C5-C12Cycloalkylalkenyl radical, C5-C12Cycloalkyl alkynyl, C3-C8Cycloalkyl radical, C3-C8Halogenocycloalkyl, C4-C10Alkyl cycloalkyl radical, C6-C12Cycloalkyl, C3-C8Cycloalkenyl radical, C3-C8Halogenated cycloalkenyl radical, C2-C8Alkoxyalkyl group, C2-C8Haloalkoxyalkyl, C3-C8Haloalkoxyalkoxy group, C1-C4Hydroxyalkyl radical, C4-C10Cycloalkoxyalkyl radical, C3-C10Alkoxyalkoxyalkyl group, C2-C8Alkylthio alkyl, C2-C8Alkylsulfinylalkyl radical, C2-C8Alkylsulfonylalkyl group, C2-C8Alkylaminoalkyl, C2-C8Haloalkyl aminoalkyl radical, C4-C10Cycloalkylaminoalkyl radical, C3-C10Dialkylaminoalkyl, -CHO, C2-C8Alkylcarbonyl group, C2-C8Halogenoalkylcarbonyl group, C4-C10Cycloalkyl-carbonyl, -C (═ O) OH, C2-C8Alkoxycarbonyl group, C2-C8Halogenoalkoxycarbonyl, C4-C10Cycloalkoxycarbonyl radical, C5-C12Cycloalkyl alkoxycarbonyl, -C (═ O)NH2、C2-C8Alkylaminocarbonyl radical, C4-C10Cycloalkylaminocarbonyl group, C3-C10Dialkylaminocarbonyl group, C1-C8Alkoxy radical, C1-C8Haloalkoxy, C2-C8Alkoxyalkoxy radical, C2-C8Alkenyloxy radical, C2-C8Haloalkenyloxy, C2-C8Haloalkoxy, C3-C8Alkynyloxy, C3-C8Haloalkynyloxy, C3-C8Cycloalkoxy, C3-C8Halogenocycloalkoxy, C4-C10Cycloalkylalkoxy radical, C3-C10Alkylcarbonylalkoxy, C2-C8Alkylcarbonyloxy, C2-C8Halogenoalkylcarbonyloxy or C4-C10A cycloalkyl carbonyloxy group.
An embodiment 54. the compound of embodiment 53, wherein each R9Independently halogen, cyano, nitro, C1-C8Alkyl radical, C1-C4Cyanoalkyl, C1-C4Cyanoalkoxy group, C1-C8Haloalkyl, C1-C8Nitroalkyl, C2-C8Alkenyl radical, C2-C8Haloalkenyl, C2-C8Nitroalkenyl radical, C2-C8Alkynyl, C2-C8Halogenated alkynyl, C4-C10Cycloalkylalkyl radical, C4-C10Halocycloalkylalkyl radical, C5-C12Alkyl cycloalkyl alkyl, C5-C12Cycloalkylalkenyl radical, C5-C12Cycloalkyl alkynyl, C3-C8Cycloalkyl radical, C3-C8Halogenocycloalkyl, C4-C10Alkyl cycloalkyl radical, C6-C12Cycloalkyl, C3-C8Cycloalkenyl radical, C3-C8Halogenated cycloalkenyl radical, C2-C8Alkoxyalkyl group, C2-C8Haloalkoxyalkyl, C3-C8Haloalkoxyalkoxy group, C1-C4Hydroxyalkyl radical, C4-C10Cycloalkoxyalkyl radical, C3-C10Alkoxyalkoxyalkyl group, C2-C8Alkylthio alkyl, C2-C8Alkylsulfinylalkyl radical, C2-C8Alkylsulfonylalkyl group, C2-C8Alkylaminoalkyl, C2-C8Haloalkyl aminoalkyl radical, C4-C10Cycloalkylaminoalkyl radical or C3-C10A dialkylaminoalkyl group.
Embodiment 55. the compound of embodiment 54, wherein each R9Independently halogen, cyano, nitro, C1-C8Alkyl radical, C1-C4Cyanoalkyl, C1-C4Cyanoalkoxy group, C1-C8Haloalkyl, C1-C8Nitroalkyl, C2-C8Alkenyl radical, C2-C8Haloalkenyl, C2-C8Nitroalkenyl radical, C2-C8Alkynyl, C2-C8Halogenated alkynyl, C4-C10Cycloalkylalkyl radical, C4-C10Halocycloalkylalkyl radical, C5-C12Alkyl cycloalkyl alkyl, C5-C12Cycloalkylalkenyl radical, C5-C12Cycloalkyl alkynyl, C3-C8Cycloalkyl radical, C3-C8Halogenocycloalkyl, C4-C10Alkylcycloalkyl or C6-C12Cycloalkyl radicals.
Embodiment 56. the compound of embodiment 55, wherein each R9Independently halogen, cyano, nitro, C1-C8Alkyl radical, C1-C4Cyanoalkyl, C1-C4Cyanoalkoxy or C1-C8A haloalkyl group.
Embodiment 57. the compound of embodiment 56, wherein each R9Independently is halogen or C1-C8A haloalkyl group.
Example 58 As examples57, wherein each R is9Independently F, Cl or CF3。
Embodiment 59. the compound of embodiment 58, wherein each R9Independently is F or CF3。
Embodiment 60. the compound of any one of embodiments 1 to 59, wherein each R11Independently halogen, cyano, nitro, C1-C8Alkyl radical, C1-C4Cyanoalkyl, C1-C4Cyanoalkoxy group, C1-C8Haloalkyl, C1-C8Nitroalkyl, C2-C8Alkenyl radical, C2-C8Haloalkenyl, C2-C8Nitroalkenyl radical, C2-C8Alkynyl, C2-C8Halogenated alkynyl, C4-C10Cycloalkylalkyl radical, C4-C10Halocycloalkylalkyl radical, C5-C12Alkyl cycloalkyl alkyl, C5-C12Cycloalkylalkenyl radical, C5-C12Cycloalkyl alkynyl, C3-C8Cycloalkyl radical, C3-C8Halogenocycloalkyl, C4-C10Alkyl cycloalkyl radical, C6-C12Cycloalkyl, C3-C8Cycloalkenyl radical, C3-C8Halogenated cycloalkenyl radical, C2-C8Alkoxyalkyl group, C2-C8Haloalkoxyalkyl, C3-C8Haloalkoxyalkoxy group, C1-C4Hydroxyalkyl radical, C4-C10Cycloalkoxyalkyl radical, C3-C10Alkoxyalkoxyalkyl group, C2-C8Alkylthio alkyl, C2-C8Alkylsulfinylalkyl radical, C2-C8Alkylsulfonylalkyl group, C2-C8Alkylaminoalkyl, C2-C8Haloalkyl aminoalkyl radical, C4-C10Cycloalkylaminoalkyl radical, C3-C10Dialkylaminoalkyl, -CHO, C2-C8Alkylcarbonyl group, C2-C8Halogenoalkylcarbonyl group, C4-C10Cycloalkyl-carbonyl, -C (═ O) OH, C2-C8Alkoxycarbonyl group, C2-C8Halogenoalkoxycarbonyl, C4-C10Cycloalkoxycarbonyl radical, C5-C12Cycloalkylalkoxycarbonyl, -C (═ O) NH2、C2-C8Alkylaminocarbonyl radical, C4-C10Cycloalkylaminocarbonyl group, C3-C10Dialkylaminocarbonyl group, C1-C8Alkoxy radical, C1-C8Haloalkoxy, C2-C8Alkoxyalkoxy radical, C2-C8Alkenyloxy radical, C2-C8Haloalkenyloxy, C2-C8Haloalkoxy, C3-C8Alkynyloxy, C3-C8Haloalkynyloxy, C3-C8Cycloalkoxy, C3-C8Halogenocycloalkoxy, C4-C10Cycloalkylalkoxy radical, C3-C10Alkylcarbonylalkoxy, C2-C8Alkylcarbonyloxy, C2-C8Halogenoalkylcarbonyloxy group, C4-C10Cycloalkyl carbonyloxy, C1-C8Alkylsulfonyloxy, C1-C8Haloalkylsulfonyloxy, C1-C8Alkylthio radical, C1-C8Haloalkylthio, C3-C8Cycloalkylthio radical, C1-C8Alkylsulfinyl radical, C1-C8Haloalkylsulfinyl radical, C1-C8Alkylsulfonyl radical, C1-C8Haloalkylsulfonyl group, C3-C8Cycloalkyl sulfonyl, carboxamido, C2-C8Alkylcarbonylamino, C2-C8Haloalkylcarbonylamino or C2-C8An alkoxycarbonylamino group.
Embodiment 61. the compound of embodiment 60, wherein each R11Independently halogen, cyano, nitro, C1-C8Alkyl radical, C1-C4Cyanoalkyl, C1-C4CyanoalkaneOxy radical, C1-C8Haloalkyl, C1-C8Nitroalkyl, C2-C8Alkenyl radical, C2-C8Haloalkenyl, C2-C8Nitroalkenyl radical, C2-C8Alkynyl, C2-C8Halogenated alkynyl, C4-C10Cycloalkylalkyl radical, C4-C10Halocycloalkylalkyl radical, C5-C12Alkyl cycloalkyl alkyl, C5-C12Cycloalkylalkenyl radical, C5-C12Cycloalkyl alkynyl, C3-C8Cycloalkyl radical, C3-C8Halogenocycloalkyl, C4-C10Alkyl cycloalkyl radical, C6-C12Cycloalkyl, C3-C8Cycloalkenyl radical, C3-C8Halogenated cycloalkenyl radical, C2-C8Alkoxyalkyl group, C2-C8Haloalkoxyalkyl, C3-C8Haloalkoxyalkoxy group, C1-C4Hydroxyalkyl radical, C4-C10Cycloalkoxyalkyl radical, C3-C10Alkoxyalkoxyalkyl group, C2-C8Alkylthio alkyl, C2-C8Alkylsulfinylalkyl radical, C2-C8Alkylsulfonylalkyl group, C1-C8Alkylsulfonyloxy, C1-C8Haloalkylsulfonyloxy, C1-C8Alkylthio radical, C1-C8Haloalkylthio, C3-C8Cycloalkylthio radical, C1-C8Alkylsulfinyl radical, C1-C8Haloalkylsulfinyl radical, C1-C8Alkylsulfonyl radical, C1-C8Haloalkylsulfonyl or C3-C8A cycloalkylsulfonyl group.
Embodiment 62. the compound of embodiment 61, wherein each R11Independently halogen, cyano, nitro, C1-C8Alkyl radical, C1-C4Cyanoalkyl, C1-C4Cyanoalkoxy group, C1-C8Haloalkyl, C1-C8Nitroalkyl, C2-C8Alkenyl radical, C2-C8Haloalkenyl, C2-C8Nitroalkenyl radical, C2-C8Alkynyl, C2-C8Halogenated alkynyl, C4-C10Cycloalkylalkyl radical, C4-C10Halocycloalkylalkyl radical, C5-C12Alkyl cycloalkyl alkyl, C5-C12Cycloalkylalkenyl radical, C5-C12Cycloalkyl alkynyl, C3-C8Cycloalkyl radical, C1-C8Alkylsulfonyl radical, C1-C8Haloalkylsulfonyl or C3-C8A cycloalkylsulfonyl group.
Embodiment 63. the compound of embodiment 62, wherein each R11Independently of one another is halogen, C1-C8Alkyl radical, C1-C8Haloalkyl or C1-C8An alkylsulfonyl group.
Embodiment 64. the compound of embodiment 63, wherein each R11Independently F, Cl, CH3、CF3or-SO2CF3。
Embodiment 65. the compound of embodiment 64, wherein each R11Independently F, Cl, CH3、CF3or-SO2CF3。
Embodiment 66. the compound of any one of embodiments 1 to 65, wherein each R10And R12Independently is C1-C3Alkyl radical, C3-C6Cycloalkyl radical, C2-C3Alkoxyalkyl group, C2-C3Alkylcarbonyl group, C2-C3Alkoxycarbonyl or C2-C3An alkylaminoalkyl group.
Embodiment 67. the compound of embodiment 66, wherein each R10And R12Independently is C1-C3Alkyl radical, C3-C6Cycloalkyl or C2-C3An alkoxyalkyl group.
Embodiment 68. the compound of embodiment 67, whereinEach R10And R12Independently is C1-C3An alkyl group.
Embodiment 69. the compound of embodiment 68, wherein each R10And R12Independently is CH3。
Embodiment 70. the compound of embodiment 1, wherein Q1Is an 8-to 10-membered heteroaromatic bicyclic ring system, each ring system containing ring members selected from carbon atoms and 1 to 4 heteroatoms independently selected from up to 2O and up to 2N atoms, wherein up to 3 carbon ring members are independently selected from C (═ O) and C (═ S), each ring system being optionally substituted with up to 4 substituents independently selected from R on the carbon atom ring members9And said substituents on the ring members of the nitrogen atom are independently selected from R10。
Embodiment 71. the compound of embodiment 70, wherein Q1Is an 8-to 9-membered heteroaromatic bicyclic ring system, each ring system containing ring members selected from carbon atoms and 1 to 4 heteroatoms independently selected from up to 2O atoms, each ring system optionally substituted with up to 4 substituents independently selected from R on carbon atom ring members9。
Embodiment 72A compound of embodiment 71, wherein Q1Is a 9-membered heteroaromatic bicyclic ring system containing ring members selected from carbon atoms and 1 to 4 heteroatoms independently selected from up to 2O atoms, each ring system optionally substituted with up to 4 substituents independently selected from R on carbon atom ring members9。
Embodiment 73. the compound of embodiment 72, wherein Q1Is a 9-membered heteroaromatic bicyclic ring system containing ring members selected from carbon atoms and 2O atoms, optionally substituted with up to 3 substituents independently selected from R on the carbon atom ring members9(i.e., U-103 in example 3).
Embodiment 74. the compound of embodiment 73, wherein Q1Is U-103A.
Embodiment 75. the compound of any one of embodiments 1,2, and 10 to 69, wherein Q1Is optionally substituted with 1 to 4 substituents independently selected from R9A benzene ring substituted with the substituent of (1); or is a 5-to 6-membered heteroaromatic ring comprising ring members selected from carbon atoms and 1 to 4 heteroatoms independently selected from up to 2O, up to 2S and up to 4N atoms, optionally substituted with up to 4 substituents independently selected from R on carbon atom ring members9And said substituents on the ring members of the nitrogen atom are independently selected from R10。
Embodiment 76 the compound of embodiment 1, wherein Q2Is optionally selected from R by up to 511A benzene ring substituted with the substituent of (1); or is a 5-to 6-membered fully unsaturated heterocyclic ring, each ring containing ring members selected from carbon atoms and 1 to 4 heteroatoms independently selected from up to 2O, up to 2S and up to 4N atoms, each ring or ring system being optionally substituted with up to 5 substituents independently selected from R on the carbon atom ring members11And said substituents on the ring members of the nitrogen atom are independently selected from R12。
Embodiment 77A compound as described in embodiment 1 or 76, wherein Q2Is optionally selected from R by up to 511A benzene ring substituted with the substituent of (1); or is a 6-membered fully unsaturated heterocyclic ring, each ring containing ring members selected from carbon atoms and 1 to 4 heteroatoms independently selected from up to 4N atoms, each ring or ring system optionally substituted with up to 5 heteroatoms independently selected from R11Is substituted on a carbon atom ring member.
Embodiment 78. the compound of embodiment 77, wherein Q2Is optionally selected from R by up to 411A benzene ring substituted with the substituent of (1); or is a pyridine ring, optionally substituted with up to 4 substituents independently selected from R11Substituent(s) ofSubstitution on a carbon atom ring member.
Embodiment 79A compound of embodiment 78, wherein Q2Is optionally selected from R by up to 311A 3-pyridine ring substituted on a carbon atom ring member.
Embodiment 80. the compound of embodiment 79, wherein Q2Is optionally up to 3 independently selected from C1-C8Alkyl or C1-C8A 3-pyridine ring substituted with a substituent of a haloalkyl group.
Embodiment 81. the compound of any one of embodiments 1 to 56 or 60 to 80, wherein each R9Independently of one another is halogen, C1-C8Alkyl or C1-C8A haloalkyl group.
Embodiment 82. the compound of embodiment 81, wherein each R9Independently Cl, F, CH3Or CF3。
Embodiment 83. the compound of embodiment 82, wherein each R9Independently is CH3。
Embodiment 84. the compound of any one of embodiments 1 to 64 or 66 to 83, wherein each R11Independently F, Cl, CH3Or CF3。
Embodiment 85. the compound of embodiment 24, wherein A is-CH2CH2CH2-、-CH＝N-、-C(＝O)CH2-or-CH ═ CH-, wherein the bond projecting to the left is linked to the nitrogen of the-N-J-moiety, and the bond projecting to the right is linked to the nitrogen of the-N ═ C- (or-N-CH-) moiety of formula 1.
Embodiment 86. the compound of any one of embodiments 1 to 24 or 30 to 84, wherein A is-CH2CH2CH2-、-CH＝N-、-C(CH3)＝N-、-C(CH2CH3)＝N-、-C(CH2CH2CH3)＝N-、-C(CF3)＝N-、-C(＝O)CH2-or-CH ═ CH-, wherein the bond projecting to the left is linked to the nitrogen of the-N-J-moiety, and the bond projecting to the right is linked to the-N ═ C- (or-N-CH-) moiety of formula 1And (3) nitrogen.
Embodiment 87. the compound of embodiment 86, wherein a is-CH ═ N-, -C (CH)3)＝N-、-C(CH2CH3)＝N-、-C(CH2CH2CH3) N-or-C (CF)3) N-, wherein the bond extending to the left is linked to the nitrogen of the-N-J-moiety and the bond extending to the right is linked to the nitrogen of the-N ═ C- (or-N-CH-) moiety of formula 1.
The compound of any one of embodiments 1 to 24 or 30 to 84, wherein a is-C (R)3) N-, wherein the bond extending to the left is linked to the nitrogen of the-N-J-moiety and the bond extending to the right is linked to the nitrogen of the-N ═ C- (or-N-CH-) moiety of formula 1.
An embodiment 89. the compound of embodiment 88 wherein a is-CH ═ N-.
Embodiment 90. the compound of embodiment 88, wherein A is-C (CH)3)＝N-。
An embodiment 91. the compound of embodiment 88, wherein A is-C (CH)2CH3)＝N-。
Embodiments of the present invention, including the above embodiments 1-91, as well as any other embodiments described herein, can be combined in any manner, and the description of the variables in the embodiments refers not only to the compounds of formula 1, but also to the starting compounds and intermediate compounds useful for preparing the compounds of formula 1. Furthermore, embodiments of the present invention, including the above embodiments 1-91, as well as any other embodiments described herein, and any combination thereof, relate to the compositions and methods of the present invention.
Embodiment a. a compound of formula 1, wherein:
Q1is a phenyl or benzyl ring or a naphthalene ring system, each ring or ring system optionally being selected up to 5 independently from R9Substituted with the substituent(s); or is a 5-to 6-membered fully unsaturated heterocyclic ring, each ring or ring system containing ring members selected from carbon atoms and 1 to 4 heteroatoms independently selected from up to 2O, up to 2S and up to 4N atoms, wherein up to 3 carbon ring members are independently selected from C (═ O) and C (O) and (C: (a) and (b)S) and these sulfur atom ring members are independently selected from S (═ O)u(＝NR8)vEach ring or ring system is optionally substituted with up to 5 substituents independently selected from R on carbon atom ring members9And said substituents on the ring members of the nitrogen atom are independently selected from R10；
Q2Is a benzene ring or a naphthalene ring system, each ring or ring system optionally being selected up to 5 independently from R11Substituted with the substituent(s); or is a 5-to 6-membered fully unsaturated heterocyclic ring, each ring containing ring members selected from carbon atoms and 1 to 4 heteroatoms independently selected from up to 1O, up to 1S and up to 2N atoms, wherein up to 2 carbon ring members are independently selected from C (═ O) and C (═ S), and the sulfur ring members are independently selected from S (═ O)u(＝NR8)vEach ring or ring system is optionally substituted with up to 5 substituents independently selected from R on carbon atom ring members11And said substituents on the ring members of the nitrogen atom are independently selected from R12；
R1And R2Each independently is H, halogen or C1-C4An alkyl group;
y is O or S;
a is a saturated, partially unsaturated or fully unsaturated chain containing 2 to 4 atoms selected from up to 3 carbons, up to 1O, up to 1S and up to 1N atom, wherein up to 2 carbon members are independently selected from C (═ O) and C (═ S) and the sulfur atom member is selected from S (═ O)u(＝NR8)v(ii) a Said chain being optionally substituted with up to 3 substituents independently selected from R on carbon3And on the nitrogen atom the substituents are independently selected from R4；
Each R3Independently halogen, cyano, hydroxy, -CO2H、C1-C4Alkyl radical, C1-C4Haloalkyl, C1-C4Alkoxy radical, C1-C4Alkylthio radical, C3-C6Cycloalkyl or C4-C6A cycloalkylalkyl group;
each R4Independently is C1-C4Alkyl radical, C1-C4Haloalkyl or C3-C6A cycloalkyl group;
R5and R6Each independently is H, halogen, hydroxy or CH3；
R5aAnd R6aEach independently is H or C1-C4An alkyl group;
R7is H, hydroxy, amino, C1-C6Alkyl radical, C1-C6Haloalkyl, C2-C6Alkenyl radical, C3-C6Alkynyl, C2-C8Alkoxyalkyl group, C2-C8Haloalkoxyalkyl, C2-C8Alkylthio alkyl, C2-C8Alkylsulfinylalkyl radical, C2-C8Alkylsulfonylalkyl group, C2-C8Alkylcarbonyl group, C2-C8Halogenoalkylcarbonyl group, C4-C10Cycloalkyl carbonyl group, C2-C8Alkoxycarbonyl group, C2-C8Halogenoalkoxycarbonyl, C4-C10Cycloalkoxycarbonyl radical, C2-C8Alkylaminocarbonyl radical, C3-C10Dialkylaminocarbonyl or C4-C10A cycloalkylaminocarbonyl group;
each R8Independently is H, cyano or C2-C3An alkylcarbonyl group;
each R9Independently halogen, cyano, nitro, C1-C8Alkyl radical, C1-C4Cyanoalkyl, C1-C4Cyanoalkoxy group, C1-C8Haloalkyl, C1-C8Nitroalkyl, C2-C8Alkenyl radical, C2-C8Haloalkenyl, C2-C8Nitroalkenyl radical, C2-C8Alkynyl, C2-C8Halogenated alkynyl, C4-C10Cycloalkylalkyl radical, C4-C10Halocycloalkylalkyl radical, C5-C12Alkyl cycloalkyl alkyl, C5-C12Cycloalkylalkenyl radical, C5-C12Cycloalkyl alkynyl, C3-C8Cycloalkyl radical, C3-C8Halogenocycloalkyl, C4-C10Alkyl cycloalkyl radical, C6-C12Cycloalkyl, C3-C8Cycloalkenyl radical, C3-C8Halogenated cycloalkenyl radical, C2-C8Alkoxyalkyl group, C2-C8Haloalkoxyalkyl, C3-C8Haloalkoxyalkoxy group, C1-C4Hydroxyalkyl radical, C4-C10Cycloalkoxyalkyl radical, C3-C10Alkoxyalkoxyalkyl group, C2-C8Alkylthio alkyl, C2-C8Alkylsulfinylalkyl radical, C2-C8Alkylsulfonylalkyl group, C2-C8Alkylaminoalkyl, C2-C8Haloalkyl aminoalkyl radical, C4-C10Cycloalkylaminoalkyl radical, C3-C10Dialkylaminoalkyl, -CHO, C2-C8Alkylcarbonyl group, C2-C8Halogenoalkylcarbonyl group, C4-C10Cycloalkyl-carbonyl, -C (═ O) OH, C2-C8Alkoxycarbonyl group, C2-C8Halogenoalkoxycarbonyl, C4-C10Cycloalkoxycarbonyl radical, C5-C12Cycloalkylalkoxycarbonyl, -C (═ O) NH2、C2-C8Alkylaminocarbonyl radical, C4-C10Cycloalkylaminocarbonyl group, C3-C10Dialkylaminocarbonyl group, C1-C8Alkoxy radical, C1-C8Haloalkoxy, C2-C8Alkoxyalkoxy radical, C2-C8Alkenyloxy radical, C2-C8Haloalkenyloxy, C2-C8Haloalkoxy, C3-C8Alkynyloxy, C3-C8Haloalkynyloxy, C3-C8Cycloalkoxy, C3-C8Halogenocycloalkoxy, C4-C10Cycloalkylalkoxy radical, C3-C10Alkylcarbonylalkoxy, C2-C8Alkylcarbonyloxy, C2-C8Halogenoalkylcarbonyloxy or C4-C10A cycloalkyl carbonyloxy group;
each R11Independently halogen, cyano, nitro, C1-C8Alkyl radical, C1-C4Cyanoalkyl, C1-C4Cyanoalkoxy group, C1-C8Haloalkyl, C1-C8Nitroalkyl, C2-C8Alkenyl radical, C2-C8Haloalkenyl, C2-C8Nitroalkenyl radical, C2-C8Alkynyl, C2-C8Halogenated alkynyl, C4-C10Cycloalkylalkyl radical, C4-C10Halocycloalkylalkyl radical, C5-C12Alkyl cycloalkyl alkyl, C5-C12Cycloalkylalkenyl radical, C5-C12Cycloalkyl alkynyl, C3-C8Cycloalkyl radical, C3-C8Halogenocycloalkyl, C4-C10Alkyl cycloalkyl radical, C6-C12Cycloalkyl, C3-C8Cycloalkenyl radical, C3-C8Halogenated cycloalkenyl radical, C2-C8Alkoxyalkyl group, C2-C8Haloalkoxyalkyl, C3-C8Haloalkoxyalkoxy group, C1-C4Hydroxyalkyl radical, C4-C10Cycloalkoxyalkyl radical, C3-C10Alkoxyalkoxyalkyl group, C2-C8Alkylthio alkyl, C2-C8Alkylsulfinylalkyl radical, C2-C8Alkylsulfonylalkyl group, C2-C8Alkylaminoalkyl, C2-C8Haloalkyl aminoalkyl radical, C4-C10Cycloalkylaminoalkyl radical, C3-C10Dialkylaminoalkyl, -CHO, C2-C8Alkylcarbonyl group, C2-C8Halogenoalkylcarbonyl group, C4-C10Cycloalkyl-carbonyl, -C (═ O) OH, C2-C8Alkoxycarbonyl group, C2-C8Halogenoalkoxycarbonyl, C4-C10Cycloalkoxycarbonyl radical, C5-C12Cycloalkylalkoxycarbonyl, -C (═ O) NH2、C2-C8Alkylaminocarbonyl radical, C4-C10Cycloalkylaminocarbonyl group, C3-C10Dialkylaminocarbonyl group, C1-C8Alkoxy radical, C1-C8Haloalkoxy, C2-C8Alkoxyalkoxy radical, C2-C8Alkenyloxy radical, C2-C8Haloalkenyloxy, C2-C8Haloalkoxy, C3-C8Alkynyloxy, C3-C8Haloalkynyloxy, C3-C8Cycloalkoxy, C3-C8Halogenocycloalkoxy, C4-C10Cycloalkylalkoxy radical, C3-C10Alkylcarbonylalkoxy, C2-C8Alkylcarbonyloxy, C2-C8Halogenoalkylcarbonyloxy group, C4-C10Cycloalkyl carbonyloxy, C1-C8Alkylsulfonyloxy, C1-C8Haloalkylsulfonyloxy, C1-C8Alkylthio radical, C1-C8Haloalkylthio, C3-C8Cycloalkylthio radical, C1-C8Alkylsulfinyl radical, C1-C8Haloalkylsulfinyl radical, C1-C8Alkylsulfonyl radical, C1-C8Haloalkylsulfonyl group, C3-C8Cycloalkyl sulfonyl, carboxamido, C2-C8Alkylcarbonylamino, C2-C8Haloalkylcarbonylamino or C2-C8An alkoxycarbonylamino group; and is
Each R10And R12Independently is C1-C3Alkyl radical, C3-C6Cycloalkyl radical, C2-C3Alkoxyalkyl group, C2-C3Alkylcarbonyl group, C2-C3Alkoxycarbonyl or C2-C3An alkylaminoalkyl group.
A compound as in example A, wherein
Q1Is optionally selected from R by up to 59A benzene ring substituted with the substituent of (1); or is a 5-to 6-membered fully unsaturated heterocyclic ring, each ring containing ring members selected from carbon atoms and 1 to 4 heteroatoms independently selected from up to 2O, up to 2S and up to 4N atoms, wherein up to 3 carbon ring members are independently selected from C (═ O) and C (═ S), and the sulfur ring members are independently selected from S (═ O)u(＝NR8)vEach ring or ring system is optionally substituted with up to 5 substituents independently selected from R on carbon atom ring members9And said substituents on the ring members of the nitrogen atom are independently selected from R10；
Q2Is optionally selected from R by up to 511A benzene ring substituted with the substituent of (1);
R1and R2Each independently is H, Cl, or CH3；
Y is O;
a is a saturated or partially unsaturated chain containing 2 to 4 atoms selected from up to 2 carbons and up to 1N atom, wherein up to 1 carbon member is independently selected from C (═ O) and C (═ S); said chain being optionally substituted with up to 2 substituents independently selected from R on carbon3And on the nitrogen atom the substituents are independently selected from R4；
Each R3Independently cyano, -CO2H、C1-C4Alkyl radical, C1-C4Haloalkyl, C1-C4Alkylthio or C4-C6A cycloalkylalkyl group;
each R4Independently is C1-C4An alkyl group;
j is-CR5R6-；
R5And R6Each independently is H or halogen;
R7is H, hydroxy, amino, C1-C6Alkyl radical, C1-C6Haloalkyl, C2-C6Alkenyl radical, C3-C6Alkynyl, C2-C8Alkoxyalkyl group, C2-C8Haloalkoxyalkyl or C2-C8An alkylthio alkyl group;
each R8Independently is H;
each R9Independently halogen, cyano, nitro, C1-C8Alkyl radical, C1-C4Cyanoalkyl, C1-C4Cyanoalkoxy group, C1-C8Haloalkyl, C1-C8Nitroalkyl, C2-C8Alkenyl radical, C2-C8Haloalkenyl, C2-C8Nitroalkenyl radical, C2-C8Alkynyl, C2-C8Halogenated alkynyl, C4-C10Cycloalkylalkyl radical, C4-C10Halocycloalkylalkyl radical, C5-C12Alkyl cycloalkyl alkyl, C5-C12Cycloalkylalkenyl radical, C5-C12Cycloalkyl alkynyl, C3-C8Cycloalkyl radical, C3-C8Halogenocycloalkyl, C4-C10Alkyl cycloalkyl radical, C6-C12Cycloalkyl, C3-C8Cycloalkenyl radical, C3-C8Halogenated cycloalkenyl radical, C2-C8Alkoxyalkyl group, C2-C8Haloalkoxyalkyl, C3-C8Haloalkoxyalkoxy group, C1-C4Hydroxyalkyl radical, C4-C10Cycloalkoxyalkyl radical, C3-C10Alkoxyalkoxyalkyl group, C2-C8Alkylthio alkyl, C2-C8Alkylsulfinylalkyl radical, C2-C8Alkylsulfonylalkyl group, C2-C8Alkylaminoalkyl, C2-C8Haloalkyl groupAminoalkyl radical, C4-C10Cycloalkylaminoalkyl radical or C3-C10A dialkylaminoalkyl group;
each R11Independently halogen, cyano, nitro, C1-C8Alkyl radical, C1-C4Cyanoalkyl, C1-C4Cyanoalkoxy group, C1-C8Haloalkyl, C1-C8Nitroalkyl, C2-C8Alkenyl radical, C2-C8Haloalkenyl, C2-C8Nitroalkenyl radical, C2-C8Alkynyl, C2-C8Halogenated alkynyl, C4-C10Cycloalkylalkyl radical, C4-C10Halocycloalkylalkyl radical, C5-C12Alkyl cycloalkyl alkyl, C5-C12Cycloalkylalkenyl radical, C5-C12Cycloalkyl alkynyl, C3-C8Cycloalkyl radical, C3-C8Halogenocycloalkyl, C4-C10Alkyl cycloalkyl radical, C6-C12Cycloalkyl, C3-C8Cycloalkenyl radical, C3-C8Halogenated cycloalkenyl radical, C2-C8Alkoxyalkyl group, C2-C8Haloalkoxyalkyl, C3-C8Haloalkoxyalkoxy group, C1-C4Hydroxyalkyl radical, C4-C10Cycloalkoxyalkyl radical, C3-C10Alkoxyalkoxyalkyl group, C2-C8Alkylthio alkyl, C2-C8Alkylsulfinylalkyl radical, C2-C8Alkylsulfonylalkyl group, C1-C8Alkylsulfonyloxy, C1-C8Haloalkylsulfonyloxy, C1-C8Alkylthio radical, C1-C8Haloalkylthio, C3-C8Cycloalkylthio radical, C1-C8Alkylsulfinyl radical, C1-C8Haloalkylsulfinyl radical, C1-C8Alkylsulfonyl radical, C1-C8Haloalkylsulfonyl or C3-C8A cycloalkylsulfonyl group; and areAnd is
Each R10And R12Independently is C1-C3Alkyl radical, C3-C6Cycloalkyl or C2-C3An alkoxyalkyl group.
The compound of embodiment B, wherein
Q1Is optionally selected from R by up to 59A benzene ring substituted with the substituent of (1);
Q2is optionally selected from R by up to 311A benzene ring substituted with the substituent of (1);
R1and R2Each independently is H or Cl;
a is a saturated or partially unsaturated chain containing 2 to 3 atoms selected from up to 2 carbons and up to 1N atom, wherein up to 1 carbon member is independently selected from C (═ O); said chain being optionally substituted with up to 1 substituent independently selected from R on carbon3And on the nitrogen atom the substituents are independently selected from R4；
Each R3Independently cyano, -CO2H or C1-C4An alkyl group;
each R4Is CH3；
R5And R6Each independently is H or halogen;
R7is H, C1-C6Alkyl radical, C2-C6Alkenyl radical, C3-C6Alkynyl or C2-C8An alkoxyalkyl group;
each R9Independently halogen, cyano, nitro, C1-C8Alkyl radical, C1-C4Cyanoalkyl, C1-C4Cyanoalkoxy group, C1-C8Haloalkyl, C1-C8Nitroalkyl, C2-C8Alkenyl radical, C2-C8Haloalkenyl, C2-C8Nitroalkenyl radical, C2-C8Alkynyl, C2-C8HalogenatedAlkynyl, C4-C10Cycloalkylalkyl radical, C4-C10Halocycloalkylalkyl radical, C5-C12Alkyl cycloalkyl alkyl, C5-C12Cycloalkylalkenyl radical, C5-C12Cycloalkyl alkynyl, C3-C8Cycloalkyl radical, C3-C8Halogenocycloalkyl, C4-C10Alkylcycloalkyl or C6-C12Cycloalkyl groups; and is
Each R11Independently halogen, cyano, nitro, C1-C8Alkyl radical, C1-C4Cyanoalkyl, C1-C4Cyanoalkoxy group, C1-C8Haloalkyl, C1-C8Nitroalkyl, C2-C8Alkenyl radical, C2-C8Haloalkenyl, C2-C8Nitroalkenyl radical, C2-C8Alkynyl, C2-C8Halogenated alkynyl, C4-C10Cycloalkylalkyl radical, C4-C10Halocycloalkylalkyl radical, C5-C12Alkyl cycloalkyl alkyl, C5-C12Cycloalkylalkenyl radical, C5-C12Cycloalkyl alkynyl, C3-C8Cycloalkyl radical, C1-C8Alkylsulfonyl radical, C1-C8Haloalkylsulfonyl or C3-C8A cycloalkylsulfonyl group.
The compound of embodiment C, wherein
Q1Is selected from 1 to 3 independently from R9A benzene ring substituted with the substituent of (1);
Q2is at the 3-position selected from R by 111A benzene ring substituted with the substituent of (1);
R1and R2Each is H;
a is-CH2CH2CH2-、-NCH2-、-C(＝O)CH2-or-CH ═ CH-, wherein the bond projecting to the left is linked to the nitrogen of the-N-J-moiety and the bond projecting to the right is linked to the nitrogen of the-N ═ C-moiety of formula 1;
each R9Independently halogen, cyano, nitro, C1-C8Alkyl radical, C1-C4Cyanoalkyl, C1-C4Cyanoalkoxy or C1-C8A haloalkyl group; and is
Each R11Independently of one another is halogen, C1-C8Alkyl radical, C1-C8Haloalkyl or C1-C8An alkylsulfonyl group.
The compound of embodiment E, wherein
Q1Is selected from 1 to 2 independently from R9A benzene ring substituted with the substituent of (1);
a is-CH2CH2CH2-；
Each R9Independently is halogen or C1-C8A haloalkyl group; and is
Each R11Independently F, Cl, CH3、CF3or-SO2CF3。
The compound of embodiment F, wherein
Q1Is selected from 1 to 2 independently from R9A benzene ring substituted with the substituent of (1);
a is-NCH2-wherein the bond extending to the left is linked to the nitrogen of the-N-J-moiety and the bond extending to the right is linked to the nitrogen of the-N ═ C-moiety of formula 1;
each R9Independently F, Cl, CF3(ii) a And is
Each R11Independently F, Cl, CH3、CF3or-SO2CF3。
The compound of embodiment C, wherein
A is-CH2CH2CH2-、-CH＝N-、-C(CH3)＝N-、-(CH2CH3)＝N-、-C(CH2CH2CH3)＝N-、-C(CF3)＝N-、-C(＝O)CH2-or-CH ═ CH-, where the radicals extend to the leftThe bond extending out is linked to the nitrogen of the-N-J-moiety and the bond extending to the right is linked to the nitrogen of the-N ═ C- (or-N-CH-) moiety of formula 1;
each R9Independently halogen, cyano, nitro, C1-C8Alkyl radical, C1-C4Cyanoalkyl, C1-C4Cyanoalkoxy or C1-C8A haloalkyl group; and is
Each R11Independently of one another is halogen, C1-C8Alkyl radical, C1-C8Haloalkyl or C1-C8An alkylsulfonyl group.
The compound of embodiment G, wherein
A is-CH-N-, -C (CH)3)＝N-、-C(CH2CH3)＝N-、-C(CH2CH2CH3) N-or-C (CF)3) N-, wherein the bond extending to the left is linked to the nitrogen of the-N-J-moiety and the bond extending to the right is linked to the nitrogen of the-N ═ C- (or-N-CH-) moiety of formula 1;
each R9Independently of one another is halogen, C1-C8Alkyl or C1-C8A haloalkyl group; and is
Each R11Independently F, Cl, CH3Or CF3。
Particular embodiments of the invention include compounds of the inventive content selected from the group consisting of:
n- (2-fluorophenyl) -6, 7-dihydro-6- [3- (trifluoromethyl) phenyl ] -5H-pyrrolo [2,1-c ] -1,2, 4-triazole-7-carboxamide; and
n- (2-fluorophenyl) -2,3,6, 7-tetrahydro-3-oxo-6- [3- (trifluoromethyl) phenyl ] -5H-pyrrolo [1,2-a ] imidazole-7-carboxamide.
The invention also relates to a method for controlling undesirable vegetation which comprises applying to the locus of the vegetation a herbicidally effective amount of a compound of the invention (e.g. as a composition as described herein). It should be noted that the examples as to the method of use are those relating to the compounds of the above examples. The compounds of the invention are particularly useful for selectively controlling broadleaf weeds in crops such as wheat, barley, maize, soybean, sunflower, cotton, oilseed rape and rice, and specialty crops such as sugarcane, citrus, fruit and nut crops.
Further noteworthy as examples are herbicidal compositions of the present invention comprising the compounds of the above examples.
The present invention also includes a herbicidal mixture comprising (a) a compound selected from formula 1, the N-oxides and salts thereof and (b) at least one additional active ingredient selected from the group consisting of: (b1) photosystem II inhibitors, (b2) acetohydroxyacid synthase (AHAS) inhibitors, (b3) acetyl-coa carboxylase (ACCase) inhibitors, (b4) auxin mimics, (b5) 5-enol-pyruvylshikimate-3-phosphate (EPSP) synthase inhibitors, (b6) photosystem I electron diverters, (b7) protoporphyrinogen oxidase (hpp) inhibitors, (b8) Glutamine Synthetase (GS) inhibitors, (b9) Very Long Chain Fatty Acid (VLCFA) elongase inhibitors, (b10) auxin transport inhibitors, (b11) Phytoene Dehydrogenase (PDS) inhibitors, (b12) 4-hydroxyphenyl-pyruvate dioxygenase (d) inhibitors, (b13) Homogentisate Solanesyltransferase (HST) inhibitors, (b14) cellulose biosynthesis inhibitors, (b15) other herbicides, including mitotic disruptors, organic arsenic-containing compounds, asulam, bebutamid, cinmethylin, prosulfuron, dazomet, difenzoquat, prosulfuron, ethoxybenclamide, butastatin, phosphinothricin-ammonium, hydantocidin, metam, meturon-methyl, oleic acid, oxaziclomefone, pelargonic acid and pyributicarb, and (b16) herbicide safeners; and salts of the compounds of (b1) to (b 16).
The "photosystem II inhibitor" (b1) is at QBBinding to the D-1 protein at the binding site and thus blocking of electrons from Q in the chloroplast thylakoid membraneAIs transmitted to QBThe compound of (1). Electrons blocked by passage through photosystem II are transferred through a series of reactions to form toxic compounds that disrupt the cell membrane and cause chloroplast swelling, membrane leakage, and ultimately cell rupture. QBThe binding site has three distinct binding sites: the binding site A binds to a triazine such as atrazine, a triazinone such as a hexazinone,And uracils such as bromacil, binding site B to phenylureas such as diuron, and binding site C to benzothiadiazoles such as bentazon, nitriles such as bromoxynil, and phenyl-pyridazines such as pyridate. Examples of photosystem II inhibitors include ametryn, amicarbazone, atrazine, bentazon, bromacil, desmetryn, bromoxynil, chlorsulfuron, mesoxyfen, chlorotoluron, chlortoluron, subtilon, prosulfuron, cyanazine, desmodium, desmedipham, desmetryn, oxazolon, prenetryn, sulfothiouron, fensulfuron-methyl, fluometuron, hexazinone, ioxynil, isoproturon, isoxauron, cyclanil, linuron, metamitron, methabenzthiauron, bromuron, metoxuron, metribuzin, glusulfuron, prosulfuron, mechlorethamine, bendioate, prometryn, propanil, prometryn, pyridaben (pyridabel), pyridate, cycloate, sima, simetryn, tebuthiuron, terbutryn, darunavir, and bentazone. Of note are compounds of the present invention in admixture with atrazine, bromoxynil or metribuzin.
"AHAS inhibitors" (b2) are compounds that inhibit acetohydroxyacid synthase (AHAS), also known as acetolactate synthase (ALS), and thus kill plants by inhibiting the production of branched-chain aliphatic amino acids such as valine, leucine and isoleucine, which are required for protein synthesis and cell growth. Examples of AHAS inhibitors include amidosulfuron, azimsulfuron, bensulfuron-methyl, bispyribac-sodium, cloransulam-methyl, chlorimuron-ethyl, chlorsulfuron, cinosulfuron, cyclosulfamuron, diclosulam, ethametsulfuron, ethoxysulfuron, flazasulfuron, florasulam, flucarbazone-sodium, flumetsulam, flupyrsulfuron-methyl, foramsulfuron, halosulfuron-methyl, imazamox, imazapyr, imazaquin, imazosulfuron, iodosulfuron (including sodium salt), iodosulfuron (iofensulfuron) (2-iodo-N- [ [ (4-methoxy-6-methyl-1, 3, 5-triazin-2-yl) amino ] carbonyl ] benzenesulfonamide), mesosulfuron, metribusulfuron (3-chloro-4- (5, 6-dihydro-5-methyl-1, 4, 2-dioxazin-3-yl) -N- [ [ (4, 6-dimethoxy-2-pyrimidinyl) amino ] carbonyl ] -1-methyl-1H-pyrazole-5-sulfonamide, sulfluramid, metsulfuron-methyl, nicosulfuron, epoxysulfuron, penoxsulam, fluchlorsulfuron, prosulfuron-sodium, propyrisulfuron (2-chloro-N- [ [ (4, 6-dimethoxy-2-pyrimidinyl) amino ] carbonyl ] -6-propylimidazo [1,2-b ] pyridazine-3-sulfonamide), prosulfuron, pyrazosulfuron, pyribenzoxim-ethyl, pyriminobac-methyl, pyriminobac-sodium, pyriminothium ether-sodium, Rimsulfuron, sulfometuron, sulfosulfuron, thiencarbazone, thifensulfuron, triafamone (N- [2- [ (4, 6-dimethoxy-1, 3, 5-triazin-2-yl) carbonyl ] -6-fluorophenyl ] -1, 1-difluoro-N-methylmethanesulfonamide), triasulfuron, tribenuron, trifloxysulfuron (including sodium salt), triflusulfuron and triflusulfuron. Of note are compounds of the present invention mixed with nicosulfuron, primisulfuron-methyl, or chlorimuron-ethyl.
"ACCase inhibitors" (b3) are compounds that inhibit acetyl-CoA carboxylase, the enzyme responsible for catalyzing the early steps in lipid and fatty acid synthesis in plants. Lipids are the major components of cell membranes, and without lipids, new cells cannot be generated. Inhibition of acetyl-coa carboxylase and lack of subsequent lipid production results in loss of cell membrane integrity, especially in actively growing areas such as meristems. Eventually seedling and rhizome growth ceases and seedling meristems and rhizome buds begin to die. Examples of ACCase inhibitors include diclofop-methyl, butroxen, clethodim, clomazone, cyhalofop-butyl, diclofop-methyl, fenoxaprop-ethyl, fluazifop-butyl, haloxyfop-ethyl, pinoxaden, propaquizafop, sethoxydim, dyzone and oxyzone, including resolved forms such as fenoxaprop-ethyl, fluazifop-p-ethyl, haloxyfop-ethyl and quizalofop-p-ethyl and ester forms such as clodinafop-propargyl, cyhalofop-butyl, diclofop-ethyl and fenoxaprop-ethyl. Of note are compounds of the present invention in admixture with pinoxaden or quizalofop-ethyl.
Auxins are plant hormones that regulate the growth of many plant tissues. "auxin mimics" (b4) are compounds that mimic the auxin, a plant growth hormone, and thus lead to uncontrolled and disordered growth, resulting in the death of plants of susceptible species. Examples of auxin mimics include aminocyclopyrachlor (6-amino-5-chloro-2-cyclopropyl-4-pyrimidinecarboxylic acid) and methyl and ethyl esters thereof and sodium and potassium salts thereof, aminopyralid, benazolin-ethyl ester, benazepin, dichlorpyric acid, dicamba, 2,4-D, 2,4-DB, dichlorprop-propionic acid, fluroxypyr, halauxifen (halauxifen) (4-amino-3-chloro-6- (4-chloro-2-fluoro-3-methoxyphenyl) -2-pyridinecarboxylic acid), halauxifen-methyl (4-amino-3-chloro-6- (4-chloro-2-fluoro-3-methoxyphenyl) -2-pyridinecarboxylic acid), MCPA, MCPB, 2-methyl-4-chloropropionic acid, picloram, quinclorac, chloroquinolinic acid, 2,3,6-TBA, triclopyr, and methyl 4-amino-3-chloro-6- (4-chloro-2-fluoro-3-methoxyphenyl) -5-fluoro-2-pyridinecarboxylate. Of note are compounds of the present invention in admixture with dicamba.
"EPSP synthase inhibitors" (b5) are compounds that inhibit the enzyme, 5-enol-pyruvylshikimate-3-phosphate synthase, which is involved in the synthesis of aromatic amino acids such as tyrosine, tryptophan and phenylalanine. EPSP inhibitor herbicides are readily absorbed by plant leaves and translocated to the growing point in the phloem. Glyphosate is a relatively non-selective post-emergence herbicide belonging to this group. Glyphosate includes esters and salts such as ammonium, isopropylammonium, potassium, sodium (including sesquisodium) and trimethylsulfonium salts (otherwise known as sulfoglufosinate).
A "photosystem I electron redirector" (b6) is a compound that receives electrons from photosystem I and generates hydroxyl radicals after a number of cycles. These free bases are reactive and tend to break down unsaturated lipids, including membrane fatty acids and chlorophyll. This disrupts cell membrane integrity, allowing cells and organelles to "leak," resulting in rapid leaf wilting and drying out, and ultimately, plant death. Examples of this second type of photosynthesis inhibitor include diquat and paraquat.
"PPO inhibitors" (b7) are compounds that inhibit the enzyme protoporphyrinogen oxidase, which rapidly leads to the formation of highly reactive compounds in plants that disrupt the cell membrane, leading to the exudation of the cellular fluid. Examples of PPO inhibitors include acifluorfen-sodium, carfentrazone-ethyl, bensulfuron-methyl, bifenoxafen, bifenox, butafenacil, carfentrazone-ethyl, metoclopramide, cinidon-ethyl, isoxafluazinam, fluazinam-ethyl, flumiclorac-methyl, fluorothiacet-methyl, fomesafen, fluorosulfamide (halosafen), lactofen, oxadiargyl, oxadiazon, oxyfluorfen, pentoxazone, flumetsulam, pyraclonil, pyraflufen-ethyl, bensulfuron-methyl, sulfentrazone, thiadiazolyl, triflumimoxazin (dihydro-1, 5-dimethyl-6-thio-3- [2,2, 7-trifluoro-3, 4-dihydro-3-oxy-4- (2-prop-1-yl) -2H-1, 4-benzoxazin-6-yl ] -1,3, 5-triazine-2, 4(1H,3H) -dione and butafenacil (tiafenacil) (N- [2- [ [ 2-chloro-5- [3, 6-dihydro-3-methyl-2, 6-dioxy-4- (trifluoromethyl) -1(2H) -pyrimidinyl ] -4-fluorophenyl ] thio ] -1-oxopropyl ] - β -alanine methyl ester).
"GS inhibitors" (b8) are compounds that inhibit the activity of glutamine synthetase, which plants use to convert ammonia to glutamine. Thus, ammonia accumulates and glutamine levels decrease. Plant damage may occur due to the combined effects of ammonia toxicity and the lack of other amino acids required for metabolic processes. GS inhibitors include glufosinate and esters and salts thereof, such as glufosinate and other glufosinate derivatives, glufosinate-P ((2S) -2-amino-4- (hydroxymethyl phosphinyl) butanoic acid), and bialaphos (bialaphos).
"VLCFA elongase inhibitors" (b9) are herbicides with various chemical structures that inhibit elongases. The elongase is one of the enzymes located in or near the chloroplast, which are involved in the biosynthesis of VLCFA. In plants, very long chain fatty acids are the main component of hydrophobic polymers, which prevent drying at the leaf surface and provide stability of the pollen grains. Such herbicides include acetochlor, alachlor, anilofos, butachlor, fenpyrozole, dimethachlor, dimethenamid, bisphenamid, isoxasulfone (fenoxasulfone) (3- [ [ (2, 5-dichloro-4-ethoxyphenyl) methyl ] sulfonyl ] -4, 5-dihydro-5, 5-dimethylisoxazole), fentrazamide, flufenacet, indandim, mefenacet, metazachlor, metolachlor, napropamide, dexam-M ((2R) -N, N-diethyl-2- (1-naphthyloxy) propanamide), pethoxamid, mephos, pretilachlor, propyzamide, propisochlor, roxysulfone (pyroxasulfone), and methoxyfenacet, including resolved forms such as s-metolachlor and chloroacetamide and oxyacetamide. Of note are compounds of the present invention in admixture with flufenacet.
An "auxin transport inhibitor" (b10) is a chemical that inhibits auxin transport in plants, such as by binding to an auxin-carrier protein. Examples of auxin transport inhibitors include diflufenzopyr, naproxen (also known as N- (1-naphthyl) -o-carbamoylbenzoic acid and 2- [ (1-naphthylamino) carbonyl ] benzoic acid).
"PDS inhibitors (b 11)" are compounds which inhibit the carotenoid biosynthetic pathway at the phytoene desaturase step. Examples of PDS inhibitors include beflubutamid, diflufenican, fluridone, flurtamone, norflurzon, and picolinafen.
An "HPPD inhibitor" (b12) is a biosynthetic chemical that inhibits the synthesis of 4-hydroxy-phenyl-pyruvate dioxygenase. Examples of HPPD inhibitors include benzobicyclon, bicyclon (4-hydroxy-3- [ [2- [ (2-methoxyethoxy) methyl ] -6- (trifluoromethyl) -3-pyridinyl ] carbonyl ] bicyclo [3.2.1] oct-3-en-2-one), fenkunomrione (fenquinotrione) (2- [ [ 8-chloro-3, 4-dihydro-4- (4-methoxyphenyl) -3-oxo-2-quinoxalinyl ] carbonyl ] -1, 3-cyclohexanedione), isoxachlorotole, isoxaflutole, mesotrione, sulfonyloxypyr, pyrazolate, fenchlorazole, sulcotrione, tefurotrione, tembotrione, tolpyralate (1- [ [ 1-ethyl-4- [3- (2-methoxyethoxy) -2-methyl-ethoxy) -2-methyl-sulcotrione) Yl-4- (methylsulfonyl) benzoyl ] -1H-pyrazol-5-yl ] oxy ] ethyl methyl carbonate), topramezone, 5-chloro-3- [ (2-hydroxy-6-oxy-1-cyclohexen-1-yl) carbonyl ] -1- (4-methoxyphenyl) -2(1H) -quinoxalinone, 4- (2, 6-diethyl-4-methylphenyl) -5-hydroxy-2, 6-dimethyl-3 (2H) -pyridazinone, 4- (4-fluorophenyl) -6- [ (2-hydroxy-6-oxy-1-cyclohexen-1-yl) carbonyl ] -2-methyl-1, 2, 4-triazine-3, 5(2H,4H) -dione, 5- [ (2-hydroxy-6-oxy-1-cyclohexen-1-yl) carbonyl ] -2- (3-methoxyphenyl) -3- (3-methoxypropyl) -4(3H) -pyrimidone, 2-methyl-N- (4-methyl-1, 2, 5-oxadiazol-3-yl) -3- (methylsulfinyl) -4- (trifluoromethyl) benzamide and 2-methyl-3- (methylsulfonyl) -N- (1-methyl-1H-tetrazol-5-yl) -4- (trifluoromethyl) benzamide. Of note are compounds of the present invention admixed with mesotrione or pyrasulfotole.
"HST inhibitors" (b13) disrupt the ability of plants to convert homogentisate to 2-methyl-6-solanyl-1, 4-benzoquinone, thereby disrupting carotenoid biosynthesis. Examples of HST inhibitors include flazamox, triclopyr, cycloprim (6-chloro-3- (2-cyclopropyl-6-methylphenoxy) -4-pyridazinyl 4-morpholinecarboxylate), 3- (2-chloro-3, 6-difluorophenyl) -4-hydroxy-1-methyl-1, 5-naphthyridin-2 (1H) -one, 7- (3, 5-dichloro-4-pyridyl) -5- (2, 2-difluoroethyl) -8-hydroxypyrrolo [2,3-b ] pyrazin-6 (5H) -one, and 4- (2, 6-diethyl-4-methylphenyl) -5-hydroxy-2, 6-dimethyl-3 (2H) -pyridazinone.
HST inhibitors also include compounds of formulas a and B.
Wherein R isd1Is H, Cl or CF3；Rd2Is H, Cl or Br; rd3Is H or Cl; rd4Is H, Cl or CF3；Rd5Is CH3、CH2CH3Or CH2CHF2(ii) a And R isd6Is OH, or-OC (═ O) -i-Pr; and R ise1Is H, F, Cl, CH3Or CH2CH3；Re2Is H or CF3；Re3Is H, CH3Or CH2CH3；Re4Is H, F or Br; re5Is Cl, CH3、CF3、OCF3Or CH2CH3；Re6Is H, CH3、CH2CHF2Or C ≡ CH; re7Is OH, -OC (═ O) Et, -OC (═ O) -i-Pr or-OC (═ O) -t-Bu; and A ise8Is N or CH.
"cellulose biosynthesis inhibitors" (b14) inhibit cellulose biosynthesis in certain plants. Young or fast-growing plants are most effective when applied pre-emergence or early post-emergence. FiberExamples of the vitamin biosynthesis inhibitor include chloramben, dichlobenil, flubenconazole, indazinam (N)2- [ (1R,2S) -2, 3-dihydro-2, 6-dimethyl-1H-inden-1-yl]-6- (1-fluoroethyl) -1,3, 5-triazine-2, 4-diamine), isoxaben and triazineaamong.
"other herbicides" (b15) include herbicides that act through a variety of different modes of action, such as mitotic disruptors (e.g., methyl fluromet and isopropyl wheat straw), organic arsenic-containing compounds (e.g., DSMA and MSMA), 7, 8-dihydrofolate synthesis inhibitors, chloroplast isoprenoid synthesis inhibitors, and cell wall biosynthesis inhibitors. Other herbicides include those that have an unknown mode of action or do not fall within the specific categories listed under (b1) to (b14) or act through a combination of the modes of action listed above. Examples of other herbicides include aclonifen, asulam, diquat, beflubutamid, cycloheptane, clomazone, prosulfuron, difloran, difenzoquat, ethoxybenclamide, fluometuron, butafenadine, fosinophosphine, fosinophosphonium, dazomet, prosulfuron, triafamone (1- (2, 4-dichlorophenyl) -N- (2, 4-difluorophenyl) -1, 5-dihydro-N- (1-methylethyl) -5-oxo-4H-1, 2, 4-triazole-4-carboxamide), metam, methabenzuron, oleic acid, oxaziclomefone, pelargonic acid, pyributicarb and 5- [ [ (2, 6-difluorophenyl) methoxy ] methyl ] -4, 5-dihydro-5-methyl-3- (3-methyl-2-thienyl) isoxazole .
An "herbicide safener" (b16) is a substance added to herbicide formulations to eliminate or reduce the phytotoxic effects of the herbicide on certain crops. These compounds protect crops from herbicides, but generally do not prevent herbicides from controlling undesirable vegetation. Examples of herbicide safeners include, but are not limited to, clomazone, cloquintocet-mexyl, prosulfocarb, cyprosulfamide, prosulfuron, dichlormid, dacarbazone (diclonon), phosmet (dietholate), penflufen, fenchlorazole, fenclorim, fenchlorazole-ethyl, fluxoxime, furilazole, isoxadifen, pyracloquine, mefenate, tralkoxydim, naphthalic anhydride, oxabetrinil, N- (aminocarbonyl) -2-methylbenzenesulfonamide and N- (aminocarbonyl) -2-fluorobenzenesulfonamide, 1-bromo-4- [ (chloromethyl) sulfonyl ] benzene, 2- (dichloromethyl) -2-methyl-1, 3-dioxolane (MG191), 4- (dichloroacetyl) -1-oxa-4-azaspiro [4.5] decane (MON 4660), 2, 2-dichloro-1- (2,2, 5-trimethyl-3-oxazolidinyl) -ethanone and 2-methoxy-N- [ [4- [ [ (methylamino) carbonyl ] amino ] phenyl ] sulfonyl ] -benzamide.
The compounds of formula 1 can be prepared by general methods known in the art of synthetic organic chemistry in combination with the methods shown below in schemes 1 to 21 and variations thereof. R in the following compounds of formulae 1 to 171、R2、R3、R4、R5、R6、R5a、R6a、Q1、Q2And Y is as defined in the summary above, unless otherwise indicated. The compounds of formulae 1a, 2a, 4a, 6a, 8a, 10a and 13a are different subsets of the compounds of formulae 1,2,4, 8,10 and 13, respectively. The compounds of formulae 1b, 2b, 8b, 10b and 13b are a different subset of the compounds of formulae 1,2, 8,10 and 13, respectively. The compounds of formulae 1c, 8c, 10c, and 13c are different subsets of the compounds of formulae 1,8, 10, and 13, respectively. The compounds of formulae 10d and 10e are a different subset of the compounds of formula 10. Unless otherwise indicated, substituents for each subfamily are as defined for its parent formula. Are mainly found by Q1And C (Y) N (Q)2)(R7) The substituents of the compounds of formula 1 are in the trans configuration. In some cases, the presence of a small amount of the cis isomer can be detected by NMR.
As shown in scheme 1, compounds of formula 1a (i.e., wherein R is1Is H; r2Is H; and Y is O) can be prepared by reaction of the ester of formula 2 with an excess of the amine of formula 3 by heating at a temperature above 100 ℃, optionally in the presence of a solvent. The method of scheme 1 is illustrated by step E in synthesis example 1, step D in synthesis examples 2 and 3, and step a in synthesis example 4.
Scheme 1
As shown in scheme 2, the compounds of formula 1b (i.e., wherein A is a chain containing carbon or oxygen atoms; R7Is H; and Y is O) can be prepared by cyclization of a compound of formula 4. The cyclization is carried out under neutral or acidic conditions using suitable nitrogen-containing compounds of formula 5, such as, but not limited to, aminoacetals, aminoaldehydes, aminoketones, and hydrazides. Suitable acids for the reaction include inorganic acids such as hydrochloric acid, hydrobromic acid and sulfuric acid, and organic acids such as acetic acid and trifluoroacetic acid. A wide variety of co-solvents are suitable for use in the reaction, including but not limited to water, methanol, ethanol, and tetrahydrofuran. The reaction is carried out at a temperature in the range from-20 ℃ to the boiling point of the solvent, and typically from 0 ℃ to 10 ℃. The method of scheme 2 is illustrated by step D of synthesis example 1, step F of synthesis example 3, step C of synthesis example 4, and step a of synthesis example 5.
Scheme 2
As shown in scheme 3, compounds of formula 1c (i.e., wherein R is1Is H; r2Is H; y is O; and A is-NHA2-the compound of formula 1) can be prepared by cyclization of an N-aminolactam of formula 6 below in the presence of a "coupling partner". The "coupling partners" used in the reaction may be selected from primary amides, acid chlorides, carbon disulfide, cyanides such as sodium or potassium cyanide, or ammonia, either alone or in combination. The cyclization can optionally be carried out in the presence of an activator and typically in the presence of a co-solvent. Suitable activators for the reaction include, but are not limited to, metal chlorides such as zinc chloride and carboxylic acids such as acetic acid and propionic acid. A wide variety of co-solvents are suitable for use in the reaction, including but not limited to acetic acid, toluene, benzene, xylene, carbon disulfide, N-dimethylformamide, and tetrahydrofuran. The reaction is carried out at a temperature in the range from-20 ℃ to the boiling point of the solvent, and typically from 0 ℃ to 150 ℃. Scheme 3 procedure from Synthesis of example 1And G, explaining.
Scheme 3
As shown in scheme 4, the compounds of formula 1a can also be prepared by cyclization of the azidolactam of formula 8. The cyclization can be carried out by an organophosphine of formula 7, typically in the presence of a co-solvent. Suitable organic phosphines for the reaction include, but are not limited to, triphenylphosphine or tri-n-butylphosphine. A wide variety of co-solvents are suitable for use in the reaction, including but not limited to benzene, chlorobenzene, carbon tetrachloride, and tetrahydrofuran. The reaction is carried out at a temperature in the range from-20 ℃ to the boiling point of the solvent, and typically from 0 ℃ to 100 ℃. The method of scheme 4 is illustrated by step C of synthesis example 2.
Scheme 4
As shown in scheme 5, the compound of formula 2a can be prepared by cyclization of the compound of formula 4 a. The cyclization can be carried out under neutral or acidic conditions using suitable nitrogen-containing compounds such as, but not limited to, aminoacetals, aminoaldehydes, aminoketones, and hydrazides. Suitable acids for the reaction include, but are not limited to, inorganic acids such as hydrochloric acid, hydrobromic acid, and sulfuric acid, and organic acids such as acetic acid and trifluoroacetic acid. A wide variety of co-solvents are suitable for use in the reaction, including but not limited to water, methanol, ethanol, and tetrahydrofuran. The reaction is carried out at a temperature in the range from-20 ℃ to the boiling point of the solvent, and typically from 0 ℃ to 100 ℃.
Scheme 5
As shown in scheme 6, compounds of formula 2b can be prepared by cyclization of azidolactams of formula 8 a. The cyclization can be carried out by an organic phosphine, typically in the presence of a co-solvent. Exemplary organic phosphines for the reaction include triphenylphosphine or tri-n-butylphosphine. A wide variety of co-solvents are suitable for use in the reaction, including but not limited to benzene, chlorobenzene, carbon tetrachloride, and tetrahydrofuran. The reaction is carried out at a temperature in the range from-20 ℃ to the boiling point of the solvent, and typically from 0 ℃ to 100 ℃.
Scheme 6
As shown in scheme 7, compounds of formula 8b can be prepared by substitution of lactams of formula 9. The substitution is carried out with an inorganic azide or trialkylsilylazide, typically in the presence of a cosolvent. Suitable azides for use in the reaction include, but are not limited to, inorganic azides such as sodium azide and trialkylsilyl azides such as azidotrimethylsilane. A wide variety of co-solvents are suitable for use in the reaction, including but not limited to N, N-dimethylformamide, N-methyl-2-pyrrolidone, dimethyl sulfoxide, and ethanol. The reaction is carried out at a temperature in the range from-20 ℃ to the boiling point of the solvent, and typically from 0 ℃ to 100 ℃. The method of scheme 7 is illustrated by step B of synthesis example 2.
Scheme 7
As shown in scheme 8, the compound of formula 8c can be prepared by Mitsunobu substitution method through substitution of alcohol of formula 9. Typically with azides, phosphines and azodicarboxylates, in the presence of a co-solvent. Suitable azides for use in the reaction include, but are not limited to, diphenylphosphorylazide and azidotrimethylsilane. Suitable phosphines for the reaction include, but are not limited to, triphenylphosphine or tri-n-butylphosphine. Suitable phosphines for the reaction include, but are not limited to, diethyl azodicarboxylate and di-tert-butyl azodicarboxylate. A wide variety of co-solvents are suitable for use in the reaction, including but not limited to N, N-dimethylformamide and tetrahydrofuran. The reaction is carried out at a temperature in the range from-20 ℃ to the boiling point of the solvent, and typically from 0 ℃ to 100 ℃. For example, this type of transformation is described in org.Lett. [ organic chemistry Commission ]2008,10(14),2997- & 3000 and J.O.C. [ organic chemistry journal ]1999,64(16),6049- & 6055.
Scheme 8
As shown in scheme 9, the compound of formula 8b can be prepared by reacting the compound of formula 10 with the compound of formula 11. The substitution is optionally carried out in the presence of a base, typically in the presence of a co-solvent. Suitable bases for the reaction include, but are not limited to, hydroxides such as sodium hydroxide and potassium hydroxide, carbonates such as sodium carbonate and potassium carbonate, and nitrogen-containing bases such as triethylamine, N-diisopropylamine, and 1, 8-diazabicyclo [5.4.0]]Undec-7-ene. A wide variety of co-solvents are suitable for the reaction, including but not limited to benzene, toluene, N-dimethylformamide, N-methyl-2-pyrrolidone, dimethyl sulfoxide, ethanol, methanol, acetonitrile, and tetrahydrofuran. The reaction is carried out at a temperature in the range from-20 ℃ to the boiling point of the solvent, and typically from 0 ℃ to 100 ℃. A compound of formula 10 (wherein J is-CR)5R6-) can be prepared in a variety of ways, as described in PCT/US2014/068073(WO 2015/084796). A compound of formula 10 (wherein J is-CR)5R6-CR5aR6a-) can be prepared in a variety of ways, as described in PCT/US2014/38473(WO 2016/003997).
Scheme 9
As shown in scheme 10, the compounds of formula 6 can be prepared by N-amination of lactams of formula 10. The amination is carried out using an electrophilic amination reagent, optionally in the presence of a base and typically in the presence of a co-solvent. Suitable electrophilic amination reagents include, but are not limited to, N-chloramine, O-diphenylphosphorylhydroxylamine, O-lyyl (mesityl) sulfonylhydroxylamine, O-sulfonic hydroxylamine, O-lycylhydroxylamine and O-2, 4-dinitrophenylhydroxylamine. Suitable bases for the reaction include, but are not limited to, hydroxides such as sodium hydroxide and potassium hydroxide, alkoxides such as sodium ethoxide and potassium ethoxide, carbonates such as sodium carbonate and potassium carbonate, sodium hydride, metal amides such as lithium diisopropylamide and sodium hexamethyldisilazane, and neutral nitrogenous bases such as triethylamine, N-diisopropylamine, and 1, 8-diazabicyclo [5.4.0] undec-7-ene. A wide variety of co-solvents are suitable for use in the reaction, including but not limited to xylene, toluene, benzene, diethyl ether, N-dimethylformamide, and tetrahydrofuran. The reaction is carried out at a temperature in the range from-20 ℃ to the boiling point of the solvent, and typically from 0 ℃ to 150 ℃.
Alternatively, N-amination can be achieved by a two-step procedure through the formation of the intermediate N-nitrosolactam of formula 12 followed by reduction. The N-nitrosolactam compound of formula 12 may be obtained by reacting a lactam of formula 10 with a suitable nitrosating agent in the presence of an activator and typically in the presence of a co-solvent. Suitable nitrosating bases include, but are not limited to, nitrites such as sodium nitrite and potassium nitrite, and nitrogen oxides. Suitable activators for the reaction include, but are not limited to, acetates such as sodium acetate and potassium acetate, carboxylic acids such as acetic acid and propionic acid, and lewis acids such as bismuth (III) trichloride and tin (IV) tetrachloride. A wide variety of co-solvents are suitable for use in the reaction, including but not limited to acetic anhydride, carbon tetrachloride, and methylene chloride. The reaction is carried out at a temperature in the range from-20 ℃ to the boiling point of the solvent, and typically from 0 ℃ to 100 ℃. The N-amino compound of formula 6 can be obtained by performing the reaction of N-nitrosolactam of formula 12 with a suitable reducing agent, typically in the presence of a co-solvent. Suitable reducing agents include, but are not limited to, zinc metal. A wide variety of co-solvents are suitable for useReactions, including but not limited to acetic acid and aqueous hydrochloric acid. The reaction is carried out at a temperature in the range from-20 ℃ to the boiling point of the solvent, and typically from-20 ℃ to 100 ℃. For a representative procedure see Synthesis]2006,14,2371-2375 and Synthetic Communications]2009,39,604-612. A compound of formula 10 (i.e., wherein J is-CR)5R6-) can be prepared in a variety of ways, as taught in PCT/US2014/068073(WO 2015/084796). A compound of formula 10 (wherein J is-CR)5R6-CR5aR6a-) can be prepared in a variety of ways, as described in PCT/US2014/38473(WO 2016/003997).
Scheme 10
Alternatively, as shown in scheme 11, the compound of formula 6a may be prepared by reacting the compound of formula 10a with an amination reagent such as O- (diphenylphosphinyl) hydroxylamine and hydroxyamino-O-sulfonic acid. See Bioorg. & med. chem.lett. [ bio-organic chemistry and medicinal chemistry communications ]2009,19, 5924-.
Scheme 11
As shown in scheme 12, compounds of formula 10b can be prepared by hydrolysis of esters of formula 10 a. The hydrolysis is typically carried out with an aqueous base or an aqueous acid in the presence of a co-solvent. Suitable bases for the reaction include, but are not limited to, hydroxides such as sodium hydroxide and potassium hydroxide, and carbonates such as sodium carbonate and potassium carbonate. Suitable acids for the reaction include, but are not limited to, inorganic acids such as hydrochloric acid, hydrobromic acid, and sulfuric acid, and organic acids such as acetic acid and trifluoroacetic acid. A wide variety of co-solvents are suitable for use in the reaction, including but not limited to methanol, ethanol, and tetrahydrofuran. The reaction is carried out at a temperature in the range from-20 ℃ to the boiling point of the solvent, and typically from 0 ℃ to 100 ℃.
Scheme 12
As shown in scheme 13, compounds of formula 4 can be obtained by reduction of compounds of formula 13 and subsequent in situ cyclization of the resulting intermediate amine. Various methods for reducing the aliphatic nitro group in compounds of formula 13 are known in the literature. Typical reduction processes include catalytic hydrogenation in the presence of raney nickel, iron or zinc metal (see, e.g., Berichte der Deutschen Chemischen Gesellschaft 1904, 37, 3520-. Reduction can also be achieved with samarium (II) iodide in the presence of a proton source such as methanol (see, e.g., Tet. Lett. [ tetrahedron communication ]1991, 32(14), 1699-. Alternatively, sodium borohydride in the presence of a nickel catalyst such as nickel (II) acetate or nickel (II) chloride may be used (see, e.g., tet. lett. [ tetrahedral communication ]1985, 26(52), 6413-. The method of scheme 12 using sodium borohydride in the presence of nickel (II) chloride hexahydrate is illustrated by step C of synthesis example 1.
Scheme 13
As shown in scheme 14, compounds of formula 13a (wherein J is-CR)5R6-a compound of formula 13) can be prepared by reacting a diester of formula 14 with a nitroalkane of formula 15, typically in the presence of a base. Suitable bases for the reaction include alkali metal lower alkoxides such as sodium methoxide in methanol or sodium ethoxide in ethanol. The method of scheme 14 is illustrated by step B of synthesis example 1. Compounds of formula 14 can be readily prepared by methods known to those skilled in the art, for example, by reacting an aldehyde with malonic acidKennager condensation of esters (see, e.g., G.Jones, Organic Reactions [. ORGANIC REACTIONs ]]Volume 15, john wili parent-child publisher, 1967).
Scheme 14
Formula 13a (i.e., wherein J is-CR)5R6-the compound of formula 13) of (a) can be prepared by reacting the nitroalkene of formula 16 with the malonate of formula 17 in the presence of a base, as shown in scheme 15. Suitable bases for this reaction include, but are not limited to, alkali metal lower alkoxides such as sodium methoxide in methanol or sodium ethoxide in ethanol, or bases such as lithium bis (trimethylsilyl) amide, sodium bis (trimethylsilyl) amide and lithium diisopropylamide in solvents such as tetrahydrofuran. Typically, the reaction is carried out in the range of from-78 ℃ to 23 ℃. Conditions for carrying out this transformation are described in Synthesis]2005, 2239-2245. Conditions for this conversion in reflux water in the absence of catalyst have been reported in Synthetic Communications 2013, 43, 744-748. The nitroolefins of formula 16 can be readily prepared from aldehydes and nitromethane by known methods.
Scheme 15
The compounds of formulae 13b and 13c can be prepared stereoselectively by reacting a nitroolefin of formula 16 with a malonate of formula 17 in the presence of a chiral catalyst and optionally in the presence of a suitable base, as shown in scheme 16. Suitable catalysts include, but are not limited to, ni (II) with ortho diamine ligands such as bis [ (R, R) -N, N ' -dibenzylcyclohexane-1, 2-diamine ] nickel (II) dibromide, bis [ (S, S) -N, N ' -dibenzylcyclohexane-1, 2-diamine ] nickel (II) dibromide, or nickel (II) bromide with chiral 1,1 ' -bis (tetrahydroisoquinoline) type diamines. Suitable organic bases for this reaction include, but are not limited to, piperidine, morpholine, triethylamine, 4-methylmorpholine or N, N-diisopropylethylamine. This conversion can be accomplished neat or in a solvent such as tetrahydrofuran, toluene or methylene chloride. Typically, the reaction is carried out in the range from-78 ℃ to 80 ℃ using 0 to 1 equivalent of catalyst and 0 to 1 equivalent of base. The conditions under which this transformation is carried out have been reported in J.Am.chem.Soc. [ Prof. Chem. J.Org.chem. [ 2005,9958- ] or Eur.J.Org.chem. [ Eur. J.Org.chem. ]2011,5441- ] 5446. The nitroolefins of formula 16 can be readily prepared from aldehydes and nitromethane by methods known to those skilled in the art.
Scheme 16
As shown in scheme 17, formula 10b (i.e., wherein Y is O; R)1Is halogen; and R is2Formula 10) and 10c (i.e., wherein Y is O; r1Is H; and R is2Mixtures of compounds of formula 10) that are halogens can be prepared by reacting a compound of formula 10a with a halogen source in a solvent, in the presence or absence of an initiator. The separation of the regioisomers produced in this reaction can be achieved by standard methods such as chromatography or fractional crystallization. Suitable halogen sources for the reaction include bromine, chlorine, N-chlorosuccinimide, N-bromosuccinimide, and N-iodosuccinimide. Suitable initiators for this reaction include 2,2' -Azobisisobutyronitrile (AIBN) and benzoyl peroxide. Typically, the reaction is carried out in a solvent such as dichloromethane in the range from 0 ℃ to the boiling point of the solvent.
Scheme 17
As shown in scheme 18, compounds of formulae 10d and 10e (i.e., wherein R is1And R2Is H, and Y is O (10d) or S (respectively)10e) The compound of formula 10) can be prepared by reacting a compound of formula 10a with at least two equivalents of a sulfurizing reagent, such as Lawesson's reagent, tetraphosphorus decasulfide, or diphosphorus pentasulfide, in a solvent such as tetrahydrofuran or toluene. Typically, the reaction is carried out at a temperature ranging from 0 ℃ to 115 ℃. Those skilled in the art will recognize that the use of less than 2 equivalents of the sulfurizing reagent can provide a mixture of products comprising compounds of formulae 10d and 10e (i.e., wherein Y is S or O, respectively), which can be isolated by conventional methods such as chromatography and crystallization. The method of scheme 18 is illustrated by step D of synthesis example 1.
Scheme 18
As shown in scheme 19, formula 4 (i.e., wherein R is1And R2Is H; and Y is O can be prepared by alkylating a compound of formula 10a with a suitable alkylating agent, optionally in the presence of a base. Suitable alkylating agents include, but are not limited to, trimethyloxonium tetrafluoroborate, triethyloxonium tetrafluoroborate, methyl iodide, ethyl iodide, methyl bromide, and methyl p-toluenesulfonate. Suitable bases for the reaction include, but are not limited to, carbonates such as sodium and potassium carbonate and neutral nitrogen bases such as triethylamine and 1, 8-diazabicyclo [5.4.0]]Undec-7-ene. A wide variety of co-solvents are suitable for use in the reaction, including but not limited to acetonitrile, N-dimethylformamide, and tetrahydrofuran. The reaction is carried out at a temperature in the range from-20 ℃ to the boiling point of the solvent, and typically from 0 ℃ to 150 ℃. The method of scheme 19 is illustrated by step F of synthesis example 1.
Scheme 19
One skilled in the art recognizes that various functional groups can be converted to others to provide different compounds of formula 1. For a valuable resource that illustrates the interconversion of functional groups in a simple and straightforward manner, see Larock, r.c., integrated organic transformations: guidance for Functional Group preparation (Comprehensive Organic Transformations: A Guide to Functional groups Preparations), 2 nd edition, Wiley-VCH, New York, 1999. For example, intermediates used to prepare compounds of formula 1 may contain aromatic nitro groups that can be reduced to amino groups and then converted to various halides via reactions well known in the art (such as sandmeyer reactions), providing compounds of formula 1. In many cases, the above reactions can also be carried out in an alternating sequence.
It will be appreciated that certain of the reagents and reaction conditions described above for preparing the compounds of formula 1 may not be compatible with certain functional groups present in the intermediates. In these cases, incorporating protection/deprotection sequences or functional group interconversions into the synthesis will help to obtain the desired product. The use and selection of protecting Groups will be apparent to those skilled in the art of chemical Synthesis (see, e.g., Greene, T.W.; Wuts, P.G.M.protective Groups in Organic Synthesis, 2 nd edition; Wiley: New York, 1991). One skilled in the art will recognize that in some cases, following the introduction of a given reagent as depicted in any individual scheme, additional conventional synthetic steps not described in detail may be required to complete the synthesis of the compound of formula 1. One skilled in the art will also recognize that it may be desirable to perform the combination of steps shown in the above schemes in an order different from that specifically presented for the preparation of compounds of formula 1.
One skilled in the art will also recognize that the compounds of formula 1 and intermediates described herein can be subjected to various electrophilic, nucleophilic, radical, organometallic, oxidation, and reduction reactions to add substituents or modify existing substituents.
Without further elaboration, it is believed that one skilled in the art can, using the preceding description, utilize the present invention to its fullest extent. The following non-limiting examples are illustrative of the present invention. In the following examplesThe steps of (a) show the procedure for each step in the overall synthetic transformation, and the starting materials for each step do not have to be prepared by a specific preparative run whose procedure is described in other examples or steps. Percentages are by weight, except for chromatographic solvent mixtures or unless otherwise indicated. Parts and percentages of chromatographic solvent mixtures are by volume unless otherwise indicated.1The H NMR spectrum is reported in ppm downfield from tetramethylsilane. "s" means a single peak, "d" means a double peak, "m" means multiple peaks, and "br s" means a broad single peak.
Synthesis example 1
Preparation of N- (2-fluorophenyl) -6, 7-dihydro-6- [3- (trifluoromethyl) phenyl ] -5H-pyrrolo [2,1-c ] -1,2, 4-triazole-7-carboxamide (Compound 2)
Step A: 2- [ [3- (trifluoromethyl) phenyl group]Methylene group]Preparation of 1, 3-diethyl malonate
A mixture of 3- (trifluoromethyl) benzaldehyde (7.55g, 43.3mmol), diethyl malonate (6.6g, 41.3mmol), piperidine (0.91g, 10.7mmol) and benzene (50mL) was refluxed for 17 hours with continuous removal of water using a dean-Stark trap. The cooled reaction mixture was concentrated under reduced pressure, and the residue was chromatographed on silica gel (eluting with 0% to 30% ethyl acetate in hexanes) to provide the title compound as a clear colorless oil (10.9 g).
1H NMRδ7.74(m,1H),7.71(m,1H),7.64(m,2H),7.52(m,1H),4.33(m,4H),1.35(m,3H),1.29(m,3H)。
And B: 2- [ 2-Nitro-1- [3- (trifluoromethyl) phenyl]Ethyl radical]Preparation of 1, 3-diethyl malonate
2- [ [3- (trifluoromethyl) phenyl group]Methylene group]A mixture of 1, 3-diethyl malonate (i.e. the product of step A, 10.9g, 34.5mmol), nitromethane (18.5mL, 345mmol) and sodium methoxide in methanol (25 wt%, 0.76g, 3.45mmol) in ethanol (150mL) was stirred at 23 ℃ for 21 h. The reaction mixture was then concentrated under reduced pressure to give a thick oil, which was diluted with 25% ethyl acetate in hexane and passed throughA pad of diatomaceous earth filter aid was filtered to remove insoluble particulates. The filtrate was concentrated under reduced pressure to give the title compound (11.0g) as a yellow oil.
1H NMRδ7.57(m,1H),7.51(m,1H),7.47(m,2H),4.97(m,1H),4.89(m,1H),4.32(m,1H),4.23(m,4H),3.82(d,J＝9.0Hz,1H),1.27(m,3H),1.07(m,3H)。
And C: 2-oxo-4- [3- (trifluoromethyl) phenyl]Preparation of ethyl (E) -3-pyrrolidinecarboxylate
2- [ 2-nitro-1- [3- (trifluoromethyl) phenyl]Ethyl radical]A stirred mixture of 1, 3-diethyl malonate (i.e. the product of step B, 11.0g, 29.0mmol), nickel (II) chloride hexahydrate (13.8g, 58.0mmol) and ethanol (250mL) was cooled in an ice bath and treated with 0.5g portion of added sodium borohydride (6.6g, 174mmol) over 45 minutes. The resulting mixture was stirred at 23 ℃ for 4 hours. Saturated ammonium chloride solution (500mL) was then added and the mixture was stirred for 2 hours. The aqueous layer was extracted with ethyl acetate (3X 200 mL). The combined organic extracts were washed with brine and dried (MgSO)4) And concentrated under reduced pressure. The residue was dissolved in ethyl acetate (100mL) and stirred vigorously with a saturated ammonium chloride solution (100mL) for 1 hour when all black particles had disappeared. The layers were separated and the organic layer was washed with water and dried (MgSO)4) And concentrated under reduced pressure. The residue was chromatographed on silica gel (eluting with 0% to 100% ethyl acetate in hexanes) to provide the title compound as a clear colorless oil.
1H NMRδ7.57(m,1H),7.51(m,1H),7.48(m,2H),6.47(br s,1H),4.26(m,2H),4.19(m,1H),3.86(m,1H),3.54(d,J＝9.5Hz,1H),3.46(m,1H),1.29(m,3H)。
Step D: 2-thio-4- [3- (trifluoromethyl) phenyl]Preparation of ethyl (E) -3-pyrrolidinecarboxylate
A mixture of ethyl 2-oxo-4- [3- (trifluoromethyl) phenyl ] -3-pyrrolidinecarboxylate (i.e., the product of step C, 1.0g, 3.3mmol) and thionine (0.67g, 1.7mmol) in toluene (15mL) was stirred at reflux for 4 hours. The cooled reaction mixture was concentrated under reduced pressure, and the residue was chromatographed on silica gel (eluting with 0% to 100% ethyl acetate in hexanes) to provide the title compound as a yellow oil (0.60 g).
1H NMRδ8.07(br s,1H),7.57(m,1H),7.49(m,2H),7.44(m,1H),4.28(m,3H),4.16(m,1H),3.90(m,1H),3.72(m,1H),1.31(m,3H)。
Step E: n- (2-fluorophenyl) -2-thio-4- [3- (trifluoromethyl) phenyl]Preparation of (E) -3-pyrrolidinecarboxamide
A mixture of ethyl 2-thio-4- [3- (trifluoromethyl) phenyl ] -3-pyrrolidinecarboxylate (i.e. the product of step D, 0.55g, 1.7mmol) and 2-fluoroaniline (2.0mL, 20.7mmol) was heated to 120 ℃ under nitrogen for 71 hours. The mixture was chromatographed on silica gel (eluting with 0% -40% ethyl acetate in hexane) to provide the title product as an off-white solid (0.49 g).
1H NMRδ9.68(br s,1H),8.21(m,1H),7.75(br s,1H),7.57(m,2H),7.52(m,2H),7.10(m,3H),4.62(m,1H),4.16(m,1H),3.94(d,J＝6.0Hz,1H),3.72(m,1H)。
Step F: n- (2-fluorophenyl) -3, 4-dihydro-5-methylthio-3- [3- (trifluoromethyl) phenyl]-2H-pyrrole-4-carboxylic acid methyl ester Preparation of amides
Reacting N- (2-fluorophenyl) -2-thio-4- [3- (trifluoromethyl) phenyl]A mixture of-3-pyrrolidinecarboxamide (i.e., the product of step E, 0.49g, 1.3mmol), iodomethane (0.090mL, 1.4mmol) and potassium carbonate (0.36g, 2.6mmol) in acetonitrile (10mL) was stirred at 23 ℃ for 4 hours. The mixture was concentrated under reduced pressure. The residue was taken up in ethyl acetate (20mL) and washed with water (2X 10 mL). The organic extract was dried (MgSO)4) And concentrated under reduced pressure to give the title product as a brown oil (0.39 g).
1H NMRδ8.29(m,1H),7.60(br s,1H),7.52(m,1H),7.44(m,3H),7.11(m,3H),4.52(m,1H),4.22(m,1H),4.00(m,1H),3.77(s,1H),2.57(m,3H)。
Step G: n- (2-fluorophenyl) -6, 7-dihydro-6- [3- (trifluoromethyl) group) Phenyl radical]-5H-pyrrolo [2,1-c]-1, Preparation of 2, 4-triazole-7-carboxamide
A mixture of N- (2-fluorophenyl) -3, 4-dihydro-5-methylsulfanyl-3- [3- (trifluoromethyl) phenyl ] -2H-pyrrole-4-carboxamide (i.e., the product of step F, 0.13g, 0.33mmol) and formhydrazide (0.030g, 0.50mmol) in N, N-dimethylacetamide (0.4mL) was stirred at 120 ℃ for 15 hours. The mixture was concentrated under reduced pressure. The residue was chromatographed on silica gel (eluting with 0% to 100% ethyl acetate in hexanes, then 0% to 5% methanol in ethyl acetate) to provide the title compound, the compound of the invention (0.065g), as a brown oil.
1H NMRδ9.17(br s,1H),8.26(s,1H),8.15(m,1H),7.62(m,2H),7.56(m,3H),7.09(m,3H),4.93(m,1H),4.61(m,1H),4.36(d,J＝7.4Hz,1H),4.14(m,1H)。
Synthesis example 2
Preparation of N- (2-fluorophenyl) -2,3,6, 7-tetrahydro-3-oxo-6- [3- (trifluoromethyl) phenyl ] -5H-pyrrolo [1,2-a ] imidazole-7-carboxamide (Compound 3)
Step A: 1- (2-chloroacetyl) -2-oxo-4- [3- (trifluoromethyl) phenyl]Preparation of ethyl (E) -3-pyrrolidinecarboxylate Prepare for
A mixture of ethyl 2-oxo-4- [3- (trifluoromethyl) phenyl ] -3-pyrrolidinecarboxylate (i.e., the product of example 1, step C, 0.30g, 1.0mmol) and chloroacetyl chloride (0.16mL, 2.0mmol) in benzene (3mL) was stirred at 75 deg.C for 16 h. The cooled reaction mixture was concentrated under reduced pressure to give the title compound (0.37g) as a dark brown oil.
1H NMRδ7.61(m,1H),7.53(m,2H),7.46(m,1H),4.73(m,2H),4.42(m,1H),4.27(m,2H),4.10(m,1H),3.82(d,J＝10.7Hz,1H),3.78(m,1H),1.30(m,3H)。
And B: 1- (2-azidoacetyl) -2-oxo-4- [3- (trifluoromethyl) phenyl]Process for preparing ethyl (E) -3-pyrrolidinecarboxylate Preparation of
Reacting 1- (2-chloroacetyl) -2-oxo-4- [3- (trifluoromethyl) phenyl]-3-Pyrrolidinecarboxylic acid ethyl ester (i.e. product of step A)A mixture of 0.37g, 1.0mmol) and sodium azide (0.20g, 3.0mmol) in N, N-dimethylformamide (3mL) was stirred at 23 ℃ for 6 hours. The reaction mixture was diluted with ethyl acetate (40 mL). The mixture was washed successively with water (2X 15mL) and saturated sodium chloride (15 mL). The organic layer was dried (MgSO4) And concentrated under reduced pressure to give the title compound (0.37g) as a red oil.
1H NMRδ7.61(m,1H),7.52(m,2H),7.45(m,1H),4.51(s,2H),4.42(m,1H),4.27(m,2H),4.10(m,1H),3.80(d,J＝10.9Hz,1H),3.77(m,1H),1.29(m,3H)。
And C: 2,3,6, 7-tetrahydro-3-oxo-6- [3- (trifluoromethyl) phenyl]-5H-pyrrolo [1,2-a]Imidazole- Preparation of ethyl 7-carboxylate
A mixture of ethyl 1- (2-azidoacetyl) -2-oxo-4- [3- (trifluoromethyl) phenyl ] -3-pyrrolidinecarboxylate (i.e., the product of step B, 0.37g, 1.0mmol) and triphenylphosphine (0.29g, 1.1mmol) in benzene (10mL) was stirred at reflux for 1 hour. The solution was allowed to stand at 23 ℃ for 20 hours, during which time a solid formed. The mixture was filtered and washed with toluene to give the title compound (0.20g) as a colorless solid. The filtrate was concentrated. The residue was dissolved in toluene (4 mL). Magnesium chloride (0.30g) was added and the mixture was stirred at 65 ℃ for 1 hour. The cooled reaction mixture was filtered. The filtrate was concentrated under reduced pressure to give an additional amount of the title compound (0.12g) as a colorless solid.
1H NMRδ7.49(m,2H),7.43(m,2H),5.72(br s,1H),4.67(m,1H),4.38(m,2H),4.15(m,1H),4.02(m,2H),3.59(m,1H),1.08(br s,3H)。
Step D: n- (2-fluorophenyl) -2,3,6, 7-tetrahydro-3-oxo-6- [3- (trifluoromethyl) phenyl]-5H-pyrrolo [1,2-a]Preparation of imidazole-7-carboxamides
2,3,6, 7-tetrahydro-3-oxo-6- [3- (trifluoromethyl) phenyl]-5H-pyrrolo [1,2-a]A mixture of imidazole-7-carboxylic acid ethyl ester (i.e. the product of step C, 0.10g, 0.29mmol) and 2-fluoroaniline (0.50mL, 5.2mmol) in toluene (3mL) was heated to 200 ℃ in a microwave reactor for a period of timeFor 2 hours. The cooled reaction mixture was chromatographed on silica gel (eluting with 0% -100% ethyl acetate in hexanes) to provide the title product, the compound of the invention (0.027g) as a yellow oil.1H NMR showed a mixture of enamine to amidine tautomers of about 2: 1.
1H NMR δ enamine tautomers 8.20(m,1H),7.58(m,4H),7.07(m,3H),6.37(br s,1H),6.27(br s,1H),4.56(m,2H),4.51(m,1H),4.02(m,1H),3.59(m, 1H); amidine tautomers 9.49(br s,1H),8.20(m,1H),7.58(m,4H),7.07(m,3H),4.77(m,1H),4.41(s,2H),4.28(m,1H),4.14(m,1H),3.59(m, 1H).
Synthesis example 3
Preparation of N- (2-fluorophenyl) -6, 7-dihydro-methyl-6- [4- (trifluoromethyl) phenyl ] -5H-pyrrolo [2,1-c ] -1,2, 4-triazole-7-carboxamide (Compound 24)
Step A: 2- [ 2-Nitro-1- [4- (trifluoromethyl) phenyl]Ethyl radical]Preparation of 1, 3-dimethyl malonate
A mixture of 4- (trifluoromethyl) benzaldehyde (25.0g, 112mmol), dimethyl malonate (15.6g, 118mmol), piperidine (2.39g, 28.0mmol) and benzene (75mL) was refluxed for 2 hours with continuous removal of water (dean-Stark trap). Acetic acid (3.47g, 57.7mmol) was added and the reaction heated for an additional 1.5 hours. The cooled reaction mixture was washed successively with aqueous hydrochloric acid (1M, 2X 40mL) and saturated sodium bicarbonate (2X 40 mL). The organic layer was dried (Na)2SO4) And concentrated under reduced pressure to give a yellow oil (0.37 g). A mixture of this yellow oil, nitromethane (60.0mL, 1.12mol) and sodium methoxide in methanol (25 wt%, 2.42g, 11.2mmol) was stirred at 23 ℃ for 17 h. The reaction mixture was then concentrated under reduced pressure to afford a thick oil. The crude material was filtered through a pad of silica (eluting with 50% ethyl acetate in hexanes) to provide the title compound (29.0g) as an orange oil.
1H NMRδ7.60(m,2H),7.38(m,2H),4.93(m,2H),4.32(m,1H),3.87(d,J＝8.8Hz,1H),3.78(s,3H),3.60(s,3H)。
And B: 2-oxo-4- [4-(trifluoromethyl) phenyl]Preparation of (E) -3-pyrrolidine-carboxylic acid methyl ester
2- [ 2-nitro-1- [4- (trifluoromethyl) phenyl]Ethyl radical]A stirred mixture of 1, 3-dimethyl malonate (i.e. the product of step A, 29.0g, 83.0mmol), nickel (II) chloride hexahydrate (19.8g, 83.0mmol) and methanol (275mL) was cooled in an ice bath and treated with 0.5g portion of added sodium borohydride (9.5g, 250mmol) over 1 hour. The resulting mixture was stirred at 0 ℃ for 1.5 hours and then at 23 ℃ for 17 hours. Saturated ammonium chloride solution (300mL) and ethyl acetate (300mL) were then added and the mixture was stirred vigorously for 2 hours. The light blue mixture was separated. The aqueous layer was extracted with ethyl acetate (2X 100 mL). The combined organic extracts were washed with saturated ammonium chloride solution (100mL) and dried (MgSO)4) And concentrated under reduced pressure. The crude mixture was triturated with 1-chlorobutane (100mL) to give the title compound (12.3g) as a colourless solid.
1H NMRδ7.63(m,2H),7.40(m,2H),6.23(br s,1H),4.21(m,1H),3.86(m,1H),3.80(s,3H),3.57(d,J＝9.6Hz,1H),3.45(m,1H)。
And C: 2-thio-4- [4- (trifluoromethyl) phenyl]Preparation of methyl (E) -3-pyrrolidinecarboxylate
A mixture of methyl 2-oxo-4- [4- (trifluoromethyl) phenyl ] -3-pyrrolidinecarboxylate (i.e., the product of step B, 8.0g, 27.9mmol) and thionine (5.63g, 13.9mmol) in toluene (70mL) was stirred at reflux for 4.5 hours. The cooled reaction mixture was concentrated under reduced pressure and the residue was chromatographed on silica gel (eluting with 0% to 100% ethyl acetate in hexane) to provide a yellow solid consisting of the title compound and 20% of unknown impurities. The mixture was recrystallized from ethyl acetate (100mL, hot) and hexane (200mL, cold) to provide the title compound (5.0g) as a pale yellow solid.
1H NMRδ8.20(br s,1H),7.62(m,2H),7.37(m,2H),4.24(m,1H),4.15(m,1H),3.94(d,J＝8.2Hz,1H),3.82(s,3H),3.71(m,1H)。
Step D: n- (2-fluorophenyl) -2-thio-4- [4- (trifluoromethyl) phenyl]Preparation of (E) -3-pyrrolidinecarboxamide
A mixture of methyl 2-thio-4- [4- (trifluoromethyl) phenyl ] -3-pyrrolidinecarboxylate (i.e. the product of step C, 1.00g, 3.3mmol) and 2-fluoroaniline (2.55mL, 26mmol) was heated to 130 ℃ under a nitrogen atmosphere for 22 hours. The reaction was concentrated under reduced pressure to remove most of the excess aniline. The remaining residue was triturated with 1-chlorobutane to give the title compound (1.18g) as a colourless solid.
1H NMRδ9.67(br s,1H),8.21(m,1H),7.73(br s,1H),7.64(m,2H),7.45(m,2H),7.10(m,3H),4.62(m,1H),4.16(m,1H),3.93(d,J＝5.8Hz,1H),3.71(m,1H)。
Step E: n- (2-fluorophenyl) -3, 4-dihydro-5- (methylthio) -3- [4- (trifluoromethyl) phenyl]-2H-pyrrole- Preparation of 4-carboxamides
Reacting N- (2-fluorophenyl) -2-thio-4- [4- (trifluoromethyl) phenyl]A mixture of 3-pyrrolidinecarboxamide (i.e., the product of step D, 1.11g, 2.9mmol), iodomethane (0.22mL, 3.5mmol) and potassium carbonate (0.81g, 5.8mmol) in acetonitrile (15mL) was stirred at 23 ℃ for 18 hours. The mixture was diluted with water (100mL) and extracted with ethyl acetate (2X 100 mL). The organic extract was dried (MgSO)4) And concentrated under reduced pressure to give the title product (0.97g) as a brown solid.
1H NMRδ8.29(m,1H),7.60(br s,1H),7.52(m,1H),7.44(m,3H),7.11(m,3H),4.52(m,1H),4.22(m,1H),4.00(m,1H),3.77(s,1H),2.57(s,3H)。
Step F: n- (2-fluorophenyl) -6, 7-dihydro-3-methyl-6- [4- (trifluoromethyl) phenyl]-5H-pyrrolo [2 ], 1-c]preparation of (E) -1,2, 4-triazole-7-carboxamide
A mixture of N- (2-fluorophenyl) -3, 4-dihydro-5- (methylthio) -3- [4- (trifluoromethyl) phenyl ] -2H-pyrrole-4-carboxamide (i.e., the product of step E, 0.100g, 0.25mmol) and acethydrazide (0.028g, 0.38mmol) in acetic acid (1.2mL) was stirred at 110 ℃ for 75 minutes. The mixture was concentrated onto silica gel and chromatographed on silica gel (eluting with 10% to 100% ethyl acetate in hexane, then 0% to 5% methanol in ethyl acetate) to provide the title compound contaminated with several other impurities. The mixture was chromatographed on C18-silica gel (eluting with 10% to 100% 1:1 acetonitrile/methanol in water) to provide the title compound, the compound of the invention (0.021g) as a yellow oil.
1H NMR(d6Acetone) delta 9.65(br s,1H),8.25(m,1H),7.76(m,4H),7.15(m,3H),7.09(m,3H),4.92(m,1H),4.63(m,2H),4.17(m,1H),2.39(s, 3H).
Synthesis example 4
Preparation of N- (2, 3-difluorophenyl) -3-ethyl-6, 7-dihydro-6- [4- (trifluoromethyl) phenyl ] -5H-pyrrolo [2,1-c ] -1,2, 4-triazole-7-carboxamide (Compound 8)
Step A: n- (2, 3-difluorophenyl) -2-thioxo-4- [4- (trifluoromethyl) phenyl]Preparation of (E) -3-pyrrolidinecarboxamide Prepare for
A mixture of methyl 2-thio-4- [4- (trifluoromethyl) phenyl ] -3-pyrrolidinecarboxylate (i.e., the product of example 3, step C, 1.00g, 3.3mmol) and 2, 3-difluoroaniline (3.4g, 26mmol) was heated to 130 ℃ under nitrogen for 22 hours. The reaction was concentrated under reduced pressure to remove most of the excess aniline. The remaining residue was triturated with 1-chlorobutane to give the title compound (1.13g) as a colourless solid.
1H NMRδ9.84(br s,1H),7.97(m,1H),7.75(br s,1H),7.64(m,2H),7.45(m,2H),7.04(m,1H),6.92(m,1H),4.60(m,1H),4.15(m,1H),3.94(d,J＝6.3Hz,1H),3.72(m,1H)。
And B: n- (2, 3-difluorophenyl) -3, 4-dihydro-5- (methylthio) -3- [4- (trifluoromethyl) phenyl]-2H-pyridine Preparation of pyrrole-4-carboxamides
Reacting N- (2, 3-difluorophenyl) -2-thio-4- [4- (trifluoromethyl) phenyl]A mixture of 3-pyrrolidinecarboxamide (i.e., the product of step A, 1.16g, 2.9mmol), iodomethane (0.22mL, 3.5mmol) and potassium carbonate (0.81g, 5.8mmol) in acetonitrile (15mL) was stirred at 23 ℃ for 18 hours. The mixture was diluted with water (100mL) and extracted with ethyl acetate (2X 100 mL). The organic extract was dried (MgSO)4) And concentrated under reduced pressure to give as a brown solidThe title product (1.10 g).
1H NMRδ8.06(m,1H),7.60(m,3H),7.33(m,2H),7.07(m,1H),6.94(m,1H),4.51(m,1H),4.22(m,1H),4.01(m,1H),3.77(s,1H),2.58(s,3H)。
And C: n- (2, 3-difluorophenyl) -3-ethyl-6, 7-dihydro-6- [4- (trifluoromethyl) phenyl]-5H-pyrrolo [2,1-c]Preparation of (E) -1,2, 4-triazole-7-carboxamide
Reacting N- (2, 3-difluorophenyl) -3, 4-dihydro-5- (methylthio) -3- [4- (trifluoromethyl) phenyl]A mixture of-2H-pyrrole-4-carboxamide (i.e., the product of step B, 0.200g, 0.48mmol) and hydrazine hydrate (0.036mL, 0.72mmol) in propionic acid (2.4mL) was stirred at 110 ℃ for 16.5H. Concentrating the mixture toOver celite filter aid and chromatography on C18-silica gel (eluting with 10% to 100% 1:1 acetonitrile/methanol in water) to afford the title compound, a compound of the invention (0.037g), as a brown solid.
1H NMRδ10.19(br s,1H),7.82(m,1H),7.64(m,2H),7.47(m,2H),6.92(m,1H),6.83(m,1H),4.99(m,1H),4.50(m,2H),3.98(m,1H),2.81(m,2H),1.37(m,3H)。
Synthesis example 5
Preparation of N- (2, 3-difluorophenyl) -6, 7-dihydro-3- (trifluoromethyl) -6- [4- (trifluoromethyl) phenyl ] -5H-pyrrolo [2,1-c ] -1,2, 4-triazole-7-carboxamide (Compound 22)
Step A: n- (2, 3-difluorophenyl) -6, 7-dihydro-3- (trifluoromethyl) -6- [4- (trifluoromethyl) phenyl]-5H- Pyrrolo [2,1-c]Preparation of (E) -1,2, 4-triazole-7-carboxamide
Reacting N- (2, 3-difluorophenyl) -3, 4-dihydro-5- (methylthio) -3- [4- (trifluoromethyl) phenyl]A mixture of-2H-pyrrole-4-carboxamide (i.e. the product of example 4 step B, 0.220g, 0.53mmol), trifluoroacetohydrazide (0.076g, 0.58mmol) and pivalic acid (2.7g) was stirred at 130 ℃ for 90 min. The cooled mixture was diluted with ethyl acetate (100mL) and successively saturated with saturated sodium bicarbonate (50mL), water (50mL) and saturatedSodium chloride (50mL) was washed. The organic layer was dried (MgSO4) Concentrating toOver celite filter aid and chromatographed on C18-silica gel (eluting with 10% to 100% 1:1 acetonitrile/methanol in water) to afford the title compound contaminated with some impurities. The mixture was triturated with 1-chlorobutane to give the title compound, a compound of the invention (0.029g), as a colorless solid.
1H NMRδ9.25(br s,1H),7.89(m,1H),7.70(m,2H),7.51(m,2H),7.03(m,1H),6.92(m,1H),5.04(m,1H),4.71(m,1H),4.46(d,J＝7.6Hz,1H),4.24(m,1H)。
The following compounds in tables 1 to 140 may be prepared by the procedures described herein together with methods known in the art. The following abbreviations are used in the following tables: i-Pr means isopropyl, Bu means butyl, Ph means phenyl, OMe means methoxy, OEt means ethoxy, SMe means methylthio, \ S (O) Me means methylsulfinyl, and S (O)2Me means methylsulfonyl.
TABLE 1
J is-CH2-；Q2Is Ph (2-F); and Q1Is that
Table 2 is constructed in the same manner except thatThe line heading "J is-CH2-；Q2Is Ph (2-F); and Q1Is "replaced with the line heading listed for Table 2 below (i.e.," J is-CH)2-；Q2Is Ph (2, 3-di-F); and Q1Yes "). Thus, the first entry in Table 2 is a compound of formula I, wherein J is-CH2-；Q2Is Ph (2, 3-di-F); and Q1Is Ph (3-Cl) (i.e., 3-chlorophenyl). Tables 3 to 20 are similarly constructed.
Watch (A)
Line head
2
J is-CH2-；Q2Is Ph (2, 3-di-F); and Q1Is that
3
J is-CH2-；Q2Is Ph (2, 4-di-F); and Q1Is that
4
J is-CH2-；Q2Is Ph (2,3, 4-tri-F); and Q1Is that
5
J is-CH2-；Q2Is Ph (2-CF)3) (ii) a And Q1Is that
6
J is-CH2-；Q2Is Ph (2-Me); and Q1Is that
7
J is-CH2-；Q2Is Ph (2-NO)2) (ii) a And Q1Is that
8
J is-CH2-；Q2Is Ph (2-Cl); and Q1Is that
9
J is-CH2-；Q2Is Ph (2-SO)2Me); and Q1Is that
10
J is-CH2-；Q2Is Ph (2-F, 3-Cl); and Q1Is that
11
J is-CH2CH2-；Q2Is Ph (2-F); and Q1Is that
12
J is-CH2CH2-；Q2Is Ph (2, 3-di-F); and Q1Is that
13
J is-CH2CH2-；Q2Is Ph (2, 4-di-F); and Q1Is that
14
J is-CH2CH2-；Q2Is Ph (2,3, 4-tri-F); and Q1Is that
15
J is-CH2CH2-；Q2Is Ph (2-CF)3) (ii) a And Q1Is that
16
J is-CH2CH2-；Q2Is Ph (2-Me); and Q1Is that
17
J is-CH2CH2-；Q2Is Ph (2-NO)2) (ii) a And Q1Is that
18
J is-CH2CH2-；Q2Is Ph (2-Cl); and Q1Is that
19
J is-CH2CH2-；Q2Is Ph (2-SO)2Me); and Q1Is that
20
J is-CH2CH2-；Q2Is Ph (2-F, 3-Cl); and Q1Is that
TABLE 21
Table 21 is constructed in the same manner as table 1 above, except that the structure is replaced with the following structure:
tables 22 to 40
The present disclosure also includes tables 22 to 40, each of which is constructed in the same manner as in tables 2 to 20 above, except that the structure is replaced with the structure in table 21 above.
Table 41
Table 41 is constructed in the same manner as table 1 above, except that the structure is replaced with the following structure:
tables 42 to 60
The present disclosure also includes tables 42 to 60, each of which is constructed in the same manner as in tables 2 to 20 above, except that the structure is replaced with the structure in table 41 above.
Watch 61
Table 61 is constructed in the same manner as table 1 above, except that the structure is replaced with the following structure:
tables 62 to 80
The present disclosure also includes tables 62 to 80, each of which is constructed in the same manner as in tables 2 to 20 above, except that the structure is replaced with the structure in table 61 above.
Watch 81
Table 81 is constructed in the same manner as table 1 above, except that the structure is replaced with the following structure:
tables 82 to 100
The present disclosure also includes tables 82 to 100, each constructed in the same manner as tables 2 to 20 above, except that the structure is replaced with the structure in table 81 above.
Watch 101
The watch 101 is constructed in the same manner as in the above table 1 except that the structure is replaced with the following structure:
tables 102 to 120
The present disclosure also includes tables 102-120, each constructed in the same manner as tables 2-20 above, except that the structure is replaced with the structure in table 101 above.
Table 121
The watch 121 is constructed in the same manner as in the above table 1 except that the structure is replaced with the following structure:
tables 122 to 140
The present disclosure also includes tables 122 through 140, each of which is constructed in the same manner as tables 2 through 20 above, except that the structure is replaced with the structure in table 121 above.
The compounds of the present invention will generally be used as herbicidal active ingredients in compositions (i.e., formulations) wherein at least one additional component is selected from the group consisting of: surfactants, solid diluents and liquid diluents, which act as carriers. The formulation or composition ingredients are selected to be consistent with the physical characteristics of the active ingredient, the 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, oil-in-water emulsions, flowable concentrates, and/or suspoemulsions), and the like, which optionally can be thickened into gels. Common types of aqueous liquid compositions are soluble concentrates, suspension concentrates, capsule suspensions, concentrated emulsions, microemulsions, oil-in-water emulsions, flowable concentrates and suspoemulsions. Common types of non-aqueous liquid compositions are emulsifiable concentrates, micro-emulsifiable concentrates, dispersible concentrates and oil dispersions.
The general types of solid compositions are powders, granules, pellets, granules, lozenges, tablets, filled films (including seed coatings), and the like, which may be water-dispersible ("wettable") or water-soluble. Films and coatings formed from film-forming solutions or flowable suspensions are particularly useful for seed treatment. The active ingredient may be (micro-) encapsulated and further formed into a suspension or solid formulation; alternatively, the entire formulation of the active ingredient may be encapsulated (or "coated"). Encapsulation may control or delay the release of the active ingredient. Emulsifiable granules combine the advantages of both emulsifiable concentrate formulations and dry granule formulations. The high strength compositions are mainly used as intermediates for further formulations.
Sprayable formulations are typically dispersed in a suitable medium prior to spraying. Such liquid and solid formulations are formulated to be readily dilutable in a spray medium, usually water, but occasionally another suitable medium like aromatic or paraffinic hydrocarbons or vegetable oils. The spray volume may range from about one to several thousand liters per hectare, but more typically ranges from about ten to several hundred liters per hectare. The sprayable formulation may be mixed with water or another suitable medium in a tank for foliar treatment by air or ground application, or for application to the growing medium of the plant. The liquid and dry formulations can be metered directly into the drip irrigation system or into the furrow during planting.
The formulation will typically contain effective amounts of active ingredient, diluent and surfactant within the following approximate ranges (up to 100 weight percent in total).
Solid diluents include, for example, clays such as bentonite, montmorillonite, attapulgite and kaolin, gypsum, cellulose, titanium dioxide, zinc oxide, starches, dextrins, 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 Handbook of Insecticide Dust Diluents and Carriers, Watkins et al, 2 nd edition, Dorland Books, codeville, new jersey.
Liquid diluents include, for example, water, N, N-dimethyl alkylamides (e.g., N, N-dimethylformamide), limonene, dimethyl sulfoxide, N-alkylpyrrolidones (e.g., N-methylpyrrolidone), alkyl phosphates (e.g., triethyl phosphate), ethylene glycol, triethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, propylene carbonate, butylene carbonate, paraffins (e.g., white mineral oil, N-paraffin, isoparaffin), alkylbenzenes, alkylnaphthalenes, glycerin, triacetin, sorbitol, 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, methyl ethyl acetate, methyl acetate, ethyl, Octyl acetate, nonyl acetate, tridecyl acetate and isobornyl acetate, other esters such as, for example, alkylated lactates, dibasic esters, alkyl and aryl benzoates and gamma-butyrolactones, and alcohols which may be linear, branched, saturated or unsaturated, such as methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, n-hexanol, 2-ethylhexanol, n-octanol, decanol, isodecanol, isostearyl alcohol, cetyl alcohol, lauryl alcohol, tridecyl alcohol, oleyl alcohol, cyclohexanol, tetrahydrofurfuryl alcohol, diacetone alcohol, cresol and benzyl alcohol. Liquid diluents also include saturated and unsaturated fatty acids (typically C)6-C22) Such as vegetable seed and fruit oils (e.g., olive oil, castor oil, linseed oil, sesame oil, corn oil (corn oil), peanut oil, sunflower oil, grape seed oil, safflower oil, cottonseed oil, soybean oil, rapeseed oil, coconut oil, and palm kernel oil), animal-derived fats (e.g., beef tallow, lard, cod liver oil, fish oil), and mixtures thereof. Liquid diluents also include alkylated (e.g., methylated, ethylated, butylated) fatty acids, wherein the fatty acids may be obtained by hydrolysis of glycerides from plant and animal sources and may be purified by distillation. Typical liquid diluents are listed in Marsden, Solvents Guide [ solvent Guide ]]2 nd edition, Interscience, New York1950.
The solid and liquid compositions of the present invention often include one or more surfactants. Surfactants (also referred to as "surface active agents") generally alter, most often reduce, the surface tension of liquids when added to liquids. Surfactants can be used as wetting agents, dispersing agents, emulsifying agents, or defoaming agents, depending on the nature of the hydrophilic and lipophilic groups in the surfactant molecule.
Surfactants can be classified as nonionic, anionic or cationic. Nonionic surfactants useful in the compositions of the present invention 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 alcohols and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof; amine ethoxylates, alkanolamides, and ethoxylated alkanolamides; alkoxylated triglycerides, such as ethoxylated soybean oil, castor oil, and rapeseed oil; alkylphenol ethoxylates such as octylphenol ethoxylate, nonylphenol ethoxylate, dinonylphenol ethoxylate and dodecylphenol ethoxylate (prepared from phenol and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); block polymers prepared from ethylene oxide or propylene oxide and trans-block polymers in which the end blocks are prepared from propylene oxide; ethoxylated fatty acids; ethoxylated fatty esters and oils; ethoxylated methyl esters; ethoxylated tristyrylphenols (including those prepared from ethylene oxide, propylene oxide, butylene oxide, or mixtures thereof); fatty acid esters, glycerol esters, lanolin-based derivatives, polyethoxylated 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 (pegs); polyethylene glycol fatty acid esters; a silicone-based surfactant; and sugar derivatives such as sucrose esters, alkyl polyglycosides and alkyl polysaccharides.
Useful anionic surfactants include, but are not limited to: alkyl aryl sulfonic acids and salts thereof; carboxylated alcohol or alkylphenol ethoxylates; a diphenyl sulfonate derivative; lignin and lignin derivatives, such as lignosulfonates; maleic or succinic acid or anhydrides thereof; olefin sulfonates; phosphate esters such as alcohol alkoxylate phosphate esters, alkylphenol alkoxylate phosphate esters, and styrylphenol ethoxylate phosphate esters; a protein-based surfactant; a sarcosine derivative; styrylphenol ether sulfate; sulfates and sulfonates of oils and fatty acids; sulfates and sulfonates of ethoxylated alkylphenols; sulfates of alcohols; sulfates of ethoxylated alcohols; amine and amide sulfonates such as N, N-alkyl taurates; benzene, cumene, toluene, xylene, and the sulfonates of dodecylbenzene and tridecylbenzene; a sulfonate of condensed polynaphthalene; sulfonates of naphthalene and alkylnaphthalenes; sulfonates of fractionated petroleum; sulfosuccinamates; and sulfosuccinates and their derivatives, such as dialkyl sulfosuccinates.
Useful cationic surfactants include, but are not limited to: amides and ethoxylated amides; amines such as N-alkyl propylene diamine, tripropylene triamine and dipropylene tetramine, and ethoxylated, ethoxylated and propoxylated amines (prepared from amines and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); amine salts such as ammonium acetate and diamine salts; quaternary ammonium salts such as quaternary salts, ethoxylated quaternary salts and diquaternary salts; and amine oxides such as alkyldimethylamine oxide and bis- (2-hydroxyethyl) -alkylamine oxide.
Also useful in the compositions of the present invention 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 number of published references, including The McCutcheon division, The Manufacturing conditioner Publishing Co. [ Emulsifiers and Detergents for McCutcheon ], annual and International specifications [ U.S. and International annual edition ]; sisely and Wood, Encyclopedia of Surface Active Agents [ surfactant Encyclopedia ], Chemical publication. And a.s.davidson and b.milwidsky, Synthetic Detergents, seventh edition, john wili father-son press, new york, 1987.
The compositions of the present invention may also contain formulation adjuvants and additives known to those skilled in the art as co-formulations (some of which may also be considered to act as solid diluents, liquid diluents or surfactants). Such formulation aids and additives may control: pH (buffer), foaming during processing (antifoam agents such as polyorganosiloxanes), sedimentation of the active ingredient (suspending agents), viscosity (thixotropic thickeners), microbial growth in the container (antimicrobials), product freezing (antifreeze), color (dye/pigment dispersion), elution (film former or sticker), evaporation (evaporation retarder), and other formulation attributes. Film formers include, for example, polyvinyl acetate copolymers, polyvinylpyrrolidone-vinyl acetate copolymers, polyvinyl alcohol copolymers, and waxes. Examples of formulation aids and additives include The second volume of McCutcheon published by The subsection of McCutcheon, The Manufacturing conditioner Publishing co: functional Materials [ Functional Materials ], international and north american year versions; and those listed in PCT publication WO 03/024222.
The compound of formula 1 and any other active ingredient are typically incorporated into the compositions of the present invention 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 the liquid composition intended for use as an emulsifiable concentrate is water-immiscible, an emulsifier is typically added to emulsify the solvent containing the active ingredient upon dilution with water. Slurries of active ingredient having a particle size of up to 2,000 μm can be wet-milled using a media mill to give particles having an average particle size of less than 3 μm. The aqueous slurry can be made into a finished suspension concentrate (see, e.g., U.S.3,060,084) or further processed by spray drying to form water dispersible granules. Dry formulations typically require a dry milling process, which results in an average particle size in the range of 2 to 10 μm. Powders and powders may be prepared by blending and typically by grinding (e.g. with a hammer mill or fluid energy mill). Granules and pellets can be prepared by spraying the active substance onto a preformed granule carrier or by agglomeration techniques. See, Browning, "Agglomeration ]", Chemical Engineering, 12.4.1967, pages 147-48; perry's Chemical Engineers ' Handbook [ Parry's Handbook of Chemical Engineers ], 4 th edition, McGraw-Hill [ McGray Hill group ], New York, 1963, pages 8-57 and beyond, and WO 91/13546. Spheroids may 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 may be prepared as taught in U.S.5,180,587, U.S.5,232,701 and U.S.5,208,030. Membranes may be prepared as taught in GB 2,095,558 and u.s.3,299,566.
For further information on The field of formulation, see "The formulations's Toolbox-Product Forms for model Agriculture analysis" in The Food-environmental Challenge [ Pesticide Chemistry and Bioscience, formulation kit-Modern agricultural Product form ], editions of t.brooks and t.r.roberts, Proceedings of The 9th International conference on Pesticide Chemistry [ ninth International conference on Pesticide Chemistry ], The Royal Society of Chemistry [ chemical Society ], cambridge, 1999, p.120. 133. See also U.S.3,235,361, column 6, line 16 to column 7, line 19 and examples 10-41; U.S. Pat. No. 3,309,192, column 5, column 43 to column 7, column 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, column 3, line 66 to column 5, line 17 and examples 1-4; klingman, Weed Control as a Science, john william, new york, 1961, pages 81-96; hance et al, Weed Control Handbook, 8 th edition, Blackwell Scientific Publications, blakewell Scientific publishers, oxford, 1989; and development in formulation technology, PJB publishing company (PJB Publications), Riston, UK, 2000.
In the following examples, all percentages are by weight and all formulations are prepared in a conventional manner. Compound number refers to the compound in index table a. Without further elaboration, it is believed that one skilled in the art can, using the preceding description, utilize the present invention to its fullest extent. Accordingly, the following examples are to be construed as merely illustrative, and not limitative of the disclosure in any way whatsoever. Percentages are by weight unless otherwise indicated.
Example A
High strength concentrate
Compound 198.5%
0.5 percent of silicon dioxide aerogel
Synthetic amorphous Fine silica 1.0%
Example B
Wettable powders
Example C
Granules
Compound 110.0%
Attapulgite granule (low volatile matter, 0.71/0.30 mm; U.S. S. 90.0% No.25-50 sieve)
Example D
Extrusion spheronization agent
Example E
Emulsifiable concentrate
Compound 110.0%
Polyoxyethylene sorbitol hexaoleate 20.0%
C6-C10Fatty acid methyl ester 70.0%
Example F
Microemulsion
Example G
Suspension concentrates
Example H
Emulsions in water
Example I
Oil dispersion
The disclosure also includes the above formulation examples a through I, except that "compound 1" in each of the above examples a through I is replaced with "compound 2", "compound 3", "compound 4", "compound 5", "compound 6", "compound 7", "compound 8", "compound 9", "compound 10", "compound 11", "compound 12", "compound 13", "compound 14", "compound 15", "compound 16", "compound 17", "compound 18", "compound 19", "compound 20", "compound 21", "compound 22", "compound 23", "compound 24", "compound 25", "compound 26", "compound 27", or "compound 28".
The test results show that the compounds of the invention are observed to be highly active pre-and/or post-emergence herbicides and/or plant growth regulators. It was observed that the compounds of the present invention generally showed the highest activity for both post-emergence weed control (i.e. application after emergence of the weeds from the soil) and pre-emergence weed control (i.e. application before emergence of the weeds from the soil). It has been observed that many of them have utility for a wide range of pre-emergence and/or post-emergence weed control in areas where complete control of all vegetation is desired, such as around fuel storage tanks, industrial storage areas, parking lots, open car movie theaters, airports, riverbanks, irrigation and other waterways, billboards and highway and railway structures. It was observed that many of the compounds of the present invention can be used to selectively control grasses and broadleaf weeds in crop/weed mixed growth via: by selective metabolism in the crop versus the weeds, or by selective activity at physiological inhibition sites in the crop and weeds, or by selective application on or in the environment where the crop and weeds are mixed. One skilled in the art will recognize that within a compound or group of compounds, preferred combinations of these selectivity factors can be readily determined by performing conventional biological and/or biochemical assays. It was observed that the compounds of the invention show tolerance to important crops including, but not limited to, alfalfa, barley, cotton, wheat, canola, sugar beet, corn (maize), sorghum, soybean, rice, oat, peanut, vegetable, tomato, potato, perennial plantation crops including coffee, cocoa, oil palm, rubber, sugar cane, citrus, grapes, fruit trees, nut trees, banana, plantain, pineapple, hops, tea and trees such as eucalyptus and conifers (e.g. loblolly pine), and turf varieties (e.g. kentucky bluegrass, santoprene, kentucky and bermudagra). The compounds of the invention may be used in genetically transformed or colonized crops to incorporate herbicide resistance, to express proteins toxic to invertebrate pests (such as bacillus thuringiensis toxins) and/or to express other useful traits. It will be appreciated by those skilled in the art that not all compounds are equally effective against all weeds. Alternatively, the subject compounds may be used to alter plant growth.
Since the compounds of the present invention have both pre-and post-emergence herbicidal activity to control undesirable vegetation by killing or damaging vegetation or slowing its growth, the compounds are typically effectively applied by a variety of methods involving contacting a herbicidally effective amount of a compound of the present invention, or a composition comprising the compound and at least one of a surfactant, a solid diluent, or a liquid diluent, with foliage or other parts of the undesirable vegetation, or with an environment of the undesirable vegetation, such as soil or water, in which the undesirable vegetation is growing, or which surrounds seeds or other propagules of the undesirable vegetation.
The herbicidally effective amount of the compounds of the present invention is determined by a number of factors. These factors include: the formulation selected, the method of application, the amount and type of vegetation present, the growth conditions, and the like. Generally, herbicidally effective amounts of the compounds of the invention are from about 0.001kg/ha to 20kg/ha, with a preferred range being from about 0.004kg/ha to 1 kg/ha. One skilled in the art can readily determine the herbicidally effective amount required for the desired level of weed control.
In one common embodiment, the compounds of the present invention are typically applied in a formulated composition to a locus that includes both desired vegetation (e.g., crops) and undesirable vegetation (i.e., weeds), both of which can be seeds, seedlings and/or larger plants that are in contact with a growing medium (e.g., soil). At the locus, the compositions comprising the compounds of the invention may be applied directly to the plants or parts thereof, in particular to the undesirable vegetation, and/or to the growing medium with which the plants come into contact.
Plant varieties and cultivars of desired vegetation in a locus treated with a compound of the invention can be obtained by conventional propagation and breeding methods or by genetic engineering methods. Genetically modified plants (transgenic plants) are those in which a heterologous gene (transgene) has been stably integrated into the plant genome. A transgene defined by its specific location in the plant genome is referred to as a transformation or transgenic event.
Genetically modified plant cultivars of the locus that may be treated according to the invention include those resistant to one or more biotic stresses (pests such as nematodes, insects, mites, fungi and the like) or abiotic stresses (drought, low temperature, soil salinization and the like), or those comprising other desirable characteristics. Plants may be genetically modified to exhibit traits such as herbicide tolerance, insect resistance, modified oil characteristics, or drought tolerance. Useful genetically modified plants comprising a single genetic transformation event or a combination of transformation events are listed in example C. Additional information for the genetic modifications listed in example C can be obtained from publicly available databases maintained by, for example, the u.s.department of Agriculture (agricuture).
The following abbreviations T1 to T37 are used for the traits in example C. "-" indicates that the item is not available; "tol." refers to "tolerance" and "res." refers to resistance.
Example C
Argentina brassicae rape (brassica napus),' polatoda bok cabbage (turnip (b.rapa)), # aubergine (Eggplant)
Although most typically, the compounds of the invention are used to control undesirable vegetation, contacting desirable vegetation with the compounds of the invention in the locus treated may result in superadditive or synergistic effects with the genetic trait of the desired vegetation, including traits introduced by genetic modification. For example, resistance to phytophagous pests or plant diseases, tolerance to biotic/abiotic stress, or storage stability may be greater than desired in the genetic trait of the desired vegetation.
The compounds of the present invention may also be mixed with one or more other biologically active compounds or agents, including herbicides, herbicide safeners, fungicides, insecticides, nematocides, bactericides, acaricides, growth regulators such as molting inhibitors and root growth stimulators, chemosterilants, semiochemicals, repellents, attractants, pheromones, feeding stimulants, phytonutrients, other biologically active compounds or entomopathogenic bacteria, viruses or fungi to form a multi-component pesticide to impart an even wider range of agricultural protection. Mixtures of the compounds of the present invention with other herbicides can extend the spectrum of activity against additional weed species and inhibit proliferation of any resistant biotype. Accordingly, the present invention also relates to a composition comprising a compound of formula 1 (in a herbicidally effective amount) and at least one additional biologically active compound or agent (in a biologically effective amount), and the composition may further comprise at least one of a surfactant, a solid diluent or a liquid diluent. Other biologically active compounds or agents may be formulated into compositions comprising at least one of a surfactant, a solid or a liquid diluent. For the mixtures of the invention, one or more other biologically active compounds or agents may be formulated together with the compound of formula 1 to form a premix, or one or more other biologically active compounds or agents may be formulated separately from the compound of formula 1 and the formulations combined together prior to administration (e.g., in a spray can), or alternatively, administered sequentially.
Mixtures of one or more of the following herbicides with the compounds of the invention are particularly useful for weed control: acetochlor, acifluorfen and its sodium salt, aclonifen, acrolein (2-propenal), alachlor, dichlorate, ametryn, amicarbazone, amidosulfuron, aminocyclopyrachlor and its esters (e.g. methyl, ethyl) and salts (e.g. sodium, potassium), aminopyralid, desmodium, ammonium sulfamate, anilofos, asulam, atrazine, azimsulfuron, beflubutamid, benazolin ethyl, bensulfuron methyl (bencanazone), flufenacet, bensulfuron-methyl, bentazon, bentazone, benzobiciflam, pyraflufen-ethyl, bifenox and its sodium salt, brombutachlor, bromucol oxime, bromoxynil octanoate, butachlor, butafenacil, pyrazofos, butafenap-methyl, butafenap-butyl, butafenacet, fenbutazone, carfentrazone-ethyl, carfentrazone, trazone-ethyl, triafolpet, carfentrazone, butazone, carfentrazone, fentrazone-methyl, fentrazone, fenflurbenflurbenflurbenflurbenflurbenflurbenfluroxyphos, benflurbenfluroxyphos, benfluroxyphos, benflurbenfluroxyphos, benfluroxyphos, benfluridil, benflurbenflurbenfluroxypyr, benflurbenfluridil, benflurbenflurbenflurbenflurbenfluridil, benflurbenfluridil, benflurbenflurbenflurbenflurbenflurbenflurbenflurbenfluridil, benfluridil, benflurbenfluridil, benfluridil, benflurbenfluridil, benflurbenflurbenflurbenfluridil, benfluridil, benflurbenfluridil, benfluridil, benflurbenflurbenfluridil, benfluridil, benflurbenflurbenflurbenflurbenflurbenflurbenflurbenflurbenflurbenflurbenflurbenflurbenflurbenfluridil, benfluridil, benflurbenfluridil, benfluridil, benfluridi, Catechins, metoxyfen, benazepin, chlorsulfuron, chlordane, oxamyl, chlorimuron-ethyl, chlortoluron, chlorpropham, chlorsulfuron, dimethyl chlorophthalate, methimazone, indolone ester, cinmethylin, cinosulfuron, clofenphos, clethodim, clodinafop-propargyl, clomazone, clomeprop, clopyralid, ethanolamine clopyralid, cloransulam, bensulfuron-methyl, cyanazine, cyclamate, ciclesonide, cyclosulfamuron, cycloxydim, thiacetone, cyhalofop-ethyl, 2,4-D and its butoxyester, butyl, isooctyl and isopropyl esters and their dimethylammonium salts, diethanolamine and triethanolamine salts, metsulfuron, dalapon, dazomet sodium, dazomet, 2,4-DB and its dimethylammonium salts, potassium and sodium salts, betanin, dimethachlon and its diethyleneglycol ammonium salt, dimethylammonium salt, dicamba, Potassium and sodium salts, dichlobenil, dichlorvopropionic acid, diclofop-methyl, diclosulam, difloram-dimethyl sulfate, diflufenzopyr, fenoxaprop-ethyl, prosulfocarb, dimethachlor, isobutan, dimethenam-P, thiabendazole, arsonic acid and its sodium salt, dimethomon, terbufol, bisphenamid, diquat, dithiopyr, diuron, DNOC, endothal, EPTC, penflufen, ethalfuron, ethametsulfuron, ethiozin, ethametsulfuron-methyl, fluroxypyr, fenoxaprop-ethyl, isoxasulfone, fenkunotrione, fentrazamide, fenoxuron-TCA, meflon-methyl, meflolan-ethyl, flazasulfuron, triflusulfuron, fluazifop-methyl, fluazifop, isoxafen-ethyl, isoxathion, pyrazosulfuron-ethyl, isoxathion, fluazifop-methyl, Fluazincarbazone, flumiclorac, flufenacet, fluoropyridazine, fluazifop-p-butyl, flumetsulam, flumioxazin, fluroxypyr, fluazifop, flupyrsulfuron-methyl and its sodium salt, butafenacet, fluorenol butyl, fluazifop-methyl, fludioxonil, fluroxypyr, flurtamone, fluthiacet-methyl, fomesafen, foramsulfuron, fosmidonium, glufosinate, glyphosate and salts thereof such as ammonium, isopropylammonium, potassium, sodium (including sesquisodium) and trimethylsulfonium (alternatively called sulfosate), halauxifen-methyl, fluorochloropyridinate, halosulfuron-methyl, fluazifop-ethyl, haloxyfop-methyl, azinone, hydantoin, imazamox, imazapic, imazapyr, imazaquin, imazamox, imazapyr, imazamox, imazapyr, imazamoxi, imazamox, imazapyr, imazapine, imazapyr, imazapine, imazapyr, imazapine, imazapyr, imazapine, imazapyr, imazapine, imazachlor, imazapine, imazapyr, imazapine, imazapyr, imazapine, imazapyr, imazachlor, imazapine, imazachlor, imazapine, imazachlor, imazapine, imazachlor, imazapine, imazachlor, imab, ima, Pyrazosulfuron-ethyl, indoxacarb, triazinethionam, iodosulfuron, iodobenzonitrile, ioxynil octanoate, sodium ioxynil, triafenamidone, isoproturon, isooxauron, isoxaben, isoxaflutole, isoxaclomazone, lactofen, lenacil, linuron, prosulfuron, prosulfocarb, MCPA and its salts (e.g., MCPA-dimethylammonium, MCPA-potassium, and MCPA-sodium), esters (e.g., MCPA-2-ethylhexyl ester, MCPA-butoxyethyl ester), and thioesters (e.g., MCPA-ethyl thioester), MCPB and its salts (e.g., MCPB-sodium) and esters (e.g., MCPB-ethyl ester), 2-methyl-4-chloropropionic acid, mefenacetalone, sulfluramid, mesotrione, metam sodium, metamifop, Metamitron, pyraflufen, metazosulfuron, methabenzthiazuron, arsonic acid and its calcium salts, monoammonium salts, mono-and disodium salts, metsulfuron, metoxuron, bromuron, metolachlor, metosulam, metoxuron, metribuzin, metsulfuron-methyl, molydate, chlorsulfuron, napropamide, alachlor-M, napropamide, oxasulfuron, pyridyluron, prosulfocarb, pyribensulfuron-methyl, oryzalin, oxadiargyl, oxadiazon, oxazasulfuron, oxyfluorfen, paraquat dichloride, clindamycin, nonanoic acid, pendimethalin, penoxsulam, mechlorfentrazone, pentoxazone, fomesafen, dimethoxamide, dimethenamid, penoxlamid, penflufen, penoxulam, pyraflufen-ethyl, pretilachlor, propiconazole, metolachlor, bencarb, metolachlor, bencarb, metolachlor, metod, bencarb, metolachlor, bencarb, metod, bencarb, ben, Primisulfuron, propafop-flufen, clethodim, prometryn, propyzamide, propanil, propaquizafop-p-butyl, anilazine, propisochlor, prosulfuron, pentyne, prosulfocarb, prosulfuron, pyrazoxyfen, pyrafluazinyl-ethyl, pyrazosulfuron-ethyl (pyrazogyl), pyrazoxate, pyrazoxazole, pyrazosulfuron-ethyl, saflufenacil, pyributicarb, dalate, pyriftalid, pyriminobac-methyl, pyrithiobac-methyl (pyrimisufan), pyrithiobac-methyl, pyrithiobac-sodium, rochlorfensulfuron-methyl, pyroxsulam, quinclorac, cloquinclorac, imazaquin, quizalofop-p, quizalofop-p-ethyl, pyribenzoxim-methyl, sethoxydim, siduron-p-methyl, metosulam, sulfometuron-2, TCA, etc., a, and so, TCA, etc., tebuthiuron, tefurazone, tembotrione, tebufenon, terbacil, terbutone, terbuthylazine, dimethomofenacet, dimethenamid, thiencarbazone, thifensulfuron-methyl, thiobencarb, prosulfocarb, penflufen, dimerca, topiramate, topyrazole, tralkoxydim, triallate, triafamone, triasulfuron, triclopyr, bentazone, prodrazine, trifluoxazine, trifluralin, triflusulfuron, dichlofluazuron, 3- (2-chloro-3, 6-difluorophenyl) -4-hydroxy-1-methyl-1, 5-naphthyridin-2 (1H) -one, 5-chloro-3- [ (2-hydroxy-6-1-oxo-1-cyclohexenyl ] -1-cyclohexenyl) 1, 5-chloro-3- [ (2-hydroxy-6-oxo-1-cyclohexenyl) cyclohexene-1-yl) carbonyl ] -1H) -one - (4-methoxyphenyl) -2(1H) -quinoxalinone, 2-chloro-N- (1-methyl-1H-tetrazol-5-yl) -6- (trifluoromethyl) -3-pyridinecarboxamide, 7- (3, 5-dichloro-4-pyridinyl) -5- (2, 2-difluoroethyl) -8-hydroxypyrido [2,3-b ] pyrazin-6 (5H) -one), 4- (2, 6-diethyl-4-methylphenyl) -5-hydroxy-2, 6-dimethyl-3 (2H) -pyridazinone), 5- [ [ (2, 6-difluorophenyl) methoxy ] methyl ] -4, 5-dihydro-5-methyl-3- (3-methyl-2-thienyl) isoxazole (methioxolin as described above), 4- (4-fluorophenyl) -6- [ (2-hydroxy-6-oxy-1-cyclohexen-1-yl) carbonyl ] -2-methyl-1, 2, 4-triazine-3, 5(2H,4H) -dione, methyl 4-amino-3-chloro-6- (4-chloro-2-fluoro-3-methoxyphenyl) -5-fluoro-2-picolinate, 2-methyl-3- (methylsulfonyl) -N- (1-methyl-1H-tetrazol-5-yl) -4- (trifluoromethyl) benzoyl Amines and 2-methyl-N- (4-methyl-1, 2, 5-oxadiazol-3-yl) -3- (methylsulfinyl) -4- (trifluoromethyl) benzamide. Other herbicides also include biological herbicides such as Alternaria destructor (Simmons), Colletotrichum gloeosporiodes (Penz.) Penz. & Sacc.), Verticillium barnyi (Drechsiera monoceras) (MTB-951), Myrothecium verrucaria (Albertii & Schweinitiz) ditar: Fries), Phytophthora palmae (Butl.) Palmivora, and Phosphaerella Capsella (Puccinia thyosa Schubu.).
The compounds of the invention may also be used in combination with plant growth regulators such as, for example, evericin, N- (phenylmethyl) -1H-purin-6-amine, propionyl brassinolide, gibberellic acid, gibberellin A4And A7Hypersensitive proteins, mepiquat chloride, prohexadione calcium, jasmone, sodium nitrophenolate and trinexapac-methyl, and plant growth modifying organisms such as Bacillus cereus strain BP 01.
General references to agricultural protectants (i.e., herbicides, herbicide safeners, insecticides, fungicides, nematicides, acaricides, and biological agents) include The Pesticide Manual, 13 th edition, c.d. s.tomlin editions, British Crop Protection Council, Farnham, Surrey, u.k., 2003, and The BioPesticide Manual, 2 nd edition, l.g. copping editions, British Crop Protection Council, Farnham, Surrey, u.k., 2001.
For embodiments in which one or more of these various mixing components are used, these mixing components are generally used in amounts similar to the conventional amounts for the individual mixing components. More specifically, in the mixture, the active ingredient is usually applied at an application rate between one-half and the full application rate indicated on the product label for the individual use of the active ingredient. These amounts are listed in references such as The Pesticide Manual and The BioPesticide Manual. The weight ratio of these various mixing components (total amount) to the compound of formula 1 is generally between about 1:3000 and about 3000: 1. Of note is a weight ratio of between about 1:300 and about 300:1 (e.g., a ratio of between about 1:30 and about 30: 1). The biologically effective amount of the active ingredient necessary for the desired range of biological activity can be readily determined by one skilled in the art by simple experimentation. It will be apparent that the inclusion of these additional components may extend the weed control range beyond that controlled by the compound of formula 1 alone.
In certain instances, the combination of a compound of the present invention with other biologically active, particularly herbicidal, compounds or agents (i.e., active ingredients) can result in a more than additive (i.e., synergistic) effect on weeds and/or a less than additive (i.e., safening) effect on crops or other desired plants. It has been desirable to reduce the amount of active ingredient released into the environment while ensuring effective pest control. The ability to use larger amounts of active ingredients to provide more effective weed control without excessive crop injury is also desirable. Such combinations can be advantageously used to reduce crop production costs and reduce environmental loads when the herbicidal active ingredients produce a synergistic effect on weeds at application rates that achieve agronomically satisfactory levels of weed control. When safening of the herbicidal active ingredients occurs on the crop plants, such combinations can be advantageously used to increase crop protection by reducing weed competition.
Of note are combinations of the compounds of the present invention with at least one other herbicidal active ingredient. Of particular note are combinations of other herbicidally active ingredients with different sites of action of the compounds of the invention. In certain cases, a combination with at least one other herbicidal active ingredient having a similar control range but a different site of action would be particularly advantageous for resistance management. Thus, the compositions of the present invention may further comprise (in a herbicidally effective amount) at least one additional herbicidal active ingredient having a similar control range but a different site of action.
The compounds of the present invention may also be used in combination with herbicide safeners such as: diacrylam, clomazone, cloquintocet-mexyl, prosulfuron, clomazone, cyprosulfamide, prosulfuron, dichloracrylamide, dexrazoxane, triazophos, penoxsulam, fenchlorazole, fenclorim, cloquintocet-mexyl, fluxofenim, oxazazole, isoxadifen, pyracloquine, mefenacet, clomazone, naphthalic anhydride (1, 8-naphthalic anhydride), oxanil, N- (aminocarbonyl) -2-methylbenzenesulfonamide, N- (aminocarbonyl) -2-fluorobenzenesulfonamide, 1-bromo-4- [ (chloromethyl) sulfonyl ] Benzene (BCS), 4- (dichloroacetyl) -1-oxa-4-azaspiro [4.5] decane (MON 4660), 2- (dichloromethyl) 2-methyl-1, 3 dioxolane (MG191), 1, 6-dihydro-1- (2-methoxyphenyl) -6-oxo-2-phenyl-5-pyrimidinecarboxylic acid ethyl ester, 2-hydroxy-N, n-dimethyl-6- (trifluoromethyl) pyridine-3-carboxamide, and 3-oxy-1-cyclohexen-l-yl 1- (3, 4-dimethylphenyl) -l, 6-dihydro-6-oxo-2-phenyl-5-pyrimidinecarboxylate, 2-dichloro-1- (2,2, 5-trimethyl-3-oxazolidinyl) -ethanone and 2-methoxy-N- [ [4- [ [ (methylamino) carbonyl ] amino ] phenyl ] sulfonyl ] -benzamide. A detoxifically effective amount of a herbicide safener may be applied simultaneously with the compounds of the present invention or as a seed treatment. Accordingly, one aspect of the present invention relates to a herbicidal mixture comprising a compound of the present invention and a detoxifying effective amount of a herbicide safener. Seed treatment is particularly useful for selective weed control because it physically limits detoxification to crop plants. Thus, a particularly useful embodiment of the invention is a method for selectively controlling the growth of undesirable vegetation in a crop, the method comprising contacting the locus of the crop with a herbicidally effective amount of a compound of the invention, wherein the seed from which the crop grows is treated with a detoxifically effective amount of a safener. A detoxifying effective amount of a safener can be readily determined by one skilled in the art by simple experimentation.
The compounds of the invention may also be mixed with: (1) polynucleotides, including but not limited to DNA, RNA, and/or chemically modified nucleotides that affect the amount of a particular target by down-regulating, interfering, inhibiting, or silencing a gene-derived transcript that exhibits herbicidal effects; or (2) polynucleotides, including but not limited to DNA, RNA, and/or chemically modified nucleotides that affect the amount of a particular target by down-regulating, interfering, suppressing, or silencing a gene-derived transcript that exhibits a safening effect.
Of note is a composition comprising a compound of the present invention (in a herbicidally effective amount), at least one additional active ingredient (in a herbicidally effective amount) selected from the group consisting of other herbicides and herbicide safeners, and at least one component selected from the group consisting of surfactants, solid diluents and liquid diluents.
Table a1 lists specific combinations of component (a) and component (b) illustrating the mixtures, compositions, and methods of the present invention. Compound 1 in column component (a) is identified in index table a. The second column of Table A1 lists specific component (b) compounds (e.g., "2, 4-D" in the first row). The third, fourth and fifth columns of table a1 list the weight ratio ranges for component (b) relative to component (a) (i.e., (a): (b)) for rates at which the component (a) compound is typically applied to field-grown crops. Thus, for example, the first row of table a1 specifically discloses that the combination of component (a) (i.e. compound 1 in the index tables a to D) and 2,4-D is typically applied in a weight ratio of between 1:192 and 6: 1. The remaining rows of table a1 would be similarly constructed.
TABLE A1
Table A2 was constructed identically to Table A1 above, except that the entries below the column heading "component (a)" were replaced with the corresponding column entries for component (a) shown below. Compound 1 in column component (a) is identified in index table a. Thus, for example, in table a2, the entries below the column heading "component (a)" all recite "compound 2" (i.e., index compound 2 identified in table a), and the first row below the column heading in table a2 specifically discloses mixtures of compound 2 with 2, 4-D. Tables A3-a 7 were similarly constructed.
Preferred for better control of undesirable vegetation (e.g., such as lower use rates from synergy, broader controlled weed spectrum, or enhanced crop safety) or for preventing the development of resistant weeds are mixtures of the compounds of the present invention with herbicides selected from the group consisting of: chlorimuron-ethyl, nicosulfuron, mesotrione, thifensulfuron-methyl, flazasulfuron, tribenuron-methyl, rochlorfensulfuron, pinoxaden, tembotrione, pyroxsulam, metolachlor and metolachlor.
The following tests demonstrate the control efficacy of the compounds of the present invention against specific weeds. However, the weed control provided by the compounds is not limited to these species. Compound descriptions see index tables a to D. The abbreviation "cmpd.no." stands for "compound number". The abbreviation "ex." stands for "example" and is followed by a number indicating in which synthesis example the compound was prepared. Mass Spectra (MS) are reported with an estimated accuracy within ± 0.5Da as the molecular weight of the highest isotopically abundant parent ion (M +1) formed by adding H + (molecular weight 1) to the molecule or (M-1) formed by losing H + (molecular weight 1) from the molecule, observed using atmospheric pressure chemical ionization (AP +) by using liquid chromatography in combination with a mass spectrometer (LCMS), where "amu" represents unity atomic mass units.
Index table A
Index table B
To1See the synthesis examples for H NMR data.
Index table C
To1See the synthesis examples for H NMR data.
Index table D
Biological examples of the invention
Test A
Seeds of plant species selected from the group consisting of barnyard grass (barnyardgrass) (Echinochloa crus-galli), Kochia (broom), ragweed (ragweed), hogwort (common ragweed), Italian rye grass (Italian rye grass, Lolium multifluorum), Setaria (foxtail, Setaria (large crabgrass, Setaria faberi)), and Amaranthus (Piggeed) were planted into a blend of loam and sandy soil and pre-treated with a directed soil spray using a non-toxic mixture formulated in a solvent containing a surfactant for pre-treatment.
At the same time, plants selected from these weed species and also black grass (alopecuroids), cleavers (Galium) (Galium aparine), wheat (Triticum aestivum)), and maize (corn) (Zea mays) were planted in pots containing the same blend of loam and sandy soil, and post-emergence application treatment with test compounds formulated in the same manner plants ranging in height from 2 to 10cm and at one to two leaf stage were used for post-emergence treatment the treated plants were kept in the greenhouse for about 10 days with untreated controls before all treated plants were compared to untreated controls and visually assessed for damage the plant response ratings summarized in table a were based on a 0 to 100 scale, where 0 is no effect and 100 is full control, dash (-) response means no test result.
Test B
Plant species selected from rice (rice) (Oryza sativa), cymbidium floribundum (ridge, umbrella) (cymbidium floribundum, Cyperus heterophylla (Cyperus difformis)), marshlia palustris (ducksalad) (heternthera limosa), and barnyard grass (barnyard grass) were grown to the 2-leaf stage in the flooded rice field test for testing. At treatment, the test pots were flooded to 3cm above the soil surface, treated by applying the test compounds directly to the field water, and then the water depth was maintained during the test. The treated plants and controls were kept in the greenhouse for 13 to 15 days, after which all species were compared to controls and visually evaluated. The plant response ratings summarized in table B are based on a scale of 0 to 100, where 0 is no effect and 100 is full control. Dash (-) response means no test result.
