Patent Application
20070167631
The present invention relates to novel, herbicidally active picolinoylcyclohexanediones, to processes for their preparation, to compositions comprising those compounds, and to their use in controlling weeds, especially in crops of useful plants, or in inhibiting plant growth.
Certain herbicidally active derivatives of picolinic acids disubstituted in the 3,5-position are known, such as, for example from EP-A-O 316 491, the 3,5-substituted picolinoyl derivatives of 1,3-cyclohexanediones substituted in the 2-position.
It has now been found that picolinoylcyclohexanediones that are substituted in the 5,6-position of the pyridine and unsubstituted in the 3,4-position of the pyridine exhibit excellent herbicidal and growth-inhibiting properties.
The present invention accordingly relates to compounds of formula I
wherein
R1 is -L10-R4, -L11-X1—R5, —NR6R7, —X2—R8 or —X3-L1-R9;
L2, L4, L6 and L8 are each independently of the others C1-C4alkylene which may be substituted once, twice or three times by C1-C4alkyl, halogen or by C1-C4alkoxy and to which C1-C4alkylene group there may additionally be spirocyclically bound a C2-C5alkylene group, and wherein that C2-C5alkylene group may in turn be interrupted once or twice by oxygen, sulfur, sulfinyl or by sulfonyl and/or substituted by C1-C4alkyl or by C1-C4alkoxy;
L3, L5, L7 and L9 are each independently of the others C1-C4alkylene which may be substituted once, twice or three times by C1-C4alkyl, halogen or by C1-C4alkoxy;
R2 is halogen, C1-C4haloalkyl, cyano, C1-C3haloalkoxy, C1-C4alkylthio, C1-C4alkylsulfinyl, C1-C4alkylsulfonyl, C1-C4haloalkylthio, C1-C4haloalkylsulfinyl or C1-C4haloalkylsulfonyl;
L10 is a direct bond or a C1-C6alkylene, C2-C6alkenylene or C2-C6alkynylene group which may be substituted once, twice or three times by C1-C6alkyl, halogen, hydroxy, C1-C6alkoxy, C3-C6cycloalkyloxy, C1-C6alkoxy-C1-C6alkoxy, C1-C6alkoxy-C1-C6alkoxy-C1-C6alkoxy or by C1-C2alkylsulfonyloxy;
R4 is halogen, cyano, rhodano, C1-C6alkoxycarbonyl, C3-C6alkenyloxycarbonyl, C3-C6alkynyl-oxycarbonyl, benzyloxycarbonyl, C(O)NR25aR26a, formyl, C1-C6alkylcarbonyl, C1-C6haloalkylcarbonyl, C1-C4alkoxy-C1-C4alkylcarbonyl, C1-C4alkoxy-C1-C4alkoxy-C1-C4alkylcarbonyl, N—(C1-C4alkyl)-C1-C4alkylsulfonylamino-C1-C4alkylcarbonyl, C1-C6haloalkyl, C2-C6alkenyl, C2-C6-haloalkenyl, C2-C6alkynyl, C2-C6haloalkynyl, C3-C6cycloalkyl, C1-C6alkylsulfonyloxy or phenylsulfonyloxy, wherein the phenyl groups may be substituted by one or more C1-C6alkyl, C1-C6-haloalkyl, C1-C6alkoxy, C1-C6haloalkoxy, halogen, cyano, hydroxy or nitro groups;
or R4 is a three- to ten-membered, monocyclic or fused bicyclic ring system which may be aromatic, saturated or partially saturated and which may contain from 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur, and wherein the ring system may contain not more than 2 oxygen atoms and not more than two sulfur atoms, and each ring system may itself be substituted once, twice or three times by C1-C6alkyl, C1-C6haloalkyl, C1-C4alkoxy-C1-C2alkyl, C2-C6alkenyl, C2-C6haloalkenyl, C2-C6alkynyl, C2-C6haloalkynyl, C1-C6alkoxy, hydroxy, C1-C6haloalkoxy, C3-C6alkenyloxy, C3-C6alkynyloxy, mercapto, C1-C6alkylthio, C1-C6haloalkylthio, C3-C6alkenylthio, C3-C6haloalkenylthio, C3-C6alkynylthio, C2-C5alkoxyalkylthio, C3-C5acetylalkylthio, C3-C6alkoxycarbonylalkylthio, C2-C4cyanoalkylthio, C1-C6alkylsulfinyl, C1-C6haloalkylsulfinyl, C1-C6alkylsulfonyl, C1-C6haloalkylsulfonyl, aminosulfonyl, C1-C2alkylaminosulfonyl, di(C1-C2alkyl)aminosulfonyl, di(C1-C4alkyl)amino, halogen, cyano, nitro, phenyl or by benzylthio, and wherein phenyl and benzylthio may in turn be substituted on the phenyl ring by C1-C3alkyl, C1-C3haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, halogen, cyano or by nitro, and wherein the substituent on the nitrogen in the heterocyclic ring are other than halogen;
or R4 is hydrogen when L10 is a C1-C6alkylene group which may be substituted once, twice or three times by C1-C6alkyl or by halogen; or when L10 is a C2-C6alkenylene or C2-C6alkynylene group which may be substituted once, twice or three times by C1-C6alkyl, halogen, hydroxy, C1-C6alkoxy, C3-C6cycloalkyloxy, C1-C6alkoxy-C1-C6alkoxy, C1-C6alkoxy-C1-C6alkoxy-C1-C6-alkoxy or by C1-C2alkylsulfonyloxy;
R25a is hydrogen, C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl or phenyl which may be substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3-haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
R26a is hydrogen, C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl;
or R25a together with R26a and the respective N atom to which they are bonded form a carbocyclic 3- to 6-membered ring which may be interrupted by oxygen or by sulfur and/or substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3-haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
L11 is a C1-C6alkylene, C2-C6alkenylene or C2-C6alkynylene group which may be substituted once, twice or three times by halogen, hydroxy, C1-C6alkoxy, C3-C6cycloalkyloxy, C1-C6-alkoxy-C1-C6alkoxy, C1-C6alkoxy-C1-C6alkoxy-C1-C6alkoxy or by C1-C2alkylsulfonyloxy;
X1 is oxygen, —OC(O)—, —C(O)—, —C(═NR14a)—, —C(O)O—, —C(O)NR14b—, —OC(O)O—, —N(R10)—O—, —O—NR11—, thio, sulfinyl, sulfonyl, —SO2NR12—, —NR13SO2—, —N(SO2R14c)—, —N(R14d)C(O)— or —NR14—;
R10, R11, R12, R13, R14b, R14d and R14 are each independently of the others hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxycarbonyl, C1-C6alkylcarbonyl, C1-C6alkoxy-C1-C6alkyl, or C1-C6alkoxy-C1-C6alkyl substituted by C1-C6alkoxy, or benzyl or phenyl, wherein phenyl and benzyl may in turn be substituted once, twice or three times by C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy, C1-C6haloalkoxy, halogen, cyano, hydroxy or by nitro;
R14a is hydroxy, C1-C6alkoxy, C3-C6alkenyloxy, C3-C6alkynyloxy or benzyloxy;
R14c is C1-C6alkyl;
R5 is hydrogen or a C1-C8alkyl, C3-C8alkenyl or C3-C8alkynyl or C3-C6cycloalkyl group which may be substituted once, twice or three times by chlorine, bromine, iodine, hydroxy, amino, formyl, nitro, cyano, mercapto, C1-C6alkoxy, C2-C6alkenyl, C2-C6haloalkenyl, C2-C6alkynyl, C2-C6haloalkynyl, C3-C6cycloalkyl, halo-substituted C3-C6cycloalkyl, C3-C6alkenyloxy, C3-C6alkynyloxy, C1-C6haloalkoxy, C3-C6haloalkenyloxy, cyano-C1-C6alkoxy, C1-C6alkoxy-C1-C6alkoxy, C1-C6alkoxy-C1-C6alkoxy-C1-C6alkoxy, C1-C6alkylthio-C1-C6alkoxy, C1-C6alkylsulfinyl-C1-C6alkoxy, C1-C6alkylsulfonyl-C1-C6alkoxy, C1-C6alkoxycarbonyl-C1-C6alkoxy, C1-C6alkoxycarbonyl, C1-C6alkylcarbonyl, phenylcarbonyl, C1-C6alkylthio, C1-C6alkylsulfinyl, C1-C6alkylsulfonyl, C1-C6haloalkylthio, C1-C6haloalkylsulfinyl, C1-C6haloalkylsulfonyl, benzyloxy, benzylthio, benzylsulfinyl, benzylsulfonyl, C1-C6alkylamino, di(C1-C6alkyl)amino, R15aC(X23)N(R18a)—, R16aN(R17a)C(X24)—, R16bN(R17b)C(X25)NR18b—, R15cSO2N(R18c)—, R16cN(R17c)C(X26)O—, R15bC(X27)O—, R19R20C═NO—, R15S(O)2O—, R16N(R17)SO2—, rhodano, phenyl, phenoxy, phenylthio, phenylsulfinyl or by phenylsulfonyl or which may be substituted from one to seventeen times by fluorine; wherein the phenyl- or benzyl-containing groups may in turn be substituted by one or more C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy, C1-C6haloalkoxy, halogen, cyano, hydroxy or nitro groups;
R15a, R15b and R15c are hydrogen, C1-C6alkyl, C2-C6alkenyl, C3-C6cycloalkyl, phenyl, benzyl, C1-C6alkoxy, C3-C6alkenyloxy, C3-C6alkynyloxy or benzyloxy, wherein the phenyl groups may be substituted once, twice or three times by C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy, C1-C6haloalkoxy, halogen, cyano, hydroxy or by nitro;
R16a, R16b and R16c are hydrogen, C1-C6alkyl, C3-C6alkenyl, C3-C6alkynyl, C3-C6cycloalkyl or phenyl, wherein phenyl may be substituted once, twice or three times by C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy, C1-C6haloalkoxy, halogen, cyano, hydroxy or by nitro;
R17a, R17b, R17c, R18a, R18b and R18c are hydrogen, C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl;
X23, X24, X25, X26 and X27 are oxygen or sulfur;
R15, R16, R17, R19 and R20 are each independently of the others hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxycarbonyl, C1-C6alkylcarbonyl, C1-C6alkoxy-C1-C6alkyl, or C1-C6alkoxy-C1-C6alkyl substituted by C1-C6alkoxy, or benzyl or phenyl, wherein phenyl and benzyl may in turn be substituted once, twice or three times by C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy, C1-C6haloalkoxy, halogen, cyano, hydroxy or by nitro;
or R5 is a three- to ten-membered monocyclic or fused bicyclic ring system which may be aromatic, saturated or partially saturated and may contain from 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur, and wherein the ring system is bound to the substituent X1 directly or via a C1-C4alkylene, C2-C4alkenylene, C2-C4alkynylene, —N(R18)—C1-C4alkylene, —O—C1-C4alkylene, —S—C1-C4alkylene, —S(O)—C1-C4alkylene or —SO2—C1-C4alkylene chain, wherein the ring system may not be interrupted by —C(═O)—, —C(═S)—, —C(═NR5a)—, —N(═O)—, —S(═O)— or by —SO2—, and each ring system may contain not more than 2 oxygen atoms and not more than two sulfur atoms, and the ring system itself may be substituted once, twice or three times by C1-C6alkyl, C1-C6haloalkyl, C2-C6alkenyl, C2-C6haloalkenyl, C2-C6alkynyl, C2-C6haloalkynyl, C1-C6alkoxy, hydroxy, C1-C6haloalkoxy, C3-C6alkenyloxy, C3-C6alkynyloxy, mercapto, C1-C6alkylthio, C1-C6haloalkylthio, C3-C6alkenylthio, C3-C6haloalkenylthio, C3-C6-alkynylthio, C2-C5alkoxyalkylthio, C3-C5acetylalkylthio, C3-C6alkoxycarbonylalkylthio, C2-C4-cyanoalkylthio, C1-C6alkylsulfinyl, C1-C6haloalkylsulfinyl, C1-C6alkylsulfonyl, C1-C6haloalkylsulfonyl, aminosulfonyl, C1-C2alkylaminosulfonyl, di(C1-C2alkyl)aminosulfonyl, di(C1-C4alkyl)amino, halogen, cyano, nitro, phenyl or by benzylthio, wherein phenyl and benzylthio may in turn be substituted on the phenyl ring by C1-C3alkyl, C1-C3haloalkyl, C1-C3alkoxy, C1-C3-haloalkoxy, halogen, cyano or by nitro, and wherein the substituents on the nitrogen in the heterocyclic ring are other than halogen;
R5a is C1-C6alkyl, hydroxy, C1-C6alkoxy, cyano or nitro;
R18 is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxycarbonyl, C1-C6alkylcarbonyl, C1-C6alkoxy-C1-C6alkyl, or C1-C6alkoxy-C1-C6alkyl substituted by C1-C6alkoxy, or benzyl or phenyl, wherein phenyl and benzyl may in turn be substituted once, twice or three times by C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy, C1-C6haloalkoxy, halogen, cyano, hydroxy or by nitro;
R6 is hydrogen, C1-C6alkyl, C3-C6alkenyl, C3-C6alkynyl, C1-C6haloalkyl, hydroxy, C1-C6alkoxy, —C(O)R19a or —C(S)R20a;
R19a and R20a are each independently of the other hydrogen, C1-C6alkyl, C3-C6cycloalkyl, phenyl, benzyl, heteroaryl, C1-C6alkoxy, C3-C6alkenyloxy, benzyloxy, C1-C4alkylthio or a group NR21R22;
R21 and R22 are each independently of the other hydrogen, C1-C6alkyl, C3-C6alkenyl, C3-C6alkynyl or phenyl, and wherein phenyl, benzyl, benzyloxy and heteroaryl in R19a, R20a, R21 and R22 may be substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
or R21 together with R22 and the respective N atom to which they are bonded form a carbocyclic 3- to 6-membered ring which may be interrupted by oxygen or by sulfur and/or substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
or R6 is -L2-X4—R24; wherein
X4 is oxygen, —NR23—, —S—, —S(O)— or —S(O)2—;
R23 is hydrogen, C1-C6alkoxy, C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl or is phenyl which may be substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3-alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
R24 is hydrogen or a C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl group, which groups may be substituted once, twice or three times by halogen, hydroxy, C1-C6alkoxy, C1-C3alkoxy-C1-C3alkoxy, C3-C6alkenyloxy, C3-C6alkynyloxy, C1-C6alkylthio, C1-C6alkylsulfinyl, C1-C6-alkylsulfonyl, cyano, C(X5)NR25R26, C3-C6cycloalkyl, phenyl, phenoxy or by 5- or 6-membered heteroaryl or heteroaryloxy, wherein heteroaryl or heteroaryloxy may in turn be interrupted once by oxygen or by sulfur or once, twice or three times by nitrogen and may be bonded to the C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl group either via a C atom or via a N atom, and wherein the phenyl- and heteroaryl-containing groups may be substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
or R24 is C(O)—R74 or C(S)—R75;
X5 is oxygen or sulfur;
R25 is hydrogen, C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl or phenyl which may be substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
R26 is hydrogen, C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl;
or R25 together with R26 and the respective N atom to which they are bonded form a carbocyclic 3- to 6-membered ring which may be interrupted by oxygen or by sulfur and/or substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
or R6 is -L3-R27;
The alkyl groups in the substituent definitions may be straight-chained or branched and are, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, pentyl, hexyl, heptyl and octyl and branched isomers thereof. Alkoxy, alkylthio, alkenyl and alkynyl radicals are derived from the mentioned alkyl radicals. The alkenyl and alkynyl groups may be mono- or poly-unsaturated, in which case an allenyl group and a mixed alkene-alkynyl group are also included.
Alkoxy groups are accordingly methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, isobutoxy, tert-butoxy.
Alkylthio groups and oxidised forms thereof preferably have a chain length of from 1 to 3 carbon atoms; preference is given to, for example, methylthio, ethylthio, n-propylthio and isopropylthio; especially methyl- and ethyl-thio. Alkylsulfinyl is, for example, methylsulfinyl, ethylsulfinyl, n-propylsulfinyl or isopropylsulfinyl, and alkylsulfonyl is preferably methylsulfonyl, ethylsulfonyl, propylsulfonyl or isopropylsulfonyl; preferably methylsulfonyl or ethylsulfonyl.
Halogen is generally fluorine, chlorine, bromine or iodine; preferably fluorine, chlorine or bromine. Halo-substituted alkyl groups, that is to say haloalkyl groups, preferably have a chain length of from 1 to 6 carbon atoms. C1-C4Haloalkyl is, for example, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 2-fluoroethyl, 2-chloroethyl, pentafluoroethyl, 1,1-difluoro-2,2,2-trichloroethyl, 2,2,2-trichloroethyl, 1,1,2,2-tetrafluoroethyl, 2,2,3,3-tetrafluoropropyl, 2,2,3,3,3-pentafluoropropyl or 2,2,3,4,4,4-hexafluorobutyl; preferably fluoromethyl, difluoromethyl, difluorochloromethyl, dichlorofluoromethyl, trifluoromethyl, 2-chloroethyl, 2,2,2-trifluoroethyl, 2,2,3,3-tetrafluoropropyl or 2,2,3,3,3-pentafluoropropyl.
As haloalkenyl groups, alkenyl groups substituted once or more than once by halogen are suitable, halogen being especially fluorine or chlorine, for example 2, 2-difluoro-1-methylvinyl, 3-fluoropropenyl, 3-chloropropenyl, 3-bromopropenyl, 2,3,3-trifluoropropenyl, 2,3,3-trichloro-propenyl or 4,4,4-trifluoro-but-2-en-1-yl. As haloalkynyl, for example alkynyl groups substituted once or more than once by halogen are suitable, halogen being bromine or iodine or also fluorine or chlorine, for example 3-fluoropropynyl, 3-chloropropynyl, 3-bromopropynyl, 3,3,3-trifluoropropynyl or 4,4,4-trifluoro-but-2-yn-1-yl. The same is also correspondingly true for halogen in association with other definitions such as haloalkoxy, haloalkylthio, haloalkylsulfinyl, haloalkylsulfonyl or halophenyl.
The definition of R4 or R5 as a three- to ten-membered monocyclic or fused bicyclic ring system which may be aromatic, saturated or partially saturated and which may contain from 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur, and wherein the ring system may contain not more than 2 oxygen atoms and not more than two sulfur atoms, and the ring system may itself be substituted, is to be understood in the context of the present invention as meaning especially ring systems in which two oxygen atoms and/or one oxygen atom and one sulfur atom are not located next to one another, such as, for example, phenyl, naphthyl, indenyl, cyclopentenyl, cyclohexenyl or C3-C8cycloalkyl, C3-C6oxacycloalkyl, C2-C5dioxacycloalkyl or similar ring systems, such as especially aromatic five- or six-membered heteroaryl groups containing from 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur, and partially or fully saturated three- to six-membered ring systems which especially contain 1 or 2 oxygen atoms, such as, for example, oxiranyl, oxetan-3-yl, tetrahydrofuran-3-yl, tetrahydropyran-2-yl, 1,3-dioxacyclopent-2-yl, 1,3-dioxacyclopent-4-yl, 1,3-dioxacyclohex-2-yl, 1,3-dioxacyclohex-5-yl or cis- and/or trans-1,3-dioxa-4,5-dimethyl-cyclopent-2-yl, or fully saturated three- to six-membered ring systems that contain 1 or 2 sulfur atoms, such as, for example, 1,3-oxathio-cyclopent-2-yl, tetrahydrothien-2-yl, 1,3-oxathio-cyclopent-2-yl or 1,3-dithiacyclopent-2-yl.
Heteroaryl, such as, for example, in the definition of R6, R7, R8 or R9 or in the case of a five- or six-membered, monocyclic or fused bicyclic, aromatic ring system R4 or R5, is understood to be especially an aromatic 5- or 6-membered heteroaryl group bonded via a carbon atom, which group may be interrupted once by oxygen, once by sulfur and/or once, twice or three times by nitrogen, for example 1-methyl-1H-pyrazol-3-yl, 1-ethyl-1H-pyrazol-3-yl, 1-propyl-1H-pyrazol-3-yl, 1H-pyrazol-3-yl, 1,5-dimethyl-1H-pyrazol-3-yl, 4-chloro-1-methyl-1H-pyrazol-3-yl, 3-isoxazolyl, 5-methyl-3-isoxazolyl, 3-methyl-5-isoxazolyl, 5-isoxazolyl, 1H-pyrrol-2-yl, 1-methyl-1H-pyrrol-2-yl, 1-methyl-1H-pyrrol-3-yl, 2-furyl, 5-methyl-2-furyl, 3-furyl, 5-methyl-2-thienyl, 2-thienyl, 3-thienyl, 1-methyl-1H-imidazol-2-yl, 1H-imidazol-2-yl, 1-methyl-1H-imidazol-4-yl, 1-methyl-1H-imidazol-5-yl, 4-methyl-2-oxazolyl, 5-methyl-2-oxazolyl, 2-oxazolyl, 2-methyl-5-oxazolyl, 2-methyl-4-oxazolyl, 4-methyl-2-thiazolyl, 5-methyl-2-thiazolyl, 2-thiazolyl, 2-methyl-5-thiazolyl, 2-methyl-4-thiazolyl, 3-methyl-4-isothiazolyl, 3-methyl-5-isothiazolyl, 5-methyl-3-isothiazolyl, 1-methyl-1H-1,2,3-triazol-4-yl, 2-methyl-2H-1,2,3-triazol-4-yl, 4-methyl-2H-1,2,3-triazol-2-yl, 1-methyl-1H-1,2,4-triazol-3-yl, 1,5-dimethyl-1H-1,2,4-triazol-3-yl, 4,5-dimethyl-4H-1,2,4-triazol-3-yl, 4-methyl-4H-1,2,4-triazol-3-yl, 5-methyl-1,2,3-oxadiazol-4-yl, 1,2,3-oxadiazol-4-yl, 3-methyl-1,2,4-oxadiazol-5-yl, 5-methyl-1,2,4-oxadiazol-3-yl, 5-methyl-1,2,3-thiadiazol-4-yl, 1,2,3-thiadiazol-4-yl, 3-methyl-1,2,4-thiadiazol-5-yl, 5-methyl-1,2,4-thiadiazol-3-yl, 4-methyl-1,2,5-thiadiazol-3-yl, 5-methyl-1,3,4-thiadiazol-2-yl, 2-pyridyl, 6-methyl-2-pyridyl, 4-pyridyl, 3-pyridyl, 6-methyl-3-pyridazinyl, 5-methyl-3-pyridazinyl, 3-pyridazinyl, 4,6-dimethyl-2-pyrimidinyl, 4-methyl-2-pyrimidinyl, 2-pyrimidinyl, 2-methyl-4-pyrimidinyl, 2-chloro-4-pyrimidinyl, 2,6-dimethyl-4-pyrimidinyl, 4-pyrimidinyl, 2-methyl-5-pyrimidinyl, 6-methyl-2-pyrazinyl, 2-pyrazinyl, 4,6-dimethyl-1,3,5-triazin-2-yl, 4,6-dichloro-1,3,5-triazin-2-yl, 1,3,5-triazin-2-yl, 4-methyl-1,3,5-triazin-2-yl, 3-methyl-1,2,4-triazin-5-yl or 3-methyl-1,2,4-triazin-6-yl. A heteroaryl group bonded via the N atom is understood to be, for example, 1H-pyrrol-1-yl, 1H-pyrazol-1-yl, 3-methyl-1H-pyrazol-1-yl, 3,5-dimethyl-1H-pyrazol-1-yl, 3-trifluoromethyl-1H-pyrazol-1-yl, 3-methyl-1H-1,2,4-triazol-1-yl, 5-methyl-1H-1,2,4-triazol-1-yl or 4H-1,2,4-triazol-4-yl.
The definition of L1 as C1-C4alkylene which may be substituted once, twice or three times by C1-C4alkyl, halogen or by C1-C4alkoxy, wherein a carbon atom of the L1 chain forms together with R9 a C2-C6alkylene chain which may be interrupted once or twice by oxygen, sulfur, sulfinyl or by sulfonyl and may be substituted by C1-C4alkyl or by C1-C4alkoxy, is to be understood in the context of the present invention as being, for example, the following cyclic C2-C6alkylene groups: C3-C6oxacycloalkyl, C2-C5dioxacycloalkyl, C3-C6oxacycloalkyl-C1-C2-alkyl, C3-C6dioxacycloalkyl-C1-C2alkyl or similar oxygen- or sulfur-containing groups, especially a C3-C6cycloalkyl group interrupted once or twice by oxygen, such as, for example, oxetan-3-yl, tetrahydrofuran-3-yl, tetrahydropyran-2-yl, 1,3-dioxacyclohex-4-yl, or
wherein in each case the marked ′C atom is bonded to X3; or oxiranyl-methyl, 3-oxetanyl-methyl, tetrahydrofuran-3-yl-methyl, tetrahydrofuran-2-yl-methyl, 1,3-dioxacyclopent-3-yl-methyl, 1,3-dioxa-4,5-dimethyl-cyclopent-3-yl-methyl,
or a C3-C6cycloalkyl group interrupted once or twice by sulfur, e.g. 1,3-oxathio-cyclopent-2-yl, tetrahydrothien-2-yl-methyl, 1,3-oxathio-cyclopent-2-yl-methyl, 1,3-dithiacyclopent-2-yl-methyl,
etc., wherein in each case the marked ′C atom is bonded to X1.
The definition of NR6R7 wherein R6 together with R7 and the common N atom forms a carbocyclic 3- to 7-membered, saturated or partially saturated monocyclic or bicyclic ring system is to be understood as meaning, for example, morpholino (=morpholin-4-yl), cis- and/or trans-2,6-dimethylmorpholin-4-yl, thiomorpholin-4-yl, N-methyl-piperidin-1-yl, 1H-pyrrol-1-yl, 1H-pyrazol-1-yl, 3-methyl-1H-pyrazol-1-yl, 3,5-dimethyl-1H-pyrazol-1-yl, 3-trifluoromethyl-1H-pyrazol-1-yl, 3-methyl-1H-1,2,4-triazol-1-yl, 5-methyl-1H-1,2,4-triazol-1-yl, 4H-1,2,4-triazol-4-yl, or groups according to the formulae
etc., wherein in each case the marked ′N atom is bonded to the picolinyl group.
The definition of L1, L2, L4, L6 and L8 as C1-C4alkylene, to which C1-C4alkylene group there may be spirocyclically bound a C2-C5alkylene group, is to be understood as meaning, for example, a C1-C3alkylene chain that contains a cyclopropyl group or that is substituted by a 1,3-dioxolan-2-yl group, such as, for example,
wherein in each case the marked ′C atom represents the left-hand side valence of the definitions containing the respective substituent L. For example, in —X3-L1-R9 the marked ′C atom is linked to the substituent X3. In general, such alkylene chains, for example C1-C4alkylene for L1 and L4, can also be substituted by one or more C1-C3alkyl groups, especially by methyl groups. Such alkylene chains and the alkylene chains and groups interrupted by oxygen or by sulfur are preferably unsubstituted. Preferably, groups containing C3-C6cycloalkyl, oxiranyl, oxetanyl, C3-C5oxacycloalkyl, C3-C5thiacycloalkyl, C3-C4dioxacycloalkyl, C3-C4dithiacycloalkyl or C3-C4oxathiacycloalkyl and also the groups A1, A2 and A3 are also unsubstituted.
In the case that a chemical group is substituted more than once by substituents listed in a list of substituents, such as for example L2 in the meaning of C1-C4alkylene which is substituted twice or three times by C1-C4alkyl, halogen or by C1-C4alkoxy, said chemical group can be substituted by different substituents from said list of substituents. The same applies mutatis mutandis for ring systems that are substituted more than once, such as for example R5 in the meaning of a three- to ten-membered ring system, which is substituted twice or three times by C1-C6alkyl, C1-C6haloalkyl, C2-C6alkenyl, C2-C6haloalkenyl, C2-C6alkynyl, C2-C6haloalkynyl, C1-C6alkoxy, hydroxy, C1-C6haloalkoxy, C3-C6alkenyloxy, C3-C6alkynyloxy, mercapto, C1-C6alkylthio, C1-C6haloalkylthio, C3-C6alkenylthio, C3-C6haloalkenylthio, C3-C6-alkynylthio, C2-C5alkoxyalkylthio, C3-C5acetylalkylthio, C3-C6alkoxycarbonylalkylthio, C2-C4-cyanoalkylthio, C1-C6alkylsulfinyl, C1-C6haloalkylsulfinyl, C1-C6alkylsulfonyl, C1-C6haloalkylsulfonyl, aminosulfonyl, C1-C2alkylaminosulfonyl, di(C1-C2alkyl)aminosulfonyl, di(C1-C4alkyl)amino, halogen, cyano, nitro, phenyl or by benzylthio.
The compounds of formula I may occur in various tautomeric forms, as shown by way of example for compounds of formula I wherein R3 is hydroxy by formulae I′, I″, I′″ and I″″, the forms I″ and I″″ being preferred as isolated forms and formula I″″ also representing a rota-meric form of I″.
When there is a C═C or C═N double bond in compounds of formula I, such as, especially, in the groups R1, the compounds of formula I may, when asymmetry exists, be in the ‘E’ or in the ‘Z’ form. If a further asymmetric centre is present, for example an asymmetric carbon atom in the group R1, or as a result of the spatial arrangement of A1, A2, A3 and the substituents R112, R113, R115, R116, R118 and R119, chiral ‘R’ and ‘S’ forms and/or constitutional isomeric forms may also occur. The present invention accordingly includes also all those stereoisomeric and tautomeric forms of the compound of formula I.
The invention relates also to the salts which the compounds of formula I are able to form preferably with amines, alkali metal and alkaline earth metal cations or quaternary ammonium bases. Suitable salt formers are described, for example, in WO 98/41089. Among the alkali metal and alkaline earth metal hydroxides as salt formers, special mention may be made of the hydroxides of lithium, sodium, potassium, magnesium and calcium, but especially the hydroxides of sodium and potassium.
Examples of amines suitable for ammonium salt formation include ammonia as well as primary, secondary and tertiary C1-C18alkylamines, C1-C4hydroxyalkylamines and C2-C4alkoxyalkylamines, for example methylamine, ethylamine, n-propylamine, isopropylamine, the four butylamine isomers, n-amylamine, isoamylamine, n-hexylamine, heptylamine, octylamine, nonylamine, decylamine, pentadecylamine, hexadecylamine, heptadecyl-amine, octadecylamine, methyl-ethylamine, methyl-isopropylamine, methyl-hexylamine, methyl-nonylamine, methyl-pentadecylamine, methyl-octadecylamine, ethyl-butylamine, ethyl-heptylamine, ethyl-octylamine, hexyl-heptylamine, hexyl-octylamine, dimethylamine, diethylamine, di-n-propylamine, diisopropylamine, di-n-butylamine, di-n-amylamine, diisoamylamine, dihexylamine, diheptylamine, dioctylamine, ethanolamine, n-propanolamine, isopropanolamine, N,N-diethanolamine, N-ethylpropanolamine, N-butylethanolamine, allylamine, n-butenyl-2-amine, n-pentenyl-2-amine, 2,3-dimethylbutenyl-2-amine, dibutenyl-2-amine, n-hexenyl-2-amine, propylenediamine, trimethylamine, triethylamine, tri-n-propylamine, triisopropylamine, tri-n-butylamine, triisobutylamine, tri-sec-butylamine, tri-n-amylamine, methoxyethylamine and ethoxyethylamine; heterocyclic amines, for example pyridine, quinoline, isoquinoline, morpholine, piperidine, pyrrolidine, indoline, quinuclidine and azepine; primary arylamines, for example anilines, methoxyanilines, ethoxyanilines, o-, m- and p-toluidines, phenylenediamines, benzidines, naphthylamines and o-, m- and p-chloroanilines; but especially triethylamine, isopropylamine and diisopropylamine.
Preferred quaternary ammonium bases suitable for salt formation correspond, for example, to the formula [+N(RaRbRcRd)−OH] wherein Ra, Rb, Rc and Rd are each independently of the others C1-C4alkyl. Other suitable tetraalkylammonium bases with other anions can be obtained, for example, by anion exchange reactions.
In preferred compounds of formula I:
a) A1 is —C(R112R113)—, A2 is —C(R115R116)—, A3 is —C(R118R119)—, R112 is hydrogen, methyl, methoxy, methylthio, methylsulfinyl, methylsulfonyl, methoxycarbonyl or ethoxycarbonyl and R113, R115, R116, R118 and R119 are each independently of the others hydrogen or methyl; especially preferably A1, A2 and A3 are unsubstituted methylene;
b) A1 is —C(R112R113)—, R112 together with R113 ethylene is a spirocyclic 3-membered ring, A2 is —C(R115R116)—, A3 is C(R118R119)— and R115, R116, R118 and R119 are each independently of the others hydrogen or methyl; especially A2 and A3 are unsubstituted methylene;
c) A1 is —C(R112R113)—, A3 is —C(R118R119)—, R112, R113, R118 and R119 are each methyl and A2 is carbonyl or oxygen, especially carbonyl;
d) R3 is hydroxy, O−M+, C1-C8alkylthio, C3-C8alkenylthio, C3-C8alkynylthio, benzylthio or phenylthio, especially hydroxy or a salt of formula O−M+ wherein M+ is an agronomically acceptable metal cation or ammonium cation;
e) R2 is chlorine, bromine, cyano, trifluoromethyl, difluoromethyl, difluorochloromethyl, difluoromethoxy, trifluoromethoxy, trifluoroethoxy, difluoromethylthio, trifluoromethylthio, trifluoroethylthio, methylthio, ethylthio, methylsulfonyl or ethylsulfonyl, especially trifluoromethyl;
or f) R1 is a group —NR6R7 or a group —X2—R8 wherein X2 is —O— or —NR42—, or a group —X3-L1-R9 wherein X3 is —O— or —NR57—.
Of those preferred compounds of formula I, special preference is given to the following compounds wherein
g) R1 is a group —X3-L1-R9 wherein X3 is oxygen;
h) L1 is a methylene or ethylene chain which may be substituted by methyl, ethyl, methoxy or by ethoxy, special emphasis being given to those compounds wherein R1 as —X3-L1-R9 is the side chain —O-L1-O—R70 wherein R70 is C1-C3alkyl, allyl, propargyl, C1-C2alkoxy-C1-C2alkyl or C(O)—R78 and R78 is NR127R128;
i) R1 as —X3-L1-R9 is the group —O-L1-X20—R70 wherein X20 is especially oxygen and a carbon atom of the chain L1 together with R70 forms a C2-C6alkylene chain which may be interrupted once by oxygen and may be substituted once or twice by methyl;
j) R1 is —X3-L1-X20—R70 wherein R70 is C(O)NR127R128;
k) R1 is the group —O-L1-N(R71)C(O)R78 wherein R71 is especially hydrogen and R78 is especially C1-C4alkyl, cyclopropyl, phenyl, C1-C4alkoxy, methylamino or dimethylamino.
In a further especially preferred group of compounds that are preferred under the provisions of a) to f):
l) R1 is a group —NR6R7 or a group —X3-L1-R9 wherein X3 is —NR57— and wherein L1 is a methylene or ethylene chain which may be substituted by methyl, ethyl, methoxy or by ethoxy, and of that group of compounds of formula I special mention should be made of those wherein —NR6R7 is a heterocyclic group selected from morpholin-4-yl, thiomorpholinyl-4-yl, pyrazol-1-yl and 1,2,4-triazol-1-yl, and wherein those groups may be substituted by methyl, trifluoromethyl, methoxy or by ethoxy;
m) R1 is a group —NR6R7 wherein R7 is C(X7)R30; and preferably R6 is methyl or ethyl; X7 is oxygen; and R30 is C1-C6alkyl, C3-C6cycloalkyl or phenyl.
Also preferred are compounds of formula I wherein at least one of the linking members X3 or X20 is oxygen; preferably both are oxygen.
L1 is preferably an unsubstituted C1-C3alkylene chain or a C2alkylene chain substituted once by methyl.
In an outstanding group of compounds that are preferred under the provisions of a) to e):
o) R1 is a group -L11-X1—R5 wherein L11 is C1-C2alkylene which may be substituted by methyl, ethyl, methoxy or by ethoxy, especially unsubstituted methylene;
p) R1 is a group -L11-X1—R5 wherein X1 is oxygen, —C(O)—, —C(═NR14a)—, —C(O)O—, —C(O)NR14b—, thio, sulfonyl, —NR13SO2—, —N(SO2R14c)— or —NR14— wherein R14 is C1-C6alkoxycarbonyl or C1-C6alkylcarbonyl, X1 being especially oxygen or —N(SO2R14c)—;
q) R1 is a group -L11-X1—R5 wherein R5 is C1-C6alkyl which may be substituted by halogen, cyano, C1-C4alkoxy, C1-C4alkoxycarbonyl, C2-C4alkenyl, C2-C4haloalkenyl, C2-C4alkynyl, C3-C6cycloalkyl, C3-C4alkenyloxy, C3-C4alkynyloxy, C1-C4haloalkoxy, C3-C4haloalkenyloxy, cyano-C1-C3alkoxy or by C1-C3alkoxy-C1-C3alkoxy; R5 being especially C1-C4alkyl, C3-C4-alkenyl or C3-C4alkynyl, or C1-C3alkyl which is substituted from one to three times by fluorine, once or twice by chlorine, once or twice by methoxy or by ethoxy, once by cyano, allyloxy, propargyloxy, difluoromethoxy, trifluoromethoxy, methoxyethoxy or by C3-C6cycloalkyl;
r) R1 is a group -L11-X1—R5 wherein R5 is phenyl or a three- to six-membered monocyclic ring system which may be aromatic, saturated or partially saturated and contains from 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur, wherein phenyl or the ring system is bound to the substituent X1 directly or via a C1-C2alkylene group, and each ring system contains not more than 2 oxygen atoms and not more than two sulfur atoms, and wherein the ring system itself may be substituted from one to four times by C1-C3alkyl or by halogen and/or once by C1-C3alkoxy, C1-C3haloalkoxy, allyloxy, propargyloxy, C1-C3alkylthio or by C1-C3alkylsulfonyl; R5 being especially phenyl or a three- to six-membered monocyclic, saturated ring system which contains 1 or 2 oxygen atoms, and wherein phenyl or the ring system is bound to the substituent X1 either directly or via a C1-C2alkylene group, and wherein preferably the ring system itself is unsubstituted or may be substituted from one to four times by C1-C3alkyl and/or once by methoxy or by ethoxy.
In a very especially preferred group of compounds of formula I wherein R1 is a group -L11-X1—R5
s) the bidentate linking member -L11-X1— is preferably —CH2O—, —CH2CH2O— or —CH2N(SO2CH3)—. Compounds of formula I wherein -L11-X1—R5 is CH2OCH2CH2OCH3, CH2OCH2CH2OCH2CH3, CH2OCH2CF3, CH2OCH2CH═CH2, CH2OCH2C≡CH, CH2OCH2C≡CCH3, CH2OCH2CH2C═CH, CH2OCH2C≡N, CH2OCH2CH2C≡N, CH2OCH2CH2CH2OCH3, CH2OCH2CH2OCH2CH2OCH3, CH2OCH2CH2OCF3, CH2OCH2CH2CH2OCF3, CH2CH2OCH2CH2OCH3, CH2N(SO2CH3)CH3, CH2N(SO2CH3)CH2CH3, CH2N(SO2CH3)CH2CF3 or CH2N(SO2CH3)CH2CH2OCH3 are of very special interest.
In a further outstanding group of compounds that are preferred under the provisions of a) to e):
t) R1 is a group -L10-R4 wherein L10 is a direct bond or is a C1-C3alkylene or C2-C3alkenylene group which may be substituted from one to three times by halogen, methyl, ethyl, methoxy or by ethoxy, L10 being especially a direct bond or an unsubstituted C1-C2alkylene group;
u) R1 is a group -L10-R4 wherein R4 is hydrogen, halogen, cyano or trifluoromethyl or R4 is a three- to six-membered monocyclic ring system which may be saturated, partially saturated or aromatic and may contain 1 or 2 hetero atoms selected from nitrogen, oxygen and sulfur and may itself be substituted by methyl or methoxy or by methoxymethyl. R1 as a group -L10-R4 is especially fluorine, chlorine, bromine, cyano, methyl, ethyl, n-propyl, isopropyl, cyclopropyl, trifluoromethyl, chloromethyl, bromomethyl, methoxymethyl, ethoxymethyl, dimethoxymethyl, diethoxymethyl, 1-(dimethoxy)ethyl, 1-(diethoxy)ethyl, 1-ethoxyethylene, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, 1,3-dioxolan-2-yl, 1,3-dioxolan-4-yl, (2-methyl-[1,3]dioxolan-2-yl), tetrahydropyran-2-yl, 4,5-dihydro-isoxazol-5-yl, 4,5-dihydro-isoxazol-5-yl, (3-methyl-4,5-dihydro-isoxazol-5-yl), phenyl, or phenyl substituted by halogen, methyl, trifluoromethyl, methoxy, trifluoromethoxy or by cyano.
Further groups of compounds of formula I that should be given special mention are those wherein X1, X2 and X3 are sulfur, sulfinyl or sulfonyl.
In addition, very special mention should be made of a group of compounds wherein
R1 is -L11-X1—R5, —NR6R7, —X2—R8, —X3-L1-R9, C1-C6haloalkyl, C2-C6haloalkenyl, C2-C6-haloalkynyl or halogen;
L2, L4, L6 and 8 are each independently of the others C1-C4alkylene which may be substituted once, twice or three times by C1-C4alkyl, halogen or by C1-C4alkoxy and to which C1-C4alkylene group there may additionally be spirocyclically bound a C2-C5alkylene group, and wherein that C2-C5alkylene group may in turn be interrupted once or twice by oxygen, sulfur, sulfinyl or by sulfonyl and/or substituted by C1-C4alkyl or by C1-C4alkoxy;
L3, L5, L7 and L9 are each independently of the others C1-C4alkylene which may be substituted once, twice or three times by C1-C4alkyl, halogen or by C1-C4alkoxy;
R2 is halogen, C1-C4haloalkyl, cyano, C1-C3haloalkoxy, C1-C4alkylthio, C1-C4alkylsulfinyl, C1-C4alkylsulfonyl, C1-C4haloalkylthio, C1-C4haloalkylsulfinyl or C1-C4haloalkylsulfonyl;
L11 is a C1-C6alkylene, C2-C6alkenylene or C2-C6alkynylene group which may be substituted once, twice or three times by halogen, hydroxy, C1-C6alkoxy, C3-C6cycloalkyloxy, C1-C6-alkoxy-C1-C6alkoxy, C1-C6alkoxy-C1-C6alkoxy-C1-C6alkoxy or by C1-C2alkylsulfonyloxy;
X1 is oxygen, —OC(O)—, —C(O)—, —C(═NR14a)—, —C(O)O—, —C(O)NR14b—, —OC(O)O—, —N(R10)—O—, —O—NR11—, thio, sulfinyl, sulfonyl, —SO2NR12—, —NR13SO2—, —N(SO2R14c)—, —N(R14d)C(O)— or —NR14—;
R10, R11, R12, R13, R14b, R14d and R14 are each independently of the others hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxycarbonyl, C1-C6alkylcarbonyl, C1-C6alkoxy-C1-C6alkyl or C1-C6alkoxy-C1-C6alkyl substituted by C1-C6alkoxy, or benzyl or phenyl, wherein phenyl and benzyl may in turn be substituted once, twice or three times by C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy, C1-C6haloalkoxy, halogen, cyano, hydroxy or by nitro;
R14a is hydroxy, C1-C6alkoxy, C3-C6alkenyloxy, C3-C6alkynyloxy or benzyloxy;
R14c is C1-C6alkyl;
R5 is hydrogen or C1-C8alkyl, or is a C1-C8alkyl, C3-C8alkenyl or C3-C8alkynyl or C3-C6cycloalkyl group which may be substituted once, twice or three times by halogen, hydroxy, amino, formyl, nitro, cyano, mercapto, carbamoyl, C1-C6alkoxy, C2-C6alkenyl, C2-C6haloalkenyl, C2-C6alkynyl, C2-C6haloalkynyl, C3-C6cycloalkyl, halo-substituted C3-C6cycloalkyl, C3-C5-alkenyloxy, C3-C6alkynyloxy, C1-C6haloalkoxy, C3-C6haloalkenyloxy, cyano-C1-C6alkoxy, C1-C6alkoxy-C1-C6alkoxy, C1-C6alkoxy-C1-C6alkoxy-C1-C6alkoxy, C1-C6alkylthio-C1-C6alkoxy, C1-C6alkylsulfinyl-C1-C6alkoxy, C1-C6alkylsulfonyl-C1-C6alkoxy, C1-C6alkoxycarbonyl-C1-C6-alkoxy, C1-C6alkoxycarbonyl, C1-C6alkylcarbonyl, C1-C6alkylthio, C1-C6alkylsulfinyl, C1-C6-alkylsulfonyl, C1-C6haloalkylthio, C1-C6haloalkylsulfinyl, C1-C6haloalkylsulfonyl, benzyloxy, benzylthio, benzylsulfinyl, benzylsulfonyl, C1-C6alkylamino, di(C1-C6alkyl)amino, R19R20C═NO—, R15S(O)2O—, R16N(R17)SO2—, rhodano, phenyl, phenoxy, phenylthio, phenylsulfinyl or by phenylsulfonyl; wherein the phenyl- or benzyl-containing groups may in turn be substituted by one or more C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy, C1-C6haloalkoxy, halogen, cyano, hydroxy or nitro groups;
R15, R16, R17, R19 and R20 are each independently of the others hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxycarbonyl, C1-C6alkylcarbonyl, C1-C6alkoxy-C1-C6alkyl, or C1-C6alkoxy-C1-C6alkyl substituted by C1-C6alkoxy, or benzyl or phenyl, wherein phenyl and benzyl may in turn be substituted once, twice or three times by C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy, C1-C6haloalkoxy, halogen, cyano, hydroxy or by nitro;
or R5 is a three- to ten-membered monocyclic or fused bicyclic ring system which may be aromatic, saturated or partially saturated and may contain from 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur, and wherein the ring system is bound to the substituent X1 directly or via a C1-C4alkylene, C2-C4alkenylene, C2-C4alkynylene, —N(R18)—C1-C4alkylene, —S(O)—C1-C4alkylene or —SO2—C1-C4alkylene chain, wherein each ring system may not be interrupted by —C(═O)—, —C(═S)—, —C(═NR52)—, —N(═O)—, —S(═O)— or by —SO2—, and each ring system may contain not more than 2 oxygen atoms and not more than two sulfur atoms, and the ring system itself may be substituted once, twice or three times by C1-C6alkyl, C1-C6haloalkyl, C2-C6alkenyl, C2-C6haloalkenyl, C2-C6alkynyl, C2-C6haloalkynyl, C1-C6alkoxy, hydroxy, C1-C6haloalkoxy, C3-C6alkenyloxy, C3-C6alkynyloxy, mercapto, C1-C6alkylthio, C1-C6haloalkylthio, C3-C6alkenylthio, C3-C6haloalkenylthio, C3-C6alkynylthio, C2-C5alkoxyalkylthio, C3-C5-acetylalkylthio, C3-C6alkoxycarbonylalkylthio, C2-C4cyanoalkylthio, C1-C6alkylsulfinyl, C1-C6haloalkylsulfinyl, C1-C6alkylsulfonyl, C1-C6haloalkylsulfonyl, aminosulfonyl, C1-C2alkylaminosulfonyl, di(C1-C2alkyl)aminosulfonyl, di(C1-C4alkyl)amino, halogen, cyano, nitro, phenyl or by benzylthio, wherein phenyl and benzylthio may in turn be substituted on the phenyl ring by C1-C3alkyl, C1-C3haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, halogen, cyano or by nitro, and wherein the substituents on the nitrogen in the heterocyclic ring are other than halogen;
R5a is C1-C6alkyl, hydroxy, C1-C6alkoxy, cyano or nitro;
R18 is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxycarbonyl, C1-C6alkylcarbonyl, C1-C6alkoxy-C1-C6alkyl, or C1-C6alkoxy-C1-C6alkyl substituted by C1-C6alkoxy, or benzyl or phenyl, wherein phenyl and benzyl may in turn be substituted once, twice or three times by C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy, C1-C6haloalkoxy, halogen, cyano, hydroxy or by nitro;
R6 is hydrogen, C1-C6alkyl, C3-C6alkenyl, C3-C6alkynyl, C1-C6haloalkyl, hydroxy, C1-C6alkoxy, —C(O)R19a or —C(S)R20a;
R19a and R20a are each independently of the other hydrogen, C1-C6alkyl, C3-C6cycloalkyl, phenyl, heteroaryl, C1-C6alkoxy, C3-C6alkenyloxy, benzyloxy, C1-C4alkylthio or a group NR2, R22;
R21 and R22 are each independently of the other hydrogen, C1-C6alkyl, C3-C6alkenyl, C3-C6alkynyl or phenyl, and wherein phenyl may be substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3-alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
or R21 together with R22 and the respective N atom to which they are bonded form a carbocyclic 3- to 6-membered ring which may be interrupted by oxygen or by sulfur and/or substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
or R6 is -L2-X4—R24; wherein
X4 is oxygen, —NR23—, —S—, —S(O)— or —S(O)2—;
R23 is hydrogen, C1-C6alkoxy, C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl or is phenyl which may be substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3-alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
R24 is hydrogen or a C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl group, which groups may be substituted once, twice or three times by halogen, hydroxy, C1-C6alkoxy, C1-C3alkoxy-C1-C3alkoxy, C3-C6alkenyloxy, C3-C6alkynyloxy, C1-C6alkylthio, C1-C6alkylsulfinyl, C1-C6-alkylsulfonyl, cyano, C(X5)NR25R26, C3-C6cycloalkyl, phenyl, phenoxy or by 5- or 6-membered heteroaryl or heteroaryloxy, wherein heteroaryl or heteroaryloxy may in turn be interrupted once by oxygen or by sulfur or once, twice or three times by nitrogen and may be bonded to the C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl group either via a C atom or via a N atom, and wherein the phenyl and heteroaryl-containing groups may be substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
or R24 is C(O)—R74 or C(S)—R75;
X5 is oxygen or sulfur;
R25 is hydrogen, C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl or phenyl which may be substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
R26 is hydrogen, C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl;
or R25 together with R26 and the respective N atom to which they are bonded form a carbocyclic 3- to 6-membered ring which may be interrupted by oxygen or by sulfur and/or substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3-haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
or R6 is -L3-R27;
R27 is formyl, C1-C6alkylcarbonyl, C3-C6cycloalkylcarbonyl, benzoyl, C1-C6alkoxycarbonyl, cyano, C(X6)NR28R29, phenyl or heteroaryl, wherein benzoyl and phenyl may be substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
and wherein heteroaryl may be substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro or by C1-C4alkoxycarbonyl;
or R27 is C3-C6cycloalkyl or C5-C6cycloalkenyl each of which may in turn be substituted once, twice or three times by C1-C4alkyl, halogen or by C1-C4alkoxy;
X6 is oxygen or sulfur;
R28 is hydrogen, C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl or phenyl which may be substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
R29 is hydrogen, C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl;
or R28 together with R29 and the respective N atom to which they are bonded form a carbocyclic 3- to 6-membered ring which may be interrupted by oxygen or by sulfur and/or substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
R7 is hydrogen, C1-C6alkyl, C3-C6alkenyl, C3-C6alkynyl, C1-C6haloalkyl, C3-C6cycloalkyl, phenyl, heteroaryl, C(X7)R30 or NR33R34;
X7 is oxygen or sulfur;
R30 is hydrogen, C1-C6alkyl, C3-C6cycloalkyl, phenyl, heteroaryl, C1-C6alkoxy, C3-C6alkenyloxy, benzyloxy, C1-C4alkylthio or a group NR31R32;
R31 and R33 are each independently of the other hydrogen, C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl or phenyl which may be substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
R32 and R34 are each independently of the other hydrogen, C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl;
or R31 together with R32 or R33 together with R34, in each case with the respective N atom to which they are bonded, form a carbocyclic 3- to 6-membered ring which may be interrupted by oxygen or by sulfur and/or substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
or R7 is -L4-X8—R35; wherein
X8 is oxygen, —NR36—, —S—, —S(O)— or —S(O)2—;
R36 is hydrogen, C1-C6alkoxy, C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl or is phenyl which may be substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3-alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
R35 is hydrogen or a C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl group, which groups may be substituted once, twice or three times by halogen, hydroxy, C1-C6alkoxy, C1-C3alkoxy-C1-C3alkoxy, C3-C6alkenyloxy, C3-C6alkynyloxy, C1-C6alkylthio, C1-C6alkylsulfinyl, C1-C6-alkylsulfonyl, cyano, C(X9)NR37R38, C3-C6cycloalkyl, phenyl, phenoxy or by 5- or 6-membered heteroaryl or heteroaryloxy, wherein heteroaryl or heteroaryloxy may in turn be interrupted once by oxygen or by sulfur or once, twice or three times by nitrogen and may be bonded to the C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl group either via a C atom or via a N atom, and wherein the phenyl and heteroaryl-containing groups may be substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
X9 is oxygen or sulfur;
R37 is hydrogen, C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl or phenyl which may be substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
R38 is hydrogen, C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl;
or R37 together with R38 and the respective N atom to which they are bonded form a carbocyclic 3- to 6-membered ring which may be interrupted by oxygen or by sulfur and/or substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
or R7 is -L5-R39;
R39 is formyl, C1-C6alkylcarbonyl, C3-C6cycloalkylcarbonyl, benzoyl, C1-C6alkoxycarbonyl, cyano, C(X10)NR40R41, phenyl or heteroaryl, wherein benzoyl and phenyl may be substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
and wherein heteroaryl may be substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro or by C1-C4alkoxycarbonyl;
or R39 is C3-C6cycloalkyl or C5-C6cycloalkenyl each of which may in turn be substituted once, twice or three times by C1-C4alkyl, halogen or by C1-C4alkoxy;
X10 is oxygen or sulfur;
R40 is hydrogen, C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl or phenyl which may be substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
R41 is hydrogen, C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl;
or R40 together with R4, and the respective N atom to which they are bonded form a carbocyclic 3- to 6-membered ring which may be interrupted by oxygen or by sulfur and/or substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3-haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
or R6 and R7 together with the nitrogen atom to which they are bonded form a carbocyclic 3- to 7-membered, saturated or partially saturated or unsaturated monocyclic or bicyclic ring system which may be interrupted once by oxygen, once by sulfur, from one to three times by nitrogen and/or substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3-haloalkylthio, cyano, nitro or by C1-C4alkoxycarbonyl; wherein each ring system may not be interrupted by —C(═O)—, —C(═S)—, —C(═NR5a)—, —N(═O)—, —S(═O)— or by —SO2—;
R5a is C1-C6alkyl, hydroxy, C1-C6alkoxy, cyano or nitro;
X2 is oxygen, —NR42—, sulfur, —S(O)— or —S(O)2—;
R42 is hydrogen, C1-C6alkyl, C3-C6alkenyl, C3-C6alkynyl, C1-C6haloalkyl, C3-C6cycloalkyl, phenyl, heteroaryl, C(X11)R43 or NR46R47;
X11 is oxygen or sulfur;
R43 is hydrogen, C1-C6alkyl, C3-C6cycloalkyl, phenyl, heteroaryl, C1-C6alkoxy, C3-C6alkenyloxy, benzyloxy, C1-C4alkylthio or a group NR44R45;
R44 and R45 are each independently of the other hydrogen, C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl or phenyl which may be substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
R45 and R47 are each independently of the other hydrogen, C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl;
or R44 together with R45 or R46 together with R47, in each case with the respective N atom to which they are bonded, form a carbocyclic 3- to 6-membered ring which may be interrupted by oxygen or by sulfur and/or substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
or R42 is -L6-X12—R48; wherein
X12 is oxygen, —NR49—, —S—, —S(O)— or —S(O)2;
R49 is hydrogen, C1-C6alkoxy, C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl or is phenyl which may be substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3-alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
R48 is a C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl group, which groups may be substituted once, twice or three times by halogen, hydroxy, C1-C6alkoxy, C1-C3alkoxy-C1-C3alkoxy, C3-C6alkenyloxy, C3-C6alkynyloxy, C1-C6alkylthio, C1-C6alkylsulfinyl, C1-C6alkylsulfonyl, cyano, C(X13)NR50R51, C3-C6cycloalkyl, phenyl, phenoxy or by 5- or 6-membered heteroaryl or heteroaryloxy, wherein heteroaryl or heteroaryloxy may in turn be interrupted once by oxygen or by sulfur or once, twice or three times by nitrogen and may be bonded to the C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl group either via a C atom or via a N atom, and wherein the phenyl- and heteroaryl-containing groups may be substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
X13 is oxygen or sulfur;
R50 is hydrogen, C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl or phenyl which may be substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
R51 is hydrogen, C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl;
or R50 together with R5, and the respective N atom to which they are bonded form a carbocyclic 3- to 6-membered ring which may be interrupted by oxygen or by sulfur and/or substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
or R42 is -L7-R52;
R52 is formyl, C1-C6alkylcarbonyl, C3-C6cycloalkylcarbonyl, benzoyl, C1-C6alkoxycarbonyl, cyano, C(X14)NR53R54, phenyl or heteroaryl, wherein benzoyl and phenyl may be substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
and wherein heteroaryl may be substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro or by C1-C4alkoxycarbonyl; or R52 is C3-C6cycloalkyl or C5-C6cycloalkenyl each of which may in turn be substituted once, twice or three times by C1-C4alkyl, halogen or by C1-C4alkoxy;
X14 is oxygen or sulfur;
R53 is hydrogen, C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl or phenyl which may be substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
R54 is hydrogen, C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl;
or R53 together with R54 and the respective N atom to which they are bonded form a carbocyclic 3- to 6-membered ring which may be interrupted by oxygen or by sulfur and/or substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3-haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
R8 is hydrogen or a C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl group, which groups may be substituted once, twice or three times by halogen, hydroxy, C1-C6alkoxy, C1-C3alkoxy-C1-C3alkoxy, C3-C6alkenyloxy, C3-C6alkynyloxy, C1-C6alkylthio, C1-C6alkylsulfinyl, C1-C6-alkylsulfonyl, cyano, C(X15)NR55R56, C3-C6cycloalkyl, phenyl, phenoxy or by 5- or 6-membered heteroaryl or heteroaryloxy, and wherein heteroaryl or heteroaryloxy may in turn be interrupted once by oxygen or by sulfur or once, twice or three times by nitrogen and may be bonded to the C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl group either via a C atom or via a N atom, and wherein the phenyl- and heteroaryl-containing groups may be substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
X15 is oxygen or sulfur;
R55 is hydrogen, C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl or phenyl which may be substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
R56 is hydrogen, C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl;
or R55 together with R56 and the respective N atom to which they are bonded form a carbocyclic 3- to 6-membered ring which may be interrupted by oxygen or by sulfur and/or substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
or R8 is C(O)—R76 or C(S)—R77;
X3 is oxygen, —NR57—, sulfur, —S(O)— or —S(O)2—;
R57 is hydrogen, C1-C6alkyl, C3-C6alkenyl, C3-C6alkynyl, C1-C6haloalkyl, C3-C6cycloalkyl, phenyl, heteroaryl, C(X16)R58 or NR61R62;
X16 is oxygen or sulfur;
R58 is hydrogen, C1-C6alkyl, C3-C6cycloalkyl, phenyl, heteroaryl, C1-C6alkoxy, C3-C6alkenyloxy, benzyloxy, C1-C4alkylthio or a group NR59R60;
R59 and R61 are each independently of the other hydrogen, C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl or phenyl which may be substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
R60 and R62 are each independently of the other hydrogen, C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl;
or R59 together with R60 or R61 together with R62, in each case with the respective N atom to which they are bonded, form a carbocyclic 3- to 6-membered ring which may be interrupted by oxygen or by sulfur and/or substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
or R57 is -L8-X17—R63; wherein
X17 is oxygen, —NR64—, —S—, —S(O)— or —S(O)2—;
R64 is hydrogen, C1-C6alkoxy, C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl or is phenyl which may be substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3-alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
R63 is a C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl group, which groups may be substituted once, twice or three times by halogen, hydroxy, C1-C6alkoxy, C1-C3alkoxy-C1-C3alkoxy, C3-C6alkenyloxy, C3-C6alkynyloxy, C1-C6alkylthio, C1-C6alkylsulfinyl, C1-C6alkylsulfonyl, cyano, C(X18)NR65R66, C3-C6cycloalkyl, phenyl, phenoxy or by 5- or 6-membered heteroaryl or heteroaryloxy, wherein heteroaryl or heteroaryloxy may in turn be interrupted once by oxygen or by sulfur or once, twice or three times by nitrogen and may be bonded to the C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl group either via a C atom or via a N atom, and wherein the phenyl- and heteroaryl-containing groups may be substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
X18 is oxygen or sulfur;
R65 is hydrogen, C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl or phenyl which may be substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
R66 is hydrogen, C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl;
or R65 together with R66 and the respective N atom to which they are bonded form a carbocyclic 3- to 6-membered ring which may be interrupted by oxygen or by sulfur and/or substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
or R57 is -L9-R67;
R67 is formyl, C1-C6alkylcarbonyl, C3-C6cycloalkylcarbonyl, benzoyl, C1-C6alkoxycarbonyl, cyano, C(X19)NR68R69, phenyl or heteroaryl, wherein benzoyl and phenyl may be substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
and wherein heteroaryl may be substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro or by C1-C4alkoxycarbonyl;
or R67 is C3-C6cycloalkyl or C5-C6cycloalkenyl each of which may in turn be substituted once, twice or three times by C1-C4alkyl, halogen or by C1-C4alkoxy;
X19 is oxygen or sulfur;
R68 is hydrogen, C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl or phenyl which may be substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
R69 is hydrogen, C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl;
or R68 together with R69 and the respective N atom to which they are bonded form a carbocyclic 3- to 6-membered ring which may be interrupted by oxygen or by sulfur and/or substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
L1 is C1-C4alkylene which may be substituted once, twice or three times by C1-C4alkyl, halogen or by C1-C4alkoxy and to which C1-C4alkylene group there may be spirocyclically bound a further C2-C5alkylene group which may in turn be interrupted once or twice by oxygen, sulfur, sulfinyl or by sulfonyl and may be substituted by C1-C4alkyl or by C1-C4alkoxy;
or L1 is C1-C4alkylene which may be substituted once, twice or three times by C1-C4alkyl, halogen or by C1-C4alkoxy, wherein a carbon atom of that C1-C4alkylene chain together with R9 or with R70 forms a further C2-C6alkylene chain which may be interrupted once or twice by oxygen, sulfur, sulfinyl or by sulfonyl and may be substituted by C1-C4alkyl or by C1-C4alkoxy;
R9 is a group —X20—R70, wherein
X20 is oxygen, —NR71—, —S—, —S(O)— or —S(O)2—;
R71 is a C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl group, which groups may be substituted once, twice or three times by halogen, hydroxy, C1-C6alkoxy, C1-C3alkoxy-C1-C3alkoxy, C3-C6alkenyloxy, C3-C6alkynyloxy, C1-C6alkylthio, C1-C6alkylsulfinyl, C1-C6alkylsulfonyl, cyano, C(X21)NR72R73, C3-C6cycloalkyl, phenyl, phenoxy or by 5- or 6-membered heteroaryl or heteroaryloxy, wherein heteroaryl or heteroaryloxy may in turn be interrupted once by oxygen or by sulfur or once, twice or three times by nitrogen and may be bonded to the C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl group either via a C atom or via a N atom, and wherein the phenyl- and heteroaryl-containing groups may be substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
X21 is oxygen or sulfur;
R72 is hydrogen, C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl or phenyl which may be substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
R73 is hydrogen, C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl;
or R72 together with R73 and the respective N atom to which they are bonded form a carbocyclic 3- to 6-membered ring which may be interrupted by oxygen or by sulfur and/or substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
R70 is hydrogen, C1-C6alkyl, C3-C6alkenyl, C3-C6alkynyl, C(O)—R78, C(S)—R79 or phenyl which may be substituted once, twice or three-times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3-alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
or R9 is formyl, C1-C6alkylcarbonyl, C3-C6cycloalkylcarbonyl, benzoyl, C1-C6alkoxycarbonyl, cyano, C(X35)NR125R126, phenyl or heteroaryl, wherein benzoyl and phenyl may be substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
and wherein heteroaryl may be substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro or by C1-C4alkoxycarbonyl;
or R9 is C3-C6cycloalkyl or C5-C6cycloalkenyl each of which may in turn be substituted once, twice or three times by C1-C4alkyl, halogen or by C1-C4alkoxy;
X35 is oxygen or sulfur;
R125 is hydrogen, C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl or phenyl which may be substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
R126 is hydrogen, C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl;
or R125 together with R126 and the respective N atom to which they are bonded form a carbocyclic 3- to 6-membered ring which may be interrupted by oxygen or by sulfur and/or substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3-haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
R74, R75, R76, R77, R78 and R79 are each independently of the others hydrogen, C1-C6alkyl, C3-C6cycloalkyl, phenyl, heteroaryl, C1-C6alkoxy, C3-C6alkenyloxy, C1-C4alkylthio or NR127R128;
R127 is hydrogen, C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl or phenyl which may be substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3-haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
R128 is hydrogen, C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl;
or R127 together with R128 and the respective N atom to which they are bonded form a carbocyclic 3- to 6-membered ring which may be interrupted by oxygen or by sulfur and/or substituted once, twice or three times by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C3alkoxy, C1-C3-haloalkoxy, C1-C3alkylthio, C1-C3alkylsulfinyl, C1-C3alkylsulfonyl, C1-C3haloalkylthio, cyano, nitro, C1-C4alkoxycarbonyl or by C1-C4alkylcarbonylamino;
R3 is hydroxy, O−M+ wherein M+ is a metal cation or an ammonium cation, or is halogen or S(O)pR80 wherein R80 is C1-C12alkyl, C2-C12alkenyl, C2-C12alkynyl, C3-C2allenyl, C3-C12-cycloalkyl or C5-C12cycloalkenyl; and p is 0, 1 or 2;
or R80 is R121—C1-C12alkylene or R122—C2-C12alkenylene, wherein the alkylene or alkenylene chain may be interrupted by O—, —S—, —S(O)—, —SO2— or by —C(O)— and/or substituted from one to five times by R123; or R80 is phenyl which may be substituted once, twice, three times, four times or five times by R124;
R12, and R122 are each independently of the other halogen, cyano, rhodano, hydroxy, C1-C6alkoxy, C2-C6alkenyloxy, C2-C6alkynyloxy, C1-C6alkylthio, C1-C6alkylsulfinyl, C1-C6alkylsulfonyl, C2-C6alkenylthio, C2-C6alkynylthio, C1-C6alkylsulfonyloxy, phenylsulfonyloxy, C1-C6alkylcarbonyloxy, benzoyloxy, C1-C4alkoxycarbonyloxy, C1-C6alkylcarbonyl, C1-C4-alkoxycarbonyl, benzoyl, aminocarbonyl, C1-C4alkylaminocarbonyl, C3-C6cycloalkyl, phenyl, phenoxy, phenylthio, phenylsulfinyl or phenylsulfonyl, wherein the phenyl-containing groups may in turn be substituted once, twice or three times by halogen, C1-C3alkyl, C1-C3haloalkyl, hydroxy, C1-C3alkoxy, C1-C3haloalkoxy, cyano or by nitro;
R123 is hydroxy, halogen, C1-C6alkyl, C1-C6alkoxy, C1-C6alkylthio, C1-C6alkylsulfinyl, C1-C6alkylsulfonyl, cyano, carbamoyl, carboxy, C1-C4alkoxycarbonyl or phenyl, wherein phenyl may be substituted once, twice or three times by hydrogen, C1-C4alkyl, C1-C4haloalkyl, C3-C4alkenyl, C3-C4alkynyl or by C1-C4alkoxy;
R24 is halogen, C1-C3alkyl, C1-C3haloalkyl, hydroxy, C1-C3alkoxy, C1-C3haloalkoxy, cyano or nitro;
A1 is —C(R112R113)— or —NR114—;
A2 is —C(R115R116)m—, —C(═O)—, —O—, —NR117— or —S(O)q—;
A3 is —C(R118R119)— or —NR120—;
with the proviso that A2 is other than —O— or —S(O)q— when A1 is —NR114— and/or A3 is —NR120;
R112 and R118 are each independently of the other hydrogen, C1-C4alkyl, C2-C4alkenyl, C2-C4alkynyl, C1-C4alkylthio, C1-C4alkylsulfinyl, C1-C4alkylsulfonyl, C1-C4alkoxycarbonyl, hydroxy, C1-C4alkoxy, C3-C4alkenyloxy, C3-C4alkynyloxy, hydroxy-C1-C4alkyl, C1-C4alkylsulfonyloxy-C1-C4alkyl, halogen, cyano or nitro;
R113 and R119 are each independently of the other hydrogen, C1-C4alkyl or C1-C4alkylthio, C1-C4alkylsulfinyl or C1-C4alkylsulfonyl;
or R113 together with R112 and/or R119 together with R118 form a C2-C5alkylene chain which may be interrupted by —O—, —C(O)O— or by —S(O)r—;
R114 and R120 are each independently of the other hydrogen, C1-C4alkyl, C1-C4haloalkyl, C3-C4alkenyl, C3-C4alkynyl or C1-C4alkoxy;
R115 is hydrogen, hydroxy, C1-C4alkyl, C1-C4haloalkyl, C1-C3hydroxyalkyl, C1-C4alkoxy-C1-C3alkyl, C1-C4alkylthio-C1-C3alkyl, C1-C4alkylcarbonyloxy-C1-C3alkyl, C1-C4alkylsulfonyloxy-C1-C3alkyl, tosyloxy-C1-C3alkyl, di(C1-C4alkoxy)C1-C3alkyl, C1-C4alkoxycarbonyl, formyl, C3-C5oxacycloalkyl, C3-C5thiacycloalkyl, C3-C4dioxacycloalkyl, C3-C4dithiacycloalkyl, C3-C4-oxathiacycloalkyl, C1-C4alkoxyiminomethyl, carbamoyl, C1-C4alkylaminocarbonyl or di(C1-C4alkyl)aminocarbonyl;
or R15 together with R112 or R113 or R114 or R116 or R118 or R119 or R120 or, when m is 2, also with a second R115 form a C1-C4alkylene bridge;
R116 is hydrogen, C1-C3alkyl or C1-C3haloalkyl;
R117 is hydrogen, C1-C3alkyl, C1-C3haloalkyl, C1-C4alkoxycarbonyl, C1-C4alkylcarbonyl or di(C1-C4alkyl)aminocarbonyl;
m is 1 or 2; and
q and r are each independently of the other 0, 1 or 2;
and also Examples 1.009, 1.010, 1.033 to 1.045, 1.092, 1.097 to 1.110, 1.153 to 1.156, 1.158 to 1.169, 1.189, 1.192, 1.195 to 1.201, 2.009, 2.010, 2.033 to 2.045, 2.091, 2.096 to 2.109, 2.152 to 2.155, 2.157 to 2.168, 2.188, 2.191, 2.194 to 2.200, 3.009, 3.010, 3.033 to 3.045, 3.091, 3.096 to 3.109, 3.152 to 3.155, 3.157 to 3.168, 3.188, 3.191, 3.194 to 3.200.
The compounds of formula I can be prepared by means of processes that are known per se and are described, for example, in WO 00/15615, EP-A-0 316 491, EP-A-1 352 901 and WO 02/16305.
Compounds of formula I can be prepared, for example, by
a) converting a compound of formula IIa
wherein R1 and R2 are as defined hereinbefore, into a compound of formula IIb
wherein Y1 is a leaving group, e.g. halogen, cyano, acyloxy or phenoxy which may be substituted by an electron-withdrawing group, e.g. halogen, trifluoromethyl, nitro, cyano, C1-C4alkylcarbonyl, C1-C4alkoxycarbonyl or C1-C4alkylsulfonyl, or the like, and then reacting that compound in the presence of a base, e.g. triethylamine, Hünig's base, sodium hydrogen carbonate or potassium carbonate, with a dione of formula III
wherein A1, A2 and A3 are as defined hereinbefore and R3 is hydroxy or O−M+ wherein M+ is as defined hereinbefore, and then treating the reaction mixture in the presence of the base used, e.g. triethylamine, with the aid of a cyanide-containing catalyst, e.g. acetone cyanohydrin, trimethylsilyl cyanide, copper cyanide, sodium cyanide or potassium cyanide, or by means of fluoride ions, e.g. potassium fluoride, or by means of dimethylaminopyridine; or
b) converting a compound of formula XIIIa
wherein R1 and R2 are as defined hereinbefore and Y4 is halogen or trifluoromethanesulfonyloxy, under carbonylation conditions at elevated pressure and elevated temperature in the presence of a palladium catalyst having suitable ligands, e.g. PdCl2(PPh3)2, Pd(PPh3)4, Pd2(dba)3, Pd(CH3CN)2(PPh3)2, Pd(OAc)2 or (racBINAP)PdCl2, and optionally in the presence of an auxiliary catalyst, e.g. triphenylphosphine, tri(tert-butyl)phosphine, (Ph3)2PCH2CH2P(Ph3)2 or (Ph3)2PCH2CH2CH2P(Ph3)2, and in the presence of a base, e.g. triethylamine, and optionally further adjuvants, e.g. LiCl or Li2CO3, using carbon monoxide and a dione of formula III or using the tautomeric form of a dione of formula IIIa
wherein A1, A2 and A3 are as defined hereinbefore and R3 is hydroxy, into a compound of formula XIa
and/or its isomeric form XIb
wherein A1, A2, A3, R1 and R2 are as defined hereinbefore, and then treating that compound with the aid of a cyanide-containing catalyst, e.g. acetone cyanohydrin, trimethylsilyl cyanide, copper cyanide, sodium cyanide or potassium cyanide, in the presence of a trialkylamine base, e.g. triethylamine, to obtain a compound of formula I; or
c) when X2 or X3 is oxygen or sulfur, reacting a compound of formula Ia
wherein A1, A2, A3, R2 and R3 are as defined hereinbefore and X2 is oxygen or sulfur, in the presence of a suitable base, e.g. potassium carbonate, anhydrous sodium hydroxide or sodium hydride, with an alkylating agent of formula IVa or IVb
Y2—R8 (IVa)
or
Y2-L1-R9 (IVb),
wherein R8 is an unsubstituted or substituted C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl group, and R9 and L1 are as defined hereinbefore, and Y2 is a leaving group such as chlorine, bromine, iodine, mesyloxy or tosyloxy; or
d) when X2 or X3 is oxygen, reacting a compound of formula Ia
wherein A1, A2, A3, R2 and R3 are as defined hereinbefore and X2 is oxygen, in the presence of a bis-diaza-alkoxycarboxylate of formula ROC(O)—N═C═N—COOR or a bis-diazaalkyl-carbamoyl of formula RNHC(O)—N═C═N—C(O)NHR, wherein R is a C1-C6alkyl or C5-C6-cycloalkyl group, and a phosphine, e.g. triphenylphosphine or tri(tert-butyl)phosphine, with an alcohol of formula Va or Vb
HO—R8 (Va)
or
HO-L1-R9 (Vb),
wherein R8 is an unsubstituted or substituted C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl group, and R9 and L1 are as defined hereinbefore; or
e) reacting a compound of formula Ib
wherein A1, A2, A3, R2 and R3 are as defined hereinbefore and K1 is a leaving group, e.g. halogen or alkylsulfonyl, in the presence of a base, e.g. potassium tert-butanolate, sodium amylate, sodium hydride, dry sodium or potassium hydroxide, or an amine, e.g. triethylamine, Hünig's base or dimethylaminopyridine, with an alcohol or a mercaptan of formula Vc or Vd
HX2—R8 (Vc)
or
HX3-L1-R9 (Vd),
wherein R8 is an unsubstituted or substituted C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl group, and L1 and R9 are as defined hereinbefore, and X2 or X3 is oxygen or sulfur, or with an amine of formula Ve or VI
HNR57-L1-R9 (Ve)
or
HNR6R7 (VI),
wherein L1, R6, R7, R9 and R57 are as defined hereinbefore; or
f) reacting a compound of formula Ic
wherein A1, A2, A3, R2 and R3 are as defined hereinbefore and K2 is a group capable of appropriate functionalisation -L10-K20, -L11-X1—K21, —X2—K22, —X3-L1-K23 wherein L10, L11, L1, X1, X2 and X3 are as defined hereinbefore and K20, K21, K22 and K23 are a functionalisation group, e.g. hydroxy, chlorine, bromine, iodine, mesyloxy, tosyloxy, formyl or carbonyl, either with an appropriate alkylating agent of formula VII or VIIa
Y3—R9 (VII)
or
Y3—X20—R70 (VIIa),
or with a ketalisation agent or a nucleophilic reagent of formula VIII
HX20—R70 (VII),
or its salt of formula VIIIa
M+ −X20—R70 (VIIIa),
wherein R9, R70 and X20 are as defined hereinbefore and Y3 is a leaving group such as bromine, iodine, tosyloxy or C1-C4alkylsulfonyloxy, and M+ is a metal cation of an alkali metal base, such as lithium, sodium or potassium, optionally in the presence of an additional base, or, in the case of ketalisation of a carbonyl function, in the presence of an additional acid, e.g. p-toluenesulfonic acid, trifluoroacetic acid or sulfuric acid; or
g) when R1 is -L10-R4 or -L11-X1—R5 wherein L10 or L11 is especially an unsubstituted or substituted C2-C6alkenylene or a C2-C6alkynylene group and R4, when L10 is a direct bond, is especially a five- to ten-membered, monocyclic or fused bicyclic ring system which may be aromatic or partially saturated and which may contain from 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur, reacting a compound of formula Id
wherein A1, A2, A3, R2 and R3 are as defined hereinbefore and K3 is a group capable of functionalisation, such as chlorine, bromine, iodine or trifluoromethylsulfonyloxy, by means of a —C—C— linking Suzuki, Stille, Sonogashira or Heck reaction, in the presence of a noble metal catalyst having suitable ligands, e.g. PdCl2(PPh3)2, Pd(PPh3)4, Pd2(dba)3, Pd(CH3CN)2(PPh3)2, Pd(OAc)2, Rh, Cu, CuCl or CuI, and in the presence of a base, e.g. triethylamine, Hünig's base, sodium tert-butanolate, potassium tert-butanolate, sodium carbonate, potassium carbonate, caesium carbonate, potassium fluoride or caesium fluoride, and optionally further adjuvants, e.g. LiCl or Li2CO3, or an additional auxiliary catalyst, e.g. triphenylphosphine, tri(tert-butyl)phosphine, (Ph3)2PCH2CH2P(Ph3)2 or (Ph3)2PCH2CH2CH2P(Ph3)2, with a boronic acid, e.g. of formula Xa or Xb
(HO)2B-L10-R4 (Xa)
or
(HO)2B-L11-X1—R5 (Xb),
or with a tin compound of formula Xc or Xd
ReRfRgSn-L10-R4 (Xc)
or
ReRfRgSn-L11-X1—R5 (Xd),
or with an ethynyl compound of formula Xe or Xf having a functionality in accordance with R1
H—C≡C-L10b-R4 (Xe)
or
H—C≡C-L11b-X1—R5 (Xf),
or with a vinyl compound of formula Xg or Xh having a functionality in accordance with R1
H—CH═CH-L10a-R4 (Xg)
or
H—CH═CH-L11a-X1—R5 (Xh),
wherein L10, L11, R4, R5 and X1 are as defined hereinbefore, Re, Rf and Rg are each independently of the others C1-C8alkyl and L10a, L10b, L11a and L11b are appropriate subgroups of the groups L10 and L11, such as especially a direct bond or a C1-C4alkylene group which may be substituted once, twice or three times by C1-C6alkyl, halogen, hydroxy, C1-C6alkoxy or by C1-C3alkoxy-C1-C3alkoxy; or
h) for the preparation of compounds of formula I wherein the substituent definitions include sulfinyl or sulfonyl groups, treating a compound of formula I wherein the corresponding substituent definitions include thio groups with an oxidising agent, e.g. peracetic acid, trifluoroperacetic acid, m-chloro-perbenzoic acid, hydrogen peroxide, sodium perbromate, sodium iodate, sodium hypochloride, chlorine or bromine.
In addition, compounds of formula I wherein R3 is other than hydroxy or halogen can be prepared, in accordance with conversion methods generally known from the literature, by nucleophilic substitution reactions of chlorides of formula I wherein R3 is chlorine, which can be obtained from compounds of formula I wherein R3 is hydroxy, likewise in accordance with known methods, by reaction with a chlorinating agent, such as phosgene, thionyl chloride or oxalyl chloride. In that process, for example, mercaptans, thiophenols or heterocyclic thiols are reacted in the presence of a base, for example 5-ethyl-2-methylpyridine, diisopropylethylamine, triethylamine, sodium hydrogen carbonate, sodium acetate or potassium carbonate. Furthermore, compounds of formula I wherein the substituent R3 is a mercapto group can be oxidised in analogy to known standard methods, for example using peracids, e.g. metachloroperbenzoic acid (m-CPBA) or peracetic acid, to form the corresponding sulfoxides and/or sulfones of formula I. In the process, the degree of oxidation at the sulfur atom (—S(O)— or —SO2—) can be controlled by the amount of oxidising agent.
In the case of process a), as a result of reaction of a dione of formula III with an acid of formula IIa in the presence of a suitable coupling reagent, e.g. dicyclohexylcarbodiimide, N-ethyl-N′-(3-dimethylamino-propyl)-carbodiimide (EDC), 2-chloro-1-methyl-pyridinium iodide or N,N-dimethyl-(1-chloro-2-methyl-propen)amine, or as a result of reaction of a dione of formula III with an activated form of the acid, e.g. an acid chloride, of formula IIb, wherein Y1 is chlorine, in the presence of a base, e.g. triethylamine, Hünig's base or potassium carbonate, there is obtained a corresponding enol ester compound of formula XIa and/or Xib
wherein A1, A2, A3, R1 and R2 are as defined hereinbefore, which may then either be rearranged directly in situ by adding catalytic amounts of cyanide ions, e.g. from about 1% to about 15% acetone cyanohydrin, to form the compound of formula I, or may first be isolated and purified and then, in a second step, rearranged in the presence of catalytic amounts of from about 0.1% to about 5% potassium cyanide ions or from about 0.5% to about 10% acetone cyanohydrin, and a fresh amount of a trialkylamine base, e.g. from about 0.1 to about 3 equivalents of triethylamine, preferably from 1 to about 1.4 equivalents, to form the compound of formula I, as shown above using the exemplified formulae XIa and XIb to form compounds of formula I. This process may be shown in general terms in Scheme 1 using the example of the preparation of compounds of formula I.
In a preferred process for the preparation of compounds of formula Ia
in which A1, A2, A3, R2 and R3 are as defined hereinbefore and X2 is oxygen or sulfur and which are used as starting materials in process variants c) and d), for example, either a compound of formula Ie
wherein A1, A2, A3, R2 and R3 are as defined hereinbefore and K4 is a cleavable group, such as methoxy when X2 is oxygen, or is a disulfide bridge of a dimeric compound 1e, is reacted in the presence of an ether-cleaving reagent, e.g. boron trichloride, boron tribromide, aluminium chloride, sodium methylmercaptide, sodium ethylmercaptide or trimethylsilyl iodide, or a compound of formula Ie wherein K4 is benzyloxy or dimeric disulfide is reduced catalytically in the presence of hydrogen.
The compounds of formula If used in process variants c), d), e), f) and g)
wherein A1, A2, A3, R2 and R3 are as defined hereinbefore and K0 is a sub-group of R1 capable of functionalisation, as defined especially in accordance with the meanings of K1, K2, K3 and/or K4 above, such as especially fluorine, chlorine, bromine, iodine, hydroxy, methylthio, methylsulfonyl, bromomethyl, hydroxymethyl, formyl, methylcarbonyl, 2-hydroxyethoxy, 2-bromoethoxy, benzyloxy or dimeric disulfide, can likewise be prepared in accordance with process variant a) or in accordance with process variant b) from the corresponding compounds of formula XII or XIII
wherein K0, R2 and Y4 are as defined hereinbefore; Y is C1-C4alkoxy, benzyloxy, hydroxy, fluorine, chlorine, cyano or phenoxy which may be substituted by an electron-withdrawing group, e.g. halogen, trifluoromethyl, nitro, cyano, C1-C4alkylcarbonyl, C1-C4alkoxycarbonyl or C1-C4alkylsulfonyl, Y being especially C1-C4alkoxy, benzyloxy, hydroxy, chlorine or cyano; and K0 being especially hydroxy (corresponding to formula Ia wherein X2 is oxygen), K1 wherein K1 is, for example, halogen or methylsulfonyl (corresponding to formula Ib), K3 wherein K3 is, for example, chlorine, bromine or iodine (corresponding to formula Id), K4 wherein K4 is, for example, methylthio, benzyloxy or methoxy (corresponding to formula Ie), or a disulfide bridge of a dimeric compound XII or XIII (corresponding to formula Ie wherein X2 is sulfur),
aa) by reacting the compound in question with a dione of formula III
wherein R3 is hydroxy or O−M+ and A1, A2, A3 and M+ are as defined hereinbefore, or
bb) by reacting a hydroxy or mercapto compound of formula Ia
wherein A1, A2, A3, R2 and R3 are as defined hereinbefore and X2 is oxygen or sulfur, in accordance with process variant c) with an appropriate alkylating agent of formula IVc
Y2-L1-K23 (IVc),
or
cc) in accordance with process variant d) with the appropriate alcohol of formula Vf
HO-L1-K23 (Vf),
or
dd) in accordance with process variant e) by treating a compound of formula Ib
wherein A1, A2, A3, R2 and R3 are as defined hereinbefore and K1 is halogen or alkylsulfonyl, with an alcohol or mercaptan of formula Vg or Vh
HK1 (Vg)
or
HX3-L1-K23 (Vh),
or with an amine of formula VIc
HNR6-L1-K23 (VIc),
wherein K1 is methoxy or methylthio and X3 is oxygen or sulfur, and K23, L1, R6 and Y2 are as defined hereinbefore.
The starting materials of formula IIa
and of formula IIb
wherein R1, R2 and Y1 are as defined hereinbefore, and also compounds of formula IId
wherein Y0 is C1-C4alkoxy, benzyloxy or phenoxy which may be unsubstituted or substituted by an electron-withdrawing group such as halogen, trifluoromethyl, nitro, cyano, C1-C4alkylcarbonyl, C1-C4alkoxycarbonyl or C1-C4alkylsulfonyl, which are used as starting materials in the preparation of compounds of formula IIa, can be prepared analogously to known methods, as described e.g. in EP-A-0 353 187, by converting a compound of formula XIII
wherein R2 is as defined hereinbefore, K0 is hydrogen, methoxy, methylthio, methylsulfonyl, halogen or another group R1 that is stable in this process, and Y4 is chlorine, bromine or trifluoromethylsulfonyloxy, under carbonylation conditions at elevated pressure and elevated temperatures in the presence of a palladium catalyst having suitable ligands, e.g. PdCl2(PPh3)2, Pd(PPh3)4, Pd(CH3CN)2(PPh3)2, Pd2(dba)3, Pd(OAc)2 or (racBINAP)PdCl2, and optionally in the presence of an auxiliary catalyst, e.g. triphenylphosphine, tri(tert-butyl)phosphine, (Ph3)2PCH2CH2P(Ph3)2 or (Ph3)2PCH2CH2CH2P(Ph3)2, and in the presence of a base, e.g. triethylamine, using carbon monoxide and an alcohol of formula IX
R0—OH (IX)
wherein R0 is C1-C4alkyl, benzyl or phenyl which may be unsubstituted or substituted by an electron-withdrawing group such as halogen, trifluoromethyl, nitro, cyano, C1-C4alkylcarbonyl, C1-C4alkoxycarbonyl or C1-C4alkylsulfonyl, into a compound of formula XIIa
wherein K0, R2 and Y0 are as defined hereinbefore, and then converting that compound in known conversion reactions, e.g. hydrolysis, addition and/or substitution reactions and subsequent hydrolysis, into the compound of formula XII
or of formula II
wherein K0, R1 and R2 are as defined hereinbefore and Y is C1-C4alkoxy, benzyloxy, hydroxy, fluorine, chlorine, bromine, cyano or phenoxy which may be unsubstituted or substituted by an electron-withdrawing group, e.g. halogen, trifluoromethyl, nitro, cyano, C1-C4alkylcarbonyl, C1-C4alkoxycarbonyl or C1-C4alkylsulfonyl.
For example, a compound of formula XIIIb
wherein R2 and Y4 are as defined hereinbefore, can be converted by carbonylation or by means of a Grignard reaction and CO2 into a compound of formula XIIb
wherein R2 and Y0 are as defined hereinbefore, which is then converted in the presence of an oxidising agent, e.g. hydrogen peroxide or the hydrogen peroxide/urea adduct in the presence of trifluoroacetic anhydride, into an N-oxido compound of formula XV
wherein R2 and Y0 are as defined hereinbefore, which is then either
a) reacted in the presence of phosphorus oxychloride or trifluoroacetic anhydride to form a hydroxy compound of formula XIIc
or
b) when a suitable nucleophile of formula Vi is used
HR1 (Vi)
or when a nucleophile of formula VIb is used
HNR6C(O)R30 (VIb),
wherein R1, R6, R30 are as defined hereinbefore, converted in the presence of an activating reagent, e.g. oxalyl chloride or trifluoroacetic anhydride, and optionally in the presence of an acid-binding agent, e.g. triethylamine or Hünig's base, directly into the compounds of formula IId
wherein R1, R2 and Y0 are as defined hereinbefore and R1 is especially a group —NR4C(O)R30, which can then be converted in accordance with a) for the isolation of an intermediate of formula XIIc by known and general conversion methods such as halogenation, e.g. by means of dichlorophenyl phosphate, further nucleophilic reactions with alcohols, mercaptans or amines of formula
HX3-L1-R9 (V)
or
HNR6R7 (VI),
wherein X3, L1, R6, R7, R9 are as defined hereinbefore, as described above under process conditions c) to h) into compounds of formula XII
or of formula II
wherein K0, R1, R2 and Y are as defined hereinbefore.
The starting materials of formula IId
wherein R1 is a group —X2—R8 or —X3-L1-R9, X2 and X3 are oxygen, and L1, R2, R9 and Y0 are as defined hereinbefore, and R8 is an unsubstituted or substituted C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl group, can also be prepared either by treating a compound of formula XIId
wherein R2 and Y0 are as defined hereinbefore, and X2 is oxygen or sulfur, in accordance with process variant c) in the presence of a suitable base with an alkylating agent of formula
Y2—R8 (IVa)
or
Y2-L1-R9 (IVb),
wherein L1, R9 and Y2 are as defined hereinbefore and R8 is an unsubstituted or substituted C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl group; or
by reacting a compound of formula XIId
wherein R2 and Y0 are as defined hereinbefore and X2 is oxygen, in accordance with process variant d) simultaneously in the presence of a bis-diaza-alkoxycarboxylate of formula ROC(O)—N═C═N—COOR or a bis-diaza-alkylcarbamoyl of formula RNHC(O)—N═C═N—C(O)NHR, wherein R is a C1-C6alkyl or C5-C6cycloalkyl group, and in the presence of a phosphine, e.g. triphenylphosphine or tri(tert-butyl)phosphine, with an alcohol of formula
HO—R8 (Va)
or
HO-L1-R9 (Vb),
wherein R8 is an unsubstituted or substituted C1-C6alkyl, C3-C6alkenyl or C3-C6alkynyl group, and R9 and L1 are as defined hereinbefore, respectively.
The reaction described in accordance with process variant d) is generally known as a Mitsunobu reaction and is especially suitable for the preparation of those compounds of formulae I and lid wherein R1 is a group —X2—R8, —X3-L1-R9 or —X1-L1-X20—R70 and X2 and X3 are oxygen and R8 and L1 are a C1-C4alkylene group branched in the alpha-position or substituted in that position by halogen or by alkoxy, or together with R9 or with R70 forms, by means of a further C2-C6alkylene chain, a 3- to 6-membered ring system.
Furthermore, the starting materials of formula IId
wherein R1 is a group -L10-R4 or -L11-X1—R5 and wherein L10 and L11 are especially an unsubstituted or substituted C2-C6alkenylene or a C2-C6alkynylene group and R4, when L10 is a direct bond, is especially a three- to ten-membered, monocyclic or fused bicyclic ring system which may be aromatic or partially saturated, and which may contain from 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur, and R2, R5, X1 and Y0 are as defined hereinbefore, can advantageously be prepared by reacting a compound of formula XIIe
wherein R2 and Y0 are as defined hereinbefore, and K3 is group capable of further functionalisation, such as chlorine, bromine, iodine or trifluoromethylsulfonyloxy, in accordance with process variant g) by means of a —C—C— linking Suzuki, Stille, Sonogashira or Heck reaction, in the presence of a noble metal catalyst having suitable ligands, e.g. PdCl2(PPh3)2, Pd(PPh3)4, Pd2(dba)3, Pd(CH3CN)2(PPh3)2, Pd(OAc)2, Rh, Cu, CuCl or CuI, and in the presence of a base, e.g. triethylamine, Hünig's base, sodium tert-butanolate, potassium tert-butanolate, sodium carbonate, potassium carbonate, caesium carbonate, potassium fluoride or caesium fluoride, and optionally further adjuvants, e.g. LiCl or Li2CO3, or an additional auxiliary catalyst, e.g. triphenylphosphine, tri(tert-butyl)phosphine, (Ph3)2PCH2CH2P(Ph3)2 or (Ph3)2PCH2CH2CH2P(Ph3)2, with a boronic acid, e.g. of formula Xa or Xb
(HO)2B-L10-R4 (Xa)
or
(HO)2B-L11-X1—R5 (Xb),
or with a tin compound of formula Xc or Xd
RaRbRcSn-L10-R4 (Xc)
or
RaRbRcSn-L11-X1—R5 (Xd),
or with an ethynyl compound of formula Xe or Xf having a functionality in accordance with R1
H—C≡C-L10b-R4 (Xe)
or
H—C≡C-L11b-X1—R5 (Xf),
or with a vinyl compound of formula Xg or Xh having a functionality in accordance with R1
H—CH═CH-L10a-R4 (Xg)
or
H—CH═CH-L11a-X1—R5 (Xh),
wherein L10, L11, R4, R5 and X1 are as defined hereinbefore, Ra, Rb and Rc are each independently of the others C1-C8alkyl and L10a, L10b, L11a and L11b are appropriate subgroups of the groups L10 and L11, such as especially a direct bond or a C1-C4alkylene group which may be substituted once, twice or three times by C1-C6alkyl, halogen, hydroxy, C1-C6alkoxy or by C1-C3alkoxy-C1-C3alkoxy, and wherein the reagents Xg and Xh can each result in one or more regio-isomeric products, for example
Those process sequences are described in greater detail in Reaction schemes 2 to 5 below.
The compounds of formula XII
and XIIf
wherein K0, K2 and R2 are as defined hereinbefore and Y is accordingly Y0, hydroxy or Y1, which are used as starting materials in the preparation of compounds of general formulae If and especially Ic, can likewise be prepared in accordance with the generally known methods or in accordance with the preparation processes c) to h) given above for formulae I and IIc.
The compounds of formula II used as starting materials
wherein R1 and R2 are as defined hereinbefore and Y is C1-C4alkoxy, benzyloxy, hydroxy, fluorine, chlorine, bromine, cyano or phenoxy which may be unsubstituted or substituted by an electron-withdrawing group, e.g. halogen, trifluoromethyl, nitro, cyano, C1-C4alkylcarbonyl, C1-C4alkoxycarbonyl or C1-C4alkylsulfonyl, are novel and the present Application relates also to the use thereof in the preparation of compounds of formula I. In compounds of formula II, Y is preferably C1-C4alkoxy, benzyloxy, hydroxy, chlorine or cyano.
The compounds of formula III used as starting materials are generally known. For example, diones of formula III
and of formula IIIa
wherein A1, A2 and A3 are as defined hereinbefore and R3 is hydroxy or O−M+ wherein M+ is as defined hereinbefore, are known, for example, from DE-A-3902818, WO 00/39094, or they can be prepared in accordance with the methods described therein.
The starting materials of formulae IVa, IVb, IVc, V, Va, Vb, Vc, Vd, Ve, Vf, Vg, Vh, Vi, VI, VIa, VIb, VIc, VII, VIIa, VIII, VIIIa, IX, Xa, Xb, Xc, Xd, Xe, Xf, Xg, Xh, XIIIa, XIIIb are likewise generally known or they can be prepared analogously to known methods.
All the reactions according to the preparation processes a) to h) for forming compounds of formula I and also intermediates of formula II are advantageously carried out in aprotic and inert organic solvents. Such solvents are hydrocarbons, e.g. benzene, toluene, xylene or cyclohexane, chlorinated hydrocarbons, e.g. dichloromethane, chloroform, tetrachloromethane or chlorobenzene, ethers, e.g. diethyl ether, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tetrahydrofuran or dioxane, nitriles, e.g. acetonitrile or propionitrile, and amides, e.g. N,N-dimethylformamide, diethylformamide or N-methylpyrrolidinone. The temperatures in those reactions are preferably from −20° C. to +120° C. When the reactions are exothermic, they can usually be carried out at room temperature. In order to shorten the reaction time or also in order to initiate the reaction, the reaction mixture may, where appropriate, be heated briefly up to its boiling point. Relatively new application techniques such as ultrasound and the use of microwaves are also highly suitable. It is often possible, especially when using microwaves, for the reaction times to be substantially reduced at relatively mild temperatures of from about 100° C. to about 150° C. The reaction times can likewise be shortened by adding a suitable base as reaction catalyst. Suitable bases are, especially, tertiary amines such as trimethylamine, triethylamine, quinuclidine, 1,4-diazabicyclo[2.2.2]octane, 1,5-diazabicyclo[4.3.0]non-5-ene and 1,5-diazabicyclo[5.4.0]-undec-7-ene. However, it is also possible to use inorganic bases, such as hydrides, e.g. sodium or calcium hydride, hydroxides, e.g. dry sodium or potassium hydroxide, carbonates, e.g. sodium or potassium carbonate, or hydrogen carbonates, e.g. sodium or potassium hydrogen carbonate.
In accordance with process a), preparation of the compounds of formulae I, If, and II, IIb and XII, wherein Y1 and Y are chlorine, is carried out using a chlorinating agent, e.g. oxalyl chloride, thionyl chloride, phosgene, (1-chloro-2-methyl-propenyl)-dimethyl-amine, phosphorus pentachloride, phosphorus oxychloride or dichlorophosphate, preferably using oxalyl chloride. The reaction is preferably carried out in an inert, organic solvent, for example in an aliphatic, halogenated aliphatic, aromatic or halogenated aromatic hydrocarbon, e.g. n-hexane, benzene, toluene, xylenes, dichloromethane, 1,2-dichloroethane or chlorobenzene, at reaction temperatures in the range from −20° C. up to the reflux temperature of the reaction mixture, preferably at about 40-100° C., and in the presence of a catalytic amount of N,N-dimethylformamide. It can also, where appropriate, be carried out directly in the chlorinating agent used, without additional solvent.
The end products of formula I can be isolated in conventional manner by concentrating or evaporating off the solvent and can be separated and purified by recrystallising or by triturating the solid residue in solvents in which they are not readily soluble, such as ethers, aromatic hydrocarbons or chlorinated hydrocarbons, or by distillation or by means of column chromatography or by means of HPLC techniques using a suitable eluant.
The person skilled in the art will also be familiar with the order in which the reactions should be performed in order to avoid subsidiary reactions as far as possible. Unless synthesis is specifically aimed at the isolation of pure isomers, the product may be obtained in the form of a mixture of two or more isomers, e.g. chiral centres in the case of alkyl groups or cis/trans isomerism in the case of alkenyl groups or ‘E’ or ‘Z’ forms. All those isomers can be separated using methods known per se, e.g. chromatography or fractional crystallisation, or, by specifically controlling the reactions, a desired form can be produced in a relatively high concentration or in pure form.
The compounds of formula I according to the invention can be used as herbicides in unmodified form, that is to say as obtained in the synthesis, but they are generally formulated in various ways, using formulation adjuvants such as carriers, solvents and surface-active substances, to form herbicidal compositions. The formulations can be in various physical forms, e.g. in the form of dusting powders, gels, wettable powders, water-dispersible granules, water-dispersible tablets, effervescent tablet compacts, emulsifiable concentrates, micro-emulsifiable concentrates, oil-in-water emulsions, aqueous dispersions, dispersions in oil, suspoemulsions, water-soluble concentrates (having water or a water-miscible organic solvent as carrier), impregnated polymer films, or in other forms that are known, for example from the Manual on Development and Use of FAO Specifications for Plant Protection Products, 5th Edition, 1999. Those formulations either can be used directly or are diluted before use. The dilutions can be produced using, for example, water, liquid fertilisers, micro-nutrients, biological organisms, oil or solvents.
The formulations can be produced, for example, by mixing the active ingredient with the formulation adjuvants to obtain compositions in the form of finely divided solids, granules, spherules, solutions, dispersions or emulsions. The active ingredients can also be formulated with other adjuvants, such as finely divided solids, mineral oils, organic solvents, water, surface-active substances or combinations thereof. The active ingredients can also be contained in very fine microcapsules consisting of a polymer. Microcapsules contain the active ingredients in a porous carrier. This enables active ingredients to be released into the surroundings in controlled amounts. Microcapsules usually have a diameter of from 0.1 to 500 microns. They contain active ingredient in an amount of about from 25 to 95% by weight of the capsule weight. The active ingredients can be present in the form of a monolithic solid, in the form of fine particles in solid or liquid dispersion or in the form of a suitable solution. The encapsulating membranes comprise, for example, natural and synthetic gums, cellulose, styrene-butadiene copolymers, polyacrylonitrile, polyacrylate, polyester, polyamides, polyureas, polyurethane or chemically modified polymers and starch xanthates or other polymers known in this context to the person skilled in the art. Alternatively, it is possible for very fine microcapsules to be formed wherein the active ingredient is present in the form of finely divided particles in a solid matrix of a base substance, but in that case the microcapsules are not encapsulated.
The formulation adjuvants that are suitable for producing the compositions according to the invention are known per se. As liquid carriers there may be used: water, toluene, xylene, petroleum ether, vegetable oils, acetone, methyl ethyl ketone, cyclohexanone, acid anhydrides, acetonitrile, acetophenone, amyl acetate, 2-butanone, chlorobenzene, cyclohexane, cyclohexanol, alkyl esters of acetic acid, diacetone alcohol, 1,2-dichloropropane, diethanolamine, p-diethylbenzene, diethylene glycol, diethylene glycol abietate, diethylene glycol butyl ether, diethylene glycol ethyl ether, diethylene glycol methyl ether, N,N-dimethylformamide, dimethyl sulfoxide, 1,4-dioxane, dipropylene glycol, dipropylene glycol methyl ether, dipropylene glycol dibenzoate, diproxitol, alkylpyrrolidinone, ethyl acetate, 2-ethylhexanol, ethylene carbonate, 1,1,1-trichloroethane, 2-heptanone, alpha-pinene, d-limonene, ethylene glycol, ethylene glycol butyl ether, ethylene glycol methyl ether, gamma-butyrolactone, glycerol, glycerol acetate, glycerol diacetate, glycerol triacetate, hexadecane, hexylene glycol, isoamyl acetate, isobornyl acetate, isooctane, isophorone, isopropylbenzene, isopropyl myristate, lactic acid, laurylamine, mesityl oxide, methoxypropanol, methyl isoamyl ketone, methyl isobutyl ketone, methyl laurate, methyl octanoate, methyl oleate, methylene chloride, m-xylene, n-hexane, n-octylamine, octadecanoic acid, octylamine acetate, oleic acid, oleylamine, o-xylene, phenol, polyethylene glycol (PEG400), propionic acid, propylene glycol, propylene glycol methyl ether, p-xylene, toluene, triethyl phosphate, triethylene glycol, xylenesulfonic acid, paraffin, mineral oil, trichloroethylene, perchloroethylene, ethyl acetate, amyl acetate, butyl acetate, propylene glycol monomethyl ether, diethylene glycol monomethyl ether, methanol, ethanol, isopropanol, and alcohols of higher molecular weight such as amyl alcohol, tetrahydrofurfuryl alcohol, hexanol, octanol, etc., ethylene glycol, propylene glycol, glycerol, N-methyl-2-pyrrolidinone (NMP), and the like. Water is generally the carrier of choice for dilution of the concentrates. Suitable solid carriers are, for example, talc, titanium dioxide, pyrophyllite clay, silica, attapulgite clay, kieselguhr, chalk, calcium carbonate, bentonite, calcium montmorillonite, cottonseed husks, wheat flour, soybean flour, pumice, wood flour, ground walnut shells, lignin and similar substances such as are described, for example, in CFR 180.1001. (c) & (d).
A large number of surface-active substances can advantageously be used both in solid and in liquid formulations, especially in those which can be diluted with a carrier before application.
Surface-active substances can be anionic, cationic, non-ionic or polymeric, and they can be used as emulsifying agents, wetting agents or suspension agents or for other purposes. Typical surface-active substances include, for example, salts of alkyl sulfates, e.g. diethanolammonium lauryl sulfate; salts of alkylarylsulfonates, e.g. calcium dodecylbenzenesulfonate; addition products of alkylphenols and alkylene oxides, e.g. nonylphenol ethoxylates; addition products of alcohols and alkylene oxides, e.g. tridecylalcohol ethoxylates; soaps, e.g. sodium stearate; salts of alkylnaphthalenesulfonates, e.g. sodium dibutyl-naphthalenesulfonate; dialkyl esters of sulfosuccinate salts, e.g. sodium di(2-ethylhexyl)sulfosuccinate; sorbitol esters, e.g. sorbitol oleate; quaternary amines, e.g. lauryl trimethylammonium chloride, polyethylene glycol esters of fatty acids, e.g. polyethylene glycol stearate; block copolymers of ethylene oxide and propylene oxide; and salts of mono- and di-alkyl phosphate esters; and also further substances described, for example, in “McCutcheon's Detergents and Emulsifiers Annual” MC Publishing Corp., Ridgewood N.J., 1981.
Further adjuvants which can usually be used in herbicidal formulations include crystallisation inhibitors, viscosity-modifying substances, suspension agents, dyes, antioxidants, foaming agents, light-absorbing agents, mixing adjuvants, anti-foams, complex-formers, neutralising or pH-modifying substances and buffers, corrosion inhibitors, fragrances, wetting agents, take-up enhancers, micro-nutrients, plasticisers, glidants, lubricants, dispersants, thickening agents, antifreeze agents, microbicidal agents, and also liquid and solid fertilisers.
The formulations may also comprise additional active substances, e.g. further herbicides, herbicide safeners, plant growth regulators, fungicides and/or insecticides.
The compositions according to the invention may additionally include an additive comprising an oil of vegetable or animal origin, a mineral oil, alkyl esters thereof or mixtures of such oils and oil derivatives. The amounts of oil additive used in the composition according to the invention are generally from 0.01 to 10%, based on the spray mixture. For example, the oil additive can be added to the spray tank in the desired concentration after the spray mixture has been prepared. Preferred oil additives comprise mineral oils or an oil of vegetable origin, for example rapeseed oil, olive oil or sunflower oil, emulsified vegetable oil, such as AMIGO® (Rhône-Poulenc Canada Inc.), alkyl esters of oils of vegetable origin, for example the methyl derivatives, or an oil of animal origin, such as fish oil or beef tallow. A preferred additive e.g. NOV233 contains as active components essentially 80% by weight alkyl esters of fish oils and 15% by weight methylated rapeseed oil, and also 5% by weight of customary emulsifiers and pH modifiers.
Especially preferred oil additives comprise alkyl esters of C8-C22 fatty acids, the methyl derivatives of C12-C18 fatty acids, for example the methyl esters of lauric acid, palmitic acid and oleic acid, being especially important. Those esters are known as methyl laurate (CAS-111-82-0), methyl palmitate (CAS-112-39-0) and methyl oleate (CAS-112-62-9). A preferred fatty acid methyl ester derivative is Emery® 2230 and 2231 (Cognis GmbH). These and other oil derivatives are also known from the Compendium of Herbicide Adjuvants, 5th Edition, Southern Illinois University, 2000.
The application and action of the oil additives can be further improved by combining them with surface-active substances, such as non-ionic, anionic or cationic surfactants. Examples of suitable anionic, non-ionic and cationic surfactants are listed on pages 7 and 8 of WO 97/34485. Preferred surface-active substances are anionic surfactants of the dodecylbenzylsulfonate type, especially the calcium salts thereof, and also non-ionic surfactants of the fatty alcohol ethoxylate type. Special preference is given to ethoxylated C12-C22 fatty alcohols having a degree of ethoxylation of from 5 to 40. Examples of commercially available surfactants are the Genapol types (Clariant AG). Also preferred are silicone surfactants, especially polyalkyl-oxide-modified heptamethyltrisiloxanes, which are commercially available, for example, as Silwet L-77®, and also perfluorinated surfactants. The concentration of surface-active substances in relation to the total additive is generally from 1 to 30% by weight. Examples of oil additives that consist of mixtures of oils or mineral oils or derivatives thereof with surfactants are Edenor ME SU®, Turbocharge® (Zeneca Agro, CA) and Actipron® (BP Oil UK Limited, GB).
Where appropriate, the mentioned surface-active substances can also be used alone, that is to say without oil additives, in the formulations.
The addition of an organic solvent to the oil additive/surfactant mixture can also bring about a further enhancement of action. Suitable solvents are, for example, Solvesso® (ESSO) and Aromatic Solvent® (Exxon Corporation). The concentration of such solvents can be from 10 to 80% by weight of the total weight. Such oil additives, which are present in admixture with solvents, are described, for example, in U.S. Pat. No. 4,834,908. A commercially available oil additive known therefrom is known by the name MERGE® (BASF Corporation). A further oil additive that is preferred according to the invention is SCORE® (Syngenta Crop Protection Canada).
In addition to the oil additives listed above, it is also possible, for the purpose of enhancing the action of the compositions according to the invention, to add formulations of alkyl pyrrolidones (e.g. Agrimax®) to the spray mixture. Formulations of synthetic latices, such as, for example, polyacrylamide, polyvinyl compounds or poly-1-p-menthene (e.g. Bond®, Courier® or Emerald®), can also be used for the purpose. Solutions comprising propionic acid, for example Eurogkem Pen-e-trate®, can also be admixed as action-enhancing agents with the spray mixture.
The herbicidal formulations generally contain from 0.1 to 99% by weight, especially from 0.1 to 95% by weight, of compound of formula I and from 1 to 99.9% by weight of a formulation adjuvant which preferably contains from 0 to 25% by weight of a surface-active substance. Whereas commercial products will preferably be formulated as concentrates, the end user will normally employ dilute formulations.
The rates of application of compounds of formula I may vary within wide limits and depend on the nature of the soil, the method of application (pre- or post-emergence; seed dressing; application to the seed furrow; no tillage application etc.), the crop plant, the weed or grass to be controlled, the prevailing climatic conditions, and other factors governed by the method of application, the time of application and the target crop. The compounds of formula I according to the invention are generally applied at a rate of from 1 to 2000 g/ha.
The invention relates also to a method of selectively controlling grasses and weeds in crops of useful plants, which comprises treating the useful plants or the area of cultivation or locus thereof with the compounds of formula I.
The weeds to be controlled may be either monocotyledonous or dicotyledonous weeds, such as, for example, Stellaria, Nasturtium, Agrostis, Digitaria, Avena, Setaria, Sinapis, Lolium, Solanum, Echinochloa, Scirpus, Monochoria, Sagittaria, Bromus, Alopecurus, Sorghum, Rottboellia, Cyperus, Abutilon, Sida, Xanthium, Amaranthus, Chenopodium, Ipomoea, Chrysanthemum, Galium, Viola and Veronica.
As crops of useful plants in which the composition according to the invention can be used there come into consideration especially cereals, cotton, soybeans, sugar beet, sugar cane, plantation crops, rape, maize and rice. Crops are to be understood as including those which have been made tolerant to herbicides or classes of herbicides (e.g. ALS-, GS-, EPSPS- and HPPD-inhibitors) by means of conventional breeding or genetic engineering methods. An example of a crop that has been made tolerant by conventional breeding methods to, for example, imidazolinones such as imazamox is Clearfield® summer rape (canola). Examples of crops made tolerant to herbicides by genetic engineering methods are maize varieties resistant to, for example, glyphosate or glufosinate, which are commercially available under the trade names RoundupReady® and LibertyLink®.
Useful plants are to be understood as expressly including pest-resistant and/or fungus-resistant transgenic useful plants.
In the context of the present invention, pest-resistant transgenic crop plants are to be understood as being those which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising one or more selectively acting toxins, such as are known, for example, from toxin-producing bacteria, especially those of the genus Bacillus.
Toxins that can be expressed by such transgenic plants include, for example, insecticidal proteins, for example insecticidal proteins from Bacillus cereus or Bacillus popliae; or insecticidal proteins from Bacillus thuringiensis, such as δ-endotoxins, e.g. CryIA(b), CryIA(c), CryIF, CryIF(a2), CryIIA(b), CryIIIA, CryIIIB(b1) or Cry9c, or vegetative insecticidal proteins (VIP), e.g. VIP1, VIP2, VIP3 or VIP3A; or insecticidal proteins of bacteria-colonising nematodes, for example Photorhabdus spp. or Xenorhabdus spp., such as Photorhabdus luminescens, Xenorhabdus nematophilus; toxins produced by animals, such as scorpion toxins, arachnid toxins, wasp toxins and other insect-specific neurotoxins; toxins produced by fungi, such as Streptomycetes toxins; plant lectins, such as pea lectins, barley lectins or snowdrop lectins; agglutinins; proteinase inhibitors, such as trypsine inhibitors, serine protease inhibitors, patatin, cystatin, papain inhibitors; ribosome-inactivating proteins (RIP), such as ricin, maize-RIP, abrin, luffin, saporin or bryodin; steroid metabolism enzymes, such as 3-hydroxysteroidoxidase, ecdysteroid-UDP-glycosyl-transferase, cholesterol oxidases, ecdysone inhibitors, HMG-COA-reductase, ion channel blockers, such as blockers of sodium or calcium channels, juvenile hormone esterase, diuretic hormone receptors, stilbene synthase, bibenzyl synthase, chitinases and glucanases.
In the context of the present invention there are to be understood by S-endotoxins, for example CryIA(b), CryIA(c), CryIF, CryIF(a2), CryIIA(b), CryIIIA, CryIIIB(b1) or Cry9c, or vegetative insecticidal proteins (VIP), for example VIP1, VIP2, VIP3 or VIP3A, expressly also hybrid toxins, truncated toxins and modified toxins. Hybrid toxins are produced recombinantly by a new combination of different domains of those proteins (see, for example, WO 02/15701). An example of a truncated toxin is a truncated CryIA(b), which is expressed in Bt11 maize of Syngenta Seeds SAS, as described hereinbelow. In the case of modified toxins, one or more amino acids of the naturally occurring toxin is/are replaced. In such amino acid replacements, preferably non-naturally present protease recognition sequences are inserted into the toxin, such as, for example, in the case of CryIIIA055, a cathepsin-D-recognition sequence is inserted into a CryIIIA toxin (see WO 03/018810).
Examples of such toxins or transgenic plants capable of synthesising such toxins are disclosed, for example, in EP-A-0 374 753, WO 93/07278, WO 95/34656, EP-A-0 427 529, EP-A-451 878 and WO 03/052073.
The processes for the preparation of such transgenic plants are generally known to the person skilled in the art and are described, for example, in the publications mentioned above. CryI-type deoxyribonucleic acids and their preparation are known, for example, from WO 95/34656, EP-A-0 367 474, EP-A-0 401 979 and WO 90/13651.
The toxin contained in the transgenic plants provides the plants with tolerance to harmful insects. Such insects can occur in any taxonomic group of insects, but are especially commonly found in beetles (Coleoptera), two-winged insects (Diptera) and butterflies (Lepidoptera).
The following harmful insects from different taxonomic groups are especially common in maize crops:
Rhopalosiphum maidis, corn leaf aphid
Transgenic plants containing one or more genes that code for an insecticidal resistance and express one or more toxins are known and some of them are commercially available. Examples of such plants are: YieldGard® (maize variety that expresses a CryIA(b) toxin); YieldGard Rootworm® (maize variety that expresses a CryIIIB(b1) toxin); YieldGard Plus® (maize variety that expresses a CryIA(b) and a CryIIIB(b1) toxin); Starlink® (maize variety that expresses a Cry9(c) toxin); Herculex I® (maize variety that expresses a CryIF(a2) toxin and the enzyme phosphinothricine N-acetyltransferase (PAT) to achieve tolerance to the herbicide glufosinate ammonium); NuCOTN 33B® (cotton variety that expresses a CryIA(c) toxin); Boligard I® (cotton variety that expresses a CryIA(c) toxin); Boligard II® (cotton variety that expresses a CryIA(c) and a CryIIA(b) toxin); VIPCOT® (cotton variety that expresses a VIP toxin); NewLeaf® (potato variety that expresses a CryIIIA toxin); NatureGard® and Protecta®.
Further examples of such transgenic crops are:
1. Bt11 Maize from Syngenta Seeds SAS, Chemin de l'Hobit 27, F-31 790 St. Sauveur, France, registration number C/FR/96/05/10. Genetically modified Zea mays which has been rendered resistant to attack by the European corn borer (Ostrinia nubilalis and Sesamia nonagrioides) by transgenic expression of a truncated CryIA(b) toxin. Bt11 maize also transgenically expresses the enzyme PAT to achieve tolerance to the herbicide glufosinate ammonium.
2. Bt176 Maize from Syngenta Seeds SAS, Chemin de l'Hobit 27, F-31 790 St. Sauveur, France, registration number C/FR/96/05/10. Genetically modified Zea mays which has been rendered resistant to attack by the European corn borer (Ostrinia nubilalis and Sesamia nonagrioides) by transgenic expression of a CryIA(b) toxin. Bt176 maize also transgenically expresses the enzyme PAT to achieve tolerance to the herbicide glufosinate ammonium.
3. MIR604 Maize from Syngenta Seeds SAS, Chemin de l'Hobit 27, F-31 790 St. Sauveur, France, registration number C/FR/96/05/10. Maize which has been rendered insect-resistant by transgenic expression of a modified CryIIIA toxin. This toxin is Cry3A055 modified by insertion of a cathepsin-D-protease recognition sequence. The preparation of such transgenic maize plants is described in WO 03/018810.
4. MON 863 Maize from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-1150 Brussels, Belgium, registration number C/DE/02/9. MON 863 expresses a CryIIIB(b1) toxin and has resistance to certain Coleoptera insects.
5. IPC 531 Cotton from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-1150 Brussels, Belgium, registration number C/ES/96/02.
6. 1507 Maize from Pioneer Overseas Corporation, Avenue Tedesco, 7 B-1160 Brussels, Belgium, registration number C/NL/00/10. Genetically modified maize for the expression of the protein Cry1F for achieving resistance to certain Lepidoptera insects and of the PAT protein for achieving tolerance to the herbicide glufosinate ammonium.
7. NK603×MON 810 Maize from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-1150 Brussels, Belgium, registration number C/GB/02/M3/03. Consists of conventionally bred hybrid maize varieties by crossing the genetically modified varieties NK603 and MON 810. NK603×MON 810 Maize transgenically expresses the protein CP4 EPSPS, obtained from Agrobacterium sp. strain CP4, which imparts tolerance to the herbicide Roundup® (contains glyphosate), and also a CryIA(b) toxin obtained from Bacillus thuringiensis subsp. kurstaki which brings about tolerance to certain Lepidoptera, including the European corn borer.
Transgenic crops of insect-resistant plants are also described in BATS (Zentrum für Biosicherheit und Nachhaltigkeit, Zentrum BATS, Clarastrasse 13, 4058 Basel, Switzerland) Report 2003, (http://bats.ch).
In the context of the present invention, fungus-resistant transgenic crop plants are to be understood as being those which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising antipathogenic substances having a selective action, such as, for example, the so-called “pathogenesis-related proteins” (PRPs, see e.g. EP-A-0 392 225). Examples of such antipathogenic substances and transgenic plants capable of synthesising such antipathogenic substances are known, for example, from EP-A-0 392 225, WO 95/33818 and EP-A-0 353 191. The methods of producing such transgenic plants are generally known to the person skilled in the art and are described, for example, in the publications mentioned above.
Antipathogenic substances which can be expressed by such transgenic plants include, for example, ion channel blockers, such as blockers for sodium and calcium channels, for example the viral KP1, KP4 or KP6 toxins; stilbene synthases; bibenzyl synthases; chitinases; glucanases; the so-called “pathogenesis-related proteins” (PRPs; see e.g. EP-A-0 392 225); antipathogenic substances produced by microorganisms, for example peptide antibiotics or heterocyclic antibiotics (see e.g. WO 95/33818) or protein or polypeptide factors involved in plant pathogen defense (so-called “plant disease resistance genes”, as described in WO 03/000906).
In the context of the present invention, pest-resistant and/or fungus-resistant transgenic useful plants include expressly those useful plants which, in addition to pest-resistance and/or fungus-resistance, also possess herbicide tolerance. Of the group of herbicide-tolerant useful plants, preference is given according to the invention to those having tolerance to glyphosate, glufosinate ammonium, ALS (acetolactate synthase) inhibitors, e.g. sulfonylureas, for example primisulfuron, prosulfuron and trifloxysulfuron, or bromoxynil, such as Bt11 maize or Herculex I® maize.
Areas of cultivation are areas of land on which the crop plants are already growing and also areas of land on which it is intended to grow those crop plants.
The following Examples further illustrate, but do not limit, the invention.
197 g (2.1 mol) of hydrogen peroxide in the form of the urea adduct are stirred into a solution of 132 g (0.6 mol) of 5-trifluoromethyl-pyridine-2-carboxylic acid ethyl ester in 1000 ml of 1,2-dichloroethane. 346 g (1.65 mol) of trifluoroacetic anhydride are slowly added over 2.5 hours at a temperature of −10° C., with cooling (CO2/acetone bath). The reaction mixture is then stirred for 2 hours at a temperature of 0° C. and then for 12 hours at ambient temperature. The reaction mixture is then poured into ice-water and adjusted to pH 6-7 with 30% sodium hydroxide solution. The mixture is extracted several times with 1,2-dichloroethane, dried over sodium sulfate and concentrated to dryness by evaporation. Chromatography on silica gel (eluant:ethyl acetate/hexane 1:4) is carried out in order to separate off subsidiary products. After removal of the eluant, 98.4 g of 1-oxy-5-trifluoromethyl-pyridine-2-carboxylic acid ethyl ester (m.p. 64.5 to 65° C.) are obtained.
450 ml of trifluoroacetic anhydride are added dropwise to a mixture of 77.6 g (0.33 mol) of 1-oxy-5-trifluoromethyl-pyridine-2-carboxylic acid ethyl ester in 900 ml of dimethylformamide at a temperature of 0° C. over 3.5 hours. The mixture is then heated to a temperature of from 45 to 50° C. and is stirred for 2.5 hours. The reaction mixture is then concentrated under reduced pressure (2.5 kPa). The oily residue is poured into ice-water and adjusted to pH 5.5 with 30% sodium hydroxide solution. A crystallised product is obtained which is filtered off, washed with water and dried in vacuo at a temperature of 80° C. 61.6 g (79.4%) of 6-hydroxy-5-trifluoromethyl-pyridine-2-carboxylic acid ethyl ester (m.p. 141-141.5° C.) are obtained.
16.5 g (70 mmol) of 6-hydroxy-5-trifluoromethyl-pyridine-2-carboxylic acid ethyl ester in 20 ml of phenyl dichlorophosphate are heated in a pressure reactor for 30 minutes at a temperature of 170° C. The cooled reaction mixture is taken up in ethyl acetate, washed once with cold sodium chloride solution, dried over sodium sulfate and then concentrated. To remove phosphate-containing constituents, the residue that remains behind is chromatographed on silica gel (eluant:ethyl acetate/hexane 1:4) and is then concentrated to dryness by evaporation. 16.2 g (91.3%) of 6-chloro-5-trifluoromethyl-pyridine-2-carboxylic acid ethyl ester are obtained in the form of an oil; 1H NMR (CDCl3): 8.17, m, 2H, 4.52, q, 2H, 1.44, t, 3H.
6.45 g (25 mmol) of 6-chloro-5-trifluoromethyl-pyridine-2-carboxylic acid ethyl ester are heated at a temperature of 110° C. for 1 hour in the presence of 5.5 g (63 mmol) of morpholine and a catalytic amount of 4-N,N-dimethylaminopyridine in 50 ml of N-methylpyrrolidone. The reaction mixture is adjusted to pH 4 with dilute hydrochloric acid, extracted with ethyl acetate, dried over magnesium sulfate and then concentrated. In order to remove polar subsidiary products, the residue is chromatographed on silica gel and then concentrated to dryness by evaporation, yielding 7.08 g of 6-(morpholin-4-yl)-5-trifluoromethyl-pyridine-2-carboxylic acid ethyl ester in the form of an oil; 1H NMR (CDCl3): 7.97, d, 1H, 7.68, d, 1H, 4.42, q, 2H, 3.83, m, 4H, 3.40, m, 4H, 1.42, t, 3H.
7 g (23 mmol) of 6-(morpholin-4-yl)-5-trifluoromethyl-pyridine-2-carboxylic acid ethyl ester are added to a mixture of 30 ml of dioxane and 25 ml of water in the presence of 1.55 g of potassium hydroxide and the reaction mixture is stirred at ambient temperature for 30 minutes. The reaction mixture is then adjusted to pH 3 and extracted with ethyl acetate, dried over sodium sulfate and concentrated. Addition of hexane causes 6-(morpholin-4-yl)-5-trifluoromethyl-pyridine-2-carboxylic acid (yield 93.2%) to precipitate out (m.p.: 116-117° C.).
0.83 g (3 mmol) of 6-(morpholin-4-yl)-5-trifluoromethyl-pyridine-2-carboxylic acid and 0.46 g (3.6 mmol) of oxalyl chloride in 10 ml of dichloromethane are heated at boiling temperature for 15 minutes in the presence of a drop of dimethylformamide. The solution is then concentrated by evaporation, yielding 6-(morpholin-4-yl)-5-trifluoromethyl-pyridine-2-carboxylic acid chloride in the form of a crystalline product (m.p.: 72-73° C.).
At a temperature of 0° C., with cooling, a solution of 1.46 g (11.5 mmol) of oxalyl chloride in ml of dichloromethane is added dropwise to a solution of 0.84 g (11.5 mmol) of N-methylacetamide and 2.45 g (22.9 mmol) of lutidine in 40 ml of dichloromethane. After 20 minutes, 2.45 g (10.4 mmol) of 1-oxy-5-trifluoromethyl-pyridine-2-carboxylic acid ethyl ester dissolved in 5 ml of dichloromethane are added. The reaction mixture is heated to ambient temperature and then heated at boiling temperature for 1 hour. The reaction mixture is then extracted with water against dichloromethane, dried over MgSO4 and concentrated to dryness by evaporation. The resulting residue is chromatographed on silica gel (eluant:ethyl acetate/hexane 3:7), 6-(acetyl-methyl-amino)-5-trifluoromethyl-pyridine-2-carboxylic acid ethyl ester being isolated as main component (m.p.: 145-145.5° C.).
1.88 g (8 mmol) of 6-hydroxy-5-trifluoromethyl-pyridine-2-carboxylic acid ethyl ester and 1.47 g (8 mmol) of 2-bromomethyl-1,3-dioxolane in 30 ml of acetonitrile are heated at reflux temperature in the presence of 1.22 g (8.8 mmol) of potassium carbonate and catalytic amounts of potassium iodide and 18-crown-6 for 6 hours. The reaction mixture is then extracted with ethyl acetate against water and dilute acid at pH 3, dried over sodium sulfate and concentrated by evaporation. The residue is chromatographed on silica gel (eluant:ethyl acetate/hexane 15:85), yielding 6-([1,3]dioxolan-2-ylmethoxy)-5-trifluoromethyl-pyridine-2-carboxylic acid ethyl ester in the form of an oil; 1H NMR (CDCl3): 8.00, d, 1H, 7.76, d, 1H, 5.40, t, 1H, 4.61, d, 2H, 4.42, q, 2H, 4.09, m, 2H, 3.93, m, 2H, 1.42, t, 3H.
2.53 g (14.5 mmol) of azodicarboxylic acid diethyl ester (DEAD) are added dropwise to a solution of 2.35 g (10 mmol) of 6-hydroxy-5-trifluoromethyl-pyridine-2-carboxylic acid ethyl ester and 3.93 g (15 mmol) of triphenylphosphine in 30 ml of dimethoxyethane, the temperature being maintained at a maximum of 35° C. After 1 hour at ambient temperature, the reaction mixture is concentrated to dryness by evaporation. The residue is chromatographed on silica gel (eluant:ethyl acetate/hexane 1:4). 2.85 g (93.4%) of 6-(tetrahydrofuran-3-yloxy)-5-trifluoromethyl-pyridine-2-carboxylic acid ethyl ester are obtained (m.p.: 45-45.5° C.).
6.9 g (6 mmol) of tetrakis(triphenylphosphine)palladium and 8.3 g (66 mmol) of 2,4,6-trimethyl-cyclotriboroxane are added to a solution of 15.2 g (60 mmol) of 6-chloro-5-trifluoromethyl-pyridinecarboxylic acid ethyl ester and 33.1 g (0.24 mol) of potassium carbonate in 150 ml of dioxane and the mixture is then heated for 2.5 hours at reflux temperature. The end point of the reaction is determined by thin-layer chromatography. The reaction mixture is cooled, poured into ice-water and is then adjusted to pH 5 with concentrated hydrochloric acid. To separate off solid constituents, a filtration aid (Hyflo®) is added and filtered off. The filtrate is extracted with ethyl acetate. The filtrate, dried over sodium sulfate, is concentrated to dryness by evaporation and chromatographed on silica gel (eluant:ethyl acetate/hexane 7.5:92.5). 11.28 g (87.8%) of 6-methyl-5-trifluoromethyl-pyridinecarboxylic acid ethyl ester are obtained in the form of an oil; 1H NMR (CDCl3): 8.05, “s”, 2H, 4.48, q, 2H, 2.31, 2, 3H, 1.42, t, 3H.
A catalytic amount of aza,aza-diisobutyronitrile is added to 1 g (4.3 mmol) of 6-methyl-5-trifluoromethyl-pyridine-2-carboxylic acid ethyl ester and 0.92 g of N-bromo-succinimide in 20 ml of carbon tetrachloride. The mixture is heated at reflux temperature using a light source (200 W lamp). Cooling is then carried out and the reaction product is filtered off and purified using an HPLC technique (eluant:ethyl acetate/hexane 1:4). 6-Bromomethyl-5-trifluoromethyl-pyridine-2-carboxylic acid ethyl ester is obtained; 1H NMR (CDCl3): 6.14, “s”, 2H, 4.78, s, 2H, 4.49, q, 2H, 1.45, t, 3H.
0.6 g (2 mmol) of 6-bromomethyl-5-trifluoromethyl-pyridine-2-carboxylic acid ethyl ester, dissolved in 3 ml of tetrahydrofuran, is introduced into 0.25 g (5.8 mmol) of sodium hydride (as a 55% dispersion in oil) in 10 ml of dry tetrahydrofuran and stirring is carried out for 2 hours at room temperature. The end point of the reaction is determined by means of thin-layer chromatography. Water is then added. After hydrolysis of the ester group is complete (again demonstrated by means of thin-layer chromatography), extraction with diethyl ether is carried out. The aqueous phase, which contains the reaction product, is then adjusted to pH 2 with hydrochloric acid. Extraction with ethyl acetate is then carried out, followed by drying over sodium sulfate and concentration to dryness by evaporation. 6-(2-Methoxyethoxymethyl)-5-trifluoromethyl-pyridine-2-carboxylic acid is obtained; 1H NMR (CDCl3): 8.26, d, 1H, 8.17, d, 1H, 7.3, b, OH; 4.96, s, 2H, 3.91, m, 2H, 3.71, m, 2H, 3.48, s, 3H.
0.31 g (1 mmol) of 6-thiomorpholin-4-yl-5-trifluoromethyl-pyridine-2-carboxylic acid chloride, prepared with oxalyl chloride, is added to 0.11 g (1 mmol) of cyclohexane-1,3-dione and 0.25 g (2.5 mmol) of triethylamine in 15 ml of acetonitrile and the reaction mixture is stirred at room temperature for 2 hours. 2 drops of acetone cyanohydrin are then added and the mixture is stirred for 12 hours. The reaction mixture is taken up in ethyl acetate and extracted with dilute hydrochloric acid at pH 3. After concentration of the organic phase by evaporation, the residue that remains behind is chromatographed on silica gel (eluant:ethyl acetate/methanol/triethylamine 85:10:5). After concentration by evaporation, the triethylammonium salt of 2-(6-thiomorpholin-4-yl-5-trifluoromethyl-pyridine-2-carbonyl)-cyclohexane-1,3-dione is obtained in the form of a resinous product. In order to free the desired end product, the resinous product is taken up in ethyl acetate, extracted again with dilute hydrochloric acid, dried over sodium sulfate and again concentrated to dryness by evaporation. After recrystallization with ethyl acetate and hexane, 2-(6-thiomorpholin-4-yl-5-trifluoromethyl-pyridine-2-carbonyl)-cyclohexane-1,3-dione is obtained in crystalline form (m.p.: 106-106.5° C.).
0.32 g (1 mmol) of 2-(6-chloro-5-trifluoromethyl-pyridine-2-carbonyl)-cyclohexane-1,3-dione and 82 mg (1.2 mmol) of pyrazole are added in succession at room temperature to 0.11 g of a 55% sodium hydride dispersion (2.5 mmol) in 8 ml of N-methylpyrrolidone. The reaction mixture is stirred for 1.5 hours at a temperature of 120° C. When the reaction mixture is cool, water is added and the mixture is adjusted to pH 2 and extracted with ethyl acetate. The reaction mixture is then concentrated to dryness by evaporation. The residue is chromatographed on silica gel (eluant:ethyl acetate/hexane/formic acid 49.5:49.5:1). 2-(6-Pyrazol-1-yl-5-trifluoromethyl-pyridine-2-carbonyl)-cyclohexane-1,3-dione is obtained in the form of a resinous product; 1H NMR (CDCl3): 15.78, b, OH, 8.30, d, 1H, 8.07, d, 1H, 7.69, d, 1H, 7.54, d, 1H, 6.44, m, 1H, 2.80, m, 2H, 2.48, m, 2H, 2.10, m, 2H.
16 mg (0.05 mmol) of 2-(6-chloro-5-trifluoromethyl-pyridine-2-carbonyl)-cyclohexane-1,3-dione and 9 mg (0.05 mmol) of p-methoxyphenyl-boronic acid are dissolved in 0.98 ml of dimethoxyethane/water/ethanol (7:3:2) and, in a microwave oven, heated at 140° C. for 400 seconds in the presence of a catalytic amount of bis(triphenyl)phosphine palladium dichloride and 49 mg (0.15 mmol) of caesium carbonate. When the reaction solution is cool, it is transferred to a deep-well plate. By supplying a stream of nitrogen, the volatile constituents of the reaction solution are removed by evaporation. 0.1 ml of trifluoroacetic acid and 0.4 ml of dimethylformamide are added to the residue and stirring is carried out for 10 minutes. The soluble component is purified by means of HPLC under reversed-phase conditions (eluant:gradient of water and acetonitrile). 2-[6-(4-Methoxy-phenyl)-5-trifluoromethyl-pyridine-2-carbonyl]-cyclohexane-1,3-dione is obtained in the form of a resin.
3 g (11.8 mmol) of chloro-5-trifluoromethyl-pyridine-2-carboxylic acid ethyl ester are dissolved in degassed dioxane, and 4.13 g (13.02 mmol) of tributylvinyltin are added. After the addition of 273 mg (0.236 mmol) of Pd(Ph3P)4, the reaction mixture is stirred for 20 hours at 95° C. The reaction mixture is concentrated and is chromatographed on silica gel (eluant:ethyl acetate/isohexane 1:5). 2 g of 5-trifluoromethyl-6-vinyl-pyridine-2-carboxylic acid ethyl ester are obtained. 1H NMR (CDCl3): 8.07 (d), J=8.3 Hz, 1H, 8.034 (d), J=8.3 Hz, 1H, 7.06-7.18 (m), Jab=16.6 Hz, Jac=10.5 Hz, 1Ha; 6.77 (dd), Jba=16.6 Hz, Jbc=2 Hz, 1Hb; 5.74 (dd), Jca=10.5 Hz, Jcb=2 Hz, 1Hc; 4.487 (q), 2H, 1.455 (t), 3H.
1.6 g (6.31 mmol) of chloro-5-trifluoromethyl-pyridine-2-carboxylic acid ethyl ester are dissolved in 32 ml of degassed dioxane, and 2.5 g (6.92 mmol) of 1-ethoxy-1-tributylvinyltin are added. After the addition of 146 mg (0.126 mmol) of Pd(Ph3P)4, the reaction mixture is stirred for 20 hours at 95° C. The reaction mixture is concentrated and is chromatographed on silica gel (eluant:ethyl acetate/isohexane 1:5). 0.9 g of 6-(1-ethoxy-vinyl)-5-trifluoromethyl-pyridine-2-carboxylic acid ethyl ester are obtained. 1H NMR (CDCl3): 8.148 (s), 2H, 4.732 (d), Jab=3 Hz, 1Ha; 4.509 (d), Jba=3 Hz, 1Hb; 4.497 (q), CH2O (ester); 2H, 3.952 (q), CH2O (ether); 2H 1.436 (t), CH3 (ester), 3H, 1.376 (t), CH3 (ether).
By that means it is possible, for example, also for the compounds of formula I listed in the following Table to be prepared, those compounds that are defined as an oil, resin, wax or amorphous solid at least having been characterised in pure form by means of 1H NMR (nuclear resonance spectroscopy) and/or MS (mass spectrometry).
In general, substituents R1 are bonded to the pyridyl ring by way of the free valence at the atom on the left-hand side of the substituent R1, as in the case, for example, of compound 1.001. In that compound, the substituent R1═OCH2OCH3 is bonded to the pyridyl ring by way of the free valence of the oxygen atom on the left-hand side of the substituent. In individual cases, the linking atom is, in addition, marked by means of an apostrophe, as in the case, for example, of compound no. 1.137.
In the case of cyclic substituents R1 that are bonded directly to the pyridyl ring, the ring atom of the cyclic substituent R1 linked to the pyridyl is given special emphasis by means of an apostrophe, as, for example, in
where the linkage site is located at the nitrogen atom denoted by ′N.
Monocotyledonous and dicotyledonous test plants are sown in standard soil in pots or seed trays. Immediately after sowing, the test compounds, in the form of an aqueous suspension (prepared from a wettable powder (Example F3, b) according to WO 97/34485) or in the form of an emulsion (prepared from an emulsifiable concentrate (Example F1, c) according to WO 97/34485), are applied by spraying in a concentration of 250 g/ha. The test plants are then grown in a greenhouse under optimum conditions. After a test duration of 4 weeks, the test is evaluated in accordance with a scale of eleven ratings (10=total damage, 0=no action). Ratings of from 10 to 7 (especially from 10 to 8) indicate very good to good herbicidal action.
Monocotyledonous and dicotyledonous test plants are cultivated in a greenhouse in standard soil in plastic pots and, at the 4- to 6-leaf stage, are sprayed with an aqueous suspension of the test compounds of formula I prepared from a 25% wettable powder (Example F3, b) according to WO 97/34485) or with an emulsion of the test compounds of formula I prepared from a 25% emulsifiable concentrate (Example F1, c) according to WO 97/34485), corresponding to concentrations of 125 and 250 g of active ingredient per hectare (500 litres of water per ha). The test plants are then grown on in the greenhouse under optimum conditions. After a test duration of about 18 days, the test is evaluated in accordance with a scale of eleven ratings (10=total damage, 0=no action). Ratings of from 10 to 7 (especially from 10 to 8) indicate very good to good herbicidal action. The compounds of formula I generally exhibit a strong herbicidal action in this test.
Monocotyledonous and dicotyledonous test plants are sown in sterilised standard soil in seed trays each having 96 cells. After 8 to 9 days' cultivation under controlled conditions in a climatic chamber (cultivation at 17/23° C.; 13 hours' light; 50-60% humidity; after application at 19/24° C.), the plants are treated with an aqueous spray solution of 1000 mg/l of the active ingredient used (rate of application: 500 g/l; incl. 10% DMSO as solvent). The plants are grown on in the climatic chamber until the test is evaluated after 9 or 13 days. The test is evaluated in accordance with a scale of eleven ratings (10=total damage, 0=no action). Ratings of from 10 to 7 (especially from 10 to 8) indicate very good to good herbicidal action. The compounds of formula I generally exhibit a strong herbicidal action in this test.
The post-emergence herbicidal action of compound no. 1.095 according to the invention was compared with compound A, which is described as compound no. 1.005 on page 15, Table 1, of EP-A-0 353 187:
The results in Table B4 show that, at an application rate of 125 g/ha, compound no. 1.095 according to the invention exerts a generally substantially better herbicidal action on the tested weeds than compound A from the prior art. The improved action can be seen especially clearly in the case of the weeds Ipomea, Amaranthus and Galium, where the action of compound A from the prior art is completely inadequate at the tested rates of application. Only in the case of Stellaria does compound A from the prior art exhibit slightly better action. In view of the structural similarity between the compounds, the enhanced action of the compounds according to the invention was not to be expected.
The post-emergence herbicidal action of compound no. 1.096 according to the invention was compared with compound B, which is described as compound no. 2.088 on page 83,
The results in Table B4 show that, at an application rate of 125 g/ha, compound no. 1.096 according to the invention exerts a substantially better herbicidal action on the tested weeds than compound B from the prior art. The improved action can be seen especially clearly in the case of the weeds Bromus and Sida, where compound B from the prior art has no action at all at the tested rates of application. In addition, the compound according to the invention not only exhibits better herbicidal action but also exhibits no phytotoxicity whatsoever with respect to the useful plants (in this case, wheat and maize). At an application rate of 125 g/ha, compound B from the prior art already shows significant damage (20% phytotoxicity) to wheat and maize, which is unacceptable from an agronomic standpoint. In view of the structural similarity between the compounds, the enhanced action and improvement in selectivity of the compounds according to the invention were not to be expected.
| Number | Date | Country | Kind |
|---|---|---|---|
| 02128/03 | Dec 2003 | CH | national |
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/EP04/14113 | 12/10/2004 | WO | 6/8/2006 |
