EP1556346A1 - 1-phenylpyrrolidine-2-one-3-carboxamides - Google Patents

1-phenylpyrrolidine-2-one-3-carboxamides

Info

Publication number
EP1556346A1
EP1556346A1 EP03758015A EP03758015A EP1556346A1 EP 1556346 A1 EP1556346 A1 EP 1556346A1 EP 03758015 A EP03758015 A EP 03758015A EP 03758015 A EP03758015 A EP 03758015A EP 1556346 A1 EP1556346 A1 EP 1556346A1
Authority
EP
European Patent Office
Prior art keywords
alkyl
phenylpyrrolidin
hydrogen
alkenyl
alkynyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP03758015A
Other languages
German (de)
English (en)
Inventor
Robert Reinhard
Gerhard Hamprecht
Michael Puhl
Werner Seitz
Liliana Parra Rapado
Annegret Scannell-Lansky
Klaus Grossmann
Helmut Schiffer
Matthias Witschel
Cyrill Zagar
Andreas Landes
Michael Rack
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
BASF SE
Original Assignee
BASF SE
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by BASF SE filed Critical BASF SE
Publication of EP1556346A1 publication Critical patent/EP1556346A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/24—Oxygen or sulfur atoms
    • C07D207/26—2-Pyrrolidones
    • C07D207/273—2-Pyrrolidones with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to other ring carbon atoms
    • C07D207/277—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/36—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom five-membered rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/24—Oxygen or sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond

Definitions

  • the present invention relates to l-phenylpyrrolidin-2-one-3-car-boxamides and their agriculturally useful salts, agents which contain such compounds and the use of l-phenylpyrrolidin-2-one-3-carboxamides, their salts or agents which these contain as herbicides.
  • WO 95/33719 describes 1-arylthiazolidinones, 1-aryloxazolidinones and 1-arylpyrrolidinones of the general formula:
  • A is an aromatic or heteroaromatic radical
  • n is 0 or 1
  • X is in particular S, 0 or CH 2
  • Y is in particular S, O, CH 2 or CH (CH 3 ) or a group NR ⁇
  • Z in particular NH or 0 means
  • R 1 is preferably selected from optionally substituted alkyl, alkenyl, alkynyl, optionally substituted cycloalkyl, optionally substituted phenyl, benzyl or hetaryl, acyl, alkoxycarbonylalkyl and silyl
  • R 2 and R 3 are in particular hydrogen and R b stands inter alia for hydrogen, formyl, optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl or for optionally substituted aryl.
  • WO 95/33718 describes 1-phenylpyrrolidinethiones with herbicidal activity which have a group 0-C (0) -NR 1 R 2 in the 3-position of the pyrrolidinethione ring, where R X R 2 is , for example, hydrogen, one optionally substituted hydrocarbon radical or hetaryl, or together with the nitrogen atom to which they are attached, form a heterocycle.
  • X is hydrogen or halogen
  • Y and Z are independently O or S
  • n is 0 or 1
  • R 1 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, alkoxy, phenyl, halophenyl, benzyl, halobenzyl, or Alkyl means that is substituted by alkoxy, alkylthio, phenyl, hydroxy or cyano
  • R 2 is hydrogen or alkyl
  • R 3 is alkyl or alkenyl
  • R 4 is selected from hydrogen, halogen, methyl, trifluoromethyl, 1, 1 , 2,2-tetrafluoroethyl, 1, 1,2,2-tetrafluoroethyloxy, difluoromethoxy, trifluoromethoxy, methylsulfanyl, methylsulfinyl, methylsulfonyl, methoxyiminomethyl, methoxyimino-1-ethyl
  • the herbicidal activity of the 1-arylpyrrolidinones described in the prior art is not always satisfactory. Their selectivity towards harmful plants also leaves something to be desired. In particular, such herbicides tend to disrupt the formation of leaf green even in crop plants, even at low application rates, which is fundamentally undesirable and can lead to reduced yields.
  • the present invention has for its object to provide new herbicidally active compounds with which undesired plants can be controlled better than with the known herbicides.
  • the new herbicides should advantageously have a high activity against harmful plants.
  • a high crop tolerance is desirable.
  • they should not adversely affect leaf green synthesis in crop plants.
  • R 1 , R 2 , R 3 , X, Y, A, n, R a , R b , R c , R d and R e have the following meaning:
  • R 1 is hydrogen, OH, Cl, Br, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 alkenyl, C 3 -C 6 alkynyl, C (0) R 4 or OC ( 0) R 4 ;
  • R 2 and R 3 independently of one another hydrogen, Ci-Cio-alkyl, C 3 -C ⁇ 0 - cycloalkyl, C 7 -C ⁇ 0 polycycloalkyl, C 3 -C 8 alkenyl, C 3 -C ⁇ 0 alkynyl, C 5 -C-cycloalkenyl, C 3 -C 8 -cycloalkyl-C 4 -C 4 -alkyl, phenyl or 3 to 7-membered heterocyclyl, where the latter 9 groups may be unsubstituted, partially or completely halogenated and / or 1, 2 or 3 Radicals selected from OH, CN, N0 2 , COOH, -CC 6 -alkyl, -C-C 6 -haloalkylene, C 1 -C 6 -alkoxy, Calk-C 4 -haloalkoxy, C 2 -C 6 -alkenyl, C-Cg-alkynyl
  • -C 4 -haloalkylthio optionally substituted phenyl, COOR 5 , NR 6 R ?, C (0) NR 8 S0 2 R 13 , C (0) NR 8 R 9 and 3 to 7-membered heterocyclyl and each heterocyclyl 1, 2 or 3 heteroatoms, selected from oxygen, nitrogen, sulfur, a group NR 10 and a group S0 2 , and optionally 1, 2 or 3 carbonyl groups and / or thiocarbonyl groups as ring members and / or a fused phenyl ring which may optionally have is substituted; or
  • R 2 and R 3 with the group N- (A) n to which they are attached form a saturated, 3 to 7-membered heterocycle which, in addition to the nitrogen atom, 1, 2 or a further 3 heteroatoms, selected from oxygen, nitrogen and sulfur and a group NR 10 and optionally 1, 2 or 3 carbonyl groups and / or thiocarbonyl groups as ring members;
  • R a , R b , R c , R d and R e independently of one another hydrogen, OH, CN, N0 2 , halogen, Ci-Cio-alkyl, C 3 -C 6 cycloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, Ci-Ce-haloalkyl, C 2 -C 6 haloalkenyl, -C-C 6 - alkoxy, C !
  • X, Y independently of one another oxygen or sulfur
  • R 4 , R 8 , R 9 independently of one another are hydrogen or -CC 4 alkyl
  • R 6 , R 7 independently of one another are hydrogen, C 1 -C 6 -alkyl, C 3 -C 6 -alkenyl, C 3 -C 6 -alkynyl, C (0) R 4 , COOR 5 or S (0) 2 R n ;
  • R 10 , R 12 independently of one another for hydrogen, -CC 6 alkyl, C 3 -C 6 alkenyl or C 3 -C 6 alkynyl;
  • R 13 is phenyl which is unsubstituted or carries a 1, 2, 3 or i substituent, the substituents being selected from halogen, nitro, cyano, OH, alkyl, alkoxy, haloalkyl, haloalkoxy, COOR 5 , NR 6 R 7 and C (0) NR 8 R 9 .
  • the present invention accordingly relates to 1-phenylpyrrolidin-2-one-3-carboxamides of the general formula I and their agriculturally useful salts.
  • the invention also relates to the use of compounds I and / or their salts as herbicides;
  • Crop protection agents which contain at least one 1-phenylpyrrolidine-2-one-3-carboxamide of the formula I and / or at least one agriculturally useful salt of I as effective substances; such as
  • a herbicidally effective amount of at least one 1-phenylpyrrolidin-2-one-3-carboxamide of the formula I or an agriculturally useful salt of I is allowed to act on plants, their habitats or on seeds.
  • the compounds of the formula I can have one or more centers of chirality and are then present as mixtures of enantiomers or diastereomers.
  • the invention relates both to the pure enantiomers or diastereomers and to their mixtures.
  • the invention also relates to tautomers of compounds of the formula I.
  • R 1 is hydrogen
  • the l-phenylpyrrolidin-2-one-3-carboxamides of the formula I according to the invention can be present in the form of their agriculturally useful salts.
  • the salts of those bases or cations which do not adversely affect the herbicidal activity of the compounds I come into consideration.
  • alkali metals preferably sodium and potassium
  • the alkaline earth metals preferably calcium, magnesium and barium
  • the transition metals preferably manganese, copper, zinc and iron, and ammonium salts, in which the ammonium ion if desired a 4-alkyl substituent to four C ⁇ -C, C ⁇ -C 4 -Hydroxylkylsubstituenten, C ⁇ -C -alkoxy-C ⁇ -C 4 th 4 -alkylsubstituen- and / or may bear a phenyl or benzyl substituent, preferably diisopropylammonium, tetramethylammonium, tetra- butylammonium, trimethylbenzylammonium, trimethyl-2-hydroxyethylammonium, bis (2-hydroxyethyl) methylammonium, tris (2-hydroxyethyl) ammonium, bis (2-hydroxyethyl)
  • the organic molecule parts mentioned in the definition of the substituents R 1 to R 12 or as residues on heterocyclic rings represent - like the meaning halogen - collective terms for individual lists of the individual group members.
  • Halogenated substituents preferably carry one to five identical or different halogen atoms. Halogen is fluorine, chlorine, bromine or iodine.
  • - C 1 -C 4 alkyl for: z.
  • - CI- ⁇ —alkyl for: C1-C4 — alkyl, as mentioned above, and z.
  • - Cx-Cio-alkyl for: Ci-C ⁇ -alkyl, as mentioned above, and z.
  • B n-heptyl, 2-heptyl, 2-methylhexyl, n-octyl, 1-methyl-heptyl, 2-ethylhexyl, n-nonyl, 2-nonyl, n-decyl, 2-decyl, 2-propylheptyl and the like;
  • C 1 -C 4 -haloalkyl for: a Cx-C 4 -alkyl radical, as mentioned above, which is partially or completely substituted by fluorine, chlorine, bromine and / or iodine, that is, for. B. chloromethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl,
  • Chlorodifluoromethyl 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 2-iodoethyl, 2,2-difluoroethyl, 2,2, 2-trifluoroethyl, 2-chloro-2-fluoroethyl, 2-chloro-2,2-difluoroethyl, 2,2-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl,
  • Ci C ⁇ — haloalkyl: —CC 4 -haloalkyl, as mentioned above, and for 5 — fluoropentyl, 5-chloropentyl, 5 — bromopentyl, 5 — iodopentyl, undecafluoropentyl, 6 — fluorhexyl, 6 — chlorohexyl, 6 — bromohexyl , 6 — iodohexyl or dodecafluorohexyl;
  • 40 -C 1 -C 2 fluoroalkyl for -C 2 alkyl which carries 1, 2, 3, 4 or 5 fluorine atoms, for example for difluoromethyl, trifluoromethyl, 2-fluoroethyl, 2, 2-difluoroethyl, 2, 2, 2-trifluoroethyl, 1, 1,2, 2-tetrafluoroethyl and pentafluoroethyl;
  • Ci — C 2 —fluoroalkoxy for C ! -C 2 alkoxy which carries 1, 2, 3, 4 or 5 fluorine atoms, for example for difluoromethoxy, trifluoromethoxy, 2-fluoroethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, 1, 1,2, 2 -Tetrafluoroethoxy and Pentafluoroethoxy;
  • Ci — C 4 alkoxy for: e.g. B. methoxy, ethoxy, n-propoxy,
  • Ci — C 6 alkoxy Ci — C 4 alkoxy, as mentioned above, and z.
  • C ⁇ -C 4 haloalkoxy of: a C ⁇ -C 4 alkoxy as mentioned above which is partially or fully substituted by fluorine, chlorine, bromine and / or iodine, eg 0CH 2 F, 0CHF 2, OCF 3, 2 0CH C1, 0CH (C1) 2 , 0C (C1) 3 , chlorofluoromethoxy, dichlorofluoromethoxy, chlorodifluoromethoxy, 2-fluoroethoxy,
  • Nonafluorobutoxy preferably for 0CHF 2 or OCHF 3 ;
  • C 1 -C 4 -alkoxy-C 6 -C 6 -alkyl for: C 1 -C 4 -alkoxy - as mentioned above - substituted C 1 -C 6 -alkyl, for example for CH 2 -OCH 3 , CH 2 -OC 2 H 5 , n-propoxymethyl, CH 2 -OCH (CH 3 ) 2 , n-butoxymethyl, (1-methylpropoxy) methyl, (2-methylpropoxy) methyl, CH 2 -OC (CH 3 ) 3 , 2- (methoxy) ethyl, 2- (ethoxy) ethyl, 2- (n-propoxy) ethyl, 2- (1-methylethoxy) ethyl, 2- (n-butoxy) ethyl, 2- (1-methylpropoxy) ethyl, 2- (2-methylpropoxy) ethyl, 2- (1, 1-dimethylethoxy) ethyl,
  • -C 6 -alkylthio for -C-C4-alkylthio, as mentioned above, and for example pentylthio, 1-ethylbutylthio, 2-methylbutylthio, 3-methylbutylthio, 2, 2-dimethylpropylthio, 1-ethylpropylthio, hexylthio, 1 —Dimethylpropylthio, 1, 2 — dimethylpropylthio, 1 — methylpentylthio, 2 — methylpentylthio, 3 — methylpentylthio, 4 — methylpentylthio, 1, 1 — dimethylbutylthio, 1,2 — dimethylbutylthio, 1, 3 — dimethylbutylthio, 2,2- dimethylbutylthio , 3-dimethylbutylthio, 3, 3-dimethylbutylthio, 1-ethylbutylthio, 2-ethyl
  • Ci — C 4 —haloalkylthio for: a Ci — C 4 -alkylthio radical, as mentioned above, which is partially or completely substituted by fluorine, chlorine, bromine and / or iodine, for example fluoromethylthio, difluoromethylthio, trifluoromethylthio, chlorodifluoromethylthio, bromodifluoromethylthio, 2-fluoroethylthio, 2-chloroethylthio, 2-bromoethylthio, 2-iodoethylthio, 2,2-difluoroethylthio, 2,2,2-trifluoroethylthio, 2,2,2-trichloroethylthio,
  • 2-chloro-2-fluoroethylthio 2-chloro-2, 2-difluoroethylthio, 2,2-dichloro-2-fluoroethylthio, pentafluoroethylthio, 2-fluoropropylthio, 3-fluoropropylthio, 2-chloropropylthio, 3-chloropropylthio, 2-bromopropylthio, 3-bromopropylthio, 2,2-difluoropropylthio, 2,3-difluoropropylthio,
  • Phenyl-C ⁇ -C 4 alkyl for: z.
  • C 2 -C 6 haloalkenyl for: C 2 -C 6 alkenyl as mentioned above, which is partially or completely substituted by fluorine, chlorine and / or bromine, for example 2-chlorovinyl, 2-chloroallyl, 3-chloroallyl, 2,3-dichloroallyl,
  • CC 6 alkynyl for: an aliphatic hydrocarbon radical containing a CC triple bond and having 2 to 6 and in particular 2 to 4 carbon atoms: z.
  • C 3 -C ⁇ o-alkynyl for: a triple bond-containing aliphatic hydrocarbon radical having 3 to 10 [&], preferably 3 to 6 and in particular 3 or 4 carbon atoms as mentioned above, which preferably does not have a C-
  • Atom of the triple bond is bound, for example for one of the radicals mentioned under C 2 -C 6 -alkynyl and for l-heptin-3-yl, l-heptin-4-yl, l-heptin-5-yl, l-heptin 6-yl, l-heptin-7-yl, 3-heptin-l-yl, 2-heptin-4-yl, 3-heptin-5-yl, 3-heptin-6-yl, 3-heptin-7- yl, l-0ctin-3-yl, l-0ctin-4-yl, l-0ctin-5-yl, l-0ctin-6-yl, l-octin-7-yl, l-0ctin-8-yl, 3-octin-l-yl, 2-octin-l-yl, 2-octin-4-yl, 3-octin-5-yl, 3-octin-6
  • C 3 -Cio cycloalkyl monocyclic hydrocarbon radical having 3 to 10 C atoms, in particular 3 to 8 C atoms and especially 3 to 6 C atoms, for example cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl;
  • C 7 -C 10 polycycloalkyl bicyclic, tricyclic or tetracyclic hydrocarbon radical having 7 to 10 carbon atoms, e.g. B. Bicyclo- [2.2.1] -hept-l-yl, bicyclo- [2.2. l] hept-2- yl, bicyclo- [2.2.1] hept-7-yl, bicyclo- [2.2.2] oct-1-yl, bicyclo- [2.2.2] oct-2-yl or adamantan-1-yl;
  • C 3 -C 8 cycloalkyl-C 4 -C 4 alkyl for C 1 -C 4 alkyl which carries a C 3 -C 8 cycloalkyl radical as defined above, for example for cyclopropylimethyl, 1-cyclopropyl-ethyl, 2- Cyclopropyl-ethyl, 1-cyclopropyl-prop-1-yl, 2-cyclopropyl-prop-l-yl, 3-cyclopropyl-prop-1-yl, 1-cyclopropyl-but-l-yl, 2-cyclopropyl- but-l-yl, 3-cyclopropyl-but-l-yl, 4-cyclopropyl-but-l-yl, 1-cyclopropyl-but-2-yl, 2-cyclopropyl-but-2-yl, 3- Cyclopropyl-but-2-yl, 3-Cyclopropyl-but-2-yl, 4-Cyclopropyl-but-2-yl,
  • optionally substituted phenyl an unsubstituted or a 1, 2, 3 or 4 substituent-bearing phenyl group, the substituents being selected from halogen, nitro, cyano, OH, alkyl, alkoxy, haloalkyl, haloalkoxy, COOR 5 , NR 6 R 7 , C (0) NR 8 R 9 ;
  • heterocyclic radical which has 3, 4, 5, 6 or 7 ring members, where 1, 2 or 3 of the member members "are heteroatoms selected from oxygen, nitrogen, sulfur, a group S0 2 and a group NR 10.
  • the heterocycle can optionally have 1, 2 or 3 carbonyl groups and / or thiocarbonyl groups as ring members.
  • the heterocycle can also have a fused, optionally substituted phenyl ring.
  • the heterocycle can be aromatic (heteroaryl) or partially or be completely saturated.
  • saturated heterocycles are:
  • unsaturated heterocycles are: dihydrofuran-2-yl, 1,2-oxazolin-3-yl, 1,2-oxazolin-5-yl, 1,3-oxazolin-2-yl;
  • aromatic heterocyclyl examples include the 5- and 6-membered aromatic heterocyclic radicals, e.g. Furyl such as 2-furyl and 3-furyl, thienyl such as 2-thienyl and 3-thienyl, pyrrolyl such as 2-pyrrolyl and 3-pyrrolyl, isoxazolyl such as 3-isoxazolyl, 4-isoxazolyl and 5-isoxazolyl, isothiazolyl such as 3- Isothiazolyl, 4-isothiazolyl and 5-isothiazolyl, pyrazolyl such as 3-pyrazolyl, 4-pyrazolyl and 5-pyrazolyl, oxazolyl such as 2-0xazolyl, 4-0xazolyl and 5-0xazolyl, thiazolyl such as 2-thiazolyl, 4-thiazolyl and 5-thiazolyl, imidazolyl such as 2-imidazolyl and 4-imidazolyl, oxadiazolyl such as 1,2,
  • n is preferably 0.
  • the saturated heterocycle is then selected, for example, from 1,3-oxazolidin-3-yl, 1.1 , 2-oxazolidin-2-yl, pyrrolidin-1-yl, pyrrolidin-2-one-l-yl, tetrahydropyrazol-1-yl, 2-methyltetrahydropyrazol-l-yl, piperidin-1-yl, piperidine-2 -on-l-yl, morpholin-4-yl, hexahydropyrimidin-1-yl, piperazine-l-yl, 4-methylpiperazin-l-yl, hexahydro-l, 3,5-triazin-l-yl, 3 , 5-Dimethyltriazin-l-yl, Hexahydroazepin-1-yl, Hexahydroaze-pin-2-one-l-yl
  • two adjacent radicals R a to R e together with the atoms to which they are attached form a 5-, 6- or 7-membered saturated or unsaturated ring which contains one or two hetero atoms selected from nitrogen, oxygen, Can contain sulfur and a group NR 10 as ring-forming atom (s) and / or can carry one, two, three or four radicals selected from halogen or -CC 4 alkyl
  • there are two adjacent radicals R a to R e for example R b and R c or R c and R d , together for a 3-, 4- or 5-membered, saturated or unsaturated carbon chain, in which one or two non-adjacent carbon atoms of the chain by heteroatoms selected from 0, N, a group NR 10 and S, can be replaced and in which the carbon atoms of the chain can carry one, two, three or four substituents which are selected from halogen or -CC alkyl.
  • two adjacent radicals R a to R e for a chain of the formula -0-CH 2 -0-, -0- (CH 2 ) 2 -0-, -0- (CH 2 ) 2 -, -0- (CH 2 ) 2 -, -0- ( CH 2 ) 3 -, - (CH 2 ) 3 -, - (CH 2 ) 4 - or- (CH 2 ) 5 -.
  • the variables R 1 , R 2 , R 3 , X, Y, A, n, R a , R b , R c , R d and R e preferably have the following Meanings, independently of one another and especially in combination:
  • R 1 is hydrogen, OH, CI, Br, -CC 6 alkyl or 0C (0) R 4 , particularly preferably hydrogen;
  • R 2 is C ⁇ -C 6 alkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 alkenyl, C 3 -C 6 alkynyl, C 5 -C 6 cycloalkenyl, C 3 -C 6 -cycloalkyl-C ⁇ -C 4 -alkyl or optionally substituted phenyl, where C ⁇ -C 6 -alkyl and C 3 -C 6 -cycloalkyl can be partially or completely halogenated and / or one or two, in particular a radical, selected under C ⁇ -C 6 -alkoxy, C ⁇ -C 4 -haloalkoxy, C ⁇ -C 6 -alkylthio, C--C-haloalkylthio, optionally substituted phenyl, COOR 5 , NR 6 R 7 , C (0) NR 8 R 9 can have.
  • R 2 particularly preferably represents C ⁇ -C 6 -alkyl, C 3 -C 8 -cycloalkyl, optionally substituted phenyl, phenylalkyl or C 3 -C 8 -cycloalkyl-C ⁇ -C 4 -alkyl;
  • R 3 is hydrogen or C ⁇ -C 6 alkyl
  • a if present oxygen, a group NR 12 with R 12 hydrogen or alkyl or a group S0 2 ;
  • R a , R, R c , R d , R e are hydrogen, halogen, CN, C ⁇ -C 4 -alkyl, C ⁇ -C 4 -haloalkyl, C ⁇ -C 4 -alkoxy, C 4 -C 4 -haloalkoxy, in particular Halogen, CN, C ⁇ -C-alkyl, C ⁇ -C 2 fluoroalkyl and C ⁇ -C 2 fluoroalkoxy and especially, fluorine, chlorine, bromine, CN, C ⁇ -C-alkyl, methoxy, CF 3 , CHF 2 , 0CF 3 and OCHF 2 .
  • l-phenylpyrrolidin-2-one-3-carboxamides according to the invention of the formula I are preferred, in which no more than 3 of the radicals R a , R b , R c , R d and R e and in particular 3 or 4 of the abovementioned residues of hydrogen are different.
  • Particular preference is given to 1-phenylpyrrolidin-2-one-3-carboxamides of the formula I in which at least R b and / or R d are different from hydrogen.
  • the other radicals R a -R e , at least one of the radicals R a and R e and in particular both radicals R a and R e are then particularly preferably hydrogen.
  • Preferred radicals R a , R b , R c , R d , R e are, in addition to hydrogen, the substituents halogen, CN, CC 4 -alkyl, C ⁇ -C 4 -haloalkyl, CC 4 -alkoxy, C ⁇ -C 4 -haloalkoxy, in particular Halogen, CN, C ⁇ -C 4 alkyl, C ⁇ -C 2 fluoroalkyl and C ⁇ -C 2 fluoroalkoxy and especially, fluorine, chlorine, bromine, CN, C ⁇ -C 4 alkyl, methoxy, CF 3 , CHF 2 , 0CF 3 and 0CHF 2 .
  • a particularly preferred group of compounds of the general formula I are those compounds in which R a and R e are hydrogen. Here is the rest
  • Another preferred group of compounds of the general formula I are those compounds in which R a and optionally one of the radicals R, R c or R e are different from hydrogen and the other radicals R a -R e are hydrogen.
  • R a and optionally one of the radicals R, R c or R e are different from hydrogen and the other radicals R a -R e are hydrogen.
  • R b , R c , R d and R 2 have the meanings given above, in particular the meanings mentioned as preferred.
  • Examples of such compounds are the compounds Ic.l to Ic.1717, in which the variables R b , R c , R d and R 2 together have the meanings given in one row of Table 1.
  • R b , R c , R d and R 2 together have the meanings given in one row of Table 1.
  • the l-phenylpyrrolidin-2-one-3-carboxamides according to the invention of the general formula I can be prepared, for example, by one of the processes A to G described below.
  • Compound I according to the invention can be prepared, for example, according to scheme 1 by reacting an activated form of a pyrrolidine-3-carboxylic acid of formula II with an amine III.
  • the carboxylic acid II is preferably first activated by carrying out the reaction in the presence of a coupling agent.
  • Suitable coupling agents are, for example, N, N'-carbonyldiimidazole or carbodiimides such as dicyclohexylcarbodiimide. These are generally used at least in an equimolar amount and up to a fourfold excess, based on the carboxylic acid II.
  • dialkyl ethers such as diethyl ether, methyl tert-butyl ether or cyclic ethers such as tetrahydrofuran or dioxane, carboxamides such as dimethylformamide, N-methyllactams such as N-methylpyrrolidone, nitriles such as acetonitrile, aro- Matic hydrocarbons such as toluene, or mixtures thereof into consideration.
  • the molar ratio of amine III to carboxylic acid II is generally at least 0.9: 1, preferably at least 1: 1. If appropriate, it can be advantageous to use the amine in a slight excess, for example in an up to 30% excess, based on the carboxylic acid II.
  • the reaction temperature is generally in the range from 0 ° C. to the boiling point of the solvent.
  • the carboxylic acid II can first be activated by converting it into its acid halide, preferably its acid chloride. Measures for this are known, e.g. B. from US 4,874,422.
  • Inorganic acid halides preferably acid chlorides such as thionyl chloride, phosphoryl chloride, phosphorus pentachloride or phosphorus trichloride and organic acid chlorides such as oxalyl chloride are suitable.
  • the acid halide formed can be isolated from II and then reacted with the amine III.
  • the acid chloride of II formed can also be reacted directly with the amine III without isolation.
  • the reactivity of the acid halide is increased by adding catalytic amounts of a carboxylic acid dialkylamide such as dimethylformamide.
  • the halogenating agent is usually used at least in an equimolar amount, based on the carboxylic acid II.
  • the acid halides thionyl chloride, phosphorus trichloride or phosphoryl chloride can simultaneously act as solvents.
  • Suitable solvents are also solvents which are inert under the reaction conditions, for example chlorinated hydrocarbons such as methylene chloride, 1,2-dichloroethane, aromatic hydrocarbons such as benzene or toluene, aliphatic and cycloaliphatic hydrocarbons such as hexane, petroleum ether, cyclohexane and mixtures thereof.
  • chlorinated hydrocarbons such as methylene chloride, 1,2-dichloroethane, aromatic hydrocarbons such as benzene or toluene, aliphatic and cycloaliphatic hydrocarbons such as hexane, petroleum ether, cyclohexane and mixtures thereof.
  • the reaction temperature is usually between room temperature and the boiling point of the solvent.
  • the excess halogenating agent is generally removed.
  • the resulting acid halide of II is reacted with the amine III.
  • the amine III is dissolved in the solvent which was also used to prepare the carboxylic
  • reaction is carried out in the presence of a
  • Auxiliary base preferably in an equimolar amount or up to a fourfold excess, based on carboxylic acid II is set by.
  • Suitable bases are, for example, amines such as 1,5-dizabicyclo [4.3.0] non-5-ene (DBN), 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU), pyridine, ⁇ - , ß-, ⁇ -lutidine or triethylamine.
  • carboxylic acid ester of II (carboxylic acid ester VI), in particular the C ⁇ -C 4 -alkyl ester of II and especially the methyl or ethyl ester of II is reacted with the amine III, if appropriate in the presence of a base.
  • suitable base solvent and reaction temperatures, reference is made to what has been said above. The preparation of the carboxylic acid ester VI is described below.
  • R a , R b , R c , R f Re have the meanings mentioned above and R stands for C ⁇ -C alkyl.
  • the reaction of the aniline compound IV with butyrolactone is usually carried out in the presence of an inorganic acid such as sulfuric acid, phosphoric acid or hydrochloric acid or in the presence of an organic acid such as acetic acid.
  • the reaction can be carried out without solvent or in the presence of a solvent. Suitable solvents are all solvents which are inert under the reaction conditions. However, the reaction is preferably carried out without solvent. In the case of a solvent-free procedure, butyrolactone is used in an excess based on the aniline IV.
  • the reaction temperatures are usually in the range from 20 ° C to the boiling point of the solvent.
  • the pyrrolidinone V obtained is generally reacted in the subsequent step without further purification, for example using a carbonic acid ester (R0) 2C0 or a synthetic equivalent such as chloroformic acid ester.
  • the pyrrolidinone V is generally first converted into the corresponding enolate by treatment with a suitable base.
  • suitable bases include, in particular, organolithium compounds such as n-butyllithium, tert-butyllithium and phenyllithium, lithium amides such as lithium diisopropylamide and alkali metal hydrides such as sodium hydride.
  • the reaction is carried out in an organic solvent.
  • Suitable solvents are inert solvents such as aliphatic and cycloaliphatic hydrocarbons such as hexane, petroleum ether, cyclohexane, ether z.
  • dialkyl ethers such as diethyl ether, methyl tert-butyl ether or cyclic ethers such as tetrahydrofuran or
  • Dioxane and mixtures thereof are Dioxane and mixtures thereof.
  • the deprotonation of the compound V is carried out at low temperatures up to about room temperature, preferably about 0 ° C.
  • the base is used in at least an equimolar amount, preferably in a 1.1 to 4-fold molar excess, based on the compound V.
  • the subsequent introduction of the alkoxycarbonyl group succeeds, for example, with a carbonic acid diester such as dimethyl carbonate or diethyl carbonate.
  • a carbonic acid diester such as dimethyl carbonate or diethyl carbonate.
  • the carbonic acid diester and the enolate of compound V are used in an equimolar amount.
  • one of the two reactants can be used in a slight excess.
  • the temperature required for the reaction is generally in the range from 0 ° C. to the boiling point of the solvent.
  • the carboxylic acid ester VI is then hydrolyzed to carboxylic acid II by known processes (see, for example, Organikum, 17th edition, VEB Deutscher Verlag dermaschineen, 1988, p. 415).
  • the hydrolysis can be carried out both in an acidic medium using strong mineral acids such as concentrated hydrochloric acid or sulfuric acid or organic acids such as glacial acetic acid or mixtures thereof in the presence of water, and in an alkaline medium using bases such as alkali hydroxide, for example sodium hydroxide or potassium hydroxide, if appropriate in the presence of water respectively.
  • strong mineral acids such as concentrated hydrochloric acid or sulfuric acid or organic acids such as glacial acetic acid or mixtures thereof in the presence of water
  • bases such as alkali hydroxide, for example sodium hydroxide or potassium hydroxide, if appropriate in the presence of water respectively.
  • ethers As solvents for both the acidic and for the basic hydrolysis of esters, for example ethers come.
  • dialkyl ethers such as diethyl ether, methyl tert-butyl ether or cyclic ethers such as tetrahydrofuran or dioxane, alcohols, water and mixtures of these solvents.
  • the reaction temperature is usually between room temperature and the boiling point of the solvent.
  • the compounds II can also be prepared by aminoethylation of malonic diesters VII, in which R 1 has the abovementioned meaning and R is C ⁇ -C-alkyl, with phenylaziridines VII and subsequent hydrolysis.
  • the synthesis is shown in Scheme 3 and succeeds based on known processes, such as those in, for example, Archives of Pharmacy (Weinheim) 302 (4), 253 (1969), Justus Liebigs Ann. Chem. (1968), 716, 121-126 or in Angew. Chem. 74, 694 (1962).
  • the reaction is usually carried out in the presence of LiH / LiI in a solvent.
  • suitable solvents include aromatic solvents such as benzene, toluene or xylene.
  • Aziridine VII and malonic acid diester are frequently used in approximately equimolar amounts. It can be advantageous to use malonic diester VIII in excess, preferably in an up to 30% excess, based on aziridine VII.
  • the ester via obtained is then converted into the corresponding carboxylic acids II by known processes by hydrolysis in an acidic or alkaline medium. With regard to ester hydrolysis, reference is made to what has been said above.
  • R a , R b , R, R d , R d , R ⁇ , x, Y, A, n, R 1 , R 2 and R 3 have the meanings mentioned above.
  • Z represents halogen, preferably fluorine, chlorine or bromine, or B (0H) 2 , B (OR ') 2 or Sn (R') 3 .
  • R ' represents aryl such as phenyl or C ⁇ -C ⁇ o-alkyl.
  • the reaction is preferably carried out in a solvent, in particular a polar, aprotic solvent such as dimethylformamide, dimethyl sulfoxide, N-methylpyrrolidone, dimethylacetamide, an ether such as diethyl ether, tetrahydrofuran or dioxane and mixtures of these solvents.
  • a solvent in particular a polar, aprotic solvent such as dimethylformamide, dimethyl sulfoxide, N-methylpyrrolidone, dimethylacetamide, an ether such as diethyl ether, tetrahydrofuran or dioxane and mixtures of these solvents.
  • the reaction will be carried out at temperatures above room temperature, preferably in the range from 50 to 200.degree.
  • the compounds of the general formulas X and XI are preferably used in approximately equimolar amounts. It is of course also possible to use one component in excess, the excess preferably being not more than 50 mol%, in particular not more than
  • a pyrrolidinone X preferably in the presence of catalytically active amounts of a palladium, copper or nickel compound - fertilizer, optionally in the presence of a base in an organic solvent or a mixture of a solvent with water at ambient temperature or elevated temperatures.
  • palladium catalysts are also palladium-phophane complexes such as tetrakistriphenylphosphine palladium, bistriphenylphosphine palladium (II chloride, bis (1,2-diphenylphosphanoethane) palladium (II) chloride, bis (l , 3-diphenylphosphanopropane) palladium (II) chloride, bis (1, 4-diphenylphosphanobutane) palladium (II) chloride and bis (diphenylphosphano) ferrocenylpalladium (II) chloride are also suitable.
  • palladium-phophane complexes such as tetrakistriphenylphosphine palladium, bistriphenylphosphine palladium (II chloride, bis (1,2-diphenylphosphanoethane) palladium (II) chloride, bis (l , 3-diphenylphosphan
  • Suitable phosphine ligands are, for example, unsubstituted or in the ortho, meta or para position substituted with halogen, alkyl and / or SO 3 H arylphosphines such as triphenylphosphine, 1, 2-bis (diphenylphosphano) ethane, 1, 3-bis (diphenylphosphano) propane, 1,4-bis (diphenylphosphano) butane, bis (diphenylphosphano) ferrocene, hetarylphosphines such as trisfurylphosphine or trispyridylphosphine.
  • arylphosphines such as triphenylphosphine, 1, 2-bis (diphenylphosphano) ethane, 1, 3-bis (diphenylphosphano) propane, 1,4-bis (diphenylphosphano) butane, bis (diphenylphosphano) fer
  • kel (II) chloride [1,3-bis (diphenylphosphano) propane] nik- kel (II) chloride, [1,4-bis (diphenylphosphano) butane] nik- kel (II) chloride and [bis (diphenylphosphano) ferrocene] nickel (II) chloride are suitable.
  • Cupfer (I) compounds such as CuCl, CuBr and the like are particularly suitable as copper compounds.
  • the catalyst is usually used in a substoichiometric amount, preferably from 0.001-0.8 equivalents and particularly preferably from 0.01 to 0.5 equivalents, based on the pyrrolidinone XI used.
  • Suitable bases are, for example, alkali metal hydrides such as sodium hydride and alcoholates such as sodium methoxide and sodium ethanol, lithium amides such as lithium diisopropylamide and organolithium compounds such as butyllithium and phenyllithium.
  • the molar ratio of compound XI to compound X is preferably in the range from 0.95: 1 to 1: 1.5.
  • alkali metal and alkaline earth metal hydroxides, alkali metal (hydrogen) carbonates and phosphates such as NaOH, NaHC0 3 , NaC0 3 , KHC0 3 , K 2 C0 3 , Ba (OH) 2 , K 3 P0, alkali, Alkaline earth metal, thallium and transition metal alcoholates such as Na ethanolate, thallium ethanolate are suitable.
  • Alkali metal fluorides such as potassium fluoride, cesium fluoride, ammonium fluoride and tetrabutylammonium fluoride are also suitable as bases.
  • the base is usually used in an approximately stoichiometric amount or in up to 10-fold excess, based on compound II.
  • Organic solvents such as DMF, dimethyl acetamide, toluene, tetrahydrofuran (THF), dioxane and dimethoxyethane are suitable as solvents.
  • the aforementioned solvents can also be used in a mixture with water, e.g. in a ratio of approximately 5: 1 to 1: 5, preferably in a ratio of approximately 2: 1 to 1: 2 and in particular approximately 1: 1.
  • the reaction temperature is usually above the melting temperature and can be up to the boiling point of the solvent. It is preferably in the range between 50 and 150 ° C.
  • the pyrrolidino compounds X can be prepared by conventional methods, e.g. B. can be analogous to the procedure described in method A.
  • R 1 , R a , R b , R, R d , R d , R ⁇ , x, Y, A, n, R 1 , R 2 and R 3 have the meanings mentioned above.
  • L stands for a nucleophilically displaceable leaving group such as halogen, e.g. B. chlorine, bromine, iodine or for imidazolyl, carboxylate such as acetate, aryl or alkyl sulfonate, e.g. B. mesylate or tri-flat.
  • the reaction is usually carried out in the presence of a base.
  • Suitable bases include alkali or alkaline earth metal hydroxides, metal hydrides such as alkali metal hydrides, e.g. B. sodium hydride, tertiary alkylamines such as triethyamin, aromatic amines such as pyridine, ⁇ -, ß-, ⁇ -lutidine, lithium diisopropylamide.
  • metal hydrides such as alkali metal hydrides, e.g. B. sodium hydride
  • tertiary alkylamines such as triethyamin
  • aromatic amines such as pyridine, ⁇ -, ß-, ⁇ -lutidine, lithium diisopropylamide.
  • chlorinated hydrocarbons such as methylene chloride or 1,2-dichloroethane
  • aromatic hydrocarbons such as toluene, xylene or chlorobenzene
  • ethers such as diethyl ether, methyl tert-butyl ether, tetrahydrofuran, dioxane
  • polar aprotic solvents such as acetonitrile, dimethylformamide or dimethyl sulfoxide into consideration.
  • reaction temperature is in the range from 0 ° C. to the boiling point of the reaction mixture.
  • the variables R a , R b , R c , R d , R, R ⁇ , x, y, A, n, R 1 , R 2 and R 3 have the meanings mentioned above.
  • suitable sulfurizing agents are phosphorus (V) sulfides, organotin sulfides and organophosphorus sulfides (see also J. March, Advanced Organic Synthesis, 2nd Edition, Wiley Interscience 1985, p. 794 and the literature cited therein).
  • sulfurizing agents are phosphorus (V) sulfide and 2,4-bis (4-methoxyphenyl) -1,3,4,4-dithiadiphosphethane-2,4-dithione ("Lawesson's reagent").
  • Methods for sulfurization are described, for example, in WO 95/33718. The reaction can be carried out in a solvent or in bulk.
  • Suitable solvents are all solvents which are inert under the reaction conditions, for example aromatic hydrocarbons such as benzene, to- toluene, xylene, chlorobenzene, basic solvents such as pyridine, ethers such as diethyl ether, 1,2-dimethoxyethane or tetrahydrofuran etc.
  • aromatic hydrocarbons such as benzene, to- toluene, xylene, chlorobenzene
  • basic solvents such as pyridine
  • ethers such as diethyl ether, 1,2-dimethoxyethane or tetrahydrofuran etc.
  • the temperatures required for the reaction are generally above room temperature and are in particular in the range from 50 ° C. to the boiling point of the reaction mixture.
  • the cyclization takes place in the presence of a base. All bases mentioned under C) are suitable as the base.
  • the reaction takes place in an inert solvent.
  • the main solvents used are chlorinated hydrocarbons such as methylene chloride or 1,2-dichloroethane, aromatic hydrocarbons such as toluene, xylene or chlorobenzene, ethers such as diethyl ether, methyl tert-butyl ether, tetrahydrofuran, dioxane, polar aprotic solvents such as acetonitrile, Dimethyl formamide or dimethyl sulfoxide into consideration.
  • the starting compound XII and the difunctional compound L-CH 2 -CH 2 -L ' are advantageously used in an approximately equimolar amount; however, in order to optimize sales, it can be advantageous to use one of the two components in excess.
  • the reaction is usually carried out at one Temperature between room temperature and the boiling point of the reaction mixture.
  • the starting compounds XII can be prepared in two steps based on the method described in Synlett 12, 1209 (1969).
  • an isocyanate XIII is reacted with Meldrum's acid (2,2-dimethyl-1,3-dioxane-4,6-dione).
  • the product obtained is then reacted with a suitable amine III in the second step.
  • the variables R a , R b , R c , R d , R d , R e , X, Y, A, n, R 1 , R 2 and R 3 have the meanings mentioned above.
  • the compounds I according to the invention can be prepared, for example, by condensation of anilines IV with tetrahydro-2-furanones XIV according to the synthesis route shown in Scheme 11.
  • Analogous implementations are known, e.g. B. from Tetrahedron Letters, 31 (21), 1990, p.2991 and can be applied to the preparation of the compounds of the invention.
  • the variables R a , R, R, Rd, Rd, Re, x, Y, A, n, R 1 , R 2 and R 3 have the meanings mentioned above.
  • the anilines IV are usually reacted in a carboxylic acid such as acetic acid at temperatures in the range from 0 ° C. to 100 ° C.
  • the starting materials are used in equimolar amounts or one of the two components is used in excess.
  • the compounds I according to the invention can be prepared, for example, by condensation of anilines IV with carboxylic acid derivatives XV according to the synthesis route shown in Scheme 12.
  • the base is usually used in an up to six-fold excess, based on the carboxylic acid derivative XV.
  • the reaction is carried out in a solvent.
  • a solvent such as a solvent such.
  • dialkyl ethers such as diethyl ether, methyl tert-butyl ether or cyclic ethers such as tetrahydrofuran or dioxane, carboxamides such as dimethylformamide, N-methyllactarne such as N-methylpyrrolidone, nitriles such as acetonitrile, aromatic hydrocarbons such as toluene, aromatic amines such as pyridine or mixtures thereof into consideration.
  • the reaction temperature is in a range from 0 ° C to the boiling point of the solvent.
  • the variables R a , R b , R c , R d , Rd, Re,, y and R 1 have the meanings mentioned above.
  • R 3 ' has the meanings given for R 3 and different from hydrogen.
  • the salt is preferably an isocyanate or isothiocyanate, for example sodium or potassium iso (thio) cyanate.
  • Suitable bases include alkali metal hydrides such as sodium or potassium hydride, organolithium compounds such as lithium diisopropylamide.
  • the reaction is carried out in a solvent.
  • suitable solvents agents include ethers such as diethyl ether, methyl tert-butyl ether, tetrahydrofuran, 1,4-dioxane, anisole, glycol ethers such as dimethyl glycol ether, hydrocarbons such as hexane, petroleum ether or mixtures thereof.
  • the compounds I and their agriculturally useful salts are suitable - both as isomer mixtures and in the form of the pure isomers - as herbicides.
  • the herbicidal compositions containing I control vegetation very well on non-cultivated areas. In crops such as wheat, rice, maize, soybeans and cotton, they act against weeds and grass weeds without significantly damaging the crop plants. This effect occurs especially at low application rates.
  • the compounds I or herbicidal compositions comprising them can also be used in a further number of crop plants for eliminating unwanted plants.
  • the following crops are considered, for example:
  • the compounds I can also be used in crops which are tolerant to the action of herbicides by breeding, including genetic engineering methods.
  • the compounds I or the herbicidal compositions comprising them can be sprayed or atomized, for example in the form of directly sprayable aqueous solutions, powders, suspensions, and also high-strength aqueous, oily or other suspensions or dispersions, emulsions, oil dispersions, pastes, dusts, sprays or granules , Dusting, scattering, pouring or treating the seed or mixing with the seed.
  • the application forms depend on the purposes; in any case, they should ensure the finest possible distribution of the active compounds according to the invention.
  • the herbicidal compositions comprise a herbicidally effective amount of at least one active compound of the formula I and auxiliaries customary for the formulation of crop protection agents.
  • inert auxiliaries mineral oil fractions of medium to high boiling point such as kerosene and diesel oil, furthermore coal tarols as well as oils of vegetable or animal origin, aliphatic, cyclic and aromatic hydrocarbons, e.g. Paraffins, tetrahydronaphthalene, alkylated naphthalenes and their derivatives, alkylated benzenes and their derivatives, alcohols such as methanol, ethanol, propanol, butanol and cyclohexanol, ketones such as cyclohexanone, strongly polar solvents, e.g. Amines such as N-methylpyrrolidone and water.
  • mineral oil fractions of medium to high boiling point such as kerosene and diesel oil, furthermore coal tarols as well as oils of vegetable or animal origin
  • aliphatic, cyclic and aromatic hydrocarbons e.g. Paraffins, tetrahydronaphthalene, alky
  • Aqueous use forms can be prepared from emulsion concentrates, suspensions, pastes, wettable powders or water-dispersible granules by adding water.
  • emulsions, pastes or oil dispersions the l-phenylpyrrolidin-2-one-carboxamides I as such or dissolved in an oil or solvent can be homogenized in water by means of wetting agents, adhesives, dispersants or emulsifiers.
  • concentrates consisting of an active substance, wetting agent, tackifier, dispersant or emulsifier and possibly solvent or oil, which are suitable for dilution with water.
  • the surface-active substances are the alkali, alkaline earth and ammonium salts of aromatic sulfonic acids, for example lignin, phenol, naphthalene and dibutylnaphthalenesulfonic acid, and of fatty acids, alkyl and alkylarylsulfonates, alkyl, lauryl ether and fatty alcohol sulfates, and salts of sulfated hexa- , Hepta- and octadecanols and fatty alcohol glycol ether, condensation products of sulfonated naphthalene and its derivatives with formaldehyde, condensation products of naphthalene or naphthalenesulfonic acids with phenol and formaldehyde, polyoxyethylene octylphenol ether, ethoxylated isooctyl, octyl or Nonylphenol, alkylphenyl, tributylphenyl polyg
  • Powders, materials for broadcasting and dusts can be prepared by mixing or grinding the active substances together with a solid carrier.
  • Granules e.g. Coated, impregnated and homogeneous granules can be produced by binding the active ingredients to solid carriers.
  • Solid carriers are mineral soils such as silica, silica gels, silicates, talc, kaolin, limestone, lime, chalk, bolus, loess, clay, dolomite, diatomaceous earth, calcium and magnesium sulfate, magnesium oxide, ground plastics, fertilizers such as ammonium sulfate, ammonium phosphate, Ammonium nitrate, ureas and vegetable products such as cereal flour, tree bark, wood and nutshell flour, cellulose powder or other solid carriers.
  • the concentrations of the active ingredients I in the ready-to-use preparations can be varied over a wide range.
  • the formulations generally contain about 0.001 to 98% by weight, preferably 0.01 to 95% by weight, of at least one active ingredient I.
  • the active ingredients are in a purity of 90% to 100%, preferably 95% to 100% (according to the NMR spectrum).
  • the compounds I according to the invention can be formulated, for example, as follows:
  • the active ingredients I or the herbicidal compositions can be applied pre- or post-emergence. There is also the possibility of applying the herbicidal compositions or active ingredients by spreading seeds of a crop plant pretreated with the herbicidal compositions or active ingredients. If the active ingredients are less compatible with certain crop plants, application techniques can be used in which the herbicidal compositions are sprayed with the aid of sprayers in such a way that the leaves of the sensitive crop plants are not struck wherever possible, while the active ingredients grow on the leaves below them unwanted plants or the uncovered floor area (post-directed, lay-by).
  • the application rates of active ingredient I are 0.001 to 3.0, preferably 0.01 to 1.0 kg / ha of active substance (a.S.) depending on the control target, the season, the target plants and the growth stage.
  • the compounds I according to the invention can be mixed with numerous representatives of other herbicidal or growth-regulating active compound groups and applied together.
  • Plastic pots with loamy sand with about 3.0% humus served as the culture vessels.
  • the seeds of the test plants were sown separately according to species.
  • the active ingredients suspended or emulsified in water were applied directly after sowing by means of finely distributing nozzles.
  • the vessels were lightly sprinkled to promote germination and growth, and then covered with clear plastic covers until the plants had grown. This cover causes the test plants to germinate evenly, unless this was affected by the active ingredients.
  • test plants were first grown to a height of 3 to 15 cm, depending on the growth habit, and then treated with the active ingredients suspended or emulsified in water.
  • the test plants were either sown directly and grown in the same containers or they were first grown separately as seedlings and transplanted into the test containers a few days before the treatment.
  • the application rate for the pre- and post-emergence treatment was 3.0 kg a. S./ha.
  • the plants were kept at 10-25 ° C and 20-35 ° C depending on the species.
  • the trial period lasted 2 to 4 weeks. During this time, the plants were cared for and their response to each treatment evaluated.
  • Example 3 shows a very good herbicidal action against AVEFA and SINAL when used after emergence.
  • Example 20 18 shows a very good herbicidal action against ABUTH, SETIT and SINAL when used pre-emergence.
  • Example 26 shows a very good herbicidal action against AVEFA and SINAL when used after emergence.
  • Example 26 shows a very good herbicidal action against ABUTH, LOLMU and SINAL when used pre-emergence.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Agronomy & Crop Science (AREA)
  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Dentistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Environmental Sciences (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pyrrole Compounds (AREA)

Abstract

L'invention concerne des 1-phénylpyrrolidine-2-one-3-carboxamides de formule générale (I), dans laquelle les variables R<1>, R<2>, R<3>, X, Y, A, n, R<a>, R<b>, R<c>, R<d> et R<e> ont les significations mentionnées dans la revendication 1, ainsi que leurs sels utilisables dans le domaine agricole. L'invention concerne en outre, l'utilisation comme herbicides, de composés I et/ou de leurs sels ; des agents phytosanitaires contenant comme principe actif, au moins un 1-phénylpyrrodiline-2-one-3-carboxamide de formule (I) et/ou au moins un sel utilisable dans le domaine agricole. L'invention concerne également un procédé permettant de lutter contre la croissance indésirable de plantes, selon lequel on laisse agir une quantité à effet herbicide d'au moins un 1-phénylpyrrolidine-2-one-3-carboxamide de formule (I) ou d'un sel utilisable dans le domaine agricole de I, sur des plantes, leur habitat ou sur des semences.
EP03758015A 2002-10-18 2003-10-17 1-phenylpyrrolidine-2-one-3-carboxamides Withdrawn EP1556346A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE10248700 2002-10-18
DE10248700 2002-10-18
PCT/EP2003/011557 WO2004037787A1 (fr) 2002-10-18 2003-10-17 1-phenylpyrrolidine-2-one-3-carboxamides

Publications (1)

Publication Number Publication Date
EP1556346A1 true EP1556346A1 (fr) 2005-07-27

Family

ID=32114807

Family Applications (1)

Application Number Title Priority Date Filing Date
EP03758015A Withdrawn EP1556346A1 (fr) 2002-10-18 2003-10-17 1-phenylpyrrolidine-2-one-3-carboxamides

Country Status (6)

Country Link
US (1) US7355053B2 (fr)
EP (1) EP1556346A1 (fr)
JP (1) JP4398866B2 (fr)
AU (1) AU2003274037A1 (fr)
CA (1) CA2502478A1 (fr)
WO (1) WO2004037787A1 (fr)

Families Citing this family (62)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AR064564A1 (es) * 2007-01-03 2009-04-08 Bayer Cropscience Ag Derivados de n-alquinilcarboxamida, un procedimiento para su preparacion, una composicion fungicida que los comprende y un metodo para combatir hongos fitopatogenos que los emplea.
US8138191B2 (en) 2007-01-11 2012-03-20 Critical Outcome Technologies Inc. Inhibitor compounds and cancer treatment methods
WO2008083491A1 (fr) 2007-01-11 2008-07-17 Critical Outcome Technologies Inc. Composés et méthode de traitement un cancer
EP2025669A1 (fr) * 2007-08-14 2009-02-18 Bayer Schering Pharma Aktiengesellschaft N-acyltryptophanols à substitution alpha-alkyle
US8097712B2 (en) 2007-11-07 2012-01-17 Beelogics Inc. Compositions for conferring tolerance to viral disease in social insects, and the use thereof
WO2009079797A1 (fr) 2007-12-26 2009-07-02 Critical Outcome Technologies, Inc. Composés et procédé pour le traitement du cancer
US8962584B2 (en) 2009-10-14 2015-02-24 Yissum Research Development Company Of The Hebrew University Of Jerusalem, Ltd. Compositions for controlling Varroa mites in bees
HUE033056T2 (hu) 2010-03-08 2017-11-28 Monsanto Technology Llc Polinukleotid molekulák génszabályozáshoz növényekben
CA2999435A1 (fr) 2010-04-01 2011-10-06 Critical Outcome Technologies Inc. Composes et methodes pour le traitement du vih
DE102010048374A1 (de) * 2010-10-13 2012-04-19 Merck Patent Gmbh Pyrrolidinone als MetAP-2 Inhibitoren
WO2013040033A1 (fr) 2011-09-13 2013-03-21 Monsanto Technology Llc Procédés et compositions de lutte contre les mauvaises herbes
CN103958539B (zh) 2011-09-13 2019-12-17 孟山都技术公司 用于杂草控制的方法和组合物
UA116088C2 (uk) 2011-09-13 2018-02-12 Монсанто Текнолоджи Ллс Спосіб та композиція для боротьби з бур'янами (варіанти)
US10760086B2 (en) 2011-09-13 2020-09-01 Monsanto Technology Llc Methods and compositions for weed control
CA2848689A1 (fr) 2011-09-13 2013-03-21 Monsanto Technology Llc Procedes et compositions de lutte contre les mauvaises herbes
MX343071B (es) 2011-09-13 2016-10-21 Monsanto Technology Llc Metodos y composiciones para el control de malezas.
US10806146B2 (en) 2011-09-13 2020-10-20 Monsanto Technology Llc Methods and compositions for weed control
ES2645927T3 (es) 2011-09-13 2017-12-11 Monsanto Technology Llc Procedimientos y composiciones para el control de malezas
US10829828B2 (en) 2011-09-13 2020-11-10 Monsanto Technology Llc Methods and compositions for weed control
EP2756085B1 (fr) 2011-09-13 2019-03-20 Monsanto Technology LLC Procédés et compositions de lutte contre les mauvaises herbes
DE102012006884A1 (de) 2012-04-04 2013-10-10 Merck Patent Gmbh Cyclische Amide als MetAP-2 Inhibitoren
UY34822A (es) 2012-05-24 2013-12-31 Seeds Ltd Ab Composiciones y métodos para silenciar la expresión genética
CA2885692C (fr) * 2012-09-25 2018-05-22 Bayer Cropscience Ag 3-phenylisoxazolin-5-carboxamides a substitution 5-oxy et 3-phenylisoxazolin-5-thioamides a substitution 5-oxy presentant une action herbicide et fongicide
EP2941488B1 (fr) 2013-01-01 2023-03-22 Monsanto Technology LLC Procédés d'introduction d'arnds dans des graines de plante pour moduler l'expression des gènes
US10683505B2 (en) 2013-01-01 2020-06-16 Monsanto Technology Llc Methods of introducing dsRNA to plant seeds for modulating gene expression
CN105263329B (zh) 2013-03-13 2020-09-18 孟山都技术公司 用于杂草控制的方法和组合物
US10609930B2 (en) 2013-03-13 2020-04-07 Monsanto Technology Llc Methods and compositions for weed control
US10568328B2 (en) 2013-03-15 2020-02-25 Monsanto Technology Llc Methods and compositions for weed control
BR112015031155A2 (pt) 2013-06-20 2017-07-25 Bayer Cropscience Ag derivados de sulfureto de arila e derivados de aril sulfóxido como acaricidas e inseticidas
EP3608412A3 (fr) 2013-07-19 2020-04-08 Monsanto Technology LLC Compositions et méthodes de lutte contre leptinotarsa
US9850496B2 (en) 2013-07-19 2017-12-26 Monsanto Technology Llc Compositions and methods for controlling Leptinotarsa
US10213124B2 (en) 2013-09-25 2019-02-26 Zoll Medical Corporation Electrocardiogram package
CA2929533C (fr) 2013-11-04 2023-06-06 Monsanto Technology Llc Compositions et procedes de lutte contre les infestations de parasites de type arthropode et d'organismes nuisibles
US11589583B2 (en) 2013-12-03 2023-02-28 Fmc Corporation Pyrrolidinones herbicides
SI3077374T1 (sl) * 2013-12-03 2020-07-31 Fmc Corporation Pirolidinoni kot herbicidi
UA119253C2 (uk) 2013-12-10 2019-05-27 Біолоджикс, Інк. Спосіб боротьби із вірусом у кліща varroa та у бджіл
CN105979770B (zh) 2014-01-15 2019-07-05 孟山都技术公司 用于使用epsps多核苷酸的杂草控制的方法和组合物
US11091770B2 (en) 2014-04-01 2021-08-17 Monsanto Technology Llc Compositions and methods for controlling insect pests
WO2015200223A1 (fr) 2014-06-23 2015-12-30 Monsanto Technology Llc Compositions et méthodes de régulation de l'expression génétique par interférence par arn
US11807857B2 (en) 2014-06-25 2023-11-07 Monsanto Technology Llc Methods and compositions for delivering nucleic acids to plant cells and regulating gene expression
AU2015284280C1 (en) 2014-07-02 2020-02-13 Fmc Corporation Piperidinone herbicides
RU2754955C2 (ru) 2014-07-29 2021-09-08 Монсанто Текнолоджи Ллс Композиции и способы борьбы с насекомыми-вредителями
BR112017009701B1 (pt) 2014-12-08 2021-09-08 Fmc Corporation Composto e métodos de preparação de compostos
MX2017009521A (es) 2015-01-22 2018-11-09 Monsanto Technology Llc Composiciones y métodos para controlar leptinotarsa.
BR112017017945B1 (pt) 2015-04-10 2021-06-08 Fmc Corporation composto, composições herbicidas, mistura herbicida e método de controle do crescimento de vegetação indesejada
WO2016176082A1 (fr) 2015-04-27 2016-11-03 E I Du Pont De Nemours And Company Butyrolactones utilisées comme herbicides
CN107592862B (zh) * 2015-05-12 2021-06-15 Fmc公司 作为除草剂的芳基取代的双环化合物
US10906873B2 (en) 2015-05-29 2021-02-02 Fmc Corporation Substituted cyclic amides as herbicides
US10883103B2 (en) 2015-06-02 2021-01-05 Monsanto Technology Llc Compositions and methods for delivery of a polynucleotide into a plant
EP3303321A1 (fr) 2015-06-02 2018-04-11 E. I. du Pont de Nemours and Company Amides cycliques substitués et leur utilisation en tant qu'herbicides
AU2016270913A1 (en) 2015-06-03 2018-01-04 Monsanto Technology Llc Methods and compositions for introducing nucleic acids into plants
WO2017004797A1 (fr) * 2015-07-08 2017-01-12 Eli Lilly And Company Composés pyrrolidinone
AU2016303209B2 (en) * 2015-07-31 2021-04-01 Fmc Corporation Cyclic N-carboxamide compounds useful as herbicides
BR112019012910B1 (pt) 2016-12-21 2023-10-17 Fmc Corporation Composto, composição herbicida, mistura herbicida e método para controlar o crescimento de vegetação indesejável
CA3057300A1 (fr) 2017-03-21 2018-09-27 Fmc Corporation Melange herbicide, composition et procede
BR112019019605B1 (pt) 2017-03-21 2023-03-07 Fmc Corporation Compostos e processo para preparar um composto de fórmula ii-a
WO2018177836A1 (fr) 2017-03-30 2018-10-04 Bayer Aktiengesellschaft Dérivés de n-cyclopropyl-2-oxopyrrolidin-3-carboxamide et composés apparentés en tant qu'agents de phytoprotection herbicides
WO2018177837A1 (fr) 2017-03-30 2018-10-04 Bayer Aktiengesellschaft Dérivés de 4-cyclopentyl-2-oxopyrrolidin-3-carboxamide et de 4-cyclopropyl-2-oxopyrrolidin-3-carboxamide et composés apparentés utilisés comme produits phytosanitaires herbicides
AR111967A1 (es) 2017-05-30 2019-09-04 Fmc Corp Amidas herbicidas
AR111839A1 (es) * 2017-05-30 2019-08-21 Fmc Corp Lactamas 3-sustituidas herbicidas
WO2019025156A1 (fr) 2017-08-03 2019-02-07 Bayer Aktiengesellschaft Pyrrolidinones substituées, leurs sels et leur utilisation comme agents herbicides
TW202340171A (zh) * 2022-01-26 2023-10-16 日商住友化學股份有限公司 γ－內醯胺化合物及含有其之組成物

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4874422A (en) * 1988-12-27 1989-10-17 Ici Americas Inc. 1-Phenyl-3-carboxyamidopyrrolidones and their use as herbicides
WO1995033719A1 (fr) * 1994-06-02 1995-12-14 Zeneca Limited Pyrrolidone, thiazolidones ou oxazolidones substitues utilises comme herbicides
GB9411008D0 (en) * 1994-06-02 1994-07-20 Zeneca Ltd Herbicides
AU2002215053A1 (en) 2000-11-27 2002-06-24 Pharmacia Italia S.P.A. Phenylacetamido- pyrazole derivatives and their use as antitumor agents

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2004037787A1 *

Also Published As

Publication number Publication date
US7355053B2 (en) 2008-04-08
JP2006513995A (ja) 2006-04-27
CA2502478A1 (fr) 2004-05-06
JP4398866B2 (ja) 2010-01-13
WO2004037787A1 (fr) 2004-05-06
AU2003274037A1 (en) 2004-05-13
US20060019831A1 (en) 2006-01-26

Similar Documents

Publication Publication Date Title
EP1556346A1 (fr) 1-phenylpyrrolidine-2-one-3-carboxamides
WO1999005130A1 (fr) 3-phenylisoxazoline substituee
EP1047693A1 (fr) Derives de 3-(benzazol-4-yle)dione de pyrimidine herbicides
EP1131319A2 (fr) 3- benz(ox/thi)azol-7-yl]-1h-pyrimidin-2,4-diones
EP0944623B1 (fr) Pyrazol-3-ylbenzazoles substitues
WO1997035845A1 (fr) 1-methyle-3-benzyluraciles substitues
WO2001068644A1 (fr) Procede pour la production de 7-(pyrazol-3-yl)benzoxazoles
EP0915853B1 (fr) 3-phenylpyrazoles substitues
EP0836593B1 (fr) Derives de 5-acide benzoique de pyrazolyle utilises comme herbicides
WO2002006233A1 (fr) 1-aryl-4-halogenure d&#39;alkyl-2-(1h)-pyridones et leur utilisation en tant qu&#39;herbicides
WO1998012182A1 (fr) 1-sulfonyl-3-phenylpyrazoles et leur utilisation comme herbicides et pour le dessechement ou la defoliation de vegetaux
EP1003741A1 (fr) Amides d&#39;acide tetrazolinonecarboxylique substitues herbicides
WO1997015559A1 (fr) 4,5-di(trifluoromethyl)pyrazoles substitues et leur utilisation comme herbicides et pour la dessiccation/defoliation de plantes
WO1999055702A1 (fr) (4-brompyrazol-3-yl)benzazoles substitues
WO2000026194A1 (fr) Nouveaux 1-aryl-4-thiouraciles
EP0998472A1 (fr) 2-(benzaryl)pyridines substituees
WO1998020000A2 (fr) 3-benzylpyrazoles substitues et leur utilisation comme herbicides et pour abaisser la teneur en sucre du sang
WO2001049668A2 (fr) 4-aryl-1-difluoromethoxyimidazole
EP1289970A1 (fr) 3-arylisothiazoles et leur utilisation en tant qu&#39;herbicides
WO2001019820A1 (fr) Pyrazol-3-ylbenzoxazinones substituees
EP1218350A1 (fr) Derives de 1-aryle-1,3-dihydro-imidazole-2-(thi)ones, fabrication, et utilisation en tant qu&#39;herbicides ou pour la dessiccation/defoliation de plantes

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20050518

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LI LU MC NL PT RO SE SI SK TR

AX Request for extension of the european patent

Extension state: AL LT LV MK

DAX Request for extension of the european patent (deleted)
RAP1 Party data changed (applicant data changed or rights of an application transferred)

Owner name: BASF SE

17Q First examination report despatched

Effective date: 20090803

GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

GRAC Information related to communication of intention to grant a patent modified

Free format text: ORIGINAL CODE: EPIDOSCIGR1

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20101119