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EP2054395A2 - Piperazine compounds with a herbicidal action - Google Patents

Piperazine compounds with a herbicidal action

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Publication number
EP2054395A2
EP2054395A2 EP08760877A EP08760877A EP2054395A2 EP 2054395 A2 EP2054395 A2 EP 2054395A2 EP 08760877 A EP08760877 A EP 08760877A EP 08760877 A EP08760877 A EP 08760877A EP 2054395 A2 EP2054395 A2 EP 2054395A2
Authority
EP
European Patent Office
Prior art keywords
benzyl
ylidenemethyl
dioxopiperazin
dione
methylidene
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Withdrawn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
EP08760877A
Other languages
German (de)
French (fr)
Inventor
Eike Hupe
Thomas Seitz
Matthias Witschel
Dschun Song
William Karl Moberg
Liliana Parra Rapado
Frank Stelzer
Andrea Vescovi
Trevor William Newton
Robert Reinhard
Bernd Sievernich
Klaus Grossmann
Thomas Ehrhardt
Michael Rack
Elmar Kibler
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
Priority to EP08760877A priority Critical patent/EP2054395A2/en
Publication of EP2054395A2 publication Critical patent/EP2054395A2/en
Withdrawn legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
    • C07D241/06—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having one or two double bonds between ring members or between ring members and non-ring members
    • C07D241/08—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having one or two double bonds between ring members or between ring members and non-ring members with oxygen atoms directly attached to ring carbon 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
    • C07D403/10—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 aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
    • C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
    • C07D407/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a carbon chain containing aromatic rings
    • 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
    • C07D409/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing aromatic rings

Definitions

  • the present invention relates to piperazine compounds of the general formula I defined below and their use as herbicides.
  • the invention also relates to crop protection agents and to a method of controlling undesired plant growth.
  • the thaxtomines A and B produced by the plant pathogen S. scabies are natural products with a central piperazine 2,5- dione ring which carries a 4-nitro-indol-3-ylmethyl radical in the 3-position and a benzyl radical which may be substituted by OH in the 2-position. Because of their plant-damaging effect, the possibility of using this class of compounds as herbicides was also investigated (King R.R. et al., J. Agric. Food Chem. (2001) 49, 2298-2301).
  • R is hydrogen or NO 2.
  • R y is hydrogen or benzyl and R x is hydrogen, acetyl or Isopro- pyloxycarbonyl, as precursors for the preparation of Ecteinascidinen.
  • WO 99/48889, WO 01/53290 and WO 2005/011699 describe 2,5-Diketopiperazinitatien which in the 3- or 6-position bound via a methylene or methine 4-imidazolyl radical and in the other 3- or 6- position have a benzyl or Benzylidenrest. These compounds are antitumor agents.
  • An object of the present invention is to provide compounds having herbicidal activity.
  • compounds are to be made available which have a high herbicidal action, in particular even at low application rates, and their compatibility with crop plants for commercial exploitation is sufficient.
  • the present invention thus provides piperazine compounds of general formula I.
  • R 1a which are independently of one another halogen, CN, NO 2, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy and C 1 -C 4 -haloalkoxy are selected, and wherein Z is a covalent bond or a CH 2 group;
  • R 11 is hydrogen, C i -C 6 -alkyl, C 3 -C 6 cycloalkyl, C 2 -C 6 -alkenyl, C 5 -C 6 -
  • R 3 is hydrogen or halogen
  • R 4 is C 1 -C 4 -alkyl, C 3 -C 4 -alkenyl or C 3 -C 4 -alkynyl
  • R 6 is C 1 -C 4 -alkyl, C 1 -C 4 -hydroxyalkyl or C 1 -C 4 -haloalkyl;
  • R 7, R 8 are independently hydrogen, OH, -C 4 alkoxy, CrC 4 -Haloalkyoxy, -C 4 alkyl or CrC stand 4 haloalkyl;
  • R 9, R 10 are independently selected from hydrogen, halogen, CN, NO2, Ci-C 4 -alkyl, Ci-C 4 haloalkyl, C 2 -C 4 alkenyl, Ci-C4-alkoxy and Ci- C 4 - haloalkoxy; and the agriculturally suitable salts of these compounds.
  • the present invention also provides the use of piperazine compounds of general formula I or the agriculturally useful salts of piperazine compounds of formula I as herbicides, i. for controlling harmful plants.
  • the present invention also relates to compositions which contain at least one piperazine compound of the formula I or an agriculturally useful salt of I and auxiliaries customary for the formulation of crop protection agents.
  • the present invention also relates to a method for controlling undesired plant growth, which comprises allowing a herbicidally effective amount of at least one piperazine compound of the formula I or an agriculturally useful salt of I to act on plants, their seeds and / or their habitat.
  • the invention also relates to processes and intermediates for the preparation of compounds of the formula I.
  • the compounds of the formula I have a chiral center on the carbon atom which carries the radical R 6 . In addition, depending on the substitution pattern, they may contain one or more other chiral centers.
  • the compounds according to the invention can therefore be present as pure enantiomers or diastereomers or as mixtures of enantiomers or diastereomers.
  • the invention relates to both the pure enantiomers or diastereomers and mixtures thereof.
  • the compounds of the formula I can be present as E-isomer or as Z-isomer with respect to the exocyclic double bond.
  • the invention relates to both the pure E isomers and Z isomers and their mixtures.
  • the compounds of the formula I can also be present in the form of their agriculturally useful salts, wherein the type of salt generally does not matter. In general, the salts of those cations or the acid addition salts of those acids come into consideration whose cations, or anions, do not adversely affect the herbicidal activity of the compounds I.
  • ions of the alkali metals preferably lithium, sodium or potassium, the alkaline earth metals, preferably calcium or magnesium, and the transition metals, preferably manganese, copper, zinc or iron are suitable as cations.
  • ammonium as the cation, where, if desired, one to four hydrogen atoms are represented by C 1 -C 4 -alkyl, hydroxy-C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl, hydroxyC 1 -C 4 -alkoxy-Ci-C 4 alkyl, phenyl or benzyl may be replaced, preferably ammonium, dimethylammonium, diisopropylammonium, tetramethylammonium, tetrabutylammonium, 2- (2-hydroxyeth-1-oxy) eth-1-ylammonium, di (2-hydroxyeth -1-yl) ammonium
  • Phosphonium ions sulfonium ions, preferably tri (C 1 -C 4 -alkyl) sulfonium or sulfonoxonium ions, preferably tri (C 1 -C 4 -alkyl) sulfoxonium.
  • Anions of useful acid addition salts are primarily chloride, bromide, fluoride, hydrogen sulfate, sulfate, dihydrogen phosphate, hydrogen phosphate, nitrate,
  • organic molecular moieties mentioned for the substituents of the compounds according to the invention are collective terms for individual listings of the individual group members.
  • All hydrocarbon chains such as alkyl, halo (gen) alkyl, alkenyl, alkynyl, and the alkyl moieties and alkenyl moieties in alkoxy, halo (gen) alkoxy, Alkylamino, dialkylamino, N-alkylsulfonylamino, alkenyloxy, alkynyloxy, alkoxyamino, alkylaminosulfonylamino, dialkylaminosulfonylamino, alkenylamino, alkynylamino, N-
  • (Alkenyl) -N- (alkyl) -amino, N- (alkynyl) -N- (alkyl) -amino, N- (alkoxy) -N- (alkyl) -amino, N- (alkenyl) -N- (alkoxy ) -amino or N- (alkynyl) -N- (alkoxy) -amino can be straight-chain or branched.
  • halogenated substituents preferably carry one to five identical or different halogen atoms, in particular fluorine atoms or chlorine atoms.
  • halogen in each case represents fluorine, chlorine, bromine or iodine.
  • Alkyl and the alkyl moieties for example, in alkoxy, alkylamino, dialkylamino, N-alkylsulfonylamino, alkylaminosulfonylamino, dialkylaminosulfonylamino, N- (alkenyl) -N- (alkyl) -amino, N- (alkynyl) -N- (alkyl) -amino, N- (Alkoxy) -N- (alkyl) -amino ,: saturated, straight-chain or branched hydrocarbon radicals having one or more carbon atoms, for example 1 to 2, 1 to 4, or 1 to 6 carbon atoms, for example Ci-C 6 -alkyl, such as Methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl, 2-methylpropyl, 1, 1-dimethylethyl, pentyl,
  • Haloalkyl also referred to as haloalkyl: an alkyl radical as mentioned above, the hydrogen atoms of which are partially or completely substituted by halogen atoms such as fluorine, chlorine, bromine and / or iodine, e.g.
  • Cycloalkyl and the cycloalkyl moieties for example, in cycloalkoxy or cycloalkylcarbonyl: monocyclic, saturated hydrocarbon groups having three or more C atoms, e.g. 3 to 6 carbon ring members such as cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.
  • Alkenyl and alkenyl moieties for example, in alkenylamino, alkenyloxy, N- (alkenyl) -N- (alkyl) -amino, N- (alkenyl) -N- (alkoxy) -amino: monounsaturated, straight-chain or branched hydrocarbon radicals having two or more carbon atoms. Atoms, z. B.
  • C2-C6 alkenyl such as ethenyl, 1-propenyl, 2-propenyl, 1-methylethenyl, 1-butenyl, 2-butenyl , 3-Butenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 1-methyl-2-propenyl, 2-methyl-2-propenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4 Pentenyl, 1-methyl-1-butenyl, 2-methyl-1-butenyl, 3-methyl-1-butenyl, 1-methyl-2-butenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl , 1-methyl-3-butenyl, 2-methyl-3-butenyl, 3-methyl-3-butenyl, 1, 1 Dimethyl 2-propenyl, 1, 2-dimethyl-1-propenyl, 1, 2-dimethyl-2-propenyl, 1, 2-dimethyl-2-propenyl, 1, 2-dimethyl-2-propeny
  • Cycloalkenyl monocyclic, monounsaturated hydrocarbon groups having 5 to 6, preferably 5 to 6 carbon ring members, such as cyclopenten-1-yl, cyclopenten-3-yl, cyclohexen-1-yl, cyclohexen-3-yl, cyclohexen-4-yl.
  • Alkynyl and alkynyl moieties for example, in alkynyloxy, alkynylamino, N- (alkynyl) -N- (alkyl) -amino or N- (alkynyl) -N- (alkoxy) -amino: straight-chain or branched hydrocarbon groups having two or more carbon atoms, eg , B. 2 to 4, 2 to 6, or 3 to 6 carbon atoms and a triple bond in any position, for.
  • C 2 -C 6 -alkynyl such as ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-methyl-2-propynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1-methyl-2-butynyl, 1-methyl-3-butynyl, 2-methyl-3-butynyl, 3-methyl-1-butynyl, 1, 1-dimethyl-2-propynyl, 1-ethyl 2-propynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl, 1-methyl-2-pentynyl, 1-methyl-3-pentynyl, 1-methyl-4-pentynyl, 2 Methyl 3-pentynyl, 2-methyl-4
  • Alkoxy alkyl, as defined above, which is bonded via an oxygen atom: z.
  • Aryl mononuclear or polynuclear aromatic hydrocarbon radicals having 6 to 14 carbon atoms, such as phenyl, naphthyl, anthracenyl or phenanthrenyl, preferably phenyl or naphthyl.
  • 5- or 6-membered heterocyclic radical a heterocyclic radical having 5 or 6 ring atoms, wherein 1, 2, 3 or 4 ring atoms are heteroatoms selected from O, S and N, wherein the heterocyclic radical is saturated, partially unsaturated or aromatic.
  • heterocyclic radicals are:
  • N-linked, 5-membered, saturated rings such as: Tetrahydropy- ⁇ rol-1-yl, tetrahydropyrazol-1-yl, tetrahydroisoxazol-2-yl, tetrahydroisothiazol-2-yl, tetrahydroimidazol-1-yl, tetrahydrooxazol-3-yl, tetrahydrothiazol-3-yl;
  • N-linked, 6-membered, saturated rings such as:
  • C-linked, 6-membered, partially unsaturated rings such as: 2H-3,4-dihydropyran-6-yl, 2H-3,4-dihydropyran-5-yl, 2H-3,4-dihydropyran-4-yl, 2H-3,4-dihydropyran-3-yl, 2H- 3,4-Dihydropyran-2-yl, 2H-3,4-dihydrothiopyran-6-yl, 2H-3,4-dihydrothiopyran-5-yl, 2H-3,4-dihydrothiopyran-4-yl, 2H-3.4- Dihydrothiopyran-3-yl, 2H-3,4-dihydrothiopyran-2-yl, 1,2,3,4-tetrahydropyridin-6-yl, 1,2,3,4-tetrahydropyridin-5-yl, 1, 2, 3,4-Tetrahydropyridin-4-yl, 1, 2,3,4-
  • N-linked, 5-membered, partially unsaturated rings such as: 2,3-dihydro-1H-pyrrol-1-yl, 2,5-dihydro-1H-pyrrol-1-yl, 4,5-dihydro-1 H-pyrazol-1-yl, 2,5-dihydro-1H-pyrazol-1-yl, 2,3-dihydro-1H-pyrazol-1-yl, 2,5-dihydroisoxazol-2-yl, 2, 3-Dihydroisoxazol-2-yl, 2,5-dihydroisothiazol-2-yl, 2,3-dihydroisoxazole-2-yl yl, 4,5-dihydro-1H-imidazol-1-yl, 2,5-dihydro-1H-imidazol-1-yl, 2,3-dihydro-1H-imidazol-1-yl, 2,3 Dihydrooxazol-3-yl, 2,3-dihydrothi
  • N-linked, 6-membered, partially unsaturated rings such as: 1, 2,3,4-tetrahydropyridin-1-yl, 1, 2,5,6-tetrahydropyridin-1-yl, 1, 4-dihydro-pyridine-1 -yl, 1, 2-dihydropyridin-1-yl, 2H-5,6-dihydro-1,2-oxazin-2-yl, 2H-5.6-dihydro-1,2-thiazin-2-yl, 2H-3 , 6-Dihydro-1,2-oxazin-2-yl, 2H-3,6-dihydro-1,2-thiazin-2-yl, 2H-3,4-dihydro-1,2-oxazin-2-yl , 2H-3,4-dihydro-1,2-thiazin-2-yl, 2,3,4,5-tetrahydropyridazin-2-yl, 1, 2,5,6-tetrahydropyridazin-1-yl, 1,2 ,
  • Tetrahydropyrimidin-3-yl 1,2,3,4-tetrahydropyrazine-1-yl, 1,2,3,4-tetrahydropyrimidin-1-yl, 1,2,3,4-tetrahydropyrimidin-3-yl, 2, 3-dihydro-1, 4-thiazine-4-yl, 2H-1, 2-oxazin-2-yl, 2H-1,2-thiazin-2-yl, 4H-1,4-oxazin-4-yl, 4H-1, 4-thiazine-4-yl, 1,4-dihydropyridazin-1-yl, 1,4-dihydropyrazine-1-yl, 1,2-dihydropyrazine-1-yl, 1,4-dihydropyrimidine-1 - yl or 3,4-dihydropyrimidin-3-yl;
  • C-linked, 6-membered, heteroaromatic rings such as: pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyridazin-3-yl, pyridazin-4-yl, pyrimidin-2-yl, pyrimidine 4-yl, pyrimidin-5-yl, pyrazine-2-yl, 1, 3,5-triazin-2-yl, 1, 2,4-triazin-3-yl, 1, 2,4-triazine-5 yl and 1,2,4-triazin-6-yl;
  • N-linked, 5-membered, heteroaromatic rings such as:
  • Tetrazol-1-yl and [2H] -tetrazol-2-yl may be substituted in the manner indicated.
  • Alkenyloxy alkenyl as mentioned above, which is bonded via an oxygen atom;
  • Alkynyloxy alkynyl as mentioned above, which is bonded via an oxygen atom;
  • Alkylamino a group NHR, wherein R is alkyl as defined above;
  • Alkoxyamino a group NH (OR) wherein R is alkyl as defined above; - Alkylsulfonylamino: a group NHS (O) 2R
  • Alkylaminosulfonylamino a group NHS (O) 2NHR, wherein R is alkyl as defined above;
  • [Dialkylamino] sulfonylamino a group NHS (O) 2 NR'R, wherein R and R 'are alkyl as defined above;
  • Alkenylamino a group NHR in which R is alkenyl as defined above;
  • Alkynylamino a group NHR wherein R is alkynyl as defined above;
  • N- (alkynyl) -N- (alkyl) -amino a group NR'R, wherein R is alkynyl and R 'is alkyl as defined above;
  • N- (alkoxy) -N- (alkyl) -amino a group NR'R, wherein R is alkyl and R 'is alkoxy as defined above;
  • Alkoxy as defined above, stand.
  • variables of the compounds of the formula I have the following meanings, these being considered both individually and in combination with one another in particular embodiments of the compounds of the formula I:
  • R 1 in particular represents cyano, nitro or a 5- or 6-membered heteroaromatic radical as defined above, which is preferably either 1, 2, 3 or 4 nitrogen atoms or 1 oxygen or 1 sulfur atom and optionally 1 or 2 nitrogen atoms Having ring members and which is unsubstituted or may have 1 or 2 substituents selected from R 1a .
  • R 1 is cyano or nitro.
  • R 1 is a 5- or 6-membered heteroaromatic radical as defined above, which preferably has either 1, 2, 3 or 4 nitrogen atoms or 1 oxygen or 1 sulfur atom and optionally 1 or 2 nitrogen atoms as ring members and which is unsubstituted or may have 1 or 2 substituents selected from R 1a .
  • preferred heteroaromatic radicals are pyridazin-3-yl, pyridazin-4-yl, pyrimidin-2-yl, pyrimidin-4-yl,
  • R 1 is halogen, in particular chlorine or bromine.
  • the radical R 2 is preferably hydrogen, fluorine, chlorine, C 1 -C 2 -alkyl, C 1 -C 2 -fluoroalkyl, ethenyl, C 1 -C 2 -alkoxy or C 1 -C 2 -fluoroalkoxy, in particular fluorine, chlorine, methyl, ethyl, methoxy , Ethenyl or trifluoromethoxy.
  • R 2 particularly preferably represents hydrogen, fluorine or chlorine.
  • R 2 is halogen, in particular chlorine or fluorine, which is arranged in the ortho position to the binding site of the phenyl ring.
  • R 3 is halogen
  • R 3 is hydrogen.
  • R 4 is preferably methyl.
  • R 5 is preferably hydrogen, methyl or ethyl, especially methyl.
  • R 6 is preferably C 1 -C 3 -alkyl or C 1 -C 2 -fluoroalkyl, in particular methyl, ethyl, n-propyl or trifluoromethyl, and especially methyl or ethyl.
  • radicals R 7 and R 8 are hydrogen.
  • R 9 is a radical different from hydrogen
  • R 9 is hydrogen.
  • R 10 is preferably hydrogen.
  • R 11 is preferably hydrogen, C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl.
  • R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 9 have one of the meanings given above, in particular the meanings given as preferred.
  • the radicals R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 9 independently of one another, but preferably in combination, have the following meanings:
  • R 1 is cyano or nitro
  • R 2 is hydrogen, fluorine, chlorine, C 1 -C 2 -alkyl, ethenyl or C 1 -C 2 -alkoxy, in particular
  • R 3 is fluorine or hydrogen
  • R 4 is methyl
  • R 5 is hydrogen, methyl or ethyl, especially methyl
  • R 6 is methyl or ethyl
  • R 9 is hydrogen or halogen, in particular hydrogen or fluorine.
  • the compounds of the formula I have a center of chirality on the carbon atom which carries the group R 6 .
  • a preferred embodiment of the invention relates to the pure enantiomers of the formula given below in which R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 and R 10 is one of the abovementioned Meanings, in particular one of the preferred or given as particularly preferred meanings, as well as enantiomeric mixtures having an enantiomeric excess with respect to the enantiomer of the formula IS.
  • Enantiomeric excess preferably means an ee value (enantiomeric excess) of at least 70%, in particular at least 80% and especially at least 90%.
  • ee value enantiomeric excess
  • the agriculturally suitable salts of the enantiomers IS and enantiomeric mixtures of the salts having an enantiomeric excess with respect to the enantiomer of the formula IS are particularly preferred.
  • Another, likewise preferred embodiment relates to the racemates of I and their salts.
  • a particularly preferred embodiment relates to the pure enantiomers of the formula given below IS.a, wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 9 is one of the meanings given above, in particular one of preferred or have particularly given meanings as well as enantiomeric mixtures which have an enantiomeric excess with respect to the enantiomer of the formula IS.a.
  • R 1 is cyano or nitro
  • R 2 is hydrogen, fluorine, chlorine, C 1 -C 2 -alkyl, ethenyl or C 1 -C 2 -alkoxy, in particular hydrogen, fluorine or chlorine;
  • R 3 is fluorine or hydrogen
  • R 4 is methyl
  • R 5 is hydrogen, methyl or ethyl, especially methyl
  • R 6 is methyl or ethyl; and R 9 is hydrogen or halogen, in particular hydrogen or fluorine.
  • Another particularly preferred embodiment of the invention relates to the racemates of Ia and their salts.
  • mixtures of the (E) -isomer with the (Z) -isomer in which the Z-isomer is present in excess in particular isomer mixtures having an E / Z ratio of not more than 1: 2, in particular not more than 1: 5th
  • Examples of compounds which are preferred according to the invention are the compounds mentioned below and salts thereof: 2- [5-benzyl-1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] benzonitrile, 2- [5-benzyl- 1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-fluorobenzonitrile,
  • mixtures of the (E) -isomer with the (Z) -isomer in which the Z-isomer is present in excess in particular isomer mixtures having an E / Z ratio of not more than 1: 2, in particular not more than 1: 5th
  • the carbon atom bearing R 6 has S configuration and enantiomeric mixtures having an enantiomeric excess with respect to the S enantiomer, especially those having an ee value (enantiomeric excess) of at least 70%, more preferably at least 80% and especially at least 90%.
  • the racemates of these compounds and their salts are preferred.
  • the compounds according to the invention can be prepared by standard methods of organic chemistry, for example a process (in the following process A) which comprises the following steps:
  • R 1, R 2, R 3, R 7, R 8, R 9 and R 10 are as defined above, in particular have one of the preferred meanings mentioned, R 4a is hydrogen or a protecting group or one of the given for R 4 Has meanings and R 5a has one of the meanings given for R 5 or is a protective group;
  • R 5a is hydrogen with an alkylating agent of the formula R 5 -X 1 or an acylating agent of the formula R 5 -X 2 , wherein R 5 has the meanings given above, hydrogen-different meanings and X 1 and X 2 are a nucleophilically displaceable leaving group, in the presence of a base;
  • R 4a and / or R 5a when R 4a and / or R 5a is a protective group, removing the Schutzgrup- PE, and optionally reacting the resulting compound II, wherein R 4a and / or R 5a is hydrogen with an alkylating agent of the formula R 4 -X 1 , and / or R 5 -X 1 or an acylating agent R 5 -X 2 , wherein R 4 and R 5 have the meanings given above, other than hydrogen and X 1 and X 2 are a nucleophilically displaceable leaving group, in the presence a base.
  • radical R 4a in formula II is hydrogen
  • the radical R 4 is introduced by the alkylation step ii). If the radical R 4a in formula II is a protective group, this is first removed to obtain a compound in which R 4a is hydrogen, in which is introduced by the alkylation step ii) the radical R 4 .
  • R 5a in formula II is hydrogen
  • the radical R 5 can be introduced by an alkylation or acylation step iii). If R 4 and R 5 are identical, steps ii) and iii) can be carried out simultaneously or successively in any desired order. If the radicals R 4 , R 5 and R 6 are identical, it is possible to carry out step iv) simultaneously with or after the steps ii) and / or iii) or subsequently.
  • the alkylation in step iv) and also the alkylation or acylation in steps ii) and iii) can be carried out in analogy to standard methods of alkylation or acylation, for example according to the methods described by I.O. Donkor et al., Bioorg. Med. Chem. Lett. 11 (19) (2001), 2647-2649, B.B. Snider et al., Tetrahedron 57 (16) (2001), 3301-3307, I. Yasuhiro et al., Heterocycles, 45, 1997, 1151, J. Am. Chem. Soc. 105, 1983, 3214, J. Am. Chem. Soc. 124 (47) (2002), 14017-14019, Chem. Commun. 1998, 659 or M. Falorni et al., Europ. J. Org. Chem. (8) (2000), 1669-1675.
  • step iv) the piperazine compound of the formula II is reacted with a suitable alkylating agent, hereinafter compound XR 6 , to give a piperazine compound of the formula I (see, for example, J. Am. Chem. Soc., 105, 1983, 3214). ,
  • alkylating agents X XR 6 may be halogen, in particular chlorine, bromine or iodine or O-S ⁇ 2-R m
  • R m has the meaning of -C 4 -alkyl or aryl, which are optionally substituted by halogen, -C 4 -alkyl or halo-Ci- C 4 alkyl are substituted mean.
  • the reaction is usually carried out at temperatures in the range of -78 ° C to the boiling point of the reaction mixture, preferably from -50 0 C to 65 ° C, particularly preferably from -30 0 C to 65 ° C.
  • the reaction is carried out in a solvent, preferably in an inert organic solvent.
  • Suitable solvents are aliphatic hydrocarbons such as pentane, hexane, cyclohexane and mixtures of Cs-Cs alkanes, aromatic hydrocarbons such as toluene, o-, m- and p-xylene, halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform and chlorobenzene, ethers such as Diethyl ether, diisopropyl ether, tert-butyl methyl ether, dioxane, anisole and tetrahydrofuran, nitriles such as acetonitrile and propinonitrile, ketones such as acetone, methyl ethyl ketone, diethyl ketone and tert-butyl methyl ketone, alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol , tert
  • Preferred solvents are toluene, dichloromethane, tetrahydrofuran, N-methylpyrrolidone, dimethylformamide and mixtures thereof.
  • the alkylation of compound II in step iv) is carried out with the alkylating agent R 6 -X in the presence of a base.
  • Suitable bases are inorganic compounds such as alkali metal and alkaline earth metal hydroxides such as lithium hydroxide, sodium hydroxide, potassium hydroxide or calcium hydroxide, aqueous solution of ammonia, alkali metal or alkaline earth metal oxides such as lithium oxide, sodium oxide, calcium oxide and magnesium oxide, alkali metal and alkaline earth metal hydrides such as lithium hydride, sodium hydride, potassium hydride and Calcium hydride, alkali metal amides such as lithium amide, for example lithium diisopropylamide, sodium amide and potassium amide, alkali metal and alkaline earth metal carbonates such as lithium carbonate, potassium carbonate, cesium carbonate and calcium carbonate and alkali metal hydrogencarbonates such as sodium bicarbonate, organometallic compounds, in particular alkali metal alkyls such as methyllithium, butyl lithium and phenyllithium, alkyl magnesium halides such as methyl magnesium chloride and alkali metal and alkaline earth metal such
  • step ii) and iii) can be carried out in analogy to the methods given for step iv), e.g. according to the in Heterocycles, 45, 1997, 151, and Chem. Commun. 1998, 659 described methods.
  • step v) the optional alkylation or acylation in step v) can be carried out.
  • X 1 may be halogen or O-SO 2 -R m with R m meaning Ci-C 4 -AlkVl or aryl, which may be halogen, d- C 4 -AlkVl or halo-Ci-C 4 alkyl are substituted mean.
  • R 4 and R 5 are each independently Ci-C 4 alkyl, C 3 -C 4 - kinyl alkenyl or C 3 -C 4 -alkyl.
  • R 5 is a radical C (O) R 51 in which R 51 has the abovementioned meanings.
  • X 2 is usually halogen, for example chlorine or a group 0-C (O) -R 51 .
  • radicals R 4a and R 5a in formula II are a protective group, this protective group is removed in step v).
  • the compound I * is then or become one or two new, different from hydrogen radical (s) R 4 or R 5 by alkylation or acylation in analogy to the steps ii) and iii) introduced.
  • Suitable protecting groups for the nitrogen atoms of the piperazine ring are, in particular, the abovementioned radicals C (O) R 51 , for example the acetyl radical.
  • the introduction of these protective groups can be carried out in analogy to known methods of protecting group chemistry, for example by reaction with anhydrides of the formula (R 51 C (O)) 2 ⁇ , for example according to the Green, Wuts, Protective Groups in Organic Synthesis, 3rd ed. 1999, John Wiley and Sons, p. 553.
  • the removal of a protecting group R 4a , R 5a can be carried out in analogy to known methods of protecting group chemistry.
  • the preparation of the compounds II is generally carried out by dehydration of the corresponding alcohol IIa,
  • R 1 , R 2 , R 3 , R 4a , R 5a , R 7 , R 8 , R 9 and R 10 have the abovementioned meanings, in particular one of the meanings mentioned as preferred.
  • the alcohol function of compound IIa can first be converted into a suitable leaving group and then formally eliminated as compound H-LG.
  • the elimination reaction occurs in the presence of a suitable base.
  • the introduction of such a leaving group is carried out according to conventional methods, for example by reacting the alcohol IIa with a base and then with the corresponding sulfonic acid chloride, for example with methanesulfonyl chloride or trifluoromethanesulfonyl chloride.
  • Suitable bases are the bases listed below in the elimination. However, preference is given to using bases which are soluble in organic solvents, for example the amines or nitrogen heterocycles mentioned below.
  • bases which are soluble in organic solvents for example the amines or nitrogen heterocycles mentioned below.
  • pyridine or substituted pyridines such as dimethylaminopyridine, lutidine or collidine, or mixtures thereof.
  • the organic bases are chosen so that they also function as solvents.
  • the bases generally include inorganic compounds such as alkali metal and alkaline earth metal hydroxides such as lithium hydroxide, sodium hydroxide, potassium hydroxide or calcium hydroxide, aqueous solution of ammonia, alkali metal or alkaline earth metal oxides such as lithium oxide, sodium oxide, calcium oxide and magnesium oxide, alkali metal and alkaline earth metal hydrides such as lithium hydride, Sodium hydride, potassium hydride and calcium hydride, alkali metal amides such as lithium amide, for example lithium diisopropylamide, sodium amide and potassium amide, alkali metal and alkaline earth metal carbonates such as lithium carbonate, potassium carbonate, cesium carbonate and calcium carbonate and also alkali metal hydrogen carbonates such as sodium bicarbonate, organometallic compounds, especially alkali metal alkyls such as methyllithium, butyllithium and phenyllithium, Alkylmagnesium halides such as methylmagnesium chloride and alkal
  • tertiary amines such as trimethylamine, triethylamine, diisopropyl-ethylamine 2-hydroxypyridine and N-methylpiperidine, pyridine, substituted pyridines such as collidine, lutidine and 4-dimethylaminopyridine and bicyclic amines into consideration.
  • a mixture of different bases can be used.
  • bases which, while having sufficient basicity but substantially no nucleophilicity, e.g. sterically hindered alkali alcoholates, for example, alkali tert-butanolates such as potassium tert-butoxide, and especially cyclic amidines such as DBU (1,8-diazabicyclo [5.4.0] undec-7-ene) and DBN (1, 5 - diazabicyclo [3.4.0] non-5-ene). Preference is given to using the last-mentioned amidines.
  • alkali tert-butanolates such as potassium tert-butoxide
  • cyclic amidines such as DBU (1,8-diazabicyclo [5.4.0] undec-7-ene
  • DBN 1, 5 - diazabicyclo [3.4.0] non-5-ene
  • Suitable inert organic solvents include aromatic hydrocarbons such as toluene, o-, m- and p-xylene, halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform and chlorobenzene, ethers such as diethyl ether, diisopropyl ether, tert-butyl methyl ether, dioxane, anisole and tetrahydrofuran.
  • nitrites such as acetonitrile and propionitrile, ketones such as acetone, methyl ethyl ketone, diethyl ketone and tert-butyl methyl ketone, alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol, tert-butanol, water and dimethyl sulfoxide, dimethylformamide and dimethylacetamide and Morpholine and N-methylmorpholine. It is also possible to use mixtures of the solvents mentioned. Preference is given to using tetrahydrofuran.
  • compound II is prepared by dehydration of compound IIa in the presence of a suitable dehydrating agent.
  • DEAD diethyl azodicarboxylate
  • the combination of triphenylphosphine and DEAD is generally used for targeted inversion at a hydroxy-substituted chiral center (so-called Mitsunobu reaction); however, in the absence of nucleophiles, it acts as a mild dehydrating agent.
  • the system is preferably used in excess with respect to the compound IIa, the two components triphenylphosphine and DEAD suitably being present in an approximately equimolar ratio to one another.
  • the Burgess reagent is the zwitterion of methyl N- (triethylammonium sulfonylcarbamate ((C2H5) 3N + -S ⁇ 2-N "-COOCHs), a mild dehydrating agent which can be equimolar with respect to the alcohol II or in
  • the reaction with the Burgess reagent is usually carried out in an inert organic solvent Suitable inert organic solvents include aromatic hydrocarbons such as toluene, o-, m- and p-xylene, halogenated hydrocarbons such as dichloromethane , Dichloroethane, chloroform and chlorobenzene, ethers, such as diethyl ether, diisopropyl ether, tert-butyl methyl ether, dioxane, anisole and tetrahydrofuran, nitriles, such as acetonitrile and propionitrile, and ketones, such
  • dehydration of alcohols IIa using dehydrating agents can be carried out analogously to known processes of the prior art, for example analogously to those described in Synthesis 2003, 201 and J. Indian Sei. 2001, 81, 461, to which reference is hereby made in its entirety.
  • the alcohols of the formula IIa can be prepared, for example, in analogy to processes known from the literature by cyclization of corresponding dipeptide precursors, for example in analogy to that described by T. Kawasaki et al., Org. Lett. 2 (19) (2000), 3027-3029, Igor L. Rodionov et al., Tetrahedron 58 (42) (2002), 8515-8523 or AL Johnson et al., Tetrahedron 60 (2004), 961-965 ,
  • the alcohols of the formula IIa can also be prepared by coupling a benzaldehyde of the formula III with a piperazine compound IV in an aldol reaction, as shown in the following scheme:
  • the reaction of III with IV in the sense of an aldol reaction is generally carried out in the presence of suitable bases.
  • suitable bases are those which are commonly used in aldol reactions.
  • Suitable reaction conditions are known in the art and described, for example, in J. Org. Chem. 2000, 65 (24), 8402-8405, which is hereby incorporated by reference in its entirety.
  • the reaction of compound III with compound IV can also lead directly to the corresponding aldol condensation product, ie to compounds of formula II.
  • the radicals R 4a and R 5a represent an acyl group, for example a group of the formula R 52 C (O) -, in which R 52 has one of the meanings given for R 51 and, in particular for Ci-C 4 -alkyl such as methyl.
  • Such aldol condensations can be carried out analogously to those described in J. Org. Chem. 2000, 65 (24), 8402-8405, Synlett 2006, 677, J. Heterocycl. Chem. 1988, 25, 591, to which reference is hereby fully made.
  • the aldol condensation is typically carried out in the presence of suitable bases.
  • suitable bases are those which are commonly used in aldol condensations.
  • an alkali metal or alkaline earth metal carbonate is used as the base, e.g. Sodium carbonate, potassium carbonate or cesium carbonate or mixtures thereof.
  • the reaction is carried out in an inert, preferably aprotic organic solvent.
  • suitable solvents are, in particular, dichloromethane, dichloroethane, chlorobenzene, ethers, such as diethyl ether, diisopropyl ether, tert-butyl methyl ether, dioxane, anisole and tetrahydrofuran, nitriles, such as acetonitrile and propionitrile, and also dimethyl sulfoxide, dimethylformamide, N-methylpyrrolidone and dimethylacetamide , Preferred solvents are selected in particular from dimethylformamide, N-methylpyrrolidone and dimethylacetamide.
  • the required for the aldol condensation temperatures are generally in the range from 0 0 C up to the boiling point of the solvent used, and in particular in the range of 10 to 80 0 C.
  • the radicals R 4a and R 5a represent an acyl group, for example a group of the formula R 52 C (O) -.
  • the removal of a protecting group R 4a , R 5a can be carried out in analogy to known methods of protecting group chemistry.
  • the removal of the radicals R 4a and R 5a is generally carried out by hydrolysis, the radical R 4a often being split off already under the conditions of an aldol condensation.
  • the radical R 4 and optionally the radical R 5 is then introduced according to the steps ii) and iii).
  • R 1 , R 2 , R 3 , R 6 , R 7 , R 8 , R 9 and R 10 have the abovementioned meanings, in particular one of the meanings mentioned as preferred, R 4c is hydrogen or a protective group and R 5c is a has the meanings given for R 5 or is a protective group.
  • Preferred protective groups are the abovementioned acyl groups of the formula R 52 C (O) -, in which R 52 has one of the meanings given for R 51 and, in particular, for C 1 -C 4 -alkyl, for example methyl.
  • This compound I ' in which R 4c is hydrogen, is then reacted with an alkylating agent of the formula R 4 -X 1 , preferably in the presence of a base.
  • R 5c is hydrogen
  • the compound I ' is reacted with an alkylating agent of the formula R 5 -X 1 or an acylating agent of the formula R 5 -X 2 , preferably in the presence of a base.
  • an alkylating agent of the formula R 5 -X 1 or an acylating agent of the formula R 5 -X 2 preferably in the presence of a base.
  • the aldehyde III is either commercially available or can be synthesized according to known methods for the preparation of aldehydes.
  • the compounds of the formula IV or IVa can be prepared by intramolecular cyclization of compounds of the general formula V or Va in analogy to other methods known from the literature, for example according to T. Kawasaki et al., Org. Lett. 2 (19) (2000), 3027-3029, Igor L. Rodionov et al., Tetrahedron 58 (42) (2002), 8515-8523 or AL Johnson et al., Tetrahedron 60 (2004), 961-965 ,
  • R 4a , R 7 , R 8 , R 9 and R 10 have the meanings given above.
  • R 5b represents hydrogen, Ci-C 4 alkyl, C 3 -C 4 alkenyl or C 3 -C 4 -alkyl kinyl.
  • R x is, for example, C 1 -C 6 -alkyl, in particular methyl, ethyl or phenyl-C 1 -C 6 -alkyl, for example benzyl.
  • the variables R 4c , R 7 , R 8 , R 9 and R 10 have the meanings given above.
  • R 5b represents hydrogen, Ci-C 4 alkyl, C 3 -C 4 alkenyl or C 3 -C 4 -alkyl kinyl.
  • R x is, for example, C 1 -C 6 -alkyl, in particular methyl, ethyl or phenyl-d-ce-alkyl, for example benzyl.
  • the cyclization of the compounds of formula V or Va can be carried out in the presence of a base.
  • the reaction is then usually carried out at temperatures in the range of 0 0 C to the boiling point of the reaction mixture, preferably from 10 0 C to 50 0 C, more preferably from 15 ° C to 35 ° C.
  • the reaction can be carried out in a solvent, preferably in an inert organic solvent.
  • Suitable inert organic solvents include aliphatic hydrocarbons such as pentane, hexane, cyclohexane and mixtures of Cs-Cs-alkanes, aromatic hydrocarbons such as toluene, o-, m- and p-xylene, halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform and chlorobenzene, ethers such as diethyl ether, diisopropyl ether, tert-butyl methyl ether, dioxane, anisole and tetrahydrofuran, nitriles such as acetonitrile and propionitrile, ketones such as acetone, methyl ethyl ketone, diethyl ketone and tert-butyl methyl ketone, alcohols such as methanol, ethanol, n-propanol, isopropanol, n- Butanol,
  • Suitable bases are e.g. inorganic compounds such as alkali metal and alkaline earth metal hydroxides such as lithium hydroxide, sodium hydroxide, potassium hydroxide or calcium hydroxide, aqueous solution of ammonia, alkali metal or alkaline earth metal oxides such as lithium oxide, sodium oxide, calcium oxide and magnesium oxide, alkali metal and alkaline earth metal hydrides such as lithium hydride, sodium hydride, potassium hydride and calcium hydride, Al alkali metal amides, such as lithium amide, for example lithium diisopropylamide, sodium amide and potassium amide, alkali metal and alkaline earth metal carbonates, such as lithium carbonate, potassium carbonate, cesium carbonate and calcium carbonate, and also alkali metal bicarbonates, such as sodium bicarbonate, organometallic compounds, in particular
  • Alkali metal alkyls such as methyllithium, butyllithium and phenyllithium, alkylmagnesium halides such as methylmagnesium chloride and also alkali metal and alkaline earth metal alkoxides such as sodium methoxide, sodium ethanolate, potassium ethanolate, potassium tert-butoxide, potassium tert-pentoxide and dimethoxy magnesium, as well as organic bases, eg tertiary amines such as trimethylamine, triethylamine, diisopropylethylamine, 2-hydroxypyridine and N-methylpiperidine, pyridine, substituted pyridines such as collidine, lutidine and 4-dimethylaminopyridine as well as bicyclic amines.
  • alkylmagnesium halides such as methylmagnesium chloride and also alkali metal and alkaline earth metal alkoxides such as sodium methoxide, sodium ethanolate, potassium ethanolate, potassium
  • a mixture of different bases can be used.
  • Particularly preferred are potassium tert-butoxide, 2-hydroxypyridine or an aqueous solution of ammonia or a mixture of these bases.
  • the reaction is carried out in the presence of an aqueous solution of ammonia, which may for example be from 10 to 50 w / v%.
  • the cyclization takes place in a mixture comprising n-butanol or a mixture of butanol isomers (for example a mixture of n-butanol with 2-butanol and / or isobutanol) and N-methyl-morpholine, preferably under reflux conditions.
  • the cyclization of V or Va can also be carried out under acidic catalysis, in the presence of activating compounds or thermally.
  • the reaction of V in the presence of an acid is usually effected at temperatures in the range of 10 0 C to the boiling point of the reaction mixture, preferably from 50 0 C to the boiling point, particularly preferably at the boiling point under reflux.
  • the reaction is carried out in a solvent, preferably in an inert organic solvent.
  • Suitable solvents are, in principle, those which can also be used for the basic cyclization, in particular alcohols.
  • the reaction is carried out in n-butanol or a mixture of different butanol isomers (e.g., a mixture of n-butanol with 2-butanol and / or isobutanol).
  • Suitable acids for the cyclization of V or Va are in principle both Bronstedt and Lewis acids into consideration.
  • inorganic acids e.g. Hydrohalic acids such as hydrofluoric acid, hydrochloric acid, hydrobromic acid, inorganic oxo acids such as sulfuric acid and perchloric acid, furthermore inorganic Lewis acids such as boron trifluoride, aluminum trichloride, ferric chloride, tin IV chloride, titanium (IV) chloride and zinc (II) chloride, and organic acids, for example carboxylic acids and hydroxycarboxylic acids such as formic acid, acetic acid, propionic acid, oxalic acid, citric acid and trifluoroacetic acid, as well as organic sulfonic acids such as toluenesulfonic acid, benzenesulfonic acid, camphorsulfonic acid and the like, find use.
  • a mixture of different acids can be used.
  • the reaction is carried out in the presence of organic acids, for example in the presence of carboxylic acids such as formic acid, acetic acid or trifluoroacetic acid or a mixture of these acids. Preferably, only one of these acids is used. In a preferred embodiment, the reaction is carried out in acetic acid.
  • the acid cyclization takes place in a mixture comprising n-butanol or a mixture of butanol isomers (for example a mixture of n-butanol with 2-butanol and / or isobutanol), N-methyl-morpholine and acetic acid, preferably under reflux conditions ,
  • reaction of V or Va is carried out by treatment with an activating agent in the presence of a base.
  • R x stands for hydrogen.
  • An example of a suitable activating agent is di (N-succinimidinyl) carbonate.
  • Suitable activating agents are also polystyrene or non-polystyrene-bonded dicyclohexylcarbodiimide (DCC), diisopropylcarbodiimide, 1-ethyl-3- (dimethylaminopropyl) carbodiimide (EDAC), carbonyldiimidazole, chloroformate such as methyl chloroformate, ethyl chloroformate, isopropyl chloroformate, isobutyl chloroformate, sec-butyl chloroformate or allyl chloroformate, pivaloyl chloride, polyphosphoric acid, propanephosphonic anhydride , Bis (2-oxo-3-oxazolidinyl) -phosphoryl chloride (BOPCI) or sulfonyl chlorides such as methanesulfonyl chloride, toluenesulfonyl chloride or benzenesulfonyl chloride.
  • DCC
  • Suitable bases are the compounds cited for the basic cyclization.
  • the base used is triethylamine or N-ethyldiisopropylamine or mixtures thereof, particularly preferably N-ethyldiisopropylamine.
  • the reaction of V or Va is carried out exclusively by heating the reaction mixture (thermal cyclization).
  • the reaction is usually carried out at temperatures in the range of 10 ° C to the boiling point of the reaction mixture, preferably from 50 ° C to
  • Boiling point of the reaction mixture particularly preferably at the boiling point of the reaction mixture under reflux.
  • the reaction is carried out in a solvent, preferably in an inert organic solvent.
  • Suitable solvents are, in principle, those which are used in the basic cyclization.
  • Preferred are polar aprotic solvents, e.g. Dimethyl sulfoxide or dimethylformamide or mixtures thereof.
  • the reaction is carried out in dimethyl sulfoxide.
  • R 4a and R 4c and / or R 5b is hydrogen in compound V or Va
  • the piperazine nitrogens can subsequently be used to introduce the radicals R 4a or R 4c and / or R 5a or R 5c Reaction with an alkylating agent R 4a -X 1 , R 5a -X 1 , R 4c -X 1 or R 5c -X 1 alkylated or by reaction with an acylating agent R 4a -X 2 , R 5a -X 2 , R 4c -X 2 or R 5c -X 2 are provided with a protective group.
  • R 4a , R 4c , R 5a , R 5c , X 1 and X 2 have the meanings given above.
  • the compounds of formula V or Va in turn can be prepared according to the synthesis shown in the following scheme in analogy to literature methods, for example according to Wilford L. Mendelson et al., Int. J. Peptide & Protein Research 35 (3), (1990), 249-57, Glenn L. Stahl et al., J. Org. Chem. 43 (11), (1978), 2285-6. or AK Ghosh et al., Org. Lett. 3 (4), (2001), 635-638.
  • the variables R x, R 4a, R 4c, R 5b, R 6, R 7, R 8, R 9 and R 10 have the meanings given for formula V.
  • the synthesis comprises the coupling of glycine ester compounds of the formula VII with Boc-protected phenylalanine compounds VIII or Villa in the presence of an activating reagent.
  • Boc another amino protecting group can also be used.
  • the reaction of a compound of formula VII with a compound of formula VIII or Villa is usually carried out at temperatures in the range of -30 0 C to the boiling point of the reaction mixture, preferably from 0 0 C to 50 0 C, particularly preferably from 20 0 C to 35 ° C.
  • the reaction may be carried out in a solvent, preferably in an inert organic solvent.
  • activating reagents are condensing agents, e.g. polystyrene- or non-polystyrene-bonded dicyclohexylcarbodiimide (DCC), diisopropylcarbodiimide, carbonyldiimidazole (CDI), 1-ethyl-3- (dimethylaminopropyl) carbodiimide (EDAC), chloroformate such as methyl chloroformate, ethyl chloroformate, isopropyl chloroformate, isobutyl chloroformate, sec-butyl chloroformate or allyl chloroformate , Polyvinyl chloride, polyphosphoric acid, propanephosphonic anhydride, bis (2-oxo-3-oxazolidinyl) -phosphoryl chloride (BOPCI) or sulfonyl chlorides such as methanesulfonyl chloride,
  • DCC polystyrene- or non-polys
  • the reaction of VII with VIII or Villa takes place in the presence of a base.
  • Suitable bases are the cyclization of the dipeptide V to piperazine IV cited compounds.
  • the base used is triethylamine or N-ethyldiisopropylamine or mixtures thereof, particularly preferably N-ethyldiisopropylamine.
  • the deprotection of the compounds VI or VIa to compound V or Va can be carried out by customary processes, for example as described by Glenn L. Stahl et al., J. Org. Chem. 43 (11), (1978), 2285-6 , or AK Ghosh et al., Org. Lett. 3 (4), (2001), 635-638.
  • Deprotection is typically by treatment with an acid.
  • Suitable acids are both Brönstedt and Lewis acids, preferably organic carboxylic acids, for example formic acid, acetic acid or trifluoroacetic acid or mixtures thereof.
  • the reaction is carried out in the presence of trifluoroacetic acid.
  • the reaction is usually carried out at temperatures in the range from -30 0 C to the boiling point of the reaction mixture, preferably from 0 0 C to 50 0 C, particularly preferably from 20 0 C to 35 ° C.
  • the reaction may be carried out in a solvent, preferably in an inert organic solvent.
  • Suitable solvents are, in principle, the solvents mentioned above in connection with the basic cyclization of V to IV, in particular tetrahydrofuran or dichloromethane or mixtures thereof. In a preferred embodiment, the reaction is carried out in dichloromethane.
  • the compounds IV or IVa can also be prepared by intermolecular cyclization of a glycine ester derivative VIIa with a phenylalanine compound VIIIb or VIIIc according to the following schemes:
  • R x , R 6 , R 7 , R 8 , R 9 and R 10 have the meanings given above.
  • R y is alkyl, for example methyl or ethyl.
  • the intermolecular cyclization can be effected, for example, by a base, for example ammonia.
  • the compounds VIIa and / or VIIIb or VIIIc can also be used in the form of their acid addition salts, for example as hydrochlorides.
  • the preparation of the compounds I comprises
  • R 1 , R 2 , R 3 , R 4 and R 6 have the abovementioned meanings, and R 5a has one of the meanings given for R 5 other than hydrogen or is a protective group;
  • R 7 , R 8 , R 9 and R 10 have the meanings given above and X is a nucleophilically displaceable leaving group, in the presence of a base;
  • R 5a is a protecting group, deprotecting.
  • R 5a preferably has a meaning other than hydrogen given for R 5 .
  • the variable X preferably has one of the following meanings: halogen, in particular chlorine, bromine or iodine or O-SO 2 -R m with R m in the meaning of Ci-C 4 -AlkVl or aryl, which is optionally substituted by halogen, C1 C4 alkyl or halo-Ci-C4-alkyl are substituted.
  • Suitable protective groups for the embroidery Substance atoms of the piperazine ring in IX are in particular the abovementioned radicals C (O) R 51 , for example the acetyl radical.
  • reaction of the compound IX with the compound X in step ii) can be carried out in analogy to the method described in process A, step iv) or, e.g. after in J. Am. Chem. Soc. 105, 1983, 3214.
  • the reaction takes place in the presence of sodium hydride as base in N-methylpyrrolidone as solvent.
  • the provision of the compounds IX can e.g. by reacting compound XI with a benzaldehyde compound XII, as explained in the following scheme.
  • R 1 , R 2 , R 3 , R 5a and R 6 have the meanings given above.
  • R 4a has one of the meanings given for R 4 or is a protective group.
  • Suitable protecting groups for the nitrogen atoms of the piperazine ring in XI are in particular the abovementioned radicals C (O) R 51 , for example the acetyl radical.
  • R 4a and R 5a represent one of the abovementioned radicals C (O) R 52 , for example acetyl radicals.
  • reaction of XI with XII can be carried out under the conditions of an aldol condensation, as already described for the reaction of III with IV or IVa.
  • aldol condensations can be carried out analogously to those described in J. Org. Chem. 2000, 65 (24), 8402-8405, Synlett 2006, 677, J. Heterocycl. Chem. 1988, 25, 591, to which reference is hereby fully made.
  • the reaction is usually carried out in the presence of a base.
  • a base it is preferable to use an alkali metal or alkaline earth metal carbonate, e.g. Sodium carbonate, potassium carbonate or cesium carbonate or mixtures thereof.
  • the reaction is carried out in an inert, preferably aprotic organic solvent.
  • suitable solvents are, in particular, dichloromethane, dichloroethane, chlorobenzene, ethers, such as diethyl ether, diisopropyl ether, tert-butyl methyl ether, dioxane, anisole and tetrahydrofuran, nitriles, such as acetonitrile and propylene onitrile, and dimethyl sulfoxide, dimethylformamide, N-methylpyrrolidone and dimethylacetamide
  • acetyl radical an acetyl radical
  • removal of the protective groups usually follows the condensation reaction.
  • the removal of a protective group R 4a , R 5a can be carried out in analogy to known methods of protecting group chemistry, for example according to the method described in Green, Wuts, Protective Groups in Organic Synthesis, 3rd ed. 1999, John Wiley and Sons, p.
  • a subsequent alkylation to introduce the radicals R 4 or R 5 can be carried out in the manner previously indicated in process A for the steps ii) or iii).
  • R 4a , R 5a and R 6 have the meanings given above.
  • R x is preferably C 1 -C 4 -alkyl or benzyl.
  • Boc is a tert-butoxycarbonyl radical.
  • R 4a and R 5a is a protective group, for example a radical C (O) R 51 , the introduction of these protective groups in By analogy with known methods of protecting group chemistry, for example by reaction with anhydrides of the formula (R 51 C (O)) 2 ⁇ , for example according to the in Green, Wuts, Protective Groups in Organic Synthesis, 3rd ed. 1999, John Wiley and Sons , P. 553.
  • the compounds of the formula I where R 5 * H can also be prepared by reacting a piperazine compound of the formula I in which R 5 is hydrogen with an alkylating agent or acylating agent which contains the radical R 5 other than hydrogen. Such reactions can be carried out analogously to those methods which have been explained in connection with method A steps ii), iii) and v). Competing alkylations can also be carried out at the stages of compounds VII, VIIa, VIII, VIIIa, VIIIb and VIIIc.
  • alkylating agents X 1 -R 5 X can 1 is halogen or O-SO2-R 111 with R m in the importance of Ci-C 4 -alkyl or aryl, which are optionally substituted by halogen, -C 4 -alkyl or halo-C -C 4 alkyl substituted.
  • acylating agents X 2 -R 5 X 2 may be halogen, in particular Cl.
  • R 5 stands for a radical (CO) R 51 .
  • the reaction is usually carried out at temperatures in the range of -78 ° C to the boiling point of the reaction mixture, preferably from -50 0 C to 65 ° C, particularly preferably from -30 0 C to 65 ° C.
  • the reaction is carried out in a solvent, preferably in an inert organic solvent.
  • Suitable solvents are the compounds mentioned in the cyclization of the dipeptide V to the piperazine IV, including toluene, dichloromethane, tetrahydrofuran or dimethylformamide or mixtures thereof.
  • Suitable bases are the compounds mentioned in the cyclization of the dipeptide V to the piperazine IV.
  • the bases are generally used equimolar. They can also be used in excess or even as a solvent.
  • the base is added in equimolar amount or substantially equimolar amount.
  • sodium hydride is used as the base.
  • compounds II, IV, V, VI, VIII in which R 5a or R 5b is H can be N-alkylated or N-acylated as described above.
  • precursors II, IV, V, VI, VII, in which the radical denoted by R 4 or R 4a is hydrogen can be alkylated.
  • the compounds of the formula I can also be modified on the group R 1 .
  • R 1 is CN, optionally substituted phenyl or an optionally substituted heterocyclic radical, starting from compounds I, wherein R 1 is halogen, such as chlorine, bromine or iodine, by conversion of the Substituents R 1 are prepared, for example in analogy to those of J. Tsuji, Top. Organomet. Chem. (14) (2005), 332 pp., J. Tsuji, Organic Synthesis with Palladium Compounds, (1980), 207 pp., Tetrahedron Lett. 42, 2001, p. 7473 or Org. Lett. 5, 2003, 1785.
  • a piperazine compound of formula I which as substituent R 1 has a halogen atom such as chlorine, bromine or iodine, by reaction with a coupling partner containing a group R 1 (compound R 1 -X 3 ), in another piperazine derivative of the formula I convicted.
  • a coupling partner containing a group R 1 compound R 1 -X 3
  • the reaction is usually carried out in the presence of a catalyst, preferably in the presence of a transition metal catalyst. In general, the reaction takes place in the presence of a base.
  • Suitable coupling partners X 3 -R 1 are, in particular, those compounds in which X 3 in the case of R 1 in the meaning of phenyl or heterocyclic radical (heterocyclyl) represents one of the following groups:
  • R m is H or C 1 -C 6 -alkyl, where two alkyl substituents can together form a C 2 -C 4 -alkylene chain; or SnR n 3, with R n in the meaning of Ci-C ⁇ -alkyl.
  • reaction are usually carried out at temperatures ranging from -78 ° C to the boiling point of the reaction mixture, preferably from -30 0 C to 65 ° C, particularly preferably at temperatures of 30 0 C to 65 ° C.
  • the reaction is carried out in an inert organic solvent in the presence of a base.
  • Suitable solvents are the compounds mentioned in the cyclization of the dipeptide IV to the piperazine V.
  • rens tetrahydrofuran is used with a catalytic amount of water; In another embodiment, only tetrahydrofuran is used.
  • Suitable bases are the compounds mentioned in the cyclization of the dipeptide IV to the piperazine V.
  • the bases are generally used equimolar. They can also be used in excess or even as a solvent.
  • the base is added in equimolar amount.
  • triethylamine or cesium carbonate are used as the base, particularly preferably cesium carbonate.
  • compounds of the transition metals Ni, Fe, Pd, Pt, Zr or Cu are suitable as catalysts for the process according to the invention. It is possible to use organic or inorganic compounds. By way of example, mention may be made of: Pd (PPh 3) Cl 2 , Pd (OAc) 2 , PdCl 2 or Na 2 PdCl 4. Ph stands for phenyl; Ac for acetyl.
  • the various catalysts can be used both individually and as mixtures.
  • Pd (PPhi3) 2 Cl 2 is used.
  • the compound Ia in which L is chlorine, bromine or iodine can also be reacted with copper cyanide in analogy to known processes (see, for example, Organikum, 21st Edition, 2001, Wiley 404, Tetrahedron Lett. 42, 2001, p.7473 or Org. Lett. 5, 2003, 1785 and literature cited therein).
  • reaction are usually carried out at temperatures in the range of 100 0 C to the boiling point of the reaction mixture, preferably from 100 0 C to 250 ° C.
  • the reaction is carried out in an inert organic solvent.
  • Suitable solvents are in particular aprotic polar solvents, for example dimethylformamide, N-methylpyrrolidone, N, N'-dimethylimidazolidin-2-one and dimethylacetamide.
  • the conversion of the group R 1 can alternatively also take place in the precursors of the compound I.
  • compounds II in which R 1 is a halogen atom such as chlorine, bromine or iodine be subjected to the reaction described above.
  • the alkylation or acylation of the group NR 4a , NR 5a , wherein R 4a and R 5a is H can alternatively be carried out in the precursors.
  • compounds II, IV, V, VI, VIII in which R 5a or R 5b is H can be N-alkylated or N-acylated as described above.
  • precursors II, IV, V, VI, VII, in which the radical denoted by R 4 or R 4a is hydrogen can be alkylated.
  • the compounds I and their agriculturally useful salts are suitable - both as mixtures of isomers and in the form of pure isomers - as herbicides. They are suitable as such or as appropriately formulated agent.
  • the herbicidal compositions containing compound I or Ia control plant growth on nonculture areas very well, especially at high application rates. In crops such as wheat, rice, corn, soybeans and cotton, they act against weeds and grass weeds without significantly damaging the crops. This effect occurs especially at low application rates.
  • the compounds I or Ia or agents containing them can be used in a further number of crop plants for the removal of undesirable plants.
  • the following cultures may be considered:
  • the following cultures are contemplated: Arachis hypogaea, Beta vulgaris spec. altissima, Brassica napus var. napus, Brassica oleracea, Citrus limon, Citrus sinensis, Coffea arabica (Coffea canephora, Coffea liberica), Cynodon dactylon, Glycine max, Gossypium hirsutum, (Gossypium arboreum, Gossypium herbaceum, Gossypium vitifolium), Helianthus annuus, Hordeum vulgaris, Juglans regia, Lens culinaris, Linum usitatissimum, Lycopersicon lycopersicum, Malus spec., Medicago sativa, Nicotiana tabacum (N.rustica), Olea europaea, Oryza sativa, Phaseolus lunatus, Phasolus Vulgaris, Pist
  • the compounds I can also be used in cultures that are tolerant to herbicides by breeding including genetic engineering methods.
  • the compounds I can also be used in cultures which are tolerant by breeding, including genetic engineering against insects or fungal attack.
  • the compounds of the formula I are also suitable for the defoliation and / or desiccation of plant parts, for which crop plants such as cotton, potato, oilseed rape, sunflower, soybean or field beans, in particular cotton, come into consideration.
  • compositions for the desiccation and / or defoliation of plants, processes for the preparation of these agents and methods for the desiccation and / or defoliation of plants with the compounds of formula I have been found.
  • the compounds of the formula I are particularly suitable for drying out the aerial parts of crop plants such as potato, rape, sunflower and soybean, but also cereals. This enables a completely mechanical harvesting of these important crops.
  • the compounds I or the herbicidal compositions containing them can be used, for example, in the form of directly sprayable aqueous solutions, powders, suspensions, and also high-percentage aqueous, oily or other suspensions or dispersions, Emulsions, oil dispersions, pastes, dusts, scattering agents or granules by spraying, atomizing, dusting, scattering, pouring or treatment of the seed or mixing with the seed can be applied.
  • the forms of application depend on the intended use; In any case, they should ensure the finest possible distribution of the active compounds according to the invention.
  • the herbicidal compositions contain a herbicidally effective amount of at least one compound of the formula I or an agriculturally useful salt of I and auxiliaries customary for the formulation of pesticides.
  • auxiliaries are inert auxiliaries, solid carriers, surface-active substances (such as dispersants, protective colloids, emulsifiers, wetting agents and adhesives), organic and inorganic thickeners, bactericides, antifreeze agents, defoamers, if appropriate, dyes and for seed formulations adhesives.
  • surface-active substances such as dispersants, protective colloids, emulsifiers, wetting agents and adhesives
  • organic and inorganic thickeners such as bactericides, antifreeze agents, defoamers, if appropriate, dyes and for seed formulations adhesives.
  • thickeners ie, compounds which impart modified flowability to the formulation, ie, high-level at low viscosity and low viscosity in the agitated state
  • polysaccharides such as xanthan gum (Kelzan® from Kelco), Rhodopol® 23 (Rhone Poulenc) or Veegum ® (company RT Vanderbilt) and organic and inorganic layer minerals such as Attaclay® (Engelhardt).
  • antifoam agents examples include silicone emulsions (such as, for example, Silikon® SRE, Wacker or Rhodorsil® from Rhodia), long-chain alcohols, fatty acids, salts of fatty acids, organofluorine compounds and mixtures thereof.
  • Bactericides may be added to stabilize the aqueous herbicidal formulation.
  • bactericides are bactericides based on diclorophene and benzyl alcohol hemiformal (Proxel® from ICI or Acticide® RS from Thor Chemie and Kathon® MK from Rohm & Haas) as well as isothiazolinone derivatives such as alkylisothiazolinones and benzisothiazolinones (Acticide MBS der Fa. Thor Chemie)
  • antifreeze agents are ethylene glycol, propylene glycol, urea or glycerol.
  • colorants are both water-insoluble pigments and water-soluble dyes. Examples which may be mentioned under the names rhodamine B, Cl. Pigment Red 1 12 and Cl. Solvent Red 1 known dyes, as well as pigment blue 15: 4, pigment blue 15: 3, pigment blue 15: 2, pigment blue 15: 1, pigment blue 80, pigment yellow 1, pigment yellow 13, pigment red 1 12, pigment red 48: 2, pigment red 48: 1, pigment red 57: 1, pigment red 53: 1, pigment orange 43, pigment orange 34, pigment orange 5, pigment green 36, pigment green 7, pigment white 6, pigment brown 25, basic violet 10, basic violet 49, acid red 51, acid red 52, acid red 14, acid blue 9, acid yellow 23, basic red 10, basic red 108.
  • adhesives are polyvinylpyrrolidone, polyvinyl acetate, polyvinyl alcohol and Tylose.
  • Suitable inert additives are, for example:
  • Mineral oil fractions of medium to high boiling point such as kerosene or diesel oil, coal tar oils and oils of vegetable or animal origin, aliphatic, cyclic and aromatic hydrocarbons, e.g. Paraffin, tetrahydronaphthalene, alkylated naphthalenes or their derivatives, alkylated benzenes or their derivatives, alcohols such as methanol, ethanol, propanol, butanol, cyclohexanol, ketones such as cyclohexanone or strongly polar solvents, eg. As amines such as N-methylpyrrolidone or water.
  • amines such as N-methylpyrrolidone or water.
  • Solid carriers are mineral earths such as silicic acids, 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.
  • mineral earths such as silicic acids, 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 nut
  • Suitable surface-active substances are the alkali metal, alkaline earth metal, ammonium salts of aromatic sulfonic acids, eg lignosulfonic acids (eg Borrespers types, Borregaard), phenolsulfonic acids, naphthalenesulfonic acids (Morwet types , Akzo Nobel) and dibutylnaphthalenesulfonic acid (Nekal types, BASF AG), as well as fatty acids, alkyl and alkylarylsulfonates, alkyl, lauryl ether and fatty alcohol sulfates, as well as salts of sulfated hexa-, hepta- and octadecanols and of fatty alcohol glycol ethers, condensation products of sulfonated naphthalene and its derivatives with formaldehyde, condensation products of n
  • Granules e.g. Coating, impregnation and homogeneous granules can be prepared by binding the active compounds to solid carriers.
  • Aqueous application forms can be prepared from emulsion concentrates, suspensions, pastes, wettable powders or water-dispersible granules by adding water.
  • emulsions, pastes or oil dispersions the compounds of the formula I or Ia, as such or dissolved in an oil or solvent, can be homogenized in water by means of wetting agents, tackifiers, dispersants or emulsifiers.
  • concentrates consisting of active substance, wetting, adhesion, dispersing or emulsifying agent and possibly solvent or oil, which are suitable for dilution with water.
  • the concentrations of the compounds of the formula I in the ready-to-use formulations can be varied within wide limits.
  • the formulations generally contain from 0.001 to 98% by weight, preferably from 0.01 to 95% by weight, of at least one active ingredient.
  • the active compounds are used in a purity of 90% to 100%, preferably 95% to 100% (according to NMR spectrum).
  • the compounds I according to the invention can be formulated, for example, as follows:
  • active compound 20 parts by weight are dissolved in 70 parts by weight of cyclohexanone with the addition of 10 parts by weight of a dispersant, e.g. Polyvinylpyrrolidone dissolved. Dilution in water gives a dispersion.
  • a dispersant e.g. Polyvinylpyrrolidone dissolved. Dilution in water gives a dispersion.
  • the active ingredient content is 20% by weight
  • active compound 25 parts by weight of active compound are dissolved in 35 parts by weight of an organic solvent (for example alkylaromatics) with addition of calcium dodecylbenzenesulfonate and castor oil ethoxylate (in each case 5 parts by weight).
  • organic solvent for example alkylaromatics
  • calcium dodecylbenzenesulfonate and castor oil ethoxylate in each case 5 parts by weight.
  • This mixture is added to water by means of an emulsifying machine (e.g., Ultraturax) in 30 parts by weight and made into a homogeneous emulsion. Dilution in water results in an emulsion.
  • the formulation has an active ingredient content of 25% by weight.
  • active compound 20 parts by weight of active compound are comminuted with the addition of 10 parts by weight dispersing and wetting agents and 70 parts by weight of water or an organic solvent in a stirred ball mill to a fine active substance suspension. Dilution in water results in a stable suspension of the active ingredient.
  • the active ingredient content in the formulation is 20% by weight.
  • Water-dispersible and water-soluble granules 50 parts by weight of active compound are finely ground with the addition of 50 parts by weight of dispersing and wetting agents and prepared by means of industrial equipment (for example extrusion, spray tower, fluidized bed) as water-dispersible or water-soluble granules. Dilution in water results in a stable dispersion or solution of the active ingredient.
  • the formulation has an active ingredient content of 50% by weight.
  • 0.5 parts by weight of active compound are finely ground and combined with 99.5 parts by weight of carriers. Common processes are extrusion, spray drying or fluidized bed. This gives a granulate for direct application with 0.5 wt .-% active ingredient content.
  • the application of the compounds I or the herbicidal compositions containing them can be carried out in the pre-emergence, postemergence or together with the seed of a crop. It is also possible to apply the herbicidal compositions or active ingredients characterized in that with the herbicidal agents or active ingredients pretreated seed of a crop plant is applied. If the active ingredients are less compatible with certain crops, then application techniques may be used whereby the herbicidal agents are sprayed with the sprayers so as not to hit the leaves of the sensitive crop if possible, while the active ingredients affect the leaves of growing undesirable plants or the uncovered floor surface (post-directed, lay-by).
  • the application of the compounds of the formula I or of the herbicidal compositions can be carried out by treating seed.
  • the treatment of seed comprises essentially all techniques familiar to the skilled worker (seed dressing, seed coating, seed dusting, seed soaking, seed film coating, seed multilayer coating, seed encrusting, seed dripping, and seed pelleting) based on the compounds according to the invention of the formula I or agents produced therefrom.
  • the herbicidal agents can be diluted or applied undiluted.
  • seed includes seeds of all kinds, e.g. Grains, seeds, fruits, tubers, cuttings and similar forms.
  • seed preferably describes grains and seeds here.
  • Seeds of the abovementioned crops but also the seeds of transgenic or obtained by conventional breeding methods plants can be used as seeds.
  • the application rates of active ingredient are 0.001 to 3.0, preferably 0.01 to 1.0 kg / ha active Substance (supra) -
  • the compounds I are usually used in amounts of 0.001 to 10 kg per 100 kg of seed.
  • the compounds of formula I can be mixed with numerous representatives of other herbicidal or growth-regulating active ingredient groups or with safeners and applied together.
  • Safeners are chemical compounds that prevent or reduce damage to crops without significantly affecting the herbicidal activity of the compounds of formula I on undesirable plants. They can be used both before sowing (for example, in seed treatments, in cuttings, or in seedlings) as well as in the pre- or post-emergence of the crop.
  • the safeners and the compounds of formula I can be used simultaneously or sequentially.
  • Suitable safeners are, for example, (quinoline-8-oxy) acetic acids, 1-phenyl-5-haloalkyl-1H-1, 2,4-triazole-3-carboxylic acid, 1-phenyl-4,5-dihydro-5-alkyl- 1 H-pyrazole-3,5-dicarboxylic acids, 4,5-dihydro-5,5-diaryl-3-isoxazolecarboxylic acids, dichloroacetamides, alpha-oximinophenylacetonitriles, acetophenone oximes, 4,6-dihalo-2-phenylpyrimidines, N- [ [4- (aminocarbonyl) phenyl] sulfonyl] -2-benzoic acid amides, 1,8-naphthalic anhydride, 2-halo-4- (haloalkyl) -5-thiazolecarboxylic acids, phosphorothiolates and N-alkyl-O-phenylc
  • HPLC-MS High Performance Liquid Chromatography combined with mass spectrometry; HPLC column: RP-18 column (Chromolith Speed ROD from Merck KGaA, Germany), 50 * 4.6 mm; Eluent: acetonitrile + 0.1% trifluoroacetic acid (TFA) / water + 0.1% TFA, with a gradient of 5: 95 to 100: 0 in 5 minutes at 40 0 C, flow rate 1, 8 ml / min; MS: Quadrupole electrospray ionization, 80V (positive mode).
  • the culture vessels used were plastic pots with loamy sand with about 3.0% humus as substrate.
  • the seeds of the test plants were sown separately by species.
  • the active ingredients suspended or emulsified in water were applied directly after sowing by means of finely distributing nozzles.
  • the jars were lightly rained to promote germination and growth and then covered with clear plastic hoods until the plants had grown. This cover causes a uniform germination of the test plants, if it was not affected by the active ingredients.
  • test plants were grown depending on the growth form only to a height of from 3 to 15 cm and then treated with the suspended or emulsified in water agents.
  • 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 plants were kept species-specific at temperatures of 10 - 25 ° C and 20 - 35 ° C, respectively.
  • the trial period lasted for 2 to 4 weeks. During this time, the plants were cared for, and their response to each treatment was evaluated.
  • the rating was based on a scale of 0 to 100. 100 means no emergence of the plants or complete destruction of at least the above-ground parts and 0 no damage or normal growth course.
  • a good herbicidal activity is at values of at least 70 and a very good herbicidal activity is given at values of at least 85.
  • the plants used in the greenhouse experiments were composed of the following species:
  • the compound of Example 43 shows at a rate of 0.5 kg / ha postemergence against APESV a good herbicidal action.
  • the compounds of Examples 44 and 47 show at a rate of 0.5 kg / ha postemergence against ECHCG a very good herbicidal activity.
  • the compound of Example 137 shows at a rate of 0.5 kg / ha postemergence against GALAP a good herbicidal action.
  • the compound of Example 10 shows at a rate of 0.5 kg / ha postemergence against LOLMU a good herbicidal action.
  • the compounds of Examples 24, 29, 43 and 137 show at a rate of application of 0.5 k g / ha in pre-emergence against APESV a very good herbicidal activity.
  • the compound of Example 25 shows at a rate of 0.5 kg / ha in the pre-emergence against CHEAL a good herbicidal action.
  • the compound of Example 25 shows at a rate of 0.5 kg / ha in the pre-emergence against SETVI a good herbicidal action.

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Abstract

The invention relates to piperazine compounds of the following defined general formula (I) and to their use as herbicides. The invention also relates to crop protection agents and to a method for combating undesired plant growth. In formula (I), the variables are defined as follows: R1 is selected from halogen, cyano, nitro, Z-C(=O)-R11, phenyl and a 5- or 6-membered heterocyclic group that has 1, 2, 3 or 4 heteroatoms, selected from O, N and S as ring atoms, wherein phenyl and the heterocyclic group are unsubstituted or have 1, 2, 3 or 4 substituents R1a; Z stands for a covalent bond or a CH2 group; R11 represents hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl, C2-C6 alkenyl, C5-C6 cycloalkenyl, C2-C6 alkynyl and similar; R2 represents hydrogen, halogen, nitro, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C2- C4 alkenyl, C1-C4 alkoxy, C1-C4 haloalkoxy, benzyl or a group S(O) nR21, wherein R21 stands for C1-C4 alkyl or C1-C4 haloalkyl and n stands for 0, 1 or 2; R3 represents hydrogen or halogen; R4 represents C1-C4 alkyl, C3- C4 alkenyl or C3-C4 alkynyl; R5 represents hydrogen, C1-C4 alkyl, C3-C4 alkenyl, C3-C4 alkynyl or a group (=O)R51, wherein R51 stands for hydrogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy or C1-C4 haloalkoxy; R6 stands for C1-C4 alkyl, C1-C4 hydroxy alkyl or C1-C4 haloalkyl; R7, R8 stand, independently of one another, for hydrogen, OH, C1-C4 alkoxy, C1-C4 haloalkyoxy, C1-C4 alkyl or C1-C4 haloalkyl; R9, R10 are selected, independently of one another, from hydrogen, halogen, CN, NO2, C1-C4 alkyl, C1-C4 haloalkyl, C2-C4

Description

Piperazinverbindungen mit herbizider Wirkung Piperazine compounds with herbicidal activity
Die vorliegende Erfindung betrifft Piperazinverbindungen der im Folgenden definierten allgemeinen Formel I und deren Verwendung als Herbizide. Die Erfindung betrifft außerdem Mittel für den Pflanzenschutz und ein Verfahren zur Bekämpfung von unerwünschtem Pflanzenwuchs.The present invention relates to piperazine compounds of the general formula I defined below and their use as herbicides. The invention also relates to crop protection agents and to a method of controlling undesired plant growth.
Bei den von dem Pflanzenpathogen S. Scabies produzierten Thaxtominen A und B (King R. R. et al., J. Agric. Food Chem. (1992) 40, 834-837) handelt es sich um Naturstoffe mit einem zentralen Piperazin-2,5-dion-Ring, der in der 3-Position einen 4-Nitro- indol-3-ylmethyl-Rest und in der 2-Position einen gegebenenfalls durch OH substituierten Benzyl-Rest trägt. Aufgrund ihrer pflanzenschädigenden Wirkung wurde auch die Verwendungsmöglichkeit dieser Verbindungsklasse als Herbizide untersucht (King R. R. et al., J. Agric. Food Chem. (2001) 49, 2298-2301 ).The thaxtomines A and B produced by the plant pathogen S. scabies (King RR et al., J. Agric. Food Chem. (1992) 40, 834-837) are natural products with a central piperazine 2,5- dione ring which carries a 4-nitro-indol-3-ylmethyl radical in the 3-position and a benzyl radical which may be substituted by OH in the 2-position. Because of their plant-damaging effect, the possibility of using this class of compounds as herbicides was also investigated (King R.R. et al., J. Agric. Food Chem. (2001) 49, 2298-2301).
J. Gelin et al., J. Org. Chem. 58, 1993, S. 3473-3475, und J. Moyroud et al., Tetrahedron 52, 1996, S. 8525-8543 beschreiben im Rahmen von synthetischen Untersuchungen zur Herstellung von Thaxtomin A und B Dehydrothaxtomin-Derivate. Unter anderem werden Verbindungen der Formel beschriebenJ. Gelin et al., J. Org. Chem. 58, 1993, pp. 3473-3475, and J. Moyroud et al., Tetrahedron 52, 1996, pp. 8525-8543 describe in the context of synthetic studies for the preparation of Thaxtomin A and B dehydrothaxtomin derivatives. Inter alia compounds of the formula are described
worin R für Wasserstoff oder NO2 steht. wherein R is hydrogen or NO 2.
N. Saito et al., J. Chem. Soc. Perkin Trans 1997, S. 53-69 beschreiben unter anderem Verbindungen der folgenden FormelSaito, N. et al., J. Chem. Soc. Perkin Trans 1997, pp. 53-69 describe inter alia compounds of the following formula
worin Ry für Wasserstoff oder Benzyl steht und Rx für Wasserstoff, Acetyl oder Isopro- pyloxycarbonyl steht, als Vorstufen für die Herstellung von Ecteinascidinen. wherein R y is hydrogen or benzyl and R x is hydrogen, acetyl or Isopro- pyloxycarbonyl, as precursors for the preparation of Ecteinascidinen.
Z.Z. Liu et al., Chinese Chem. Lett. 13(8) 2002, S. 701-704 beschreiben im Rahmen synthetischer Untersuchungen zur Herstellung von Phthalascidin eine Zwischenstufe der folgenden Formel, worin Bn für Benzyl steht: Currently Liu et al., Chinese Chem. Lett. 13 (8) 2002, p. 701-704 describe in synthetic studies for the preparation of phthalascidin an intermediate of the following formula in which Bn is benzyl:
J. Bryans et al., Journal of Antibiotics 49(10), 1996, S. 1014-1021 beschreiben die Verbindung der folgenden Formel:J. Bryans et al., Journal of Antibiotics 49 (10), 1996, pp. 1014-1021 describe the compound of the following formula:
Die WO 99/48889, WO 01/53290 und WO 2005/011699 beschreiben 2,5- Diketopiperazinverbindungen, die in der 3- bzw. 6-Position einen über eine Methylenoder Methingruppe gebundenen 4-lmidazolyl-Rest und in der anderen 3- bzw. 6- Position einen Benzyl- oder Benzylidenrest aufweisen. Bei diesen Verbindungen handelt es sich um Antitumor-Wirkstoffe.WO 99/48889, WO 01/53290 and WO 2005/011699 describe 2,5-Diketopiperazinverbindungen which in the 3- or 6-position bound via a methylene or methine 4-imidazolyl radical and in the other 3- or 6- position have a benzyl or Benzylidenrest. These compounds are antitumor agents.
Die ältere Patentanmeldung PCT/EP2007/050067 (= WO 2007/077247) beschreibt 2,5-Diketopiperazin-Verbindungen, die in der 3-Position einen über eine Methingruppe verknüpften Aryl- oder Hetarylrest und in der 6-Position einen über eine Methylengruppe verknüpften Aryl- oder Hetarylrest aufweisen.The earlier patent application PCT / EP2007 / 050067 (= WO 2007/077247) describes 2,5-diketopiperazine compounds which have in the 3-position an aryl or hetaryl radical linked via a methine group and in the 6-position a linked via a methylene group Have aryl or hetaryl radical.
Eine Aufgabe der vorliegenden Erfindung ist die Bereitstellung von Verbindungen mit herbizider Wirkung. Insbesondere sollen Verbindungen zur Verfügung gestellt werden, die eine hohe herbizide Wirkung, insbesondere bereits bei niedrigen Aufwandmengen, aufweisen und deren Verträglichkeit gegenüber Kulturpflanzen für eine kommerzielle Verwertung hinreichend ist.An object of the present invention is to provide compounds having herbicidal activity. In particular, compounds are to be made available which have a high herbicidal action, in particular even at low application rates, and their compatibility with crop plants for commercial exploitation is sufficient.
Diese und weitere Aufgaben werden durch die im Folgenden definierten Verbindungen der Formel I und durch ihre landwirtschaftlich geeigneten Salze gelöst.These and other objects are achieved by the compounds of the formula I defined below and by their agriculturally suitable salts.
Gegenstand der vorliegenden Erfindung sind somit Piperazinverbindungen der allgemeinen Formel I The present invention thus provides piperazine compounds of general formula I.
worin R1 ausgewählt ist unter Halogen, Cyano, Nitro, Z-C(=O)-R11, Phenyl und einem 5- oder 6-gliedrigen heterocyclischen Rest, der 1 , 2, 3 oder 4 Heteroatome, ausgewählt unter O, N und S als Ringatome aufweist, worin Phenyl und der heterocyc- lische Rest unsubstituiert sind oder 1 , 2, 3 oder 4 Substituenten R1a aufweisen können, die unabhängig voneinander unter Halogen, CN, NO2, Ci-C4-AIkVl, Cr C4-Haloalkyl, CrC4-AIkOXy und Ci-C4-Haloalkoxy ausgewählt sind, und worin Z für eine kovalente Bindung oder eine CH2-Gruppe steht; R11 Wasserstoff, Ci -C6-Al kyl, C3-C6-Cycloalkyl, C2-C6-Al kenyl, C5-C6-wherein R 1 is selected from halogen, cyano, nitro, ZC (= O) -R 11 , phenyl and a 5- or 6-membered heterocyclic radical containing 1, 2, 3 or 4 heteroatoms selected from O, N and S. in which phenyl and the heterocyclic radical are unsubstituted or may have 1, 2, 3 or 4 substituents R 1a which are independently of one another halogen, CN, NO 2, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy and C 1 -C 4 -haloalkoxy are selected, and wherein Z is a covalent bond or a CH 2 group; R 11 is hydrogen, C i -C 6 -alkyl, C 3 -C 6 cycloalkyl, C 2 -C 6 -alkenyl, C 5 -C 6 -
Cycloalkenyl, C2-C6-Al kinyl, Hydroxy, Ci-C6-Alkoxy, C3-C6-Alkenyloxy, C3- C6-Alkinyloxy, Amino, Ci-C6-Alkylamino, [Di-(Ci-C6)-alkyl]amino, CrC6- Alkoxyamino, CrC6-Alkylsulfonylamino, CrC6-Alkylaminosulfonylamino, [Di-(CrC6)-alkylamino]sulfonylamino, C3-C6-Alkenylamino, C3-C6- Alkinylamino, N-(C2-C6-Alkenyl)-N-(CrC6-alkyl)-amino, N-(C2-C6-Alkinyl)-N- (CrCe-alkyl)-amino, N-(Ci-C6-Alkoxy)-N-(CrC6-alkyl)-amino, N-(C2-C6- Alkenyl)-N-(CrCe-alkoxy)-amino, N-(C2-C6-Alkinyl)-N-(CrC6-alkoxy)-amino, Phenyl, Phenoxy oder Phenylamino bedeutet; wobei die Alkylteile in den unter R11 aufgeführten Resten teileweise oder vollständig halogeniert sein können und die Phenylteile in den unter R11 aufgeführten Resten 1 , 2, 3 oder 4 Substituenten R11a tragen können, die unter Halogen, CN, NO2, Ci-C4-Al kyl, CrC4-Haloalkyl, CrC4-Alkoxy und CrC4-Haloalkoxy ausgewählt sind; R2 Wasserstoff, Cyano, Nitro, Halogen, Ci-C4-Al kyl, CrC4-Haloalkyl, C2-C4-Alkenyl, CrC4-Alkoxy, CrC4-Haloalkoxy, Benzyl oder eine Gruppe S(O)nR21 bedeutet, worin R21 für CrC4-Alkyl oder CrC4-Haloalkyl steht und n für O, 1 oder 2 steht;Cycloalkenyl, C 2 -C 6 -alkyl kinyl, hydroxy, Ci-C 6 alkoxy, C 3 -C 6 alkenyloxy, C 3 - C 6 alkynyloxy, amino, Ci-C 6 -alkylamino, [di- (C -C 6) alkyl] amino, CrC 6 - alkoxyamino, -C 6 alkylsulfonylamino, CrC 6 -Alkylaminosulfonylamino, [di- (CrC 6) alkylamino] sulfonylamino, C 3 -C 6 alkenylamino, C 3 -C 6 - alkynylamino, N- (C 2 -C 6 -alkenyl) -N- (-C 6 alkyl) amino, N- (C 2 -C 6 -alkynyl) -N- (CRCE alkyl) amino, N- ( C 1 -C 6 -alkoxy) -N- (C 1 -C 6 -alkyl) -amino, N- (C 2 -C 6 -alkenyl) -N- (C 1 -C 6 -alkoxy) -amino, N- (C 2 -C 6 - Alkynyl) -N- (C 1 -C 6 alkoxy) amino, phenyl, phenoxy or phenylamino; where the alkyl moieties in the radicals listed under R 11 can be partially or completely halogenated and the phenyl moieties in the radicals listed under R 11 can carry 1, 2, 3 or 4 substituents R 11a which are halogen, CN, NO 2 , C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy and C 1 -C 4 haloalkoxy are selected; R 2 is hydrogen, cyano, nitro, halogen, Ci-C 4 -alkyl, -C 4 haloalkyl, C 2 -C 4 alkenyl, -C 4 alkoxy, -C 4 haloalkoxy, benzyl or a group S (O) n R 21 is wherein R 21 is C 1 -C 4 alkyl or C 1 -C 4 haloalkyl and n is O, 1 or 2;
R3 Wasserstoff oder Halogen bedeutet; R4 Ci-C4-Alkyl, C3-C4-Alkenyl oder C3-C4-Alkinyl bedeutet; R5 Wasserstoff, CrC4-Alkyl, C3-C4-Alkenyl, C3-C4-Alkinyl oder eine Gruppe C(=O)R51 bedeutet, worin R51 für Wasserstoff, Ci-C4-Al kyl, CrC4-Haloalkyl, Cr C4-Alkoxy oder CrC4-Ha loa I koxy steht;R 3 is hydrogen or halogen; R 4 is C 1 -C 4 -alkyl, C 3 -C 4 -alkenyl or C 3 -C 4 -alkynyl; R 5 is hydrogen, -C 4 alkyl, C 3 -C 4 alkenyl, C 3 -C 4 alkynyl or a group C (= O) R 51 wherein R 51 kyl 4 -alkyl, hydrogen, Ci-C, -C 4 haloalkyl, Cr C 4 alkoxy or CrC 4 -Ha loa I koxy group;
R6 für Ci-C4-Alkyl, CrC4-Hydroxyalkyl oder CrC4-Haloalkyl steht;R 6 is C 1 -C 4 -alkyl, C 1 -C 4 -hydroxyalkyl or C 1 -C 4 -haloalkyl;
R7, R8 unabhängig voneinander für Wasserstoff, OH, CrC4-Alkoxy, CrC4-Haloalkyoxy, CrC4-Alkyl oder CrC4-Haloalkyl stehen; R9, R10 unabhängig voneinander ausgewählt sind unter Wasserstoff, Halogen, CN, NO2, Ci-C4-AIkVl, Ci-C4-Haloalkyl, C2-C4-Alkenyl, Ci-C4-Alkoxy und Ci-C4- Haloalkoxy; sowie die landwirtschaftlich geeigneten Salze dieser Verbindungen.R 7, R 8 are independently hydrogen, OH, -C 4 alkoxy, CrC 4 -Haloalkyoxy, -C 4 alkyl or CrC stand 4 haloalkyl; R 9, R 10 are independently selected from hydrogen, halogen, CN, NO2, Ci-C 4 -alkyl, Ci-C 4 haloalkyl, C 2 -C 4 alkenyl, Ci-C4-alkoxy and Ci- C 4 - haloalkoxy; and the agriculturally suitable salts of these compounds.
Gegenstand der vorliegenden Erfindung ist auch die Verwendung von Piperazinverbin- dungen der allgemeinen Formel I oder der landwirtschaftlich brauchbaren Salze von Piperazinverbindungen der Formel I als Herbizide, d.h. zur Bekämpfung von Schadpflanzen.The present invention also provides the use of piperazine compounds of general formula I or the agriculturally useful salts of piperazine compounds of formula I as herbicides, i. for controlling harmful plants.
Gegenstand der vorliegenden Erfindung sind auch Mittel, welche mindestens eine Pi- perazinverbindung der Formel I oder ein landwirtschaftlich brauchbares Salz von I und für die Formulierung von Pflanzenschutzmitteln übliche Hilfsmittel enthalten.The present invention also relates to compositions which contain at least one piperazine compound of the formula I or an agriculturally useful salt of I and auxiliaries customary for the formulation of crop protection agents.
Gegenstand der vorliegenden Erfindung ist außerdem ein Verfahren zur Bekämpfung von unerwünschtem Pflanzenwuchs, bei dem man eine herbizid wirksame Menge mindestens einer Piperazinverbindung der Formel I oder eines landwirtschaftlich brauchbaren Salzes von I auf Pflanzen, deren Samen und/oder deren Lebensraum einwirken lässt.The present invention also relates to a method for controlling undesired plant growth, which comprises allowing a herbicidally effective amount of at least one piperazine compound of the formula I or an agriculturally useful salt of I to act on plants, their seeds and / or their habitat.
Die Erfindung betrifft außerdem Verfahren und Zwischenprodukte zur Herstellung von Verbindungen der Formel I.The invention also relates to processes and intermediates for the preparation of compounds of the formula I.
Weitere Ausführungsformen der vorliegenden Erfindung sind den Ansprüchen, der Be- Schreibung und den Beispielen zu entnehmen. Es versteht sich, dass die vorstehend genannten und die nachstehend noch zu erläuternden Merkmale des erfindungsgemäßen Gegenstandes nicht nur in der jeweils angegebenen Kombination, sondern auch in anderen Kombinationen verwendbar sind, ohne den Rahmen der Erfindung zu verlassen.Further embodiments of the present invention can be taken from the claims, the description and the examples. It is understood that the features mentioned above and those yet to be explained of the subject matter according to the invention can be used not only in the particular combination specified, but also in other combinations, without departing from the scope of the invention.
Die Verbindungen der Formel I weisen am Kohlenstoffatom, welches den Rest R6 trägt, ein Chiralitätszentrum auf. Zudem können sie, je nach Substitutionsmuster, ein oder mehrere weitere Chiralitätszentren enthalten. Die erfindungsgemäßen Verbindungen können daher als reine Enantiomere oder Diastereomere oder als Enantiomeren- oder Diastereomerengemische vorliegen. Gegenstand der Erfindung sind sowohl die reinen Enantiomeren oder Diastereomeren als auch deren Gemische.The compounds of the formula I have a chiral center on the carbon atom which carries the radical R 6 . In addition, depending on the substitution pattern, they may contain one or more other chiral centers. The compounds according to the invention can therefore be present as pure enantiomers or diastereomers or as mixtures of enantiomers or diastereomers. The invention relates to both the pure enantiomers or diastereomers and mixtures thereof.
Die Verbindungen der Formel I können bezüglich der exocyclischen Doppelbindung als E-Isomer oder als Z-Isomer vorliegen. Gegenstand der Erfindung sind sowohl die rei- nen E-Isomere und Z-Isomere als auch deren Gemische. Die Verbindungen der Formel I können auch in Form ihrer landwirtschaftlich brauchbaren Salze vorliegen, wobei es auf die Art des Salzes in der Regel nicht ankommt. Im Allgemeinen kommen die Salze derjenigen Kationen oder die Säureadditionssalze derjenigen Säuren in Betracht, deren Kationen, beziehungsweise Anionen, die herbizide Wirkung der Verbindungen I nicht negativ beeinträchtigen.The compounds of the formula I can be present as E-isomer or as Z-isomer with respect to the exocyclic double bond. The invention relates to both the pure E isomers and Z isomers and their mixtures. The compounds of the formula I can also be present in the form of their agriculturally useful salts, wherein the type of salt generally does not matter. In general, the salts of those cations or the acid addition salts of those acids come into consideration whose cations, or anions, do not adversely affect the herbicidal activity of the compounds I.
Es kommen als Kationen insbesondere Ionen der Alkalimetalle, vorzugsweise Lithium, Natrium oder Kalium, der Erdalkalimetalle, vorzugsweise Calcium oder Magnesium, und der Übergangsmetalle, vorzugsweise Mangan, Kupfer, Zink oder Eisen in Betracht. Ebenso kann als Kation Ammonium verwendet werden, wobei hier gewünschtenfalls ein bis vier Wasserstoffatome durch Ci-C4-AIkVl, Hydroxy-Ci-C4-alkyl, Ci-C4-Alkoxy-Ci- C4-alkyl, Hydroxy-Ci-C4-alkoxy-Ci-C4-alkyl, Phenyl oder Benzyl ersetzt sein können, vorzugsweise Ammonium, Dimethylammonium, Diisopropylammonium, Tetramethylammonium, Tetrabutylammonium, 2-(2-Hydroxyeth-1-oxy)eth-1-ylammonium, Di(2- hydroxyeth-1-yl)ammonium, Trimethylbenzylammonium. Des Weiteren kommenIn particular, ions of the alkali metals, preferably lithium, sodium or potassium, the alkaline earth metals, preferably calcium or magnesium, and the transition metals, preferably manganese, copper, zinc or iron are suitable as cations. It is likewise possible to use ammonium as the cation, where, if desired, one to four hydrogen atoms are represented by C 1 -C 4 -alkyl, hydroxy-C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl, hydroxyC 1 -C 4 -alkoxy-Ci-C 4 alkyl, phenyl or benzyl may be replaced, preferably ammonium, dimethylammonium, diisopropylammonium, tetramethylammonium, tetrabutylammonium, 2- (2-hydroxyeth-1-oxy) eth-1-ylammonium, di (2-hydroxyeth -1-yl) ammonium, trimethylbenzylammonium. Furthermore come
Phosphoniumionen, Sulfoniumionen, vorzugsweise Tri(Ci-C4-alkyl)sulfonium oder SuI- foxoniumionen, vorzugsweise Tri(Ci-C4-alkyl)sulfoxonium, in Betracht.Phosphonium ions, sulfonium ions, preferably tri (C 1 -C 4 -alkyl) sulfonium or sulfonoxonium ions, preferably tri (C 1 -C 4 -alkyl) sulfoxonium.
Anionen von brauchbaren Säureadditionsalzen sind in erster Linie Chlorid, Bromid, Fluorid, Hydrogensulfat, Sulfat, Dihydrogenphosphat, Hydrogenphosphat, Nitrat,Anions of useful acid addition salts are primarily chloride, bromide, fluoride, hydrogen sulfate, sulfate, dihydrogen phosphate, hydrogen phosphate, nitrate,
Hydrogencarbonat, Carbonat, Hexafluorosilikat, Hexafluorophosphat, Benzoat sowie die Anionen von Ci-C4-Alkansäuren, vorzugsweise Formiat, Acetat, Propionat oder Butyrat.Hydrogen carbonate, carbonate, hexafluorosilicate, hexafluorophosphate, benzoate and the anions of Ci-C 4 -alkanoic acids, preferably formate, acetate, propionate or butyrate.
Die für die Substituenten der erfindungsgemäßen Verbindungen genannten organischen Molekülteile stellen Sammelbegriffe für individuelle Aufzählungen der einzelnen Gruppenmitglieder dar. Sämtliche Kohlenwasserstoffketten, wie Alkyl, Halo(gen)alkyl, Alkenyl, Alkinyl, sowie die Alkylteile und Alkenylteile in Alkoxy, Halo(gen)alkoxy, Alky- lamino, Dialkylamino, N-Alkylsulfonylamino, Alkenyloxy, Alkinyloxy, Alkoxyamino, Alky- laminosulfonylamino, Dialkylaminosulfonylamino, Alkenylamino, Alkinylamino, N-The organic molecular moieties mentioned for the substituents of the compounds according to the invention are collective terms for individual listings of the individual group members. All hydrocarbon chains, such as alkyl, halo (gen) alkyl, alkenyl, alkynyl, and the alkyl moieties and alkenyl moieties in alkoxy, halo (gen) alkoxy, Alkylamino, dialkylamino, N-alkylsulfonylamino, alkenyloxy, alkynyloxy, alkoxyamino, alkylaminosulfonylamino, dialkylaminosulfonylamino, alkenylamino, alkynylamino, N-
(Alkenyl)-N-(alkyl)-amino, N-(Alkinyl)-N-(alkyl)-amino, N-(Alkoxy)-N-(alkyl)-amino, N- (Alkenyl)-N-(alkoxy)-amino oder N-(Alkinyl)-N-(alkoxy)-amino können geradkettig oder verzweigt sein.(Alkenyl) -N- (alkyl) -amino, N- (alkynyl) -N- (alkyl) -amino, N- (alkoxy) -N- (alkyl) -amino, N- (alkenyl) -N- (alkoxy ) -amino or N- (alkynyl) -N- (alkoxy) -amino can be straight-chain or branched.
Das Präfix Cn-Cm- gibt die jeweilige Kohlenstoffzahl der Kohlenwasserstoffeinheit an. Sofern nicht anders angegeben tragen halogenierte Substituenten vorzugsweise ein bis fünf gleiche oder verschiedene Halogenatome, insbesondere Fluoratome oder Chloratome.The prefix C n -Cm- indicates the respective carbon number of the hydrocarbon moiety. Unless otherwise stated, halogenated substituents preferably carry one to five identical or different halogen atoms, in particular fluorine atoms or chlorine atoms.
Die Bedeutung Halogen steht jeweils für Fluor, Chlor, Brom oder lod.The meaning halogen in each case represents fluorine, chlorine, bromine or iodine.
Ferner bedeuten beispielsweise: Alkyl sowie die Alkylteile beispielsweise in Alkoxy, Alkylamino, Dialkylamino, N- Alkylsulfonylamino, Alkylaminosulfonylamino, Dialkylaminosulfonylamino, N-(Alkenyl)- N-(alkyl)-amino, N-(Alkinyl)-N-(alkyl)-amino, N-(Alkoxy)-N-(alkyl)-amino,: gesättigte, geradkettige oder verzweigte Kohlenwasserstoffreste mit einem oder mehr C-Atomen, z.B. 1 bis 2, 1 bis 4, oder 1 bis 6 Kohlenstoffatomen, z.B. Ci-C6-Alkyl wie Methyl, Ethyl, Propyl, 1-Methylethyl, Butyl, 1-Methylpropyl, 2-Methylpropyl, 1 ,1-Dimethylethyl, Pentyl, 1-Methylbutyl, 2-Methylbutyl, 3-Methyl butyl, 2,2-Dimethylpropyl, 1-Ethylpropyl, Hexyl, 1 ,1-Dimethylpropyl, 1 ,2-Dimethylpropyl, 1-Methylpentyl, 2-Methylpentyl, 3- Methylpentyl, 4-Methylpentyl, 1 ,1-Dimethylbutyl, 1 ,2-Dimethylbutyl, 1 ,3-Dimethylbutyl, 2,2-Dimethylbutyl, 2,3-Dimethylbutyl, 3,3-Dimethylbutyl, 1-Ethylbutyl, 2-Ethylbutyl, 1 ,1 ,2-Trimethylpropyl, 1 ,2,2-Trimethylpropyl, 1-Ethyl-1-methylpropyl, 1 -Ethyl-2- methylpropyl. In einer erfindungsgemäßen Ausführungsform steht Alkyl für kleine Al- kylgruppen wie Ci-C4-AIkVl. In einer anderen erfindungsgemäßen Ausführungsform steht Alkyl für größere Alkylgruppen wie Cs-Cβ-Alkyl.Furthermore, for example: Alkyl and the alkyl moieties, for example, in alkoxy, alkylamino, dialkylamino, N-alkylsulfonylamino, alkylaminosulfonylamino, dialkylaminosulfonylamino, N- (alkenyl) -N- (alkyl) -amino, N- (alkynyl) -N- (alkyl) -amino, N- (Alkoxy) -N- (alkyl) -amino ,: saturated, straight-chain or branched hydrocarbon radicals having one or more carbon atoms, for example 1 to 2, 1 to 4, or 1 to 6 carbon atoms, for example Ci-C 6 -alkyl, such as Methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl, 2-methylpropyl, 1, 1-dimethylethyl, pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl , Hexyl, 1, 1-dimethylpropyl, 1, 2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1, 1-dimethylbutyl, 1, 2-dimethylbutyl, 1, 3-dimethylbutyl, 2 , 2-Dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1, 1, 2-trimethylpropyl, 1, 2,2-trimethylpropyl, 1-ethyl-1-methylpropyl, 1 -Ethyl-2-methylpropyl. In one embodiment of the invention, alkyl is a small alkyl group such as C 1 -C 4 -alkyl. In another embodiment of the invention, alkyl is greater alkyl groups such as Cs-Cβ-alkyl.
Halogenalkyl (auch als Haloalkyl bezeichnet): einen Alkylrest wie vorstehend genannt, dessen Wasserstoffatome partiell oder vollständig durch Halogenatome wie Fluor, Chlor, Brom und/oder lod substituiert sind, z.B. Chlormethyl, Dichlormethyl, Trichlor- methyl, Fluormethyl, Difluormethyl, Trifluormethyl, Chlorfluormethyl, Dichlorfluormethyl, Chlordifluormethyl, 2-Fluorethyl, 2-Chlorethyl, 2-Bromethyl, 2-lodethyl, 2,2-Difluorethyl, 2,2,2-Trifluorethyl, 2-Chlor-2-fluorethyl, 2-Chlor-2,2-difluorethyl, 2,2-Dichlor-2-fluorethyl, 2,2,2-Trichlorethyl, Pentafluorethyl, 2-Fluorpropyl, 3-Fluorpropyl, 2,2-Difluorpropyl, 2,3- Difluorpropyl, 2-Chlorpropyl, 3-Chlorpropyl, 2,3-Dichlorpropyl, 2-Brompropyl, 3- Brompropyl, 3,3,3-Trifluorpropyl, 3,3,3-Trichlorpropyl, 2,2,3,3,3-Pentafluorpropyl, Hep- tafluorpropyl, 1-(Fluormethyl)-2-fluorethyl, 1-(Chlormethyl)-2-chlorethyl, 1- (Brommethyl)-2-bromethyl, 4-Fluorbutyl, 4-Chlorbutyl, 4-Brombutyl und Nonafluorbutyl.Haloalkyl (also referred to as haloalkyl): an alkyl radical as mentioned above, the hydrogen atoms of which are partially or completely substituted by halogen atoms such as fluorine, chlorine, bromine and / or iodine, e.g. Chloromethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, 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, pentafluoroethyl, 2-fluoropropyl, 3-fluoropropyl, 2,2- Difluoropropyl, 2,3-difluoropropyl, 2-chloropropyl, 3-chloropropyl, 2,3-dichloropropyl, 2-bromopropyl, 3-bromopropyl, 3,3,3-trifluoropropyl, 3,3,3-trichloropropyl, 2,2, 3,3,3-pentafluoropropyl, hepafluoropropyl, 1- (fluoromethyl) -2-fluoroethyl, 1- (chloromethyl) -2-chloroethyl, 1- (bromomethyl) -2-bromoethyl, 4-fluorobutyl, 4-chlorobutyl, 4-bromobutyl and nonafluorobutyl.
Cycloalkyl sowie die Cycloalkylteile beispielsweise in Cycloalkoxy oder Cycloalkylcar- bonyl: monocyclische, gesättigte Kohlenwasserstoffgruppen mit drei oder mehr C- Atomen, z.B. 3 bis 6 Kohlenstoffringgliedern, wie Cyclopropyl, Cyclobutyl, Cyclopentyl und Cyclohexyl.Cycloalkyl and the cycloalkyl moieties, for example, in cycloalkoxy or cycloalkylcarbonyl: monocyclic, saturated hydrocarbon groups having three or more C atoms, e.g. 3 to 6 carbon ring members such as cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.
Alkenyl sowie Alkenylteile beispielsweise in Alkenylamino, Alkenyloxy, N-(Alkenyl)-N- (alkyl)-amino, N-(Alkenyl)-N-(alkoxy)-amino: einfach ungesättigte, geradkettige oder verzweigte Kohlenwasserstoffreste mit zwei oder mehr C-Atomen, z. B. 2 bis 4, 2 bis 6 oder 3 bis 6 Kohlenstoffatomen und einer Doppelbindung in einer beliebigen Position, z.B. C2-C6-Alkenyl wie Ethenyl, 1-Propenyl, 2-Propenyl, 1-Methylethenyl, 1-Butenyl, 2- Butenyl, 3-Butenyl, 1-Methyl-1-propenyl, 2-Methyl-1-propenyl, 1-Methyl-2-propenyl, 2- Methyl-2-propenyl, 1-Pentenyl, 2-Pentenyl, 3-Pentenyl, 4-Pentenyl, 1-Methyl-1-butenyl, 2-Methyl-1-butenyl, 3-Methyl-1-butenyl, 1-Methyl-2-butenyl, 2-Methyl-2-butenyl, 3- Methyl-2-butenyl, 1-Methyl-3-butenyl, 2-Methyl-3-butenyl, 3-Methyl-3-butenyl, 1 ,1- Dimethyl-2-propenyl, 1 ,2-Dimethyl-1-propenyl, 1 ,2-Dimethyl-2-propenyl, 1-Ethyl-1- propenyl, 1-Ethyl-2-propenyl, 1-Hexenyl, 2-Hexenyl, 3-Hexenyl, 4-Hexenyl, 5-Hexenyl, 1-Methyl-1-pentenyl, 2-Methyl-1-pentenyl, 3-Methyl-1-pentenyl, 4-Methyl-1-pentenyl, 1- Methyl-2-pentenyl, 2-Methyl-2-pentenyl, 3-Methyl-2-pentenyl, 4-Methyl-2-pentenyl, 1- Methyl-3-pentenyl, 2-Methyl-3-pentenyl, 3-Methyl-3-pentenyl, 4-Methyl-3-pentenyl, 1- Methyl-4-pentenyl, 2-Methyl-4-pentenyl, 3-Methyl-4-pentenyl, 4-Methyl-4-pentenyl, 1 ,1- Dimethyl-2-butenyl, 1 ,1-Dimethyl-3-butenyl, 1 ,2-Dimethyl-1-butenyl, 1 ,2-Dimethyl-2- butenyl, 1 ,2-Dimethyl-3-butenyl, 1 ,3-Dimethyl-1-butenyl, 1 ,3-Dimethyl-2-butenyl, 1 ,3- Dimethyl-3-butenyl, 2,2-Dimethyl-3-butenyl, 2,3-Dimethyl-1-butenyl, 2,3-Dimethyl-2- butenyl, 2,3-Dimethyl-3-butenyl, 3,3-Dimethyl-1-butenyl, 3,3-Dimethyl-2-butenyl, 1- Ethyl-1-butenyl, 1-Ethyl-2-butenyl, 1-Ethyl-3-butenyl, 2-Ethyl-1 -butenyl, 2-Ethyl-2- butenyl, 2-Ethyl-3-butenyl, 1 ,1 ,2-Trimethyl-2-propenyl, 1-Ethyl-1-methyl-2-propenyl, 1- Ethyl-2-methyl-1 -propenyl, 1 -Ethyl-2-methyl-2-propenyl.Alkenyl and alkenyl moieties, for example, in alkenylamino, alkenyloxy, N- (alkenyl) -N- (alkyl) -amino, N- (alkenyl) -N- (alkoxy) -amino: monounsaturated, straight-chain or branched hydrocarbon radicals having two or more carbon atoms. Atoms, z. B. 2 to 4, 2 to 6 or 3 to 6 carbon atoms and a double bond in any position, for example C2-C6 alkenyl such as ethenyl, 1-propenyl, 2-propenyl, 1-methylethenyl, 1-butenyl, 2-butenyl , 3-Butenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 1-methyl-2-propenyl, 2-methyl-2-propenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4 Pentenyl, 1-methyl-1-butenyl, 2-methyl-1-butenyl, 3-methyl-1-butenyl, 1-methyl-2-butenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl , 1-methyl-3-butenyl, 2-methyl-3-butenyl, 3-methyl-3-butenyl, 1, 1 Dimethyl 2-propenyl, 1, 2-dimethyl-1-propenyl, 1, 2-dimethyl-2-propenyl, 1-ethyl-1-propenyl, 1-ethyl-2-propenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1-methyl-1-pentenyl, 2-methyl-1-pentenyl, 3-methyl-1-pentenyl, 4-methyl-1-pentenyl, 1-methyl-2 pentenyl, 2-methyl-2-pentenyl, 3-methyl-2-pentenyl, 4-methyl-2-pentenyl, 1-methyl-3-pentenyl, 2-methyl-3-pentenyl, 3-methyl-3-pentenyl, 4-methyl-3-pentenyl, 1-methyl-4-pentenyl, 2-methyl-4-pentenyl, 3-methyl-4-pentenyl, 4-methyl-4-pentenyl, 1, 1-dimethyl-2-butenyl, 1, 1-dimethyl-3-butenyl, 1, 2-dimethyl-1-butenyl, 1, 2-dimethyl-2-butenyl, 1, 2-dimethyl-3-butenyl, 1, 3-dimethyl-1-butenyl, 1,3-dimethyl-2-butenyl, 1,3-dimethyl-3-butenyl, 2,2-dimethyl-3-butenyl, 2,3-dimethyl-1-butenyl, 2,3-dimethyl-2-butenyl, 2,3-dimethyl-3-butenyl, 3,3-dimethyl-1-butenyl, 3,3-dimethyl-2-butenyl, 1-ethyl-1-butenyl, 1-ethyl-2-butenyl, 1-ethyl 3-butenyl, 2-ethyl-1-butenyl, 2-ethyl-2-butenyl, 2-ethyl-3-butenyl, 1, 1, 2-trimethyl-2-propylene 1, 1-ethyl-1-methyl-2-propenyl, 1-ethyl-2-methyl-1-propenyl, 1-ethyl-2-methyl-2-propenyl.
Cycloalkenyl: monocyclische, einfach ungesättigte Kohlenwasserstoffgruppen mit 5 bis 6, vorzugsweise 5 bis 6 Kohlenstoffringgliedern, wie Cyclopenten-1-yl, Cyclopenten-3- yl, Cyclohexen-1-yl, Cyclohexen-3-yl, Cyclohexen-4-yl.Cycloalkenyl: monocyclic, monounsaturated hydrocarbon groups having 5 to 6, preferably 5 to 6 carbon ring members, such as cyclopenten-1-yl, cyclopenten-3-yl, cyclohexen-1-yl, cyclohexen-3-yl, cyclohexen-4-yl.
Alkinyl sowie Alkinylteile beispielsweise in Alkinyloxy, Alkinylamino, N-(Alkinyl)-N- (alkyl)-amino oder N-(Alkinyl)-N-(alkoxy)-amino: geradkettige oder verzweigte Kohlenwasserstoffgruppen mit zwei oder mehr C-Atomen, z. B. 2 bis 4, 2 bis 6, oder 3 bis 6 Kohlenstoffatomen und einer Dreifachbindung in beliebiger Position, z. B. C2-C6-Alkinyl wie Ethinyl, 1-Propinyl, 2-Propinyl, 1-Butinyl, 2-Butinyl, 3-Butinyl, 1-Methyl-2-propinyl, 1-Pentinyl, 2-Pentinyl, 3-Pentinyl, 4-Pentinyl, 1-Methyl-2-butinyl, 1 -Methyl-3-butinyl, 2- Methyl-3-butinyl, 3-Methyl-1 -butinyl, 1 ,1-Dimethyl-2-propinyl, 1 -Ethyl-2-propinyl, 1- Hexinyl, 2-Hexinyl, 3-Hexinyl, 4-Hexinyl, 5-Hexinyl, 1-Methyl-2-pentinyl, 1 -Methyl-3- pentinyl, 1-Methyl-4-pentinyl, 2-Methyl-3-pentinyl, 2-Methyl-4-pentinyl, 3-Methyl-1- pentinyl, 3-Methyl-4-pentinyl, 4-Methyl-1-pentinyl, 4-Methyl-2-pentinyl, 1 ,1-Dimethyl-2- butinyl, 1 ,1-Dimethyl-3-butinyl, 1 ,2-Dimethyl-3-butinyl, 2,2-Dimethyl-3-butinyl, 3,3- Dimethyl-1 -butinyl, 1-Ethyl-2-butinyl, 1-Ethyl-3-butinyl, 2-Ethyl-3-butinyl, 1-Ethyl-1- methyl-2-propinyl.Alkynyl and alkynyl moieties, for example, in alkynyloxy, alkynylamino, N- (alkynyl) -N- (alkyl) -amino or N- (alkynyl) -N- (alkoxy) -amino: straight-chain or branched hydrocarbon groups having two or more carbon atoms, eg , B. 2 to 4, 2 to 6, or 3 to 6 carbon atoms and a triple bond in any position, for. C 2 -C 6 -alkynyl, such as ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-methyl-2-propynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1-methyl-2-butynyl, 1-methyl-3-butynyl, 2-methyl-3-butynyl, 3-methyl-1-butynyl, 1, 1-dimethyl-2-propynyl, 1-ethyl 2-propynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl, 1-methyl-2-pentynyl, 1-methyl-3-pentynyl, 1-methyl-4-pentynyl, 2 Methyl 3-pentynyl, 2-methyl-4-pentynyl, 3-methyl-1-pentynyl, 3-methyl-4-pentynyl, 4-methyl-1-pentynyl, 4-methyl-2-pentynyl, 1, 1 Dimethyl-2-butynyl, 1, 1-dimethyl-3-butynyl, 1, 2-dimethyl-3-butynyl, 2,2-dimethyl-3-butynyl, 3,3-dimethyl-1-butynyl, 1-ethyl 2-butynyl, 1-ethyl-3-butynyl, 2-ethyl-3-butynyl, 1-ethyl-1-methyl-2-propynyl.
Alkoxy: Alkyl, wie vorstehend definiert, das über ein O-Atom gebunden ist: z. B. Metho- xy, Ethoxy, n-Propoxy, 1 -Methylethoxy, Butoxy, 1-Methylpropoxy, 2-Methylpropoxy oder 1 ,1-Dimethylethoxy, Pentoxy, 1-Methylbutoxy, 2-Methylbutoxy, 3-Methylbutoxy, 1 ,1-Dimethylpropoxy, 1 ,2-Dimethylpropoxy, 2,2-Dimethylpropoxy, 1-Ethylpropoxy, He- xoxy, 1-Methylpentoxy, 2-Methylpentoxy, 3-Methylpentoxy, 4-Methylpentoxy, 1 ,1- Dimethylbutoxy, 1 ,2-Dimethylbutoxy, 1 ,3-Dimethylbutoxy, 2,2-Dimethylbutoxy, 2,3- Dimethylbutoxy, 3,3-Dimethylbutoxy, 1-Ethylbutoxy, 2-Ethyl butoxy, 1 ,1 ,2- Trimethylpropoxy, 1 ,2,2-Trimethylpropoxy, 1-Ethyl-1-methylpropoxy oder 1 -Ethyl-2- methylpropoxy. Aryl: ein- oder mehrkernige aromatische Kohlenwasserstoffreste mit 6 bis 14 Kohlenstoffatomen, wie Phenyl, Naphthyl, Anthracenyl oder Phenanthrenyl, vorzugsweise Phenyl oder Naphthyl.Alkoxy: alkyl, as defined above, which is bonded via an oxygen atom: z. Methoxy, ethoxy, n-propoxy, 1-methylethoxy, butoxy, 1-methylpropoxy, 2-methylpropoxy or 1, 1-dimethylethoxy, pentoxy, 1-methylbutoxy, 2-methylbutoxy, 3-methylbutoxy, 1, 1- Dimethylpropoxy, 1, 2-dimethylpropoxy, 2,2-dimethylpropoxy, 1-ethylpropoxy, hexoxy, 1-methylpentoxy, 2-methylpentoxy, 3-methylpentoxy, 4-methylpentoxy, 1, 1-dimethylbutoxy, 1, 2-dimethylbutoxy, 1, 3-dimethylbutoxy, 2,2-dimethylbutoxy, 2,3-dimethylbutoxy, 3,3-dimethylbutoxy, 1-ethylbutoxy, 2-ethylbutoxy, 1, 1, 2-trimethylpropoxy, 1, 2,2-trimethylpropoxy, 1 Ethyl-1-methylpropoxy or 1-ethyl-2-methylpropoxy. Aryl: mononuclear or polynuclear aromatic hydrocarbon radicals having 6 to 14 carbon atoms, such as phenyl, naphthyl, anthracenyl or phenanthrenyl, preferably phenyl or naphthyl.
5- oder 6-gliedrigen heterocyclischen Rest: ein heterocyclischer Rest, der 5 oder 6 Ringatome aufweist, wobei 1 , 2, 3 oder 4 Ringatome Heteroatome sind, die unter O, S und N ausgewählt sind, wobei der heterocyclische Rest gesättigt, partiell ungesättigt oder aromatisch ist. Beispiele für heterocyclische Reste sind:5- or 6-membered heterocyclic radical: a heterocyclic radical having 5 or 6 ring atoms, wherein 1, 2, 3 or 4 ring atoms are heteroatoms selected from O, S and N, wherein the heterocyclic radical is saturated, partially unsaturated or aromatic. Examples of heterocyclic radicals are:
C-gebundene, 5-gliedrige, gesättigte Ringe wieC-linked, 5-membered, saturated rings such as
Tetrahydrofuran-2-yl, Tetrahydrofuran-3-yl, Tetrahydrothien-2-yl, Tetrahydrothien- 3-yl, Tetrahydropyrrol-2-yl, Tetrahydropyrrol-3-yl, Tetrahydropyrazol-3-yl, Tetra- hydro-pyrazol-4-yl, Tetrahydroisoxazol-3-yl, Tetrahydroisoxazol-4-yl, Tetrahydroi- soxazol-5-yl, 1 ,2-Oxathiolan-3-yl, 1 ,2-Oxathiolan-4-yl, 1 ,2-Oxathiolan-5-yl, Tetra- hydroisothiazol-3-yl, Tetrahydroisothiazol-4-yl, Tetrahydroisothiazol-5-yl, 1 ,2-Tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydrothien-2-yl, tetrahydrothien-3-yl, tetrahydropyrrol-2-yl, tetrahydropyrrol-3-yl, tetrahydropyrazol-3-yl, tetrahydropyrazol-4 yl, tetrahydroisoxazol-3-yl, tetrahydroisoxazol-4-yl, tetrahydro-soxazol-5-yl, 1,2-oxathiolan-3-yl, 1,2-oxathiolan-4-yl, 1,2-oxathiolan-5- yl, tetrahydroisothiazol-3-yl, tetrahydroisothiazol-4-yl, tetrahydroisothiazol-5-yl, 1, 2
Dithiolan-3-yl, 1 ,2-Dithiolan-4-yl, Tetrahydroimidazol-2-yl, Tetrahydroimidazol-4- yl, Tetra hydrooxazol-2-yl, Tetra hydrooxazol-4-yl, Tetrahydrooxazol-5-yl, Tetra- hydrothiazol-2-yl, Tetrahydrothiazol-4-yl, Tetrahydrothiazol-5-yl, 1 ,3-Dioxolan-2- yl, 1 ,3-Dioxolan-4-yl, 1 ,3-Oxathiolan-2-yl, 1 ,3-Oxathiolan-4-yl, 1 ,3-Oxathiolan-5- yl, 1 ,3-Dithiolan-2-yl, 1 ,3-Dithiolan-4-yl, 1 ,3,2-Dioxathiolan-4-yl;Dithiolan-3-yl, 1,2-dithiolan-4-yl, tetrahydroimidazol-2-yl, tetrahydroimidazol-4-yl, tetrahydrooxazol-2-yl, tetrahydrooxazol-4-yl, tetrahydrooxazol-5-yl, tetra-hydroxazol-4-yl hydrothiazol-2-yl, tetrahydrothiazol-4-yl, tetrahydrothiazol-5-yl, 1,3-dioxolan-2-yl, 1,3-dioxolan-4-yl, 1,3-oxathiolan-2-yl, 1, 3-oxathiolan-4-yl, 1,3-oxathiolan-5-yl, 1,3-dithiolan-2-yl, 1,3-dithiolan-4-yl, 1,2,2-dioxathiolan-4-yl;
C-gebundene, 6-gliedrige, gesättigte Ringe wie:C-linked, 6-membered, saturated rings such as:
Tetrahydropyran-2-yl, Tetrahydropyran-3-yl, Tetrahydropyran-4-yl, Piperidin-2-yl,Tetrahydropyran-2-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, piperidin-2-yl,
Piperidin-3-yl, Piperidin-4-yl, Tetrahydrothiopyran-2-yl, Tetrahydrothiopyran-3-yl, Tetrahydrothiopyran-4-yl, 1 ,3-Dioxan-2-yl, 1 ,3-Dioxan-4-yl, 1 ,3-Dioxan-5-yl, 1 ,4-Piperidin-3-yl, piperidin-4-yl, tetrahydrothiopyran-2-yl, tetrahydrothiopyran-3-yl, tetrahydrothiopyran-4-yl, 1, 3-dioxan-2-yl, 1, 3-dioxan-4-yl, 1, 3-dioxan-5-yl, 1, 4
Dioxan-2-yl, 1 ,3-Dithian-2-yl, 1 ,3-Dithian-4-yl, 1 ,3-Dithian-5-yl, 1 ,4-Dithian-2-yl, 1 ,3-Oxathian-2-yl, 1 ,3-Oxathian-4-yl, 1 ,3-Oxathian-5-yl, 1 ,3-Oxathian-6-yl, 1 ,4- Oxathian-2-yl, 1 ,4-Oxathian-3-yl, 1 ,2-Dithian-3-yl, 1 ,2-Dithian-4-yl, Hexahydropy- rimidin-2-yl, Hexahydropyrimidin-4-yl, Hexahydropyrimidin-5-yl, Hexahydropyra- zin-2-yl, Hexahydropyridazin-3-yl, Hexahydropyridazin-4-yl, Tetrahydro-1 ,3- oxazin-2-yl, Tetrahydro-1 ,3-oxazin-4-yl, Tetrahydro-1 ,3-oxazin-5-yl, Tetrahydro- 1 ,3-oxazin-6-yl, Tetrahydro-1 ,3-thiazin-2-yl, Tetrahydro-1 ,3-thiazin-4-yl, Tetra- hydro-1 ,3-thiazin-5-yl, Tetrahydro-1 ,3-thiazin-6-yl, Tetrahydro-1 ,4-thiazin-2-yl, Tetrahydro-1 ,4-thiazin-3-yl, Tetrahydro-1 ,4-oxazin-2-yl, Tetrahydro-1 ,4-oxazin-3- yl, Tetrahydro-1 ,2-oxazin-3-yl, Tetrahydro-1 ,2-oxazin-4-yl, Tetrahydro-1 ,2-oxazin-Dioxan-2-yl, 1,3-dithian-2-yl, 1,3-dithian-4-yl, 1,3-dithian-5-yl, 1,4-dithian-2-yl, 1, 3 Oxathian-2-yl, 1,3-oxathian-4-yl, 1,3-oxathian-5-yl, 1,3-oxathian-6-yl, 1,4-oxathian-2-yl, 1, 4 Oxathian-3-yl, 1,2-dithian-3-yl, 1,2-dithian-4-yl, hexahydropyrimidin-2-yl, hexahydropyrimidin-4-yl, hexahydropyrimidin-5-yl, hexahydropyrazine 2-yl, hexahydropyridazin-3-yl, hexahydropyridazin-4-yl, tetrahydro-1,3-oxazin-2-yl, tetrahydro-1,3-oxazin-4-yl, tetrahydro-1,3-oxazine-5 yl, tetrahydro-1,3-oxazin-6-yl, tetrahydro-1,3-thiazin-2-yl, tetrahydro-1,3-thiazin-4-yl, tetrahydro-1,3-thiazine-5 yl, tetrahydro-1,3-thiazin-6-yl, tetrahydro-1, 4-thiazin-2-yl, tetrahydro-1,4-thiazin-3-yl, tetrahydro-1,4-oxazin-2-yl, Tetrahydro-1,4-oxazin-3-yl, tetrahydro-1,2-oxazin-3-yl, tetrahydro-1,2-oxazin-4-yl, tetrahydro-1,2-oxazine
5-yl, Tetrahydro-1 ,2-oxazin-6-yl;5-yl, tetrahydro-1,2-oxazin-6-yl;
N-gebundene, 5-gliedrige, gesättigte Ringe wie: Tetrahydropyτrol-1-yl, Tetra hydropyrazol-1-yl, Tetrahydroisoxazol-2-yl, Tetra- hydroisothiazol-2-yl, Tetrahydroimidazol-1-yl, Tetrahydrooxazol-3-yl, Tetra- hydrothiazol-3-yl;N-linked, 5-membered, saturated rings such as: Tetrahydropy- τrol-1-yl, tetrahydropyrazol-1-yl, tetrahydroisoxazol-2-yl, tetrahydroisothiazol-2-yl, tetrahydroimidazol-1-yl, tetrahydrooxazol-3-yl, tetrahydrothiazol-3-yl;
N-gebundene, 6-gliedrige, gesättigte Ringe wie:N-linked, 6-membered, saturated rings such as:
Piperidin-1-yl, Hexahydropyrimidin-1-yl, Hexahydropyrazin-1-yl, Hexahydro- pyridazin-1-yl, Tetrahydro-1 ,3-oxazin-3-yl, Tetrahydro-1 ,3-thiazin-3-yl, Tetra- hydro-1 ,4-thiazin-4-yl, Tetrahydro-1 ,4-oxazin-4-yl, Tetrahydro-1 ,2-oxazin-2-yl;Piperidin-1-yl, hexahydropyrimidin-1-yl, hexahydropyrazine-1-yl, hexahydropyridazin-1-yl, tetrahydro-1,3-oxazin-3-yl, tetrahydro-1,3-thiazin-3-yl, Tetrahydro-1,4-thiazin-4-yl, tetrahydro-1,4-oxazin-4-yl, tetrahydro-1,2-oxazin-2-yl;
C-gebundene, 5-gliedrige, partiell ungesättigte Ringe wie:C-linked, 5-membered, partially unsaturated rings such as:
2,3-Dihydrofuran-2-yl, 2,3-Dihydrofuran-3-yl, 2,5-Dihydrofuran-2-yl, 2,5-Di- hydrofuran-3-yl, 4,5-Dihydrofuran-2-yl, 4,5-Dihydrofuran-3-yl, 2,3-Dihydro-thien-2- yl, 2,3-Dihydrothien-3-yl, 2,5-Dihydrothien-2-yl, 2,5-Dihydrothien-3-yl, 4,5- Dihydrothien-2-yl, 4,5-Dihydrothien-3-yl, 2,3-Dihydro-1 H-pyrrol-2-yl, 2,3-Dihydro- 1 H-pyrτol-3-yl, 2,5-Dihydro-1 H-pyrτol-2-yl, 2,5-Dihydro-1 H-pyrτol-3-yl, 4,5-2,3-dihydrofuran-2-yl, 2,3-dihydrofuran-3-yl, 2,5-dihydrofuran-2-yl, 2,5-dihydrofuran-3-yl, 4,5-dihydrofuran-2-yl yl, 4,5-dihydrofuran-3-yl, 2,3-dihydro-thien-2-yl, 2,3-dihydro-thien-3-yl, 2,5-dihydro-thien-2-yl, 2,5-dihydro-thienyl 3-yl, 4,5-dihydro-thien-2-yl, 4,5-dihydro-thien-3-yl, 2,3-dihydro-1H-pyrrol-2-yl, 2,3-dihydro-1H-pyrotoluene 3-yl, 2,5-dihydro-1H-pyrtol-2-yl, 2,5-dihydro-1H-pyrtol-3-yl, 4,5-
Dihydro-1 H-pyrrol-2-yl, 4,5-Dihydro-1 H-pyrrol-3-yl, 3,4-Dihydro-2H-pyrrol-2-yl, 3,4-Dihydro-2H-pyrτol-3-yl, 3,4-Dihydro-5H-pyrτol-2-yl, 3,4-Dihydro-5H-pyrτol-3-yl, 4,5-Dihydro-1 H-pyrazol-3-yl, 4,5-Dihydro-1 H-pyrazol-4-yl, 4,5-Dihydro-1 H- pyrazol-5-yl, 2,5-Dihydro-1 H-pyrazol-3-yl, 2,5-Dihydro-1 H-pyrazol-4-yl, 2,5- Dihydro-1 H-pyrazol-5-yl, 4,5-Dihydroisoxazol-3-yl, 4,5-Dihydroisoxazol-4-yl, 4,5-Dihydro-1H-pyrrol-2-yl, 4,5-dihydro-1H-pyrrol-3-yl, 3,4-dihydro-2H-pyrrol-2-yl, 3,4-dihydro-2H-pyrrole 3-yl, 3,4-dihydro-5H-pyrrolo-2-yl, 3,4-dihydro-5H-pyrrolo-3-yl, 4,5-dihydro-1H-pyrazol-3-yl, 4.5 Dihydro-1H-pyrazol-4-yl, 4,5-dihydro-1H-pyrazol-5-yl, 2,5-dihydro-1H-pyrazol-3-yl, 2,5-dihydro-1H pyrazol-4-yl, 2,5-dihydro-1H-pyrazol-5-yl, 4,5-dihydroisoxazol-3-yl, 4,5-dihydroisoxazol-4-yl, 4,5-
Dihydroisoxazol-5-yl, 2,5-Dihydroisoxazol-3-yl, 2,5-Dihydroisoxazol-4-yl, 2,5- Dihydroisoxazol-5-yl, 2,3-Dihydroisoxazol-3-yl, 2,3-Dihydroisoxazol-4-yl, 2,3- Dihydroisoxazol-5-yl, 4,5-Dihydroisothiazol-3-yl, 4,5-Dihydroisothiazol-4-yl, 4,5- Dihydroisothiazol-5-yl, 2,5-Dihydroisothiazol-3-yl, 2,5-Dihydroisothiazol-4-yl, 2,5- Dihydroisothiazol-5-yl, 2,3-Dihydroisothiazol-3-yl, 2,3-Dihydroisothiazol-4-yl, 2,3-Dihydroisoxazol-5-yl, 2,5-dihydroisoxazol-3-yl, 2,5-dihydroisoxazol-4-yl, 2,5-dihydroisoxazol-5-yl, 2,3-dihydroisoxazol-3-yl, 2,3- Dihydroisoxazol-4-yl, 2,3-dihydroisoxazol-5-yl, 4,5-dihydroisothiazol-3-yl, 4,5-dihydroisothiazol-4-yl, 4,5-dihydroisothiazol-5-yl, 2,5- Dihydroisothiazol-3-yl, 2,5-dihydroisothiazol-4-yl, 2,5-dihydroisothiazol-5-yl, 2,3-dihydroisothiazol-3-yl, 2,3-dihydroisothiazol-4-yl, 2,3-
Dihydroisothiazol-5-yl, Δ 3-1 ,2-Dithiol-3-yl, Δ 3-1 ,2-Dithiol-4-yl, Δ 3-1 ,2-Dithiol-5-yl, 4,5-Dihydro-1 H-imidazol-2-yl, 4,5-Dihydro-1 H-imidazol-4-yl, 4,5-Dihydro-1 H- imidazol-5-yl, 2,5-Dihydro-1 H-imidazol-2-yl, 2,5-Dihydro-1 H-imidazol-4-yl, 2,5- Dihydro-1 H-imidazol-5-yl, 2,3-Dihydro-1 H-imidazol-2-yl, 2,3-Dihydro-1 H-imidazol- 4-yl, 4,5-Dihydro-oxazol-2-yl, 4,5-Dihydrooxazol-4-yl, 4,5-Dihydrooxazol-5-yl, 2,5-Dihydroisothiazol-5-yl, Δ 3 -1, 2-dithiol-3-yl, Δ 3 -1, 2-dithiol-4-yl, Δ 3 -1, 2-dithiol-5-yl, 4,5-dihydro -1H-imidazol-2-yl, 4,5-dihydro-1H-imidazol-4-yl, 4,5-dihydro-1H-imidazol-5-yl, 2,5-dihydro-1H-imidazole -2-yl, 2,5-dihydro-1H-imidazol-4-yl, 2,5-dihydro-1H-imidazol-5-yl, 2,3-dihydro-1H-imidazol-2-yl, 2,3-dihydro-1H-imidazol-4-yl, 4,5-dihydro-oxazol-2-yl, 4,5-dihydrooxazol-4-yl, 4,5-dihydrooxazol-5-yl, 2.5 -
Dihydro-oxazol-2-yl, 2,5-Dihydrooxazol-4-yl, 2,5-Dihydrooxazol-5-yl, 2,3-Dihydro- oxazol-2-yl, 2,3-Dihydrooxazol-4-yl, 2,3-Dihydrooxazol-5-yl, 4,5-Dihydro-thiazol- 2-yl, 4,5-Dihydrothiazol-4-yl, 4,5-Dihydrothiazol-5-yl, 2,5-Dihydro-thiazol-2-yl, 2,5- Dihydrothiazol-4-yl, 2,5-Dihydrothiazol-5-yl, 2,3-Dihydro-thiazol-2-yl, 2,3-Dihydro- thiazol-4-yl, 2,3-Dihydrothiazol-5-yl, 1 ,3-Dioxol-2-yl, 1 ,3-Dioxol-4-yl, 1 ,3-Dithiol-2- yl, 1 ,3-Dithiol-4-yl, 1 ,3-Oxathiol-2-yl, 1 ,3-Oxathiol-4-yl, 1 ,3-Oxathiol-5-yl;Dihydrooxazol-2-yl, 2,5-dihydrooxazol-4-yl, 2,5-dihydrooxazol-5-yl, 2,3-dihydrooxazol-2-yl, 2,3-dihydrooxazol-4-yl, 2,3-dihydrooxazol-5-yl, 4,5-dihydro-thiazol-2-yl, 4,5-dihydrothiazol-4-yl, 4,5-dihydrothiazol-5-yl, 2,5-dihydro-thiazole 2-yl, 2,5-dihydrothiazol-4-yl, 2,5-dihydrothiazol-5-yl, 2,3-dihydro-thiazol-2-yl, 2,3-dihydro-thiazol-4-yl, 2, 3-Dihydrothiazol-5-yl, 1, 3-dioxol-2-yl, 1, 3-dioxol-4-yl, 1, 3-dithiol-2-yl, 1, 3-dithiol-4-yl, 1, 3-oxathiol-2-yl, 1, 3-oxathiol-4-yl, 1, 3-oxathiol-5-yl;
C-gebundene, 6-gliedrige, partiell ungesättigte Ringe wie: 2H-3,4-Dihydropyran-6-yl, 2H-3,4-Dihydropyran-5-yl, 2H-3,4-Dihydropyran-4-yl, 2H-3,4-Dihydropyran-3-yl, 2H-3,4-Dihydropyran-2-yl, 2H-3,4-Dihydrothiopyran-6- yl, 2H-3,4-Dihydrothiopyran-5-yl, 2H-3,4-Dihydrothiopyran-4-yl, 2H-3.4- Dihydrothiopyran-3-yl, 2H-3,4-Dihydrothiopyran-2-yl, 1 ,2,3,4-Tetrahydropyridin-6- yl, 1 ,2,3,4-Tetrahydropyridin-5-yl, 1 ,2,3,4-Tetrahydropyridin-4-yl, 1 ,2,3,4-Tetra- hydropyridin-3-yl, 1 ,2,3,4-Tetrahydropyridin-2-yl, 2H-5,6-Dihydropyran-2-yl, 2H- 5,6-Dihydropyran-3-yl, 2H-5,6-Dihydropyran-4-yl, 2H-5,6-Dihydropyran-5-yl, 2H- 5,6-Dihydropyran-6-yl, 2H-5,6-Dihydrothiopyran-2-yl, 2H-5,6-Dihydrothiopyran-3- yl, 2H-5,6-Dihydrothiopyran-4-yl, 2H-5,6-Dihydrothiopyran-5-yl, 2H-5.6- Dihydrothiopyran-6-yl, 1 ,2,5,6-Tetrahydropyridin-2-yl, 1 ,2,5,6-Tetrahydropyridin-C-linked, 6-membered, partially unsaturated rings such as: 2H-3,4-dihydropyran-6-yl, 2H-3,4-dihydropyran-5-yl, 2H-3,4-dihydropyran-4-yl, 2H-3,4-dihydropyran-3-yl, 2H- 3,4-Dihydropyran-2-yl, 2H-3,4-dihydrothiopyran-6-yl, 2H-3,4-dihydrothiopyran-5-yl, 2H-3,4-dihydrothiopyran-4-yl, 2H-3.4- Dihydrothiopyran-3-yl, 2H-3,4-dihydrothiopyran-2-yl, 1,2,3,4-tetrahydropyridin-6-yl, 1,2,3,4-tetrahydropyridin-5-yl, 1, 2, 3,4-Tetrahydropyridin-4-yl, 1, 2,3,4-tetrahydropyridin-3-yl, 1,2,3,4-tetrahydropyridin-2-yl, 2H-5,6-dihydropyran-2 yl, 2H-5,6-dihydropyran-3-yl, 2H-5,6-dihydropyran-4-yl, 2H-5,6-dihydropyran-5-yl, 2H-5,6-dihydropyran-6-yl, 2H-5,6-dihydrothiopyran-2-yl, 2H-5,6-dihydrothiopyran-3-yl, 2H-5,6-dihydrothiopyran-4-yl, 2H-5,6-dihydrothiopyran-5-yl, 2H- 5.6-dihydrothiopyran-6-yl, 1, 2,5,6-tetrahydropyridin-2-yl, 1, 2,5,6-tetrahydropyridine
3-yl, 1 ,2,5,6-Tetrahydropyridin-4-yl, 1 ,2,5,6-Tetrahydropyridin-5-yl, 1 ,2,5,6- Tetrahydropyridin-6-yl, 2,3,4,5-Tetrahydropyridin-2-yl, 2,3,4,5-Tetrahydropyridin- 3-yl, 2,3,4,5-Tetrahydropyridin-4-yl, 2,3,4,5-Tetrahydropyridin-5-yl, 2,3,4,5- Tetrahydropyridin-6-yl, 4H-Pyran-2-yl, 4H-Pyran-3-yl-, 4H-Pyran-4-yl, 4H- Thiopyran-2-yl, 4H-Thiopyran-3-yl, 4H-Thiopyran-4-yl, 1 ,4-Dihydropyridin-2-yl,3-yl, 1, 2,5,6-tetrahydropyridin-4-yl, 1, 2,5,6-tetrahydropyridin-5-yl, 1, 2,5,6-tetrahydropyridin-6-yl, 2,3, 4,5-tetrahydropyridin-2-yl, 2,3,4,5-tetrahydropyridin-3-yl, 2,3,4,5-tetrahydropyridin-4-yl, 2,3,4,5-tetrahydropyridine-5 yl, 2,3,4,5-tetrahydropyridin-6-yl, 4H-pyran-2-yl, 4H-pyran-3-yl, 4H-pyran-4-yl, 4H-thiopyran-2-yl, 4H Thiopyran-3-yl, 4H-thiopyran-4-yl, 1, 4-dihydropyridin-2-yl,
1 ,4-Dihydropyridin-3-yl, 1 ,4-Dihydropyridin-4-yl, 2H-Pyran-2-yl, 2H-Pyran-3-yl, 2H-Pyran-4-yl, 2H-Pyran-5-yl, 2H-Pyran-6-yl, 2H-Thiopyran-2-yl, 2H-Thiopyran-3- yl, 2H-Thiopyran-4-yl, 2H-Thiopyran-5-yl, 2H-Thiopyran-6-yl, 1 ,2-Dihydropyridin- 2-yl, 1 ,2-Dihydro-pyridin-3-yl, 1 ,2-Dihydropyridin-4-yl, 1 ,2-Dihydropyridin-5-yl, 1 ,2- Dihydro-pyridin-6-yl, 3,4-Dihydropyridin-2-yl, 3,4-Dihydropyridin-3-yl, 3,4-Dihydro- pyridin-4-yl, 3,4-Dihydropyridin-5-yl, 3,4-Dihydropyridin-6-yl, 2,5-Dihydropyridin-2- yl, 2,5-Dihydropyridin-3-yl, 2,5-Dihydropyridin-4-yl, 2,5-Dihydropyridin-5-yl, 2,5- Dihydropyridin-6-yl, 2,3-Dihydropyridin-2-yl, 2,3-Dihydropyridin-3-yl, 2,3- Dihydropyridin-4-yl, 2,3-Dihydropyridin-5-yl, 2,3-Dihydropyridin-6-yl, 2H-5.6- Dihydro-1 ,2-oxazin-3-yl, 2H-5,6-Dihydro-1 ,2-oxazin-4-yl, 2H-5,6-Dihydro-1 ,2- oxazin-5-yl, 2H-5,6-Dihydro-1 ,2-oxazin-6-yl, 2H-5,6-Dihydro-1 ,2-thiazin-3-yl, 2H- 5,6-Dihydro-1 ,2-thiazin-4-yl, 2H-5,6-Dihydro-1 ,2-thiazin-5-yl, 2H-5,6-Dihydro-1 ,2- thiazin-6-yl, 4H-5,6-Dihydro-1 ,2-oxazin-3-yl, 4H-5,6-Dihydro-1 ,2-oxazin-4-yl, 4H- 5,6-Dihydro-1 ,2-oxazin-5-yl, 4H-5,6-Dihydro-1 ,2-oxazin-6-yl, 4H-5,6-Dihydro-1 ,2- thiazin-3-yl, 4H-5,6-Dihydro-1 ,2-thiazin-4-yl, 4H-5,6-Dihydro-1 ,2-thiazin-5-yl, 4H-1, 4-dihydropyridin-3-yl, 1,4-dihydropyridin-4-yl, 2H-pyran-2-yl, 2H-pyran-3-yl, 2H-pyran-4-yl, 2H-pyran-5 yl, 2H-pyran-6-yl, 2H-thiopyran-2-yl, 2H-thiopyran-3-yl, 2H-thiopyran-4-yl, 2H-thiopyran-5-yl, 2H-thiopyran-6-yl, 1,2-dihydropyridin-2-yl, 1,2-dihydro-pyridin-3-yl, 1,2-dihydropyridin-4-yl, 1,2-dihydropyridin-5-yl, 1,2-dihydro-pyridine 6-yl, 3,4-dihydropyridin-2-yl, 3,4-dihydropyridin-3-yl, 3,4-dihydro-pyridin-4-yl, 3,4-dihydropyridin-5-yl, 3,4- Dihydropyridin-6-yl, 2,5-dihydropyridin-2-yl, 2,5-dihydropyridin-3-yl, 2,5-dihydropyridin-4-yl, 2,5-dihydropyridin-5-yl, 2,5- Dihydropyridin-6-yl, 2,3-dihydropyridin-2-yl, 2,3-dihydropyridin-3-yl, 2,3-dihydropyridin-4-yl, 2,3-dihydropyridin-5-yl, 2,3- Dihydropyridin-6-yl, 2H-5.6-dihydro-1,2-oxazin-3-yl, 2H-5,6-dihydro-1,2-oxazin-4-yl, 2H-5,6-dihydro-1, 2-oxazin-5-yl, 2H-5,6-dihydro-1,2-oxazin-6-yl, 2H-5,6-dihydro-1,2-thiazin-3-yl, 2H-5,6- Dihydro-1,2-thiazin-4-yl, 2H-5,6-dihydro-1,2-thiazin-5-yl, 2H-5,6-dihydro-1,2-thiazole in-6-yl, 4H-5,6-dihydro-1,2-oxazin-3-yl, 4H-5,6-dihydro-1,2-oxazin-4-yl, 4H-5,6-dihydro- 1, 2-oxazin-5-yl, 4H-5,6-dihydro-1,2-oxazin-6-yl, 4H-5,6-dihydro-1,2-thiazin-3-yl, 4H-5, 6-Dihydro-1,2-thiazin-4-yl, 4H-5,6-dihydro-1,2-thiazin-5-yl, 4H-
5,6-Dihydro-1 ,2-thiazin-6-yl, 2H-3,6-Dihydro-1 ,2-oxazin-3-yl, 2H-3,6-Dihydro-1 ,2- oxazin-4-yl, 2H-3,6-Dihydro-1 ,2-oxazin-5-yl, 2H-3,6-Dihydro-1 ,2-oxazin-6-yl, 2H- 3,6-Dihydro-1 ,2-thiazin-3-yl, 2H-3,6-Dihydro-1 ,2-thiazin-4-yl, 2H-3,6-Dihydro-1 ,2- thiazin-5-yl, 2H-3,6-Dihydro-1 ,2-thiazin-6-yl, 2H-3,4-Dihydro-1 ,2-oxazin-3-yl, 2H- 3,4-Dihydro-1 ,2-oxazin-4-yl, 2H-3,4-Dihydro-1 ,2-oxazin-5-yl, 2H-3,4-Dihydro-1 ,2- oxazin-6-yl, 2H-3,4-Dihydro-1 ,2-thiazin-3-yl, 2H-3,4-Dihydro-1 ,2-thiazin-4-yl, 2H- 3,4-Dihydro-1 ,2-thiazin-5-yl, 2H-3,4-Dihydro-1 ,2-thiazin-6-yl, 2,3,4,5- Tetrahydropyridazin-3-yl, 2,3,4,5-Tetrahydropyridazin-4-yl, 2,3,4,5- Tetrahydropyridazin-5-yl, 2,3,4,5-Tetrahydropyridazin-6-yl, 3,4,5,6- Tetrahydropyridazin-3-yl, 3,4,5,6-Tetrahydropyridazin-4-yl, 1 ,2,5,6- Tetrahydropyridazin-3-yl, 1 ,2,5,6-Tetrahydropyridazin-4-yl, 1 ,2,5,6-Tetra- hydropyridazin-5-yl, 1 ,2,5,6-Tetrahydropyridazin-6-yl, 1 ,2,3,6-Tetrahydro- pyridazin-3-yl, 1 ,2,3,6-Tetrahydropyridazin-4-yl, 4H-5,6-Dihydro-1 ,3-oxazin-2-yl, 4H-5,6-Dihydro-1 ,3-oxazin-4-yl, 4H-5,6-Dihydro-1 ,3-oxazin-5-yl, 4H-5,6-Dihydro-5,6-dihydro-1,2-thiazin-6-yl, 2H-3,6-dihydro-1,2-oxazin-3-yl, 2H-3,6-dihydro-1,2-oxazine-4 yl, 2H-3,6-dihydro-1,2-oxazin-5-yl, 2H-3,6-dihydro-1,2-oxazin-6-yl, 2H-3,6-dihydro-1,2-yl thiazine-3-yl, 2H-3,6-dihydro-1,2-thiazine-4-yl, 2H-3,6-dihydro-1,2-thiazin-5-yl, 2H-3,6-dihydroxy 1, 2-thiazine-6-yl, 2H-3,4-dihydro-1,2-oxazin-3-yl, 2H-3,4-dihydro-1,2-oxazin-4-yl, 2H-3, 4-dihydro-1,2-oxazin-5-yl, 2H-3,4-dihydro-1,2-oxazin-6-yl, 2H-3,4-dihydro-1,2-thiazin-3-yl, 2H-3,4-dihydro-1,2-thiazin-4-yl, 2H-3,4-dihydro-1,2-thiazin-5-yl, 2H-3,4-dihydro-1,2-thiazine 6-yl, 2,3,4,5-tetrahydropyridazin-3-yl, 2,3,4,5-tetrahydropyridazin-4-yl, 2,3,4,5-tetrahydropyridazin-5-yl, 2,3, 4,5-tetrahydropyridazin-6-yl, 3,4,5,6- Tetrahydropyridazin-3-yl, 3,4,5,6-tetrahydropyridazin-4-yl, 1, 2,5,6-tetrahydropyridazin-3-yl, 1, 2,5,6-tetrahydropyridazin-4-yl, 1, 2,5,6-tetrahydropyridazin-5-yl, 1, 2,5,6-tetrahydropyridazin-6-yl, 1,2,3,6-tetrahydropyridazin-3-yl, 1, 2,3, 6-Tetrahydropyridazin-4-yl, 4H-5,6-dihydro-1,3-oxazin-2-yl, 4H-5,6-dihydro-1,3-oxazin-4-yl, 4H-5,6- Dihydro-1,3-oxazin-5-yl, 4H-5,6-dihydro-
1 ,3-oxazin-6-yl, 4H-5,6-Dihydro-1 ,3-thiazin-2-yl, 4H-5,6-Dihydro-1 ,3-thiazin-4-yl, 4H-5,6-Dihydro-1 ,3-thiazin-5-yl, 4H-5,6-Dihydro-1 ,3-thiazin-6-yl, 3,4,5-6- TetrahydiOpyrimidin-2-yl, 3,4,5,6-Tetrahydropyrimidin-4-yl, 3,4,5,6- Tetrahydropyrimidin-5-yl, 3,4,5,6-Tetrahydropyrimidin-6-yl, 1 ,2,3,4- Tetrahydropyrazin-2-yl, 1 ,2,3,4-Tetrahydropyrazin-5-yl, 1 ,2,3,4-Tetrahydro- pyrimidin-2-yl, 1 ,2,3,4-Tetrahydropyrimidin-4-yl, 1 ,2,3,4-Tetrahydropyrimidin-5-yl, 1 ,2,3,4-Tetrahydropyrimidin-6-yl, 2,3-Dihydro-1 ,4-thiazin-2-yl, 2,3-Dihydro-1 ,4- thiazin-3-yl, 2,3-Dihydro-1 ,4-thiazin-5-yl, 2,3-Dihydro-1 ,4-thiazin-6-yl, 21-1-1 ,2- Oxazin-3-yl, 2H-1 ,2-Oxazin-4-yl, 2H-1 ,2-Oxazin-5-yl, 2H-1 ,2-Oxazin-6-yl, 21-1-1 ,2- Thiazin-3-yl, 2H-1 ,2-Thiazin-4-yl, 2H-1 ,2-Thiazin-5-yl, 2H-1 ,2-Thiazin-6-yl, 4H-1, 3-oxazin-6-yl, 4H-5,6-dihydro-1,3-thiazin-2-yl, 4H-5,6-dihydro-1,3-thiazin-4-yl, 4H-5, 6-dihydro-1,3-thiazin-5-yl, 4H-5,6-dihydro-1,3-thiazin-6-yl, 3,4,5-6-tetrahydro-pyrimidin-2-yl, 3,4, 5,6-tetrahydropyrimidin-4-yl, 3,4,5,6-tetrahydropyrimidin-5-yl, 3,4,5,6-tetrahydropyrimidin-6-yl, 1, 2,3,4-tetrahydropyrazine-2 yl, 1, 2,3,4-tetrahydropyrazine-5-yl, 1,2,3,4-tetrahydropyrimidin-2-yl, 1,2,3,4-tetrahydropyrimidin-4-yl, 1, 2, 3,4-Tetrahydropyrimidin-5-yl, 1,2,3,4-tetrahydropyrimidin-6-yl, 2,3-dihydro-1,4-thiazin-2-yl, 2,3-dihydro-1, 4- thiazine-3-yl, 2,3-dihydro-1,4-thiazin-5-yl, 2,3-dihydro-1,4-thiazin-6-yl, 21-1-1, 2-oxazine-3 yl, 2H-1, 2-oxazin-4-yl, 2H-1,2-oxazin-5-yl, 2H-1,2-oxazin-6-yl, 21-1-1, 2-thiazine-3 yl, 2H-1,2-thiazin-4-yl, 2H-1,2-thiazin-5-yl, 2H-1,2-thiazin-6-yl, 4H-
1 ,2-Oxazin-3-yl, 4H-1 ,2-Oxazin-4-yl, 4H-1 ,2-Oxazin-5-yl, 4H-1 ,2-Oxazin-6-yl, 4H- 1 ,2-Thiazin-3-yl, 4H-1 ,2-Thiazin-4-yl, 4H-1 ,2-Thiazin-5-yl, 4H-1 ,2-Thiazin-6-yl, 6H-1 ,2-Oxazin-3-yl, 6H-1 ,2-Oxazin-4-yl, 6H-1 ,2-Oxazin-5-yl, 6H-1 ,2-Oxazin-6-yl, 6H-1 ,2-Thiazin-3-yl, 6H-1 ,2-Thiazin-4-yl, 6H-1 ,2-Thiazin-5-yl, 6H-1 ,2-Thiazin-6-yl, 2H-1 ,3-Oxazin-2-yl, 2H-1 ,3-Oxazin-4-yl, 2H-1 ,3-Oxazin-5-yl, 2H-1 ,3-Oxazin-6-yl,1, 2-oxazin-3-yl, 4H-1,2-oxazin-4-yl, 4H-1,2-oxazin-5-yl, 4H-1,2-oxazin-6-yl, 4H-1, 2-Thiazin-3-yl, 4H-1,2-thiazin-4-yl, 4H-1,2-thiazin-5-yl, 4H-1,2-thiazin-6-yl, 6H-1, 2 Oxazin-3-yl, 6H-1, 2-oxazin-4-yl, 6H-1,2-oxazin-5-yl, 6H-1,2-oxazin-6-yl, 6H-1,2-thiazine 3-yl, 6H-1,2-thiazin-4-yl, 6H-1,2-thiazin-5-yl, 6H-1,2-thiazin-6-yl, 2H-1,3-oxazine-2-yl yl, 2H-1, 3-oxazin-4-yl, 2H-1, 3-oxazin-5-yl, 2H-1, 3-oxazin-6-yl,
2H-1 ,3-Thiazin-2-yl, 2H-1 ,3-Thiazin-4-yl, 2H-1 ,3-Thiazin-5-yl, 2H-1 ,3-Thiazin-6-yl, 4H-1 ,3-Oxazin-2-yl, 4H-1 ,3-Oxazin-4-yl, 4H-1 ,3-Oxazin-5-yl, 4H-1 ,3-Oxazin-6-yl, 4H-1 ,3-Thiazin-2-yl, 4H-1 ,3-Thiazin-4-yl, 4H-1 ,3-Thiazin-5-yl, 4H-1 ,3-Thiazin-6-yl, 6H-1 ,3-Oxazin-2-yl, 6H-1 ,3-Oxazin-4-yl, 6H-1 ,3-Oxazin-5-yl, 6H-1 ,3-Oxazin-6-yl, 6H-1 ,3-Thiazin-2-yl, 6H-1 ,3-Oxazin-4-yl, 6H-1 ,3-Oxazin-5-yl, 6H-1 ,3-Thiazin-6-yl,2H-1, 3-thiazine-2-yl, 2H-1, 3-thiazine-4-yl, 2H-1, 3-thiazine-5-yl, 2H-1, 3-thiazine-6-yl, 4H- 1, 3-oxazin-2-yl, 4H-1, 3-oxazin-4-yl, 4H-1,3-oxazin-5-yl, 4H-1,3-oxazin-6-yl, 4H-1, 3-thiazine-2-yl, 4H-1, 3-thiazine-4-yl, 4H-1, 3-thiazine-5-yl, 4H-1, 3-thiazine-6-yl, 6H-1, 3 Oxazin-2-yl, 6H-1, 3-oxazin-4-yl, 6H-1,3-oxazin-5-yl, 6H-1,3-oxazin-6-yl, 6H-1,3-thiazine 2-yl, 6H-1, 3-oxazin-4-yl, 6H-1, 3-oxazin-5-yl, 6H-1, 3-thiazine-6-yl,
2H-1 ,4-Oxazin-2-yl, 2H-1 ,4-Oxazin-3-yl, 2H-1 ,4-Oxazin-5-yl, 2H-1 ,4-Oxazin-6-yl, 2H-1 ,4-Thiazin-2-yl, 2H-1 ,4-Thiazin-3-yl, 2H-1 ,4-Thiazin-5-yl, 2H-1 ,4-Thiazin-6-yl, 4H-1 ,4-Oxazin-2-yl, 4H-1 ,4-Oxazin-3-yl, 4H-1 ,4-Thiazin-2-yl, 4H-1 ,4-Thiazin-3-yl, 1 ,4-Dihydropyτidazin-3-yl, 1 ,4-Dihydropyridazin-4-yl, 1 ,4-Dihydropyridazin-5-yl, 1 ,4-Dihydropyτidazin-6-yl, 1 ,4-Dihydropyrazin-2-yl, 1 ,2-Dihydropyrazin-2-yl, 1 ,2-2H-1, 4-oxazin-2-yl, 2H-1, 4-oxazin-3-yl, 2H-1, 4-oxazin-5-yl, 2H-1, 4-oxazin-6-yl, 2H- 1, 4-thiazine-2-yl, 2H-1, 4-thiazine-3-yl, 2H-1, 4-thiazine-5-yl, 2H-1, 4-thiazine-6-yl, 4H-1, 4-oxazin-2-yl, 4H-1, 4-oxazin-3-yl, 4H-1, 4-thiazin-2-yl, 4H-1,4-thiazin-3-yl, 1,4-dihydropyτidazine 3-yl, 1,4-dihydropyridazin-4-yl, 1,4-dihydropyridazin-5-yl, 1,4-dihydropyτidazin-6-yl, 1,4-dihydropyrazine-2-yl, 1,2-dihydropyrazine 2-yl, 1, 2
Dihydropyτazin-3-yl, 1 ,2-Dihydropyrazin-5-yl, 1 ,2-Dihydropyrazin-6-yl, 1 ,4- Dihydropyrimidin-2-yl, 1 ,4-Dihydropyτimidin-4-yl, 1 ,4-Dihydropyrimidin-5-yl, 1 ,4- Dihydropyrimidin-6-yl, 3,4-Dihydropyrimidin-2-yl, 3,4-Dihydropyτimidin-4-yl, 3,4- Dihydropyrimidin-5-yl oder 3,4-Dihydropyrimidin-6-yl;Dihydropyazin-3-yl, 1,2-dihydropyrazine-5-yl, 1,2-dihydropyrazine-6-yl, 1,4-dihydropyrimidin-2-yl, 1,4-dihydropyimidin-4-yl, 1, 4 Dihydropyrimidin-5-yl, 1,4-dihydropyrimidin-6-yl, 3,4-dihydropyrimidin-2-yl, 3,4-dihydropyimidin-4-yl, 3,4-dihydropyrimidin-5-yl or 3,4- dihydropyrimidine-6-yl;
N-gebundene, 5-gliedrige, partiell ungesättigte Ringe wie: 2,3-Dihydro-1 H-pyrrol-1-yl, 2,5-Dihydro-1 H-pyrrol-1-yl, 4,5-Dihydro-1 H-pyrazol-1- yl, 2,5-Dihydro-1 H-pyrazol-1-yl, 2,3-Dihydro-1 H-pyrazol-1-yl, 2,5-Dihydroisoxazol- 2-yl, 2,3-Dihydroisoxazol-2-yl, 2,5-Dihydroisothiazol-2-yl, 2,3-Dihydroisoxazol-2- yl, 4,5-Dihydro-1 H-imidazol-1-yl, 2,5-Dihydro-1 H-imidazol-1-yl, 2,3-Dihydro-1 H- imidazol-1-yl, 2,3-Dihydrooxazol-3-yl, 2,3-Dihydrothiazol-3-yl, 1 ,2,4-Δ 4- Oxadiazolin-2-yl, 1 ,2,4-Δ 2-Oxadiazolin-4-yl, 1 ,2,4-Δ 3-Oxadiazolin-2-yl, 1 ,3,4-Δ 2- Oxadiazolin-4-yl, 1 ,2,4-Δ 5-Thiadiazolin-2-yl, 1 ,2,4-Δ 3-Thiadiazolin-2-yl, 1 ,2,4- Δ 2-Thiadiazolin-4-yl, 1 ,3,4-Δ 2-Thiadiazolin-4-yl, 1 ,2,3-Δ 2-Triazolin-1-yl, 1 ,2,4-N-linked, 5-membered, partially unsaturated rings such as: 2,3-dihydro-1H-pyrrol-1-yl, 2,5-dihydro-1H-pyrrol-1-yl, 4,5-dihydro-1 H-pyrazol-1-yl, 2,5-dihydro-1H-pyrazol-1-yl, 2,3-dihydro-1H-pyrazol-1-yl, 2,5-dihydroisoxazol-2-yl, 2, 3-Dihydroisoxazol-2-yl, 2,5-dihydroisothiazol-2-yl, 2,3-dihydroisoxazole-2-yl yl, 4,5-dihydro-1H-imidazol-1-yl, 2,5-dihydro-1H-imidazol-1-yl, 2,3-dihydro-1H-imidazol-1-yl, 2,3 Dihydrooxazol-3-yl, 2,3-dihydrothiazol-3-yl, 1, 2,4-Δ 4 -oxadiazolin-2-yl, 1,2,4-Δ 2 -oxadiazolin-4-yl, 1,2 , 4-Δ 3 -oxadiazolin-2-yl, 1, 3,4-Δ 2 -oxadiazolin-4-yl, 1, 2,4-Δ 5 -thiadiazolin-2-yl, 1, 2,4-Δ 3 Thiadiazolin-2-yl, 1, 2,4-Δ 2 -thiadiazolin-4-yl, 1, 3,4-Δ 2 -thiadiazolin-4-yl, 1, 2,3-Δ 2 -triazoline-1 yl, 1, 2,4-
Δ 2-Triazolin-1-yl, 1 ,2,4-Δ 2-Triazolin-4-yl, 1 ,2,4-Δ 3-Triazolin-1-yl, 1 ,2,4-Δ 1- Triazolin-4-yl;Δ 2 -triazolin-1-yl, 1, 2,4-Δ 2 -triazolin-4-yl, 1, 2,4-Δ 3 -triazolin-1-yl, 1, 2,4-Δ 1 -triazoline 4-yl;
N-gebundene, 6-gliedrige, partiell ungesättigte Ringe wie: 1 ,2,3,4-Tetrahydropyridin-1-yl, 1 ,2,5,6-Tetrahydropyridin-1-yl, 1 ,4-Dihydro- pyridin-1-yl, 1 ,2-Dihydropyridin-1-yl, 2H-5,6-Dihydro-1 ,2-oxazin-2-yl, 2H-5.6- Dihydro-1 ,2-thiazin-2-yl, 2H-3,6-Dihydro-1 ,2-oxazin-2-yl, 2H-3,6-Dihydro-1 ,2- thiazin-2-yl, 2H-3,4-Dihydro-1 ,2-oxazin-2-yl, 2H-3,4-Dihydro-1 ,2-thiazin-2-yl, 2,3,4, 5-Tetrahydropyridazin-2-yl, 1 ,2,5,6-Tetrahydropyridazin-1-yl, 1 ,2,5,6- Tetrahydropyridazin-2-yl, 1 ,2,3,6-Tetrahydropyridazin-1-yl, 3,4,5,6-N-linked, 6-membered, partially unsaturated rings such as: 1, 2,3,4-tetrahydropyridin-1-yl, 1, 2,5,6-tetrahydropyridin-1-yl, 1, 4-dihydro-pyridine-1 -yl, 1, 2-dihydropyridin-1-yl, 2H-5,6-dihydro-1,2-oxazin-2-yl, 2H-5.6-dihydro-1,2-thiazin-2-yl, 2H-3 , 6-Dihydro-1,2-oxazin-2-yl, 2H-3,6-dihydro-1,2-thiazin-2-yl, 2H-3,4-dihydro-1,2-oxazin-2-yl , 2H-3,4-dihydro-1,2-thiazin-2-yl, 2,3,4,5-tetrahydropyridazin-2-yl, 1, 2,5,6-tetrahydropyridazin-1-yl, 1,2 , 5,6-tetrahydropyridazin-2-yl, 1, 2,3,6-tetrahydropyridazin-1-yl, 3,4,5,6-
Tetrahydropyrimidin-3-yl, 1 ,2,3,4-Tetrahydropyrazin-1 -yl, 1 ,2,3,4- Tetrahydropyrimidin-1 -yl, 1 ,2,3,4-Tetrahydropyrimidin-3-yl, 2,3-Dihdro-1 ,4-thiazin- 4-yl, 2H-1 ,2-Oxazin-2-yl, 2H-1 ,2-Thiazin-2-yl, 4H-1 ,4-Oxazin-4-yl, 4H-1 ,4-Thiazin- 4-yl, 1 ,4-Dihydropyridazin-1-yl, 1 ,4-Dihydropyrazin-1-yl, 1 ,2-Dihydropyrazin-1-yl, 1 ,4-Dihydropyrimidin-1 -yl oder 3,4-Dihydropyrimidin-3-yl;Tetrahydropyrimidin-3-yl, 1,2,3,4-tetrahydropyrazine-1-yl, 1,2,3,4-tetrahydropyrimidin-1-yl, 1,2,3,4-tetrahydropyrimidin-3-yl, 2, 3-dihydro-1, 4-thiazine-4-yl, 2H-1, 2-oxazin-2-yl, 2H-1,2-thiazin-2-yl, 4H-1,4-oxazin-4-yl, 4H-1, 4-thiazine-4-yl, 1,4-dihydropyridazin-1-yl, 1,4-dihydropyrazine-1-yl, 1,2-dihydropyrazine-1-yl, 1,4-dihydropyrimidine-1 - yl or 3,4-dihydropyrimidin-3-yl;
C-gebundene, 5-gliedrige, heteroaromatische Ringe wie: 2-Furyl, 3-Furyl, 2- Thienyl, 3-Thienyl, Pyrrol-2-yl, Pyrrol-3-yl, Pyrazol-3-yl, Pyrazol-4-yl, lsoxazol-3- yl, lsoxazol-4-yl, lsoxazol-5-yl, lsothiazol-3-yl, lsothiazol-4-yl, lsothiazol-5-yl, Imi- dazol-2-yl, lmidazol-4-yl, Oxazol-2-yl, Oxazol-4-yl, Oxazol-5-yl, Thiazol-2-yl, Thi- azol-4-yl, Thiazol-5-yl, 1 ,2,3-Oxadiazol-4-yl, 1 ,2,3-Oxadiazol-5-yl, 1 ,2,4- Oxadiazol-3-yl, 1 ,2,4,-Oxadiazol-5-yl, 1 ,3,4-Oxadiazol-2-yl, 1 ,2,3-Thiadiazol-4-yl, 1 ,2,3-Thiadiazol-5-yl, 1 ,2,4-Thiadiazol-3-yl, 1 ,2,4-Thiadiazol-5-yl, 1 ,3,4- Thiadiazolyl-2-yl, 1 ,2,3-Triazol-4-yl, 1 ,2,4-Triazol-3-yl, [1 H]-Tetrazol-5-yl und [2H]- Tetrazol-5-yl;C-linked, 5-membered, heteroaromatic rings such as: 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, pyrrol-2-yl, pyrrol-3-yl, pyrazol-3-yl, pyrazole-4 yl, isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl, isothiazol-3-yl, isothiazol-4-yl, isothiazol-5-yl, imidazol-2-yl, imidazole-4 yl, oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, 1, 2,3-oxadiazole-4 yl, l, 2,3-oxadiazol-5-yl, l, 2,4-oxadiazol-3-yl, l, 2,4, -oxadiazol-5-yl, l, 3,4-oxadiazol-2-yl , 1, 2,3-Thiadiazol-4-yl, 1, 2,3-thiadiazol-5-yl, 1, 2,4-thiadiazol-3-yl, 1, 2,4-thiadiazol-5-yl, 1 , 3,4-Thiadiazolyl-2-yl, 1, 2,3-triazol-4-yl, 1, 2,4-triazol-3-yl, [1 H] -tetrazol-5-yl and [2H] - tetrazol-5-yl;
C-gebundene, 6-gliedrige, heteroaromatische Ringe wie : Pyridin-2-yl, Pyridin-3-yl, Pyridin-4-yl, Pyridazin-3-yl, Pyridazin-4-yl, Pyrimidin-2- yl, Pyrimidin-4-yl, Pyrimidin-5-yl, Pyrazin-2-yl, 1 ,3,5-Triazin-2-yl, 1 ,2,4-Triazin-3- yl, 1 ,2,4-Triazin-5-yl und 1 ,2,4-Triazin-6-yl;C-linked, 6-membered, heteroaromatic rings such as: pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyridazin-3-yl, pyridazin-4-yl, pyrimidin-2-yl, pyrimidine 4-yl, pyrimidin-5-yl, pyrazine-2-yl, 1, 3,5-triazin-2-yl, 1, 2,4-triazin-3-yl, 1, 2,4-triazine-5 yl and 1,2,4-triazin-6-yl;
N-gebundene, 5-gliedrige, heteroaromatische Ringe wie:N-linked, 5-membered, heteroaromatic rings such as:
Pyrrol-1-yl, Pyrazol-1-yl, lmidazol-1-yl, 1 ,2,3-Triazol-1-yl, 1 ,2,4-Triazol-1-yl, [1 H]-Pyrrol-1-yl, pyrazol-1-yl, imidazol-1-yl, 1, 2,3-triazol-1-yl, 1, 2,4-triazol-1-yl, [1 H] -
Tetrazol-1-yl und [2H]-Tetrazol-2-yl. Die vorgenannten Heterocyclen können in der angegebenen Weise substituiert sein. In den vorgenannten Heterocyclen kann ein Schwefelatom zu S=O oder S(=O)2 oxidiert sein.Tetrazol-1-yl and [2H] -tetrazol-2-yl. The aforementioned heterocycles may be substituted in the manner indicated. In the aforementioned heterocycles, a sulfur atom may be oxidized to S = O or S (= O) 2.
Des Weiteren bedeuten:Furthermore, mean:
Alkenyloxy: Alkenyl wie vorstehend genannt, das über ein Sauerstoffatom gebunden ist;Alkenyloxy: alkenyl as mentioned above, which is bonded via an oxygen atom;
Alkinyloxy: Alkinyl wie vorstehend genannt, das über ein Sauerstoffatom gebun- den ist;Alkynyloxy: alkynyl as mentioned above, which is bonded via an oxygen atom;
Alkylamino: eine Gruppe NHR, worin R für Alkyl, wie zuvor definiert, steht;Alkylamino: a group NHR, wherein R is alkyl as defined above;
[Dialkyl]amino: eine Gruppe NR'R, worin R und R' für Alkyl, wie zuvor definiert, stehen;[Dialkyl] amino: a group NR'R, wherein R and R 'are alkyl as defined above;
Alkoxyamino: eine Gruppe NH(OR), worin R für Alkyl, wie zuvor definiert, steht; - Alkylsulfonylamino: eine Gruppe NHS(O)2RAlkoxyamino: a group NH (OR) wherein R is alkyl as defined above; - Alkylsulfonylamino: a group NHS (O) 2R
Alkylaminosulfonylamino: eine Gruppe NHS(O)2NHR, worin R für Alkyl, wie zuvor definiert, steht;Alkylaminosulfonylamino: a group NHS (O) 2NHR, wherein R is alkyl as defined above;
[Dialkylamino]sulfonylamino: eine Gruppe NHS(O)2NR'R, worin R und R' für Alkyl, wie zuvor definiert, stehen; - Alkenylamino: eine Gruppe NHR, worin R für Alkenyl, wie zuvor definiert, steht;[Dialkylamino] sulfonylamino: a group NHS (O) 2 NR'R, wherein R and R 'are alkyl as defined above; Alkenylamino: a group NHR in which R is alkenyl as defined above;
Alkinylamino: eine Gruppe NHR, worin R für Alkinyl, wie zuvor definiert, steht;Alkynylamino: a group NHR wherein R is alkynyl as defined above;
N-(Alkenyl)-N-(alkyl)-amino: eine Gruppe NR'R, worin R für Alkenyl und R' fürN- (alkenyl) -N- (alkyl) -amino: a group NR'R, wherein R is alkenyl and R 'is
Alkyl, wie zuvor definiert, stehen;Alkyl as defined above;
N-(Alkinyl)-N-(alkyl)-amino: eine Gruppe NR'R, worin R für Alkinyl und R' für Al- kyl, wie zuvor definiert, stehen;N- (alkynyl) -N- (alkyl) -amino: a group NR'R, wherein R is alkynyl and R 'is alkyl as defined above;
N-(Alkoxy)-N-(alkyl)-amino: eine Gruppe NR'R, worin R für Alkyl und R' für Alko- xy, wie zuvor definiert, stehen;N- (alkoxy) -N- (alkyl) -amino: a group NR'R, wherein R is alkyl and R 'is alkoxy as defined above;
N-(Alkenyl)-N-(alkoxy)-amino: eine Gruppe NR'R, worin R für Alkenyl und R' fürN- (alkenyl) -N- (alkoxy) -amino: a group NR'R, wherein R is alkenyl and R 'is
Alkoxy, wie zuvor definiert, stehen; und - N-(Alkinyl)-N-(alkoxy)-amino: eine Gruppe NR'R, worin R für Alkinyl und R' fürAlkoxy as defined above; and - N- (alkynyl) -N- (alkoxy) -amino: a group NR'R, wherein R is alkynyl and R 'is
Alkoxy, wie zuvor definiert, stehen.Alkoxy, as defined above, stand.
In einer besonderen Ausführungsform haben die Variablen der Verbindungen der Formel I folgende Bedeutungen, wobei diese sowohl für sich allein betrachtet als auch in Kombination miteinander besondere Ausgestaltungen der Verbindungen der Formel I darstellen:In a particular embodiment, the variables of the compounds of the formula I have the following meanings, these being considered both individually and in combination with one another in particular embodiments of the compounds of the formula I:
R1 steht insbesondere für Cyano, Nitro oder für einen 5- oder 6-gliedrigen heteroaromatischen Rest, wie zuvor definiert, der vorzugsweise entweder 1 , 2, 3 oder 4 Stick- stoffatome oder 1 Sauerstoff oder 1 Schwefelatom und gegebenenfalls 1 oder 2 Stickstoffatome als Ringlieder aufweist und der unsubstituiert ist oder 1 oder 2 unter R1a ausgewählte Substituenten aufweisen kann. In einer ersten bevorzugten Ausführungsform der Erfindung steht R1 für Cyano oder Nitro.R 1 in particular represents cyano, nitro or a 5- or 6-membered heteroaromatic radical as defined above, which is preferably either 1, 2, 3 or 4 nitrogen atoms or 1 oxygen or 1 sulfur atom and optionally 1 or 2 nitrogen atoms Having ring members and which is unsubstituted or may have 1 or 2 substituents selected from R 1a . In a first preferred embodiment of the invention, R 1 is cyano or nitro.
In einer weiteren bevorzugten Ausführungsform der Erfindung steht R1 für 5- oder 6- gliedrigen heteroaromatischen Rest, wie zuvor definiert, der vorzugsweise entweder 1 , 2, 3 oder 4 Stickstoffatome oder 1 Sauerstoff oder 1 Schwefelatom und gegebenenfalls 1 oder 2 Stickstoffatome als Ringlieder aufweist und der unsubstituiert ist oder 1 oder 2 unter R1a ausgewählte Substituenten aufweisen kann. Beispiele für bevorzugte hetero- aromatische Reste sind Pyridazin-3-yl, Pyridazin-4-yl, Pyrimidin-2-yl, Pyrimidin-4-yl,In a further preferred embodiment of the invention, R 1 is a 5- or 6-membered heteroaromatic radical as defined above, which preferably has either 1, 2, 3 or 4 nitrogen atoms or 1 oxygen or 1 sulfur atom and optionally 1 or 2 nitrogen atoms as ring members and which is unsubstituted or may have 1 or 2 substituents selected from R 1a . Examples of preferred heteroaromatic radicals are pyridazin-3-yl, pyridazin-4-yl, pyrimidin-2-yl, pyrimidin-4-yl,
Pyrimidin-5-yl, Pyrazin-2-yl, 2-Furyl, 3-Furyl, 2-Thienyl, 3-Thienyl, Pyrazol-1-yl, Pyrazol- 3-yl, Pyrazol-4-yl, lsoxazol-3-yl, lsoxazol-4-yl, lsoxazol-5-yl, lsothiazol-3-yl, Isothiazol- 4-yl, lsothiazol-5-yl, lmidazol-1-yl, lmidazol-2-yl, lmidazol-4-yl, lmidazol-5-yl, Oxazol-2- yl, Oxazol-4-yl, Oxazol-5-yl, Thiazol-2-yl, Thiazol-4-yl und Thiazol-5-yl, insbesondere C-gebundene heteroaromatische Reste wie Pyrazol-3-yl, lmidazol-5-yl, Oxazol-2-yl, Thiazol-2-yl, Thiazol-4-yl, Thiazol-5-yl, Pyridin-2-yl, Pyridin-3-yl, Pyridin-4-yl, Pyrimidin- 2-yl, Pyrimidin-4-yl, Pyrimidin-5-yl, Pyridazin-4-yl, Pyrazin-2-yl, [1 H]-Tetrazol-5-yl und [2H]-Tetrazol-5-yl, wobei die hier exemplarisch genannten Heterocyclen 1 oder 2 unter R1a ausgewählte Substituenten aufweisen können. Bevorzugte Reste R1a sind insbe- sondere F, Cl, CN, Nitro, Methyl, Ethyl, Methoxy, Ethoxy, Difluormethoxy, Trifluor- methoxy und Trifluormethyl.Pyrimidin-5-yl, pyrazine-2-yl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, pyrazol-1-yl, pyrazol-3-yl, pyrazol-4-yl, isoxazole-3 yl, isoxazol-4-yl, isoxazol-5-yl, isothiazol-3-yl, isothiazol-4-yl, isothiazol-5-yl, imidazol-1-yl, imidazol-2-yl, imidazol-4-yl, imidazol-5-yl, oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, thiazol-2-yl, thiazol-4-yl and thiazol-5-yl, especially C-linked heteroaromatic radicals such as pyrazole 3-yl, imidazol-5-yl, oxazol-2-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, pyridin-2-yl, pyridin-3-yl, pyridine-4 -yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyridazin-4-yl, pyrazine-2-yl, [1 H] -tetrazol-5-yl and [2H] -tetrazole 5-yl, wherein the here exemplarily mentioned heterocycles 1 or 2 may have selected substituents under R 1a . Preferred radicals R 1a are, in particular, F, Cl, CN, nitro, methyl, ethyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy and trifluoromethyl.
Ebenfalls bevorzugt sind Verbindungen der allgemeinen Formel I und deren Salze, worin R1 für Halogen, insbesondere für Chlor oder Brom, steht.Also preferred are compounds of general formula I and their salts, wherein R 1 is halogen, in particular chlorine or bromine.
Der Rest R2 steht vorzugsweise für Wasserstoff, Fluor, Chlor, Ci-C2-Alkyl, C1-C2- Fluoralkyl, Ethenyl, Ci-C2-Alkoxy oder Ci-C2-Fluoralkoxy, insbesondere für Fluor, Chlor, Methyl, Ethyl, Methoxy, Ethenyl oder Trifluormethoxy. R2 steht besonders bevorzugt für Wasserstoff, Fluor oder Chlor.The radical R 2 is preferably hydrogen, fluorine, chlorine, C 1 -C 2 -alkyl, C 1 -C 2 -fluoroalkyl, ethenyl, C 1 -C 2 -alkoxy or C 1 -C 2 -fluoroalkoxy, in particular fluorine, chlorine, methyl, ethyl, methoxy , Ethenyl or trifluoromethoxy. R 2 particularly preferably represents hydrogen, fluorine or chlorine.
Unter den Verbindungen der Formel I, in denen R2 von Wasserstoff verschieden ist, sind solche Verbindungen bevorzugt, worin R2 in ortho-Position zur Bindungsstelle des Phenylrings angeordnet ist.Among the compounds of formula I in which R 2 is other than hydrogen, those compounds are preferred wherein R 2 is located ortho to the position of attachment of the phenyl ring.
In einer besonders bevorzugten Ausführungsform steht R2 für Halogen, insbesondere Chlor oder Fluor, das in ortho-Position zur Bindungsstelle des Phenylrings angeordnet ist.In a particularly preferred embodiment, R 2 is halogen, in particular chlorine or fluorine, which is arranged in the ortho position to the binding site of the phenyl ring.
Unter den Verbindungen der Formel I, in denen R3 für Halogen steht, sind solche Ver- bindungen bevorzugt, worin R3 in para-Position zur Gruppe R1 angeordnet ist. Unter den Verbindungen der Formel I, in denen R3 für Halogen steht, sind solche Verbindungen bevorzugt, worin R3 für Fluor oder Chlor steht. In einer anderen, ebenfalls bevorzugten Ausführungsform steht R3 für Wasserstoff.Among the compounds of the formula I in which R 3 is halogen, preference is given to those compounds in which R 3 is arranged in the para position to the group R 1 . Among the compounds of the formula I in which R 3 is halogen, preference is given to those compounds in which R 3 is fluorine or chlorine. In another, likewise preferred embodiment, R 3 is hydrogen.
R4 steht vorzugsweise für Methyl.R 4 is preferably methyl.
R5 steht vorzugsweise für Wasserstoff, Methyl oder Ethyl, speziell Methyl.R 5 is preferably hydrogen, methyl or ethyl, especially methyl.
Ebenfalls bevorzugt sind Verbindungen der Formel I, worin R5 eine Gruppe C(=O)R51 bedeutet, worin R51 eine der zuvor genannten Bedeutungen aufweist und insbesondere für Wasserstoff, Ci-C4-AIkVl, speziell Methyl oder Ethyl, oder für Ci-C4-Haloalkyl, speziell Ci-C2-Fluoralkyl wie Trifluormethyl steht.Also preferred are compounds of formula I, wherein R 5 is a group C (= O) R 51 , wherein R 51 has one of the meanings given above and in particular for hydrogen, Ci-C 4 -AlkVl, especially methyl or ethyl, or for Ci-C4-haloalkyl, especially Ci-C2-fluoroalkyl such as trifluoromethyl stands.
R6 steht vorzugsweise für Ci-C3-Alkyl oder Ci-C2-Fluoralkyl, insbesondere für Methyl, Ethyl, n-Propyl oder Trifluormethyl, und speziell für Methyl oder Ethyl.R 6 is preferably C 1 -C 3 -alkyl or C 1 -C 2 -fluoroalkyl, in particular methyl, ethyl, n-propyl or trifluoromethyl, and especially methyl or ethyl.
Vorzugsweise stehen wenigstens einer und insbesondere beide Reste R7 und R8 für Wasserstoff.Preferably, at least one and in particular both radicals R 7 and R 8 are hydrogen.
Unter den Verbindungen der Formel I, in denen R9 für einen von Wasserstoff verschiedenen Rest steht, sind solche Verbindungen bevorzugt, worin R9 in para-Position zur Gruppe CR7R8 angeordnet ist.Among the compounds of the formula I in which R 9 is a radical different from hydrogen, preference is given to those compounds in which R 9 is arranged in the para position to the group CR 7 R 8 .
Unter den Verbindungen der Formel I, in denen R9 für einen von Wasserstoff verschie- denen Rest steht, sind solche Verbindungen bevorzugt, worin R9 für Halogen, insbesondere für Fluor oder Chlor steht. In einer anderen, ebenfalls bevorzugten Ausführungsform steht R9 für Wasserstoff.Among the compounds of the formula I in which R 9 is a radical different from hydrogen, preference is given to those compounds in which R 9 is halogen, in particular fluorine or chlorine. In another, likewise preferred embodiment, R 9 is hydrogen.
R10 steht vorzugsweise für Wasserstoff.R 10 is preferably hydrogen.
In der Gruppe C(O)R11 steht R11 vorzugsweise für Wasserstoff, CrC4-AIkVl oder Ci-C4- Haloalkyl.In the group C (O) R 11 , R 11 is preferably hydrogen, C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl.
Unter den Verbindungen der Formel I und deren Salzen sind die Verbindungen der allgemeinen Formel Ia sowie deren landwirtschaftlich geeigneten Salze bevorzugt: Among the compounds of the formula I and their salts, preference is given to the compounds of the general formula Ia and their agriculturally suitable salts:
worin R1, R2, R3, R4, R5, R6 und R9 eine der zuvor angegebenen Bedeutungen, insbesondere die als bevorzugt angegebenen Bedeutungen aufweisen. Insbesondere haben in Formel Ia die Reste R1, R2, R3, R4, R5, R6 und R9 unabhängig voneinander, vorzugsweise jedoch in Kombination, die nachfolgenden Bedeutungen aufweisen:wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 9 have one of the meanings given above, in particular the meanings given as preferred. In particular, in formula Ia, the radicals R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 9 independently of one another, but preferably in combination, have the following meanings:
R1 Cyano oder Nitro;R 1 is cyano or nitro;
R2 Wasserstoff, Fluor, Chlor, Ci-C2-Alkyl, Ethenyl oder Ci-C2-Alkoxy, insbesondereR 2 is hydrogen, fluorine, chlorine, C 1 -C 2 -alkyl, ethenyl or C 1 -C 2 -alkoxy, in particular
Wasserstoff, Fluor oder Chlor;Hydrogen, fluorine or chlorine;
R3 Fluor oder Wasserstoff;R 3 is fluorine or hydrogen;
R4 Methyl;R 4 is methyl;
R5 Wasserstoff, Methyl oder Ethyl, speziell Methyl;R 5 is hydrogen, methyl or ethyl, especially methyl;
R6 Methyl oder Ethyl; undR 6 is methyl or ethyl; and
R9 Wasserstoff oder Halogen, insbesondere Wasserstoff oder Fluor.R 9 is hydrogen or halogen, in particular hydrogen or fluorine.
Die Verbindungen der Formel I weisen am Kohlenstoffatom, welche die Gruppe R6 trägt, ein Chiralitätszentrum auf. Eine bevorzugte Ausführungsform der Erfindung betrifft die reinen Enantiomere der im Folgenden angegebenen Formel I-S, worin R1, R2, R3, R4, R5, R6, R7, R8, R9 und R10 eine der zuvor angegebenen Bedeutungen, insbesondere eine der als bevorzugt oder als besonders bevorzugt angegebenen Bedeutungen aufweisen, sowie Enantiomerenmischungen, die einen Enantiomerenüber- schuss bezüglich des Enantiomers der Formel I-S aufweisen.The compounds of the formula I have a center of chirality on the carbon atom which carries the group R 6 . A preferred embodiment of the invention relates to the pure enantiomers of the formula given below in which R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 and R 10 is one of the abovementioned Meanings, in particular one of the preferred or given as particularly preferred meanings, as well as enantiomeric mixtures having an enantiomeric excess with respect to the enantiomer of the formula IS.
Enantiomerenüberschuss bedeutet bevorzugt einen ee-Wert (enantiomeric excess) von wenigstens 70 %, insbesondere wenigstens 80 % und speziell wenigstens 90 %. Ebenso bevorzugt sind die landwirtschaftlich geeigneten Salze der Enantiomere I-S und Enantiomerenmischungen der Salze, die einen Enantiomerenüberschuss bezüglich des Enantiomers der Formel I-S aufweisen.Enantiomeric excess preferably means an ee value (enantiomeric excess) of at least 70%, in particular at least 80% and especially at least 90%. Likewise preferred are the agriculturally suitable salts of the enantiomers IS and enantiomeric mixtures of the salts having an enantiomeric excess with respect to the enantiomer of the formula IS.
Eine andere, ebenfalls bevorzugte Ausführungsform betrifft die Racemate von I und deren Salze.Another, likewise preferred embodiment relates to the racemates of I and their salts.
Eine besonders bevorzugte Ausführungsform betrifft die reinen Enantiomere der im Folgenden angegebenen Formel I-S.a, worin R1, R2, R3, R4, R5, R6 und R9 eine der zuvor angegebenen Bedeutungen, insbesondere eine der als bevorzugt oder als besonders bevorzugt angegebenen Bedeutungen aufweisen, sowie Enantiomerenmischungen, die einen Enantiomerenüberschuss bezüglich des Enantiomers der Formel I-S.a aufweisen.A particularly preferred embodiment relates to the pure enantiomers of the formula given below IS.a, wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 9 is one of the meanings given above, in particular one of preferred or have particularly given meanings as well as enantiomeric mixtures which have an enantiomeric excess with respect to the enantiomer of the formula IS.a.
Ebenso bevorzugt sind die landwirtschaftlich geeigneten Salze der Enantiomere I-S.a und Enantiomerenmischungen der Salze, die einen Enantiomerenüberschuss bezüglich des Enantiomers der Formel I-S.a aufweisen.Also preferred are the agriculturally suitable salts of enantiomers I-S.a and enantiomeric mixtures of the salts having an enantiomeric excess with respect to the enantiomer of formula I-S.a.
Insbesondere haben in Formel I-S.a die Reste R1, R2, R3, R4, R5, R6 und R9 unabhän- gig voneinander, vorzugsweise jedoch in Kombination, die nachfolgenden Bedeutungen:In particular, in formula IS.a the radicals R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 9, independently of one another but preferably in combination, have the following meanings:
R1 Cyano oder Nitro;R 1 is cyano or nitro;
R2 Wasserstoff, Fluor, Chlor, Ci-C2-Alkyl, Ethenyl oder Ci-C2-Alkoxy, insbesondere Wasserstoff, Fluor oder Chlor;R 2 is hydrogen, fluorine, chlorine, C 1 -C 2 -alkyl, ethenyl or C 1 -C 2 -alkoxy, in particular hydrogen, fluorine or chlorine;
R3 Fluor oder Wasserstoff;R 3 is fluorine or hydrogen;
R4 Methyl;R 4 is methyl;
R5 Wasserstoff, Methyl oder Ethyl, speziell Methyl;R 5 is hydrogen, methyl or ethyl, especially methyl;
R6 Methyl oder Ethyl; und R9 Wasserstoff oder Halogen, insbesondere Wasserstoff oder Fluor.R 6 is methyl or ethyl; and R 9 is hydrogen or halogen, in particular hydrogen or fluorine.
Eine andere besonders bevorzugte Ausführungsform der Erfindung betrifft die Racemate von Ia und deren Salze. Unter den Verbindungen der Formeln I, La, I-S und I-S.a sind solche Verbindungen bevorzugt, worin die exo-Doppelbindung am Piperazinring die (Z)-Konfiguration aufweist. Ebenso bevorzugt sind Gemische des (E)-Isomers mit dem (Z)-Isomer, worin das Z-Isomer im Überschuss vorliegt, insbesondere Isomerengemische mit einem E/Z- Verhältnis, von nicht mehr als 1 :2 insbesondere nicht mehr als 1 :5.Another particularly preferred embodiment of the invention relates to the racemates of Ia and their salts. Among the compounds of the formulas I, La, IS and IS.a preference is given to those compounds in which the exo double bond on the piperazine ring has the (Z) configuration. Likewise preferred are mixtures of the (E) -isomer with the (Z) -isomer in which the Z-isomer is present in excess, in particular isomer mixtures having an E / Z ratio of not more than 1: 2, in particular not more than 1: 5th
Beispiele für erfindungsgemäß bevorzugte Verbindungen sind die im Folgenden genannten Verbindungen sowie deren Salze: 2-[5-Benzyl-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-benzonitril, 2-[5-Benzyl-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-fluorbenzonitril,Examples of compounds which are preferred according to the invention are the compounds mentioned below and salts thereof: 2- [5-benzyl-1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] benzonitrile, 2- [5-benzyl- 1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-fluorobenzonitrile,
2-[5-Benzyl-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-methoxybenzonitril, 2-[5-Benzyl-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3,4-difluorbenzonitril, 2-[5-Benzyl-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-methylbenzonitril, 2-[5-Benzyl-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-ethenylbenzonitril, 2-[5-Benzyl-1 ,5-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-benzonitril,2- [5-Benzyl-1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-methoxybenzonitrile, 2- [5-Benzyl-1, 4,5-trimethyl-3,6-dioxopiperazine -2-ylidenemethyl] -3,4-difluorobenzonitrile, 2- [5-benzyl-1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-methylbenzonitrile, 2- [5-benzyl-1 , 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-ethenylbenzonitrile, 2- [5-benzyl-1, 5-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] benzonitrile,
2-[5-Benzyl-1 ,5-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-fluorbenzonitril, 2-[5-Benzyl-1 ,5-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-methoxybenzonitril, 2-[5-Benzyl-1 ,5-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3,4-difluorbenzonitril, 2-[5-Benzyl-1 ,5-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-methylbenzonitril, 2-[5-Benzyl-1 ,5-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-ethenylbenzonitril, 2-[5-Benzyl-5-ethyl-1 ,4-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-benzonitril 2-[5-Benzyl-5-ethyl-1 ,4-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-fluorbenzonitril, 2-[5-Benzyl-5-ethyl-1 ,4-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-methoxy- benzonitril, 2-[5-Benzyl-5-ethyl-1 ,4-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3,4-difluor- benzonitril,2- [5-Benzyl-1,5-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-fluorobenzonitrile, 2- [5-Benzyl-1, 5-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl ] -3-methoxybenzonitrile, 2- [5-benzyl-1, 5-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3,4-difluorobenzonitrile, 2- [5-benzyl-1, 5-dimethyl-3 , 6-dioxopiperazin-2-ylidenemethyl] -3-methylbenzonitrile, 2- [5-benzyl-1, 5-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-ethenylbenzonitrile, 2- [5-benzyl-5 ethyl 1, 4-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] benzonitrile 2- [5-benzyl-5-ethyl-1,4-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3 fluorobenzonitrile, 2- [5-benzyl-5-ethyl-1, 4-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-methoxybenzonitrile, 2- [5-benzyl-5-ethyl-1, 4-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3,4-difluoro-benzonitrile,
2-[5-Benzyl-5-ethyl-1 ,4-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-methyl- benzonitril, 2-[5-Benzyl-5-ethyl-1 ,4-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-ethenyl- benzonitril,2- [5-Benzyl-5-ethyl-1,4-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-methylbenzonitrile, 2- [5-benzyl-5-ethyl-1,4-dimethyl 3,6-dioxopiperazin-2-ylidenemethyl] -3-ethenylbenzonitrile,
2-[5-Benzyl-5-ethyl-1-methyl-3,6-dioxopiperazin-2-ylidenmethyl]-benzonitril, 2-[5-Benzyl-5-ethyl-1-methyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-fluorbenzonitril, 2-[5-Benzyl-5-ethyl-1-methyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-methoxybenzonitril, 2-[5-Benzyl-5-ethyl-1-methyl-3,6-dioxopiperazin-2-ylidenmethyl]-3,4-difluorbenzonitril, 2-[5-Benzyl-5-ethyl-1-methyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-methylbenzonitril, 2-[5-Benzyl-5-ethyl-1-methyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-ethenylbenzonitril, 3-Benzyl-6-[1-(2-nitrophenyl)-methyliden]-1 ,3,4-trimethylpiperazin-2,5-dion, 3-Benzyl-6-[1-(2-fluor-6-nitrophenyl)-methyliden]-1 ,3,4-trimethylpiperazin-2,5-dion, 3-Benzyl-6-[1-(2,3-difluor-6-nitrophenyl)-methyliden]-1 ,3,4-trimethylpiperazin-2,5-dion, 3-Benzyl-6-[1 -(2-methoxy-6-nitrophenyl)-methyliden]-1 ,3,4-trimethylpiperazin-2,5-dion, 3-Benzyl-6-[1-(2-methyl-6-nitrophenyl)-methyliden]-1 ,3,4-trimethylpiperazin-2,5-dion, 3-Benzyl-6-[1-(2-ethenyl-6-nitrophenyl)-methyliden]-1 ,3,4-trimethylpiperazin-2,5-dion, 3-Benzyl-6-[1-(2-nitrophenyl)-methyliden]-1 ,3-dimethylpiperazin-2,5-dion,2- [5-Benzyl-5-ethyl-1-methyl-3,6-dioxopiperazin-2-ylidene-methyl] -benzonitrile, 2- [5-benzyl-5-ethyl-1-methyl-3,6-dioxopiperazine-2 -ylidenemethyl] -3-fluorobenzonitrile, 2- [5-benzyl-5-ethyl-1-methyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-methoxybenzonitrile, 2- [5-benzyl-5-ethyl-1 -methyl-3,6-dioxopiperazin-2-ylidenemethyl] -3,4-difluorobenzonitrile, 2- [5-benzyl-5-ethyl-1-methyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-methylbenzonitrile, 2- [5-Benzyl-5-ethyl-1-methyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-ethenylbenzonitrile, 3-benzyl-6- [1- (2-nitrophenyl) -methylidene] -1, 3,4-trimethylpiperazine-2,5-dione, 3-benzyl-6- [1- (2-fluoro-6-nitrophenyl) -methylidene] -1,3,4-trimethyl-piperazine-2,5-dione, 3 Benzyl 6- [1- (2,3-difluoro-6-nitrophenyl) methylidene] -1,3,4-trimethylpiperazine-2,5-dione, 3-benzyl-6- [1- (2-methoxy) 6-nitrophenyl) methylidene] -1, 3,4-trimethylpiperazine-2,5-dione, 3-benzyl-6- [1- (2-methyl-6-nitrophenyl) -methylidene] -1, 3,4- trimethylpiperazine-2,5-dione, 3-benzyl-6- [1- (2-ethenyl-6-nitrophenyl) -methylidene] -1,3,4-trim thylpiperazin-2,5-dione, 3-Benzyl-6- [1- (2-nitrophenyl) -methylidene] -1,3-dimethylpiperazine-2,5-dione,
3-Benzyl-6-[1-(2-fluor-6-nitrophenyl)-methyliden]-1 ,3-dimethylpiperazin-2,5-dion,3-Benzyl-6- [1- (2-fluoro-6-nitrophenyl) -methylidene] -1,3-dimethylpiperazine-2,5-dione,
3-Benzyl-6-[1-(2,3-difluor-6-nitrophenyl)-methyliden]-1 ,3-dimethylpiperazin-2,5-dion,3-Benzyl-6- [1- (2,3-difluoro-6-nitrophenyl) -methylidene] -1,3-dimethylpiperazine-2,5-dione,
3-Benzyl-6-[1-(2-methoxy-6-nitrophenyl)-methyliden]-1 ,3-dimethylpiperazin-2,5-dion, 3-Benzyl-6-[1 -(2-methyl-6-nitrophenyl)-methyliden]-1 ,3-dimethylpiperazin-2,5-dion,3-Benzyl-6- [1- (2-methoxy-6-nitrophenyl) -methylidene] -1,3-dimethylpiperazine-2,5-dione, 3-benzyl-6- [1 - (2-methyl-6- nitrophenyl) methylidene] -1,3-dimethylpiperazine-2,5-dione,
3-Benzyl-6-[1-(2-ethenyl-6-nitrophenyl)-methyliden]-1 ,3-dimethylpiperazin-2,5-dion,3-Benzyl-6- [1- (2-ethenyl-6-nitrophenyl) -methylidene] -1,3-dimethylpiperazine-2,5-dione,
3-Benzyl-6-[1-(2-nitrophenyl)-methyliden]-3-ethyl-1 ,4-dimethylpiperazin-2,5-dion,3-Benzyl-6- [1- (2-nitrophenyl) methylidene] -3-ethyl-1,4-dimethylpiperazine-2,5-dione,
3-Benzyl-6-[1-(2-fluor-6-nitrophenyl)-methyliden]-3-ethyl-1 ,4-dimethylpiperazin-2,5- dion, 3-Benzyl-6-[1 -(2,3-difluor-6-nitrophenyl)-methyliden]-3-ethyl-1 ,4-dimethylpiperazin-2,5- dion,3-Benzyl-6- [1- (2-fluoro-6-nitrophenyl) -methylidene] -3-ethyl-1, 4-dimethylpiperazine-2,5-dione, 3-benzyl-6- [1 - (2, 3-difluoro-6-nitrophenyl) methylidene] -3-ethyl-1,4-dimethylpiperazine-2,5-dione,
3-Benzyl-6-[1-(2-methoxy-6-nitrophenyl)-methyliden]-3-ethyl-1 ,4-dimethylpiperazin-2,5- dion,3-Benzyl-6- [1- (2-methoxy-6-nitrophenyl) methylidene] -3-ethyl-1,4-dimethylpiperazine-2,5-dione,
3-Benzyl-6-[1-(2-methyl-6-nitrophenyl)-methyliden]-3-ethyl-1 ,4-dimethylpiperazin-2,5- dion,3-Benzyl-6- [1- (2-methyl-6-nitrophenyl) methylidene] -3-ethyl-1,4-dimethylpiperazine-2,5-dione,
3-Benzyl-6-[1-(2-ethenyl-6-nitrophenyl)-methyliden]-3-ethyl-1 ,4-dimethylpiperazin-2,5- dion,3-Benzyl-6- [1- (2-ethenyl-6-nitrophenyl) methylidene] -3-ethyl-1,4-dimethylpiperazine-2,5-dione,
3-Benzyl-6-[1-(2-nitrophenyl)-methyliden]-3-ethyl-1-methylpiperazin-2,5-dion,3-Benzyl-6- [1- (2-nitrophenyl) methylidene] -3-ethyl-1-methylpiperazine-2,5-dione,
3-Benzyl-6-[1-(2-fluor-6-nitrophenyl)-methyliden]-3-ethyl-1-methylpiperazin-2,5-dion, 3-Benzyl-6-[1 -(2,3-difluor-6-nitrophenyl)-methyliden]-3-ethyl-1 -methylpiperazin-2,5- dion,3-Benzyl-6- [1- (2-fluoro-6-nitrophenyl) -methylidene] -3-ethyl-1-methylpiperazine-2,5-dione, 3-benzyl-6- [1 - (2,3- difluoro-6-nitrophenyl) methylidene] -3-ethyl-1-methylpiperazine-2,5-dione,
3-Benzyl-6-[1-(2-methoxy-6-nitrophenyl)-methyliden]-3-ethyl-1-methylpiperazin-2,5- dion,3-Benzyl-6- [1- (2-methoxy-6-nitrophenyl) methylidene] -3-ethyl-1-methylpiperazine-2,5-dione,
3-Benzyl-6-[1-(2-methyl-6-nitrophenyl)-methyliden]-3-ethyl-1-methylpiperazin-2,5-dion, 3-Benzyl-6-[1 -(2-ethenyl-6-nitrophenyl)-methyliden]-3-ethyl-1 -methylpiperazin-2,5-dion3-Benzyl-6- [1- (2-methyl-6-nitrophenyl) -methylidene] -3-ethyl-1-methylpiperazine-2,5-dione, 3-benzyl-6- [1- (2-ethenyl-) 6-nitrophenyl) methylidene] -3-ethyl-1-methylpiperazine-2,5-dione
2-[5-(4-Fluorbenzyl)-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-benzonitril,2- [5- (4-fluorobenzyl) -1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -benzonitrile,
2-[5-(4-Fluorbenzyl)-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3- fluorbenzonitril,2- [5- (4-fluorobenzyl) -1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-fluorobenzonitrile,
2-[5-(4-Fluorbenzyl)-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-methoxy- benzonitril,2- [5- (4-fluorobenzyl) -1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-methoxybenzonitrile,
2-[5-(4-Fluorbenzyl)-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3,4-difluor- benzonitril,2- [5- (4-fluorobenzyl) -1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3,4-difluoro-benzonitrile,
2-[5-(4-Fluorbenzyl)-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-methyl- benzonitril, 2-[5-(4-Fluorbenzyl)-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-ethenyl- benzonitril,2- [5- (4-fluorobenzyl) -1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-methylbenzonitrile, 2- [5- (4-fluorobenzyl) -1, 4 , 5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-ethenylbenzonitrile,
2-[5-(4-Fluorbenzyl)-1 ,5-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-benzonitril,2- [5- (4-fluorobenzyl) -1,5-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -benzonitrile,
2-[5-(4-Fluorbenzyl)-1 ,5-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-fluorbenzonitril,2- [5- (4-fluorobenzyl) -1,5-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-fluorobenzonitrile,
2-[5-(4-Fluorbenzyl)-1 ,5-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-methoxy- benzonitril,2- [5- (4-fluorobenzyl) -1, 5-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-methoxybenzonitrile,
2-[5-(4-Fluorbenzyl)-1 ,5-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3,4-difluor- benzonitril, 2-[5-(4-Fluorbenzyl)-1 ,5-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-methyl- benzonitril,2- [5- (4-fluorobenzyl) -1, 5-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3,4-difluoro-benzonitrile, 2- [5- (4-fluorobenzyl) -1, 5-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-methylbenzonitrile,
2-[5-(4-Fluorbenzyl)-1 ,5-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-ethenyl- benzonitril, 2-[5-(4-Fluorbenzyl)-5-ethyl-1 ,4-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-benzonitril2- [5- (4-fluorobenzyl) -1, 5-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-ethenylbenzonitrile, 2- [5- (4-fluorobenzyl) -5-ethyl-1 , 4-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -benzonitrile
2-[5-(4-Fluorbenzyl)-5-ethyl-1 ,4-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-fluor- benzonitril2- [5- (4-fluorobenzyl) -5-ethyl-1,4-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-fluorobenzonitrile
2-[5-(4-Fluorbenzyl)-5-ethyl-1 ,4-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3- methoxybenzonitril 2-[5-(4-Fluorbenzyl)-5-ethyl-1 ,4-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3,4-difluor- benzonitril,2- [5- (4-fluorobenzyl) -5-ethyl-1,4-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-methoxybenzonitrile 2- [5- (4-fluorobenzyl) -5-ethyl- 1,4-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3,4-difluorobenzonitrile,
2-[5-(4-Fluorbenzyl)-5-ethyl-1 ,4-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-methyl- benzonitril,2- [5- (4-fluorobenzyl) -5-ethyl-1,4-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-methylbenzonitrile,
2-[5-(4-Fluorbenzyl)-5-ethyl-1 ,4-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-ethenyl- benzonitril,2- [5- (4-fluorobenzyl) -5-ethyl-1,4-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-ethenylbenzonitrile,
2-[5-(4-Fluorbenzyl)-5-ethyl-1-methyl-3,6-dioxopiperazin-2-ylidenmethyl]-benzonitril,2- [5- (4-fluorobenzyl) -5-ethyl-1-methyl-3,6-dioxopiperazin-2-ylidenemethyl] -benzonitrile,
2-[5-(4-Fluorbenzyl)-5-ethyl-1-methyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-fluor- benzonitril,2- [5- (4-fluorobenzyl) -5-ethyl-1-methyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-fluorobenzonitrile,
2-[5-(4-Fluorbenzyl)-5-ethyl-1-methyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-methoxy- benzonitril,2- [5- (4-fluorobenzyl) -5-ethyl-1-methyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-methoxybenzonitrile,
2-[5-(4-Fluorbenzyl)-5-ethyl-1-methyl-3,6-dioxopiperazin-2-ylidenmethyl]-3,4-difluor- benzonitril,2- [5- (4-fluorobenzyl) -5-ethyl-1-methyl-3,6-dioxopiperazin-2-ylidenemethyl] -3,4-difluoro-benzonitrile,
2-[5-(4-Fluorbenzyl)-5-ethyl-1-methyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-methyl- benzonitril, 2-[5-(4-Fluorbenzyl)-5-ethyl-1-methyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-ethenyl- benzonitril,2- [5- (4-fluorobenzyl) -5-ethyl-1-methyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-methylbenzonitrile, 2- [5- (4-fluorobenzyl) -5-ethyl 1-methyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-ethenylbenzonitrile,
3-(4-Fluorbenzyl)-6-[1-(2-nitrophenyl)-methyliden]-1 ,3,4-trimethylpiperazin-2,5-dion,3- (4-fluorobenzyl) -6- [1- (2-nitrophenyl) methylidene] -1,3,4-trimethylpiperazine-2,5-dione,
3-(4-Fluorbenzyl)-6-[1-(2-fluor-6-nitrophenyl)-methyliden]-1 ,3,4-trimethylpiperazin-2,5- dion, 3-(4-Fluorbenzyl)-6-[1 -(2,3-difluor-6-nitrophenyl)-methyliden]-1 ,3,4-trimethylpiperazin-3- (4-fluorobenzyl) -6- [1- (2-fluoro-6-nitrophenyl) -methylidene] -1,3,4-trimethyl-piperazine-2,5-dione, 3- (4-fluorobenzyl) -6- [1- (2,3-difluoro-6-nitrophenyl) methylidene] -1, 3,4-trimethylpiperazine
2,5-dion,2,5-dione,
3-(4-Fluorbenzyl)-6-[1-(2-methoxy-6-nitrophenyl)-methyliden]-1 ,3,4-trimethylpiperazin-3- (4-fluorobenzyl) -6- [1- (2-methoxy-6-nitrophenyl) methylidene] -1,3,4-trimethylpiperazine
2,5-dion,2,5-dione,
3-(4-Fluorbenzyl)-6-[1-(2-methyl-6-nitrophenyl)-methyliden]-1 ,3,4-trimethylpiperazin- 2,5-dion,3- (4-fluorobenzyl) -6- [1- (2-methyl-6-nitrophenyl) -methylidene] -1,3,4-trimethyl-piperazine-2,5-dione,
3-(4-Fluorbenzyl)-6-[1-(2-ethenyl-6-nitrophenyl)-methyliden]-1 ,3,4-trimethylpiperazin-3- (4-fluorobenzyl) -6- [1- (2-ethenyl-6-nitrophenyl) methylidene] -1,3,4-trimethylpiperazine
2,5-dion,2,5-dione,
3-(4-Fluorbenzyl)-6-[1-(2-nitrophenyl)-methyliden]-1 ,3-dimethylpiperazin-2,5-dion,3- (4-fluorobenzyl) -6- [1- (2-nitrophenyl) methylidene] -1,3-dimethylpiperazine-2,5-dione,
3-(4-Fluorbenzyl)-6-[1-(2-fluor-6-nitrophenyl)-methyliden]-1 ,3-dimethylpiperazin-2,5- dion,3- (4-fluorobenzyl) -6- [1- (2-fluoro-6-nitrophenyl) -methylidene] -1,3-dimethylpiperazine-2,5-dione,
3-(4-Fluorbenzyl)-6-[1-(2,3-difluor-6-nitrophenyl)-methyliden]-1 ,3-dimethylpiperazin-2,5- dion, 3-(4-Fluorbenzyl)-6-[1-(2-methoxy-6-nitrophenyl)-methyliden]-1 ,3-dimethylpiperazin-3- (4-fluorobenzyl) -6- [1- (2,3-difluoro-6-nitrophenyl) methylidene] -1,3-dimethylpiperazine-2,5-dione, 3- (4-fluorobenzyl) -6- [1- (2-methoxy-6-nitrophenyl) methylidene] -1,3-dimethylpiperazine
2,5-dion,2,5-dione,
3-(4-Fluorbenzyl)-6-[1-(2-methyl-6-nitrophenyl)-methyliden]-1 ,3-dimethylpiperazin-2,5- dion, 3-(4-Fluorbenzyl)-6-[1 -(2-ethenyl-6-nitrophenyl)-methyliden]-1 ,3-dimethylpiperazin-2,5- dion,3- (4-fluorobenzyl) -6- [1- (2-methyl-6-nitrophenyl) methylidene] -1,3-dimethylpiperazine-2,5-dione, 3- (4-fluorobenzyl) -6- [1 - (2-ethenyl-6-nitrophenyl) methylidene] -1,3-dimethylpiperazine-2,5-dione,
3-(4-Fluorbenzyl)-6-[1-(2-nitrophenyl)-methyliden]-3-ethyl-1 ,4-dimethylpiperazin-2,5- dion,3- (4-fluorobenzyl) -6- [1- (2-nitrophenyl) methylidene] -3-ethyl-1,4-dimethylpiperazine-2,5-dione,
3-(4-Fluorbenzyl)-6-[1-(2-fluor-6-nitrophenyl)-methyliden]-3-ethyl-1 ,4-dimethylpiperazin- 2,5-dion,3- (4-fluorobenzyl) -6- [1- (2-fluoro-6-nitrophenyl) methylidene] -3-ethyl-1,4-dimethylpiperazine-2,5-dione,
3-(4-Fluorbenzyl)-6-[1-(2,3-difluor-6-nitrophenyl)-methyliden]-3-ethyl-1 ,4-dimethyl- piperazin-2,5-dion,3- (4-fluorobenzyl) -6- [1- (2,3-difluoro-6-nitrophenyl) methylidene] -3-ethyl-1,4-dimethyl-piperazine-2,5-dione,
3-(4-Fluorbenzyl)-6-[1-(2-methoxy-6-nitrophenyl)-methyliden]-3-ethyl-1 ,4-dimethyl- piperazin-2,5-dion, 3-(4-Fluorbenzyl)-6-[1 -(2-methyl-6-nitrophenyl)-methyliden]-3-ethyl-1 ,4-dimethyl- piperazin-2,5-dion,3- (4-fluorobenzyl) -6- [1- (2-methoxy-6-nitrophenyl) methylidene] -3-ethyl-1,4-dimethyl-piperazine-2,5-dione, 3- (4-fluorobenzyl ) -6- [1- (2-methyl-6-nitrophenyl) methylidene] -3-ethyl-1,4-dimethyl-piperazine-2,5-dione,
3-(4-Fluorbenzyl)-6-[1-(2-ethenyl-6-nitrophenyl)-methyliden]-3-ethyl-1 ,4-dimethyl- piperazin-2,5-dion,3- (4-fluorobenzyl) -6- [1- (2-ethenyl-6-nitrophenyl) methylidene] -3-ethyl-1,4-dimethyl-piperazine-2,5-dione,
3-(4-Fluorbenzyl)-6-[1-(2-nitrophenyl)-methyliden]-3-ethyl-1-methylpiperazin-2,5-dion, 3-(4-Fluorbenzyl)-6-[1 -(2-fluor-6-nitrophenyl)-methyliden]-3-ethyl-1 -methylpiperazin-3- (4-fluorobenzyl) -6- [1- (2-nitrophenyl) methylidene] -3-ethyl-1-methylpiperazine-2,5-dione, 3- (4-fluorobenzyl) -6- [1 - ( 2-fluoro-6-nitrophenyl) methylidene] -3-ethyl-1-methylpiperazine
2,5-dion,2,5-dione,
3-(4-Fluorbenzyl)-6-[1-(2,3-difluor-6-nitrophenyl)-methyliden]-3-ethyl-1-methylpiperazin-3- (4-fluorobenzyl) -6- [1- (2,3-difluoro-6-nitrophenyl) methylidene] -3-ethyl-1-methylpiperazin-
2,5-dion,2,5-dione,
3-(4-Fluorbenzyl)-6-[1-(2-methoxy-6-nitrophenyl)-methyliden]-3-ethyl-1-methyl- piperazin-2,5-dion,3- (4-fluorobenzyl) -6- [1- (2-methoxy-6-nitrophenyl) methylidene] -3-ethyl-1-methylpiperazine-2,5-dione,
3-(4-Fluorbenzyl)-6-[1-(2-methyl-6-nitrophenyl)-methyliden]-3-ethyl-1-methylpiperazin-3- (4-fluorobenzyl) -6- [1- (2-methyl-6-nitrophenyl) methylidene] -3-ethyl-1-methylpiperazin-
2,5-dion,2,5-dione,
3-(4-Fluorbenzyl)-6-[1-(2-ethenyl-6-nitrophenyl)-methyliden]-3-ethyl-1-methylpiperazin-3- (4-fluorobenzyl) -6- [1- (2-ethenyl-6-nitrophenyl) methylidene] -3-ethyl-1-methylpiperazin-
2,5-dion, 2-[5-Benzyl-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-brombenzonitril,2,5-dione, 2- [5-benzyl-1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-bromobenzonitrile,
2-[5-Benzyl-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-isophtalonitril,2- [5-Benzyl-1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -isophtalonitrile,
3-Benzyl-6-[1-(2,3-difluor-6-nitrophenyl)-methyliden]-1 ,3,4-trimethylpiperazin-2,5-dion,3-Benzyl-6- [1- (2,3-difluoro-6-nitrophenyl) methylidene] -1,3,4-trimethylpiperazine-2,5-dione,
3-Benzyl-6-[1-(2-nitro-5-methoxyphenyl)-methyliden]-1 ,3,4-trimethylpiperazin-2,5-dion,3-Benzyl-6- [1- (2-nitro-5-methoxyphenyl) methylidene] -1,3,4-trimethylpiperazine-2,5-dione,
2-[5-Benzyl-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-nitrobenzonitπl, 3-Benzyl-6-[1 -(2-ethenyl-6-nitrophenyl)-methyliden]-1 ,3,4-trimethylpiperazin-2,5-dion,2- [5-Benzyl-1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-nitrobenzonitrile, 3-Benzyl-6- [1- (2-ethenyl-6-nitrophenyl) -methylidene ] -1,3,4-trimethylpiperazine-2,5-dione,
3-Benzyl-6-[1-(3-chlor-2-nitrophenyl)-methyliden]-1 ,3,4-trimethylpiperazin-2,5-dion,3-Benzyl-6- [1- (3-chloro-2-nitrophenyl) -methylidene] -1,3,4-trimethyl-piperazine-2,5-dione,
3-Benzyl-6-[1-(2-nitro-6-trifluormethylphenyl)-methyliden]-1 ,3,4-trimethylpiperazin-2,5- dion,3-Benzyl-6- [1- (2-nitro-6-trifluoromethylphenyl) -methylidene] -1,3,4-trimethylpiperazine-2,5-dione,
2-[5-Benzyl-1 ,5-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-benzonitril, 3-Benzyl-6-[1 -(2-methoxy-6-nitrophenyl)-methyliden]-1 ,3,4-trimethylpiperazin-2,5-dion,2- [5-Benzyl-1,5-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -benzonitrile, 3-Benzyl-6- [1- (2-methoxy-6-nitrophenyl) -methylidene] -1, 3,4-trimethylpiperazine-2,5-dione,
2-[5-Benzyl-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-4-fluorbenzonitπl,2- [5-Benzyl-1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -4-fluorobenzonitrile,
2-[5-Benzyl-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-5-methylbenzonitril, 2-[5-Benzyl-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-6-fluorbenzonitπl, 3-Benzyl-1 ,3,4-trimethyl-6-[2-(1 -methyl-1 H-pyrrol-2-yl)-benzyliden]-piperazin-2,5-dion, 3-Benzyl-6-(2-furan-2-yl-benzyliden)-1 ,3,4-trimethylpiperazin-2,5-dion, 2-[5-Benzyl-5-fluormethyl-1 ,4-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-benzonitπl, 3-Benzyl-1 ,3,4-trimethyl-6-(4-methyl-2-nitrobenzyliden)-piperazin-2,5-dion,2- [5-Benzyl-1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -5-methylbenzonitrile, 2- [5-Benzyl-1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -6-fluorobenzonitrile, 3-benzyl-1, 3,4-trimethyl-6- [2- (1 - methyl-1H-pyrrol-2-yl) -benzylidene] -piperazine-2,5-dione, 3-benzyl-6- (2-furan-2-yl-benzylidene) -1, 3,4-trimethyl-piperazine-2 , 5-dione, 2- [5-benzyl-5-fluoromethyl-1, 4-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -benzonitrile, 3-benzyl-1,3,4-trimethyl-6- ( 4-methyl-2-nitrobenzylidene) -piperazine-2,5-dione,
2-[5-Benzyl-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-4-methoxybenzonitπl, 3-Benzyl-6-[2-(2-chlorpyrimidin-5-yl)-benzyliden]-1 ,3,4-trimethylpiperazin-2,5-dion, 3-Benzyl-6-[2-(6-fluorpyridin-2-yl)-benzyliden]-1 ,3,4-trimethylpiperazin-2,5-dion, 2-[5-Benzyl-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-4-fluorbenzonitril, 2-[5-Benzyl-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-4-trifluormethyl- benzonitril,2- [5-Benzyl-1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -4-methoxybenzonitrile, 3-Benzyl-6- [2- (2-chloropyrimidin-5-yl) -benzylidene ] -1,3,4-trimethylpiperazine-2,5-dione, 3-benzyl-6- [2- (6-fluoropyridin-2-yl) -benzylidene] -1,3,4-trimethylpiperazine-2,5- dione, 2- [5-benzyl-1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -4-fluorobenzonitrile, 2- [5-benzyl-1, 4,5-trimethyl-3,6 -dioxopiperazin-2-ylidenemethyl] -4-trifluoromethylbenzonitrile,
3-Benzyl-1 ,3,4-trimethyl-6-[2-(1 -methyl-1 H-imidazol-2-yl)-benzyliden]-piperazin-2,5- dion, 3-Benzyl-3-fluormethyl-1 ,4-dimethyl-6-(2-nitrobenzyliden)-piperazin-2,5-dion, 3-Benzyl-6-(5-brom-2-nitrobenzyliden)-1 ,3,4-trimethylpiperazin-2,5-dion,3-Benzyl-1, 3,4-trimethyl-6- [2- (1-methyl-1H-imidazol-2-yl) -benzylidene] -piperazine-2,5-dione, 3-benzyl-3-fluoromethyl -1, 4-dimethyl-6- (2-nitrobenzylidene) piperazine-2,5-dione, 3-benzyl-6- (5-bromo-2-nitrobenzylidene) -1, 3,4-trimethylpiperazine-2,5 -dione
2-[5-Benzyl-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-4-difluormethoxy- benzonitril,2- [5-Benzyl-1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -4-difluoromethoxybenzonitrile,
2-[5-Benzyl-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-4-methansulfonyl- benzonitril, 2-[5-Benzyl-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-4-methansulfinyl- benzonitril,2- [5-Benzyl-1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -4-methanesulfonylbenzonitrile, 2- [5-Benzyl-1, 4,5-trimethyl-3,6 dioxopiperazin-2-ylidenemethyl] -4-methanesulfinylbenzonitrile,
2-[5-Benzyl-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-4-methylsulfanyl- benzonitril, 2-[5-Benzyl-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-fluor-4-methoxy- benzonitril,2- [5-Benzyl-1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -4-methylsulfanylbenzonitrile, 2- [5-Benzyl-1, 4,5-trimethyl-3,6 dioxopiperazin-2-ylidenemethyl] -3-fluoro-4-methoxybenzonitrile,
2-[5-Benzyl-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-4,6-difluorbenzonitril, 3-Benzyl-1 ,3,4-trimethyl-6-[2-(2-methyl-2H-pyrazol-3-yl)-benzyliden]-piperazin-2,5-dion, 3-Benzyl-1 ,3,4-trimethyl-6-[2-(5-methyl-thiophen-2-yl)-benzyliden]-piperazin-2,5-dion, 3-Benzyl-1 ,3,4-trimethyl-6-[2-(3-methyl-thiophen-2-yl)-benzyliden]-piperazin-2,5-dion, 2-[5-Benzyl-4-ethyl-1 ,5-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-benzonitril,2- [5-Benzyl-1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -4,6-difluorobenzonitrile, 3-benzyl-1, 3,4-trimethyl-6- [2- (2-one) 2-methyl-2H-pyrazol-3-yl) -benzylidene] -piperazine-2,5-dione, 3-benzyl-1, 3,4-trimethyl-6- [2- (5-methyl-thiophene-2] yl) -benzylidene] -piperazine-2,5-dione, 3-benzyl-1,3,4-trimethyl-6- [2- (3-methyl-thiophen-2-yl) -benzylidene] -piperazine-2, 5-dione, 2- [5-benzyl-4-ethyl-1, 5-dimethyl-3,6-dioxopiperazin-2-ylidene-methyl] -benzonitrile,
2-[5-Benzyl-4-isopropyl-1 ,5-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-benzonitril, 2-[5-Benzyl-4-butyl-1 ,5-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-benzonitril, 2-[4-Allyl-5-benzyl-1 ,5-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-benzonitril, 2-[5-Benzyl-5-trifluormethyl-1 ,4-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-benzonitril, 3-Benzyl-6-[1 -(2-nitrophenyl)-methyliden]-1 ,4-dimethyl-3-trifluormethylpiperazin-2,5- dion,2- [5-Benzyl-4-isopropyl-1,5-dimethyl-3,6-dioxopiperazin-2-ylidene-methyl] -benzonitrile, 2- [5-benzyl-4-butyl-1, 5-dimethyl-3,6 -dioxopiperazin-2-ylidenemethyl] -benzonitrile, 2- [4-allyl-5-benzyl-1,5-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -benzonitrile, 2- [5-benzyl-5-trifluoromethyl 1,4-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -benzonitrile, 3-benzyl-6- [1- (2-nitrophenyl) -methylidene] -1,4-dimethyl-3-trifluoromethylpiperazine-2, 5- dion,
3-Benzyl-6-[2-(6-chlorpyridin-3-yl)-benzyliden]-1 ,3,4-trimethylpiperazin-2,5-dion, 2-[5-Benzyl-1 ,5-dimethyl-4-prop-2-inyl-3,6-dioxopiperazin-2-ylidenmethyl]- benzonitril, 3-(3-Fluorbenzyl)-6-[1-(2-nitrophenyl)-methyliden]-1 ,3,4-trimethylpiperazin-2,5-dion, 3-(3,5-Difluorbenzyl)-6-[1 -(2-nitrophenyl)-methyliden]-1 ,3,4-trimethylpiperazin-2,5-dion, 2-[5-(2,3-Difluorbenzyl)-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-benzonitril, 2-[5-(2,5-Difluorbenzyl)-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-benzonitril, 2-[5-(2,6-Difluorbenzyl)-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-benzonitπl, 2-[5-(2-Difluormethoxybenzyl)-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]- benzonitril,3-Benzyl-6- [2- (6-chloropyridin-3-yl) -benzylidene] -1,3,4-trimethyl-piperazine-2,5-dione, 2- [5-benzyl-1, 5-dimethyl-4 -prop-2-ynyl-3,6-dioxopiperazin-2-ylidenemethyl] - benzonitrile, 3- (3-fluorobenzyl) -6- [1- (2-nitrophenyl) -methylidene] -1,3,4-trimethylpiperazine 2,5-dione, 3- (3,5-difluorobenzyl) -6- [1- (2-nitrophenyl) -methylidene] -1,3,4-trimethyl-piperazine-2,5-dione, 2- [5- (2-one) 2,3-difluorobenzyl) -1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -benzonitrile, 2- [5- (2,5-difluorobenzyl) -1, 4,5-trimethyl-3 , 6-dioxopiperazine-2-ylidenemethyl] -benzonitrile, 2- [5- (2,6-Difluorobenzyl) -1,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -benzonitrile, 2- [5- (2-Difluoromethoxybenzyl) -1, 4,5 trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] benzonitrile,
2-[5-(3-Difluormethoxybenzyl)-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]- benzonitril,2- [5- (3-difluoromethoxybenzyl) -1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] benzonitrile,
2-[5-(3-Trifluormethylbenzyl)-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]- benzonitril,2- [5- (3-trifluoromethylbenzyl) -1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -benzonitrile,
3-(3-Fluorbenzyl)-6-[1-(2-nitrophenyl)-methyliden]-1 ,3,4-trimethylpiperazin-2,5-dion, 2-[5-(2-Cyanobenzyl)-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-benzonitril, 2-[5-(3-Cyanobenzyl)-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-benzonitril, 2-[5-(3,5-Difluorbenzyl)-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-benzonitril, 2-[5-(3-Nitrobenzyl)-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-benzonitril, 2-[5-(4-Fluor-3-methylbenzyl)-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]- benzonitril, 2-[5-(4-Fluor-3-methoxybenzyl)-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]- benzonitril,3- (3-fluorobenzyl) -6- [1- (2-nitrophenyl) methylidene] -1, 3,4-trimethylpiperazine-2,5-dione, 2- [5- (2-cyanobenzyl) -1, 4 , 5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -benzonitrile, 2- [5- (3-cyanobenzyl) -1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -benzonitrile, 2- [5- (3,5-Difluorobenzyl) -1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] benzonitrile, 2- [5- (3-nitrobenzyl) -1, 4.5 trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] benzonitrile, 2- [5- (4-fluoro-3-methylbenzyl) -1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] - benzonitrile, 2- [5- (4-fluoro-3-methoxybenzyl) -1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -benzonitrile,
1 -Allyl-3-benzyl-3,4-dimethyl-6-[1 -(2-nitrophenyl)-methyliden]-piperazin-2,5-dion und 3-Benzyl-6-[1-(2-nitrophenyl)-methyliden]-1-prop-2-inyl-3,4-dimethylpiperazin-2,5-dion. Unter den hier beispielhaft genannten Verbindungen und ihren Salzen sind solche Ver- bindungen und Salze bevorzugt, worin die exo-Doppelbindung am Piperazinring die (Z)-Konfiguration aufweist. Ebenso bevorzugt Gemische des (E)-Isomers mit dem (Z)- Isomer, worin das Z-Isomer im Überschuss vorliegt, insbesondere Isomerengemische mit einem E/Z-Verhältnis, von nicht mehr als 1 :2, insbesondere nicht mehr als 1 :5.1-allyl-3-benzyl-3,4-dimethyl-6- [1- (2-nitrophenyl) -methylidene] -piperazine-2,5-dione and 3-benzyl-6- [1- (2-nitrophenyl) methylidene] -1-prop-2-ynyl-3,4-dimethylpiperazine-2,5-dione. Among the compounds exemplified here and their salts, preference is given to those compounds and salts in which the exo-double bond on the piperazine ring has the (Z) -configuration. Likewise preferred are mixtures of the (E) -isomer with the (Z) -isomer in which the Z-isomer is present in excess, in particular isomer mixtures having an E / Z ratio of not more than 1: 2, in particular not more than 1: 5th
Unter den hier beispielhaft genannten Verbindungen und ihren Salzen sind solche Verbindungen und Salze bevorzugt, worin das Kohlenstoffatom, welches den Rest R6 trägt, S-Konfiguration aufweist, sowie Enantiomerenmischungen, die einen Enantiome- renüberschuss bezüglich des S-Enantiomers aufweisen, insbesondere solche mit einen ee-Wert (enantiomeric excess) von wenigstens 70 %, besonders bevorzugt we- nigstens 80 % und speziell wenigstens 90 %. Ebenso sind die Racemate dieser Verbindungen und ihrer Salze bevorzugt.Among the compounds exemplified herein and their salts, preferred are those compounds and salts wherein the carbon atom bearing R 6 has S configuration and enantiomeric mixtures having an enantiomeric excess with respect to the S enantiomer, especially those having an ee value (enantiomeric excess) of at least 70%, more preferably at least 80% and especially at least 90%. Likewise, the racemates of these compounds and their salts are preferred.
Die erfindungsgemäßen Verbindungen können nach Standardverfahren der organischen Chemie hergestellt werden, beispielsweise einem Verfahren (im Folgenden Ver- fahren A) welches die folgenden Schritte umfasst:The compounds according to the invention can be prepared by standard methods of organic chemistry, for example a process (in the following process A) which comprises the following steps:
i) Bereitstellung einer Verbindung der allgemeinen Formel Il i) providing a compound of general formula II
worin R1, R2, R3, R7, R8, R9 und R10 die zuvor genannten Bedeutungen, insbesondere eine der als bevorzugt genannten Bedeutungen aufweisen, R4a für Wasserstoff oder eine Schutzgruppe steht oder eine der für R4 angegebenen Bedeutungen hat und R5a eine der für R5 angegebenen Bedeutungen hat oder für eine Schutzgruppe steht;wherein R 1, R 2, R 3, R 7, R 8, R 9 and R 10 are as defined above, in particular have one of the preferred meanings mentioned, R 4a is hydrogen or a protecting group or one of the given for R 4 Has meanings and R 5a has one of the meanings given for R 5 or is a protective group;
ü) gegebenenfalls Umsetzung der Verbindung II, worin R4a für Wasserstoff steht mit einem Alkylierungsmittel der Formel R4-X1 worin R4 die zuvor angegebenen Bedeutungen aufweist und X1 für eine nucleophil verdrängbare Abgangsgruppe steht, in Gegenwart einer Base;ü) if appropriate, reaction of the compound II in which R 4a is hydrogen with an alkylating agent of the formula R 4 -X 1 in which R 4 has the meanings given above and X 1 is a nucleophilically displaceable leaving group, in the presence of a base;
iii) gegebenenfalls Umsetzung der Verbindung II, worin R5a für Wasserstoff steht mit einem Alkylierungsmittel der Formel R5-X1 oder einem Acylierungsmittel der Formel R5-X2, worin R5 die zuvor angegebenen Bedeutungen, von Wasserstoff verschiedenen Bedeutungen aufweist und X1 und X2 für eine nucleophil verdrängbare Abgangsgruppe stehen, in Gegenwart einer Base;iii) optionally reacting the compound II, wherein R 5a is hydrogen with an alkylating agent of the formula R 5 -X 1 or an acylating agent of the formula R 5 -X 2 , wherein R 5 has the meanings given above, hydrogen-different meanings and X 1 and X 2 are a nucleophilically displaceable leaving group, in the presence of a base;
iv) Umsetzung der Verbindung Il mit einem Alkylierungsmittel der Formel R6-X worin R6 die zuvor angegebenen Bedeutungen aufweist und X für eine nucleophil verdrängbare Abgangsgruppe steht, in Gegenwart einer Base; undiv) reacting the compound II with an alkylating agent of the formula R 6 -X in which R 6 has the meanings given above and X is a nucleophilically displaceable leaving group, in the presence of a base; and
v) wenn R4a und/oder R5a für einen Schutzgruppe steht, Entfernen der Schutzgrup- pe, und gegebenenfalls Umsetzung der dabei erhaltenen Verbindung II, worin R4a und/oder R5a für Wasserstoff steht mit einem Alkylierungsmittel der Formel R4-X1, und/oder R5-X1 oder einem Acylierungsmittel R5-X2, worin R4 bzw. R5 die zuvor angegebenen, von Wasserstoff verschiedenen Bedeutungen aufweisen und X1 und X2 für eine nucleophil verdrängbare Abgangsgruppe stehen, in Gegenwart einer Base.v) when R 4a and / or R 5a is a protective group, removing the Schutzgrup- PE, and optionally reacting the resulting compound II, wherein R 4a and / or R 5a is hydrogen with an alkylating agent of the formula R 4 -X 1 , and / or R 5 -X 1 or an acylating agent R 5 -X 2 , wherein R 4 and R 5 have the meanings given above, other than hydrogen and X 1 and X 2 are a nucleophilically displaceable leaving group, in the presence a base.
Sofern der Rest R4a in Formel Il für Wasserstoff steht, wird durch den Alkylierungschritt ii) der Rest R4 eingeführt. Sofern der Rest R4a in Formel Il für eine Schutzgruppe steht, wird diese zunächst entfernt, wobei man eine Verbindung erhält, worin R4a für Wasser- stoff steht, in die durch den Alkylierungschritt ii) der Rest R4 eingeführt wird. Sofern R5a in Formel Il für Wasserstoff steht, kann durch einen Alkylierungs- bzw. Acylie- rungsschritt iii) der Rest R5 eingeführt werden. Wenn R4 und R5 identisch sind, können die Schritte ii) und iii) gleichzeitig oder sukzessive in beliebiger Reihenfolge durchge- führt werden. Wenn die Reste R4, R5 und R6 identisch sind, kann man den Schritt iv) gleichzeitig mit dem/den Schritten ii) und/oder iii) oder im Anschluss daran durchführen.If the radical R 4a in formula II is hydrogen, the radical R 4 is introduced by the alkylation step ii). If the radical R 4a in formula II is a protective group, this is first removed to obtain a compound in which R 4a is hydrogen, in which is introduced by the alkylation step ii) the radical R 4 . If R 5a in formula II is hydrogen, the radical R 5 can be introduced by an alkylation or acylation step iii). If R 4 and R 5 are identical, steps ii) and iii) can be carried out simultaneously or successively in any desired order. If the radicals R 4 , R 5 and R 6 are identical, it is possible to carry out step iv) simultaneously with or after the steps ii) and / or iii) or subsequently.
Die Alkylierung in Schritt iv) und ebenso die Alkylierung bzw. Acylierung in den Schrit- ten ii) und iii) können in Analogie zu Standardverfahren der Alkylierung bzw. Acylierung durchgeführt werden, beispielsweise nach den von I. O. Donkor et al., Bioorg. Med. Chem. Lett. 11 (19) (2001 ), 2647-2649, B.B. Snider et al., Tetrahedron 57 (16) (2001), 3301-3307, I. Yasuhiro et al., Heterocycles, 45, 1997, 1151 , J. Am. Chem. Soc. 105, 1983, 3214, J. Am. Chem. Soc. 124(47) (2002), 14017-14019, Chem. Commun. 1998, 659 oder M. Falorni et al., Europ. J. Org. Chem. (8) (2000), 1669-1675 beschriebenen Methoden.The alkylation in step iv) and also the alkylation or acylation in steps ii) and iii) can be carried out in analogy to standard methods of alkylation or acylation, for example according to the methods described by I.O. Donkor et al., Bioorg. Med. Chem. Lett. 11 (19) (2001), 2647-2649, B.B. Snider et al., Tetrahedron 57 (16) (2001), 3301-3307, I. Yasuhiro et al., Heterocycles, 45, 1997, 1151, J. Am. Chem. Soc. 105, 1983, 3214, J. Am. Chem. Soc. 124 (47) (2002), 14017-14019, Chem. Commun. 1998, 659 or M. Falorni et al., Europ. J. Org. Chem. (8) (2000), 1669-1675.
Hierzu wird im Schritt iv) die Piperazinverbindung der Formel Il mit einem geeigneten Alkylierungsmittel, im Folgenden Verbindung X-R6 umgesetzt, wobei man eine Pipera- zinverbindung der Formel I erhält (siehe z.B. J. Am. Chem. Soc. 105, 1983, 3214).For this purpose, in step iv), the piperazine compound of the formula II is reacted with a suitable alkylating agent, hereinafter compound XR 6 , to give a piperazine compound of the formula I (see, for example, J. Am. Chem. Soc., 105, 1983, 3214). ,
In den Alkylierungsmitteln X-R6 kann X Halogen, insbesondere Chlor, Brom oder lod oder O-Sθ2-Rm mit Rm in der Bedeutung von CrC4-AIkVl oder Aryl, welche gegebenenfalls durch Halogen, CrC4-AIkVl oder Halo-Ci-C4-alkyl substituiert sind, bedeuten.In the alkylating agents X XR 6 may be halogen, in particular chlorine, bromine or iodine or O-Sθ2-R m R m has the meaning of -C 4 -alkyl or aryl, which are optionally substituted by halogen, -C 4 -alkyl or halo-Ci- C 4 alkyl are substituted mean.
Die Umsetzung erfolgt üblicherweise bei Temperaturen im Bereich von -78°C bis zum Siedepunkt der Reaktionsmischung, bevorzugt von -500C bis 65°C, insbesondere bevorzugt von -300C bis 65°C. In der Regel wird die Umsetzung in einem Lösungsmittel vorgenommen, bevorzugt in einem inerten organischen Lösungsmittel.The reaction is usually carried out at temperatures in the range of -78 ° C to the boiling point of the reaction mixture, preferably from -50 0 C to 65 ° C, particularly preferably from -30 0 C to 65 ° C. In general, the reaction is carried out in a solvent, preferably in an inert organic solvent.
Geeignete Lösungsmittel sind aliphatische Kohlenwasserstoffe wie Pentan, Hexan, Cyclohexan und Gemische von Cs-Cs-Alkanen, aromatische Kohlenwasserstoffe wie Toluol, o-, m- und p-Xylol, halogenierte Kohlenwasserstoffe wie Dichlormethan, Dichlo- rethan, Chloroform und Chlorbenzol, Ether wie Diethylether, Diisopropylether, tert- Butylmethylether, Dioxan, Anisol und Tetrahydrofuran, Nitrile wie Acetonitril und Propi- onitril, Ketone wie Aceton, Methylethylketon, Diethylketon und tert.-Butylmethylketon, Alkohole wie Methanol, Ethanol, n-Propanol, Isopropanol, n-Butanol, tert.-Butanol, Wasser, Dimethylsulfoxid, N-Methylpyrrolidon, Dimethylformamid und Dimethylaceta- mid sowie Morpholin und N-Methylmorpholin und deren Mischungen. Bevorzugte Lö- sungsmittel sind Toluol, Dichlormethan, Tetrahydrofuran, N-Methylpyrrolidon, Dimethylformamid und deren Mischungen. In der Regel wird die Alkylierung der Verbindung Il in Schritt iv) mit dem Alkylierungs- mittel R6-X in Gegenwart einer Base durchgeführt. Geeignete Basen sind anorganische Verbindungen wie Alkalimetall- und Erdalkalimetallhydroxide wie Lithiumhydroxid, Natriumhydroxid, Kaliumhydroxid oder Calciumhydroxid, wässrige Lösung von Ammo- niak, Alkalimetall- oder Erdalkalimetalloxide wie Lithiumoxid, Natriumoxid, Calciumoxid und Magnesiumoxid, Alkalimetall- und Erdalkalimetallhydride wie Lithiumhydrid, Natriumhydrid, Kaliumhydrid und Calciumhydrid, Alkalimetallamide wie Lithiumamid, beispielsweise Lithiumdiisopropylamid, Natriumamid und Kaliumamid, Alkalimetall- und Erdalkalimetallcarbonate wie Lithiumcarbonat, Kaliumcarbonat, Cäsiumcarbonat und Calciumcarbonat sowie Alkalimetallhydrogencarbonate wie Natriumhydrogencarbonat, metallorganische Verbindungen, insbesondere Alkalimetallalkyle wie Methyllithium, Butyllithium und Phenyllithium, Alkylmagnesiumhalogenide wie Methylmagnesiumchlorid sowie Alkalimetall- und Erdalkalimetallalkoholate wie Natriummethanolat, Natriu- methanolat, Kaliumethanolat, Kalium- tert.-Butanolat, Kalium-tert.-Pentanolat und Di- methoxymagnesium, außerdem organische Basen, z.B. tertiäre Amine wie Trimethy- lamin, Triethylamin, Diisopropylethylamin, 2-Hydroxypyridin und N-Methylpiperidin, Pyridin, substituierte Pyridine wie Collidin, Lutidin und 4-Dimethylaminopyridin sowie bicyclische Amine. Die Basen werden im Allgemeinen äquimolar eingesetzt. Sie können auch im Überschuss oder selbst als Lösungsmittel verwendet werden. In einer bevorzugten Ausführungsform wird die Base in äquimolarer Menge oder im Wesentlichen äquimolarer Menge zugesetzt. In einer weiteren bevorzugten Ausführungsform wird Natriumhydrid als Base verwendet.Suitable solvents are aliphatic hydrocarbons such as pentane, hexane, cyclohexane and mixtures of Cs-Cs alkanes, aromatic hydrocarbons such as toluene, o-, m- and p-xylene, halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform and chlorobenzene, ethers such as Diethyl ether, diisopropyl ether, tert-butyl methyl ether, dioxane, anisole and tetrahydrofuran, nitriles such as acetonitrile and propinonitrile, ketones such as acetone, methyl ethyl ketone, diethyl ketone and tert-butyl methyl ketone, alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol , tert-butanol, water, dimethyl sulfoxide, N-methylpyrrolidone, dimethylformamide and dimethylacetamide and morpholine and N-methylmorpholine and mixtures thereof. Preferred solvents are toluene, dichloromethane, tetrahydrofuran, N-methylpyrrolidone, dimethylformamide and mixtures thereof. In general, the alkylation of compound II in step iv) is carried out with the alkylating agent R 6 -X in the presence of a base. Suitable bases are inorganic compounds such as alkali metal and alkaline earth metal hydroxides such as lithium hydroxide, sodium hydroxide, potassium hydroxide or calcium hydroxide, aqueous solution of ammonia, alkali metal or alkaline earth metal oxides such as lithium oxide, sodium oxide, calcium oxide and magnesium oxide, alkali metal and alkaline earth metal hydrides such as lithium hydride, sodium hydride, potassium hydride and Calcium hydride, alkali metal amides such as lithium amide, for example lithium diisopropylamide, sodium amide and potassium amide, alkali metal and alkaline earth metal carbonates such as lithium carbonate, potassium carbonate, cesium carbonate and calcium carbonate and alkali metal hydrogencarbonates such as sodium bicarbonate, organometallic compounds, in particular alkali metal alkyls such as methyllithium, butyl lithium and phenyllithium, alkyl magnesium halides such as methyl magnesium chloride and alkali metal and alkaline earth metal such as sodium methoxide, sodium methoxide, potassium ethoxide, potassium tert-butoxide, potassium m-tert-pentoxide and dimethoxymagnesium, as well as organic bases, for example tertiary amines such as trimethylamine, triethylamine, diisopropylethylamine, 2-hydroxypyridine and N-methylpiperidine, pyridine, substituted pyridines such as collidine, lutidine and 4-dimethylaminopyridine and bicyclic amines , The bases are generally used equimolar. They can also be used in excess or even as a solvent. In a preferred embodiment, the base is added in equimolar amount or substantially equimolar amount. In another preferred embodiment, sodium hydride is used as the base.
Die Alkylierung bzw. Acylierung in den optionalen Schritten ii) und iii) kann in Analogie zu den für Schritt iv) angegebenen Methoden erfolgen, z.B. nach den in Heterocycles, 45, 1997, 1 151 , und Chem. Commun. 1998, 659 beschriebenen Methoden. In gleicher Weise kann die optionale Alkylierung bzw. Acylierung in Schritt v) durchgeführt werden.The alkylation or acylation in the optional steps ii) and iii) can be carried out in analogy to the methods given for step iv), e.g. according to the in Heterocycles, 45, 1997, 151, and Chem. Commun. 1998, 659 described methods. In the same way, the optional alkylation or acylation in step v) can be carried out.
Hierzu wird in den Schritten ii) bzw. iii) die Piperazinverbindung der Formel Il mit R4a = Wasserstoff und/oder R5a = Wasserstoff mit einem geeigneten Alkylierungsmittel, im Folgenden Verbindung X1-R4, bzw. X1-R5, oder einem Acylierungsmittel, im Folgenden Verbindung X2-R5, umgesetzt, wobei man eine Piperazinverbindung der Formel I mit R5 * Wasserstoff erhält.For this purpose, in steps ii) or iii) the piperazine compound of the formula II with R 4a = hydrogen and / or R 5a = hydrogen with a suitable alkylating agent, hereinafter compound X 1 -R 4 , or X 1 -R 5 , or an acylating agent, hereinafter compound X 2 -R 5 , to give a piperazine compound of formula I with R 5 * hydrogen.
In den Alkylierungsmitteln X1-R4 bzw. X1-R5 kann X1 Halogen oder O-SO2-Rm mit Rm in der Bedeutung von Ci-C4-AIkVl oder Aryl, welche gegebenenfalls durch Halogen, d- C4-AIkVl oder Halo-Ci-C4-alkyl substituiert sind, bedeuten. In den Alkylierungsmitteln X1-R4 bzw. X1-R5 stehen R4 und R5 unabhängig voneinander für Ci-C4-Alkyl, C3-C4- Alkenyl oder C3-C4-Al kinyl. Im Acylierungsmittel R5-X2 steht R5 für einen Rest C(O)R51 worin R51 die zuvor genannten Bedeutungen aufweist. X2 steht in der Regel für Halogen, z.B. Chlor oder für eine Gruppe 0-C(O)-R51. Bezüglich Temperaturen, Basen und Lösungsmitteln gilt das für Schritt iv) Gesagte in analoger Weise.In the alkylating agents X 1 -R 4 or X 1 -R 5 , X 1 may be halogen or O-SO 2 -R m with R m meaning Ci-C 4 -AlkVl or aryl, which may be halogen, d- C 4 -AlkVl or halo-Ci-C 4 alkyl are substituted mean. In the alkylating agents X 1 -R 4 and X 1 -R 5 R 4 and R 5 are each independently Ci-C 4 alkyl, C 3 -C 4 - kinyl alkenyl or C 3 -C 4 -alkyl. In the acylating agent R 5 -X 2 , R 5 is a radical C (O) R 51 in which R 51 has the abovementioned meanings. X 2 is usually halogen, for example chlorine or a group 0-C (O) -R 51 . With regard to temperatures, bases and solvents, what has been said for step iv) applies analogously.
Sofern in Formel Il einer oder beide Reste R4a und R5a für eine Schutzgruppe stehen, wird in Schritt v) diese Schutzgruppe entfernt. Hierbei wird eine Verbindung der allgemeinen Formel I mit R4 bzw. R5 = H erhalten, die im Folgenden auch als Verbindung I* bezeichnet wird. In die Verbindung I* wird bzw. werden dann ein bzw. zwei neue(r), von Wasserstoff verschiedene(r) Rest(e) R4 bzw. R5 durch Alkylierung bzw. Acylierung in Analogie zu den Schritten ii) und iii) eingeführt.If one or both radicals R 4a and R 5a in formula II are a protective group, this protective group is removed in step v). Here, a compound of general formula I with R 4 or R 5 = H is obtained, which is also referred to below as compound I * . In the compound I * is then or become one or two new, different from hydrogen radical (s) R 4 or R 5 by alkylation or acylation in analogy to the steps ii) and iii) introduced.
Geeignete Schutzgruppen für die Stickstoffatome des Piperazinrings sind insbesondere die zuvor genannten Reste C(O)R51, z.B. der Acetylrest. Die Einführung dieser Schutzgruppen kann in Analogie zu bekannten Verfahren der Schutzgruppenchemie erfolgen, z.B. durch Umsetzung mit Anhydriden der Formel (R51C(O))2θ, z.B. nach der in Green, Wuts, Protective Groups in Organic Synthesis, 3rd ed. 1999, John Wiley and Sons, S. 553 beschriebenen Methode. Die Entfernung einer Schutzgruppe R4a, R5a kann in Analogie zu bekannten Verfahren der Schutzgruppenchemie erfolgen.Suitable protecting groups for the nitrogen atoms of the piperazine ring are, in particular, the abovementioned radicals C (O) R 51 , for example the acetyl radical. The introduction of these protective groups can be carried out in analogy to known methods of protecting group chemistry, for example by reaction with anhydrides of the formula (R 51 C (O)) 2θ, for example according to the Green, Wuts, Protective Groups in Organic Synthesis, 3rd ed. 1999, John Wiley and Sons, p. 553. The removal of a protecting group R 4a , R 5a can be carried out in analogy to known methods of protecting group chemistry.
Verbindungen der Formel Il sind im Übrigen bekannt, z.B. aus der PCT/EP2007/050067 (= WO 2007/077247), auf deren Inhalt hiermit vollumfänglich Bezug genommen wird.Incidentally, compounds of the formula II are known, e.g. from PCT / EP2007 / 050067 (= WO 2007/077247), the contents of which are hereby fully incorporated by reference.
Die Herstellung der Verbindungen Il erfolgt in der Regel durch Dehydratisierung des entsprechenden Alkohols IIa,The preparation of the compounds II is generally carried out by dehydration of the corresponding alcohol IIa,
In Formel IIa haben R1, R2, R3, R4a, R5a, R7, R8, R9 und R10 die zuvor genannten Bedeutungen, insbesondere eine der als bevorzugt genannten Bedeutungen. In einer ersten Variante (Variante A.1) kann die Alkoholfunktion der Verbindung IIa zunächst in eine geeignete Abgangsgruppe überführt werden und diese anschließend formal als Verbindung H-LG eliminiert werden. Vorzugsweise findet die Eliminierungsreaktion in Gegenwart einer geeigneten Base statt.In formula IIa, R 1 , R 2 , R 3 , R 4a , R 5a , R 7 , R 8 , R 9 and R 10 have the abovementioned meanings, in particular one of the meanings mentioned as preferred. In a first variant (variant A.1), the alcohol function of compound IIa can first be converted into a suitable leaving group and then formally eliminated as compound H-LG. Preferably, the elimination reaction occurs in the presence of a suitable base.
Bei der Abgangsgruppe LG handelt es sich um eine übliche, aus einer Hydroxygruppe leicht herzustellende Abgangsgruppe. Beispiele hierfür sind 4-Toluolsulfonyloxy (LG = -0-SO2C6H4CH3), Trifluormethansulfonyloxy (LG = -0-SO2CF3) und Methansulfonyloxy (LG = -0-SO2CH3), wobei letzteres besonders geeignet ist. Die Einführung einer solchen Abgangsgruppe erfolgt gemäß herkömmlicher Verfahren, z.B. durch Umsetzung des Alkohols IIa mit einer Base und anschließend mit dem entsprechenden Sulfonsäu- rechlorid, z.B. mit Methansulfonsäurechlorid oder Trifluormethansulfonsäurechlorid. Geeignete Basen sind die nachfolgend bei der Eliminierung aufgeführten Basen. Bevorzugt verwendet man jedoch Basen, die in organischen Lösungsmitteln löslich sind, z.B. die unten genannten Amine oder Stickstoff-Heterocyclen. Insbesondere verwendet man Pyridin oder substituierte Pyridine, wie Dimethylaminopyridin, Lutidin oder Collidin, oder Gemische davon. Günstigerweise werden die organischen Basen so gewählt, dass sie auch als Lösungsmittel fungieren.The leaving group LG is a common leaving group easily prepared from a hydroxy group. Examples of these are 4-toluenesulfonyloxy (LG = -O-SO 2 C 6 H 4 CH 3 ), trifluoromethanesulfonyloxy (LG = -O-SO 2 CF 3 ) and methanesulfonyloxy (LG = -O-SO 2 CH 3 ), the latter being particularly suitable. The introduction of such a leaving group is carried out according to conventional methods, for example by reacting the alcohol IIa with a base and then with the corresponding sulfonic acid chloride, for example with methanesulfonyl chloride or trifluoromethanesulfonyl chloride. Suitable bases are the bases listed below in the elimination. However, preference is given to using bases which are soluble in organic solvents, for example the amines or nitrogen heterocycles mentioned below. In particular, one uses pyridine or substituted pyridines, such as dimethylaminopyridine, lutidine or collidine, or mixtures thereof. Conveniently, the organic bases are chosen so that they also function as solvents.
Für die Eliminierung kommen als Basen allgemein anorganische Verbindungen wie Alkalimetall- und Erdalkalimetallhydroxide wie Lithiumhydroxid, Natriumhydroxid, KaIi- umhydroxid oder Calciumhydroxid, wässrige Lösung von Ammoniak, Alkalimetall- oder Erdalkalimetalloxide wie Lithiumoxid, Natriumoxid, Calciumoxid und Magnesiumoxid, Alkalimetall- und Erdalkalimetallhydride wie Lithiumhydrid, Natriumhydrid, Kaliumhydrid und Calciumhydrid, Alkalimetallamide wie Lithiumamid, beispielsweise Lithiumdiisopro- pylamid, Natriumamid und Kaliumamid, Alkalimetall- und Erdalkalimetallcarbonate wie Lithiumcarbonat, Kaliumcarbonat, Cäsiumcarbonat und Calciumcarbonat sowie Alkali- metallhydrogencarbonate wie Natriumhydrogencarbonat, metallorganische Verbindungen, insbesondere Alkalimetallalkyle wie Methyllithium, Butyllithium und Phenyllithium, Alkylmagnesiumhalogenide wie Methylmagnesiumchlorid sowie Alkalimetall- und Erd- alkalimetallalkoholate wie Natriummethanolat, Natriumethanolat, Kaliumethanolat, Ka- lium-tert.-Butanolat, Kalium-tert.-Pentanolat und Dimethoxymagnesium, außerdem organische Basen, z.B. tertiäre Amine wie Trimethylamin, Triethylamin, Diisopropyl- ethylamin 2-Hydroxypyridin und N-Methylpiperidin, Pyridin, substituierte Pyridine wie Collidin, Lutidin und 4-Dimethylaminopyridin sowie bicyclische Amine in Betracht. Selbstverständlich kann auch eine Mischung verschiedener Basen verwendet werden.For the elimination, the bases generally include inorganic compounds such as alkali metal and alkaline earth metal hydroxides such as lithium hydroxide, sodium hydroxide, potassium hydroxide or calcium hydroxide, aqueous solution of ammonia, alkali metal or alkaline earth metal oxides such as lithium oxide, sodium oxide, calcium oxide and magnesium oxide, alkali metal and alkaline earth metal hydrides such as lithium hydride, Sodium hydride, potassium hydride and calcium hydride, alkali metal amides such as lithium amide, for example lithium diisopropylamide, sodium amide and potassium amide, alkali metal and alkaline earth metal carbonates such as lithium carbonate, potassium carbonate, cesium carbonate and calcium carbonate and also alkali metal hydrogen carbonates such as sodium bicarbonate, organometallic compounds, especially alkali metal alkyls such as methyllithium, butyllithium and phenyllithium, Alkylmagnesium halides such as methylmagnesium chloride and alkali metal and alkaline earth metal alkoxides such as sodium methoxide, sodium ethoxide, potassium ethoxide Potassium tert-butoxide, potassium tert-pentoxide and dimethoxy magnesium, as well as organic bases, e.g. tertiary amines such as trimethylamine, triethylamine, diisopropyl-ethylamine 2-hydroxypyridine and N-methylpiperidine, pyridine, substituted pyridines such as collidine, lutidine and 4-dimethylaminopyridine and bicyclic amines into consideration. Of course, a mixture of different bases can be used.
Besonders geeignet sind jedoch Basen, die zwar eine ausreichende Basizität, jedoch im Wesentlichen keine Nucleophilie aufweisen, z.B. sterisch gehinderte Alkalialkohola- te, beispielsweise Alkali-tert-butanolate, wie Kalium-tert-butanolat, und insbesondere cyclische Amidine, wie DBU (1 ,8-Diazabicyclo[5.4.0]undec-7-en) und DBN (1 ,5- Diazabicyclo[3.4.0]non-5-en). Bevorzugt verwendet man die zuletzt genannten Amidine.However, particularly suitable are bases which, while having sufficient basicity but substantially no nucleophilicity, e.g. sterically hindered alkali alcoholates, for example, alkali tert-butanolates such as potassium tert-butoxide, and especially cyclic amidines such as DBU (1,8-diazabicyclo [5.4.0] undec-7-ene) and DBN (1, 5 - diazabicyclo [3.4.0] non-5-ene). Preference is given to using the last-mentioned amidines.
Die Eliminierung erfolgt in der Regel in einem Lösungsmittel, bevorzugt in einem inerten organischen Lösungsmittel. Geeignete inerte organische Lösungsmittel umfassen aromatische Kohlenwasserstoffe wie Toluol, o-, m- und p-Xylol, halogenierte Kohlenwasserstoffe wie Dichlormethan, Dichlorethan, Chloroform und Chlorbenzol, Ether wie Diethylether, Diisopropylether, tert.-Butylmethylether, Dioxan, Anisol und Tetrahydrofu- ran, Nitrile wie Acetonitril und Propionitril, Ketone wie Aceton, Methylethylketon, Diethylketon und tert-Butylmethylketon, Alkohole wie Methanol, Ethanol, n-Propanol, Isopropanol, n-Butanol, tert-Butanol, Wasser sowie Dimethylsulfoxid, Dimethylforma- mid und Dimethylacetamid sowie Morpholin und N-Methylmorpholin. Es können auch Gemische der genannten Lösungsmittel verwendet werden. Bevorzugt verwendet man Tetrahydrofuran.The elimination is usually carried out in a solvent, preferably in an inert organic solvent. Suitable inert organic solvents include aromatic hydrocarbons such as toluene, o-, m- and p-xylene, halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform and chlorobenzene, ethers such as diethyl ether, diisopropyl ether, tert-butyl methyl ether, dioxane, anisole and tetrahydrofuran. nitrites such as acetonitrile and propionitrile, ketones such as acetone, methyl ethyl ketone, diethyl ketone and tert-butyl methyl ketone, alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol, tert-butanol, water and dimethyl sulfoxide, dimethylformamide and dimethylacetamide and Morpholine and N-methylmorpholine. It is also possible to use mixtures of the solvents mentioned. Preference is given to using tetrahydrofuran.
Die Dehydratisierung von Alkoholen IIa durch Überführung der Alkoholfunktion in eine gute Abgangsgruppe und anschließende Eliminierung kann in Analogie zu bekannten Verfahren des Standes der Technik erfolgen, z.B. analog zu den in HeIv. Chim. Acta 1947, 30, 1454; Liebigs Ann. Chem 1992, (7), 687-692, Carbanions. 24. Rearrange- ments of (E)- and (Z)-2,2-diphenyl-3-pentenylalkali metal Compounds; Seh. Chem., Georgia Inst. Technol., Atlanta, GA, USA; J. Org. Chem. 1989, 54(7), 1671-1679; Chemical & Pharmaceutical Bulletin 1986, 34(7), 2786-2798 beschriebenen Verfahren, worauf hiermit in vollem Umfang Bezug genommen wird.The dehydration of alcohols IIa by conversion of the alcohol function into a good leaving group and subsequent elimination can be carried out in analogy to known methods of the prior art, e.g. analogous to those in HeIv. Chim. Acta 1947, 30, 1454; Liebigs Ann Chem. 1992, (7), 687-692, Carbanions. 24. Rearrangements of (E) - and (Z) -2,2-diphenyl-3-pentenylalkali metal compounds; Seh. Chem., Georgia Inst. Technol., Atlanta, GA, USA; J. Org. Chem. 1989, 54 (7), 1671-1679; Chemical & Pharmaceutical Bulletin 1986, 34 (7), 2786-2798, to which reference is hereby incorporated by reference.
In einer zweiten Variante (Variante A.2) erfolgt die Herstellung der Verbindung Il durch Dehydratisierung der Verbindung IIa in Gegenwart eines geeigneten Dehydratisie- rungsmittels.In a second variant (variant A.2), compound II is prepared by dehydration of compound IIa in the presence of a suitable dehydrating agent.
Geeignete Dehydratisierungsagenzien sind z.B. das System Triphenylphosphin/DEAD (DEAD = Diethylazodicarboxylat) und das Burgess-Reagens. Die Kombination aus Triphenylphosphin und DEAD wird zwar in der Regel zur gezielten Inversion an einem Hydroxy-substituierten Chiralitätszentrum eingesetzt (sogenannte Mitsunobu- Reaktion); in Abwesenheit von Nucleophilen wirkt es jedoch als mildes Dehydratisie- rungsmittel. Das System wird in Bezug auf die Verbindung IIa vorzugsweise im Über- schuss eingesetzt, wobei die beiden Komponenten Triphenylphosphin und DEAD geeigneterweise in einem etwa äquimolaren Verhältnis zueinander vorliegen.Suitable dehydrating agents are e.g. the triphenylphosphine / DEAD system (DEAD = diethyl azodicarboxylate) and the Burgess reagent. Although the combination of triphenylphosphine and DEAD is generally used for targeted inversion at a hydroxy-substituted chiral center (so-called Mitsunobu reaction); however, in the absence of nucleophiles, it acts as a mild dehydrating agent. The system is preferably used in excess with respect to the compound IIa, the two components triphenylphosphine and DEAD suitably being present in an approximately equimolar ratio to one another.
Beim Burgess-Reagens handelt es sich um das Zwitterion Methyl-N-(triethyl- ammoniumsulfonylcarbamat ((C2H5)3N+-Sθ2-N"-COOCHs), einem milden Dehydratisie- rungsmittel. Dieses kann in Bezug auf den Alkohol Il äquimolar oder in molarem Über- schuss eingesetzt werden. Die Umsetzung mit dem Burgess-Reagens erfolgt in der Regel in einem inerten organischen Lösungsmittel. Geeignete inerte organische Lö- sungsmittel umfassen aromatische Kohlenwasserstoffe wie Toluol, o-, m- und p-Xylol, halogenierte Kohlenwasserstoffe wie Dichlormethan, Dichlorethan, Chloroform und Chlorbenzol, Ether wie Diethylether, Diisopropylether, tert.-Butylmethylether, Dioxan, Anisol und Tetrahydrofuran, Nitrile wie Acetonitril und Propionitril, und Ketone wie Aceton, Methylethylketon, Diethylketon und tert-Butylmethylketon. Bevorzugt verwendet man aromatische Kohlenwasserstoffe oder Gemische davon und speziell Toluol. Die Dehydratisierung von Alkoholen IIa unter Verwendung von Dehydratisierungsmit- teln kann in Analogie zu bekannten Verfahren des Standes der Technik erfolgen, beispielsweise analog zu den in Synthesis 2003, 201 und J. Indian Sei. 2001 , 81 , 461 beschriebenen Verfahren, worauf hiermit in vollem Umfang Bezug genommen wird.The Burgess reagent is the zwitterion of methyl N- (triethylammonium sulfonylcarbamate ((C2H5) 3N + -Sθ2-N "-COOCHs), a mild dehydrating agent which can be equimolar with respect to the alcohol II or in The reaction with the Burgess reagent is usually carried out in an inert organic solvent Suitable inert organic solvents include aromatic hydrocarbons such as toluene, o-, m- and p-xylene, halogenated hydrocarbons such as dichloromethane , Dichloroethane, chloroform and chlorobenzene, ethers, such as diethyl ether, diisopropyl ether, tert-butyl methyl ether, dioxane, anisole and tetrahydrofuran, nitriles, such as acetonitrile and propionitrile, and ketones, such as acetone, methyl ethyl ketone, diethyl ketone and tert-butyl methyl ketone Preferably, aromatic hydrocarbons or mixtures are used and especially toluene. The dehydration of alcohols IIa using dehydrating agents can be carried out analogously to known processes of the prior art, for example analogously to those described in Synthesis 2003, 201 and J. Indian Sei. 2001, 81, 461, to which reference is hereby made in its entirety.
Die Alkohole der Formel IIa können beispielsweise in Analogie zu literaturbekannten Verfahren durch Cyclisierung entsprechender Dipeptid-Vorstufen hergestellt werden, beispielsweise in Analogie zu der von T. Kawasaki et al., Org. Lett. 2(19) (2000), 3027- 3029, Igor L. Rodionov et al., Tetrahedron 58(42) (2002), 8515-8523 oder A. L. Johnson et al., Tetrahedron 60 (2004), 961-965 beschriebenen Methode.The alcohols of the formula IIa can be prepared, for example, in analogy to processes known from the literature by cyclization of corresponding dipeptide precursors, for example in analogy to that described by T. Kawasaki et al., Org. Lett. 2 (19) (2000), 3027-3029, Igor L. Rodionov et al., Tetrahedron 58 (42) (2002), 8515-8523 or AL Johnson et al., Tetrahedron 60 (2004), 961-965 ,
Die Alkohole der Formel IIa können auch dadurch hergestellt werden, dass man in einer Aldolreaktion einen Benzaldehyd der Formel III mit einer Piperazinverbindung IV koppelt, wie im folgenden Schema skizziert ist:The alcohols of the formula IIa can also be prepared by coupling a benzaldehyde of the formula III with a piperazine compound IV in an aldol reaction, as shown in the following scheme:
(III) (IV)(III) (IV)
In den Formeln III und IV haben die Variablen R1, R2, R3, R4a, R5a, R7, R8, R9 und R10 die für Formel Il angegebenen Bedeutungen.In the formulas III and IV, the variables R 1 , R 2 , R 3 , R 4a , R 5a , R 7 , R 8 , R 9 and R 10 have the meanings given for formula II.
Die Umsetzung von III mit IV im Sinne einer Aldolreaktion erfolgt in der Regel in Gegenwart geeigneter Basen. Geeignete Basen sind solche, die üblicherweise bei Aldol- reaktionen eingesetzt werden. Geeignete Reaktionsbedingungen sind aus dem Stand der Technik bekannt und beispielsweise in J. Org. Chem. 2000, 65 (24), 8402-8405 beschrieben, worauf hiermit in vollem Umfang Bezug genommen wird.The reaction of III with IV in the sense of an aldol reaction is generally carried out in the presence of suitable bases. Suitable bases are those which are commonly used in aldol reactions. Suitable reaction conditions are known in the art and described, for example, in J. Org. Chem. 2000, 65 (24), 8402-8405, which is hereby incorporated by reference in its entirety.
Die Umsetzung der Verbindung III mit der Verbindung IV kann auch direkt zum entsprechenden Aldolkondensationsprodukt, d.h. zu Verbindungen der Formel II, führen. Dies ist insbesondere dann der Fall, wenn in der Verbindung IV die Reste R4a und R5a für eine Acylgruppe, z.B. eine Gruppe der Formel R52C(O)- stehen, worin R52 eine der für R51 angegebenen Bedeutungen hat und insbesondere für Ci-C4-AIkVl z.B. Methyl steht. Solche Aldolkondensationen können analog zu den in J. Org. Chem. 2000, 65 (24), 8402-8405, Synlett 2006, 677, J. Heterocycl. Chem. 1988, 25, 591 beschriebenen Verfahren durchgeführt werden, worauf hiermit in vollem Umfang Bezug genommen wird.The reaction of compound III with compound IV can also lead directly to the corresponding aldol condensation product, ie to compounds of formula II. This is the case in particular when, in the compound IV, the radicals R 4a and R 5a represent an acyl group, for example a group of the formula R 52 C (O) -, in which R 52 has one of the meanings given for R 51 and, in particular for Ci-C 4 -alkyl such as methyl. Such aldol condensations can be carried out analogously to those described in J. Org. Chem. 2000, 65 (24), 8402-8405, Synlett 2006, 677, J. Heterocycl. Chem. 1988, 25, 591, to which reference is hereby fully made.
Die Aldolkondensation erfolgt typischerweise in Gegenwart geeigneter Basen. Geeignete Basen sind solche, die üblicherweise bei Aldolkondensationen eingesetzt werden. Vorzugsweise verwendet man ein Alkalimetall- oder Erdalkalimetallcarbonat als Base, z.B. Natriumcarbonat, Kaliumcarbonat oder Cäsiumcarbonat oder deren Gemische.The aldol condensation is typically carried out in the presence of suitable bases. Suitable bases are those which are commonly used in aldol condensations. Preferably, an alkali metal or alkaline earth metal carbonate is used as the base, e.g. Sodium carbonate, potassium carbonate or cesium carbonate or mixtures thereof.
Vorzugsweise erfolgt die Umsetzung in einem inerten, vorzugsweise aprotischen organischen Lösungsmittel. Beispiele für geeignete Lösungsmittel sind insbesondere Di- chlormethan, Dichlorethan, Chlorbenzol, Ether wie Diethylether, Diisopropylether, tert- Butylmethylether, Dioxan, Anisol und Tetrahydrofuran, Nitrile wie Acetonitril und Propi- onitril, sowie Dimethylsulfoxid, Dimethylformamid, N-Methylpyrrolidon und Dimethyl- acetamid. Bevorzugte Lösungsmittel sind insbesondere unter Dimethylformamid, N-Methylpyrrolidon und Dimethylacetamid ausgewählt.Preferably, the reaction is carried out in an inert, preferably aprotic organic solvent. Examples of suitable solvents are, in particular, dichloromethane, dichloroethane, chlorobenzene, ethers, such as diethyl ether, diisopropyl ether, tert-butyl methyl ether, dioxane, anisole and tetrahydrofuran, nitriles, such as acetonitrile and propionitrile, and also dimethyl sulfoxide, dimethylformamide, N-methylpyrrolidone and dimethylacetamide , Preferred solvents are selected in particular from dimethylformamide, N-methylpyrrolidone and dimethylacetamide.
Die für die Aldolkondensation erforderlichen Temperaturen liegen in der Regel im Bereich von 00C bis hin zur Siedetemperatur des verwendeten Lösungsmittels und insbe- sondere im Bereich von 10 bis 800C.The required for the aldol condensation temperatures are generally in the range from 0 0 C up to the boiling point of the solvent used, and in particular in the range of 10 to 80 0 C.
Für die Umsetzung III mit IV hat es sich als vorteilhaft erwiesen, wenn in der Verbindung IV die Reste R4a und R5a für eine Acylgruppe, z.B. eine Gruppe der Formel R52C(O)- stehen. Die Einführung dieser Schutzgruppen in die Verbindung IV kann in Analogie zu bekannten Verfahren der Schutzgruppenchemie erfolgen, z.B. durch Umsetzung der entsprechenden NH-freien Verbindung (Verbindung der Formel IV mit R4a, R5a = H) mit Anhydriden der Formel (R52C(O))2O, z.B. nach der in Green, Wuts, Protec- tive Groups in Organic Synthesis, 3rd ed. 1999, John Wiley and Sons, S. 553 beschriebenen Methode. Die Entfernung einer Schutzgruppe R4a, R5a kann in Analogie zu bekannten Verfahren der Schutzgruppenchemie erfolgen.For the reaction III with IV, it has proved to be advantageous if, in the compound IV, the radicals R 4a and R 5a represent an acyl group, for example a group of the formula R 52 C (O) -. The introduction of these protective groups into the compound IV can be carried out analogously to known methods of protecting group chemistry, for example by reaction of the corresponding NH-free compound (compound of the formula IV with R 4a , R 5a = H) with anhydrides of the formula (R 52 C ( O)) 2 O, for example according to the method described in Green, Wuts, Protective Groups in Organic Synthesis, 3rd ed. 1999, John Wiley and Sons, p. The removal of a protecting group R 4a , R 5a can be carried out in analogy to known methods of protecting group chemistry.
Sofern in der Verbindung IV die Reste R4a und R5a für eine Acylgruppe stehen, wird man im Anschluss an die Aldolkondensation vorzugsweise diese Reste entfernen, wobei man eine Verbindung der Formel Il mit R4a = R5a = Wasserstoff erhält. Die Entfer- nung der Reste R4a und R5a erfolgt in der Regel durch Hydrolyse, wobei der Rest R4a häufig bereits unter den Bedingungen einer Aldolkondensation abgespalten wird. In die dabei erhaltene Verbindung Il mit R4a = R5a = Wasserstoff wird anschließend der Rest R4 und gegebenenfalls der Rest R5 gemäß den Schritten ii) und iii) eingeführt.If the radicals R 4a and R 5a in the compound IV are an acyl group, it is preferable to remove these radicals following the aldol condensation, giving a compound of the formula II where R 4a = R 5a = hydrogen. The removal of the radicals R 4a and R 5a is generally carried out by hydrolysis, the radical R 4a often being split off already under the conditions of an aldol condensation. In the thus obtained compound II with R 4a = R 5a = hydrogen, the radical R 4 and optionally the radical R 5 is then introduced according to the steps ii) and iii).
In einer zu der hier geschilderten Methode analogen Weise können auch Verbindungen der Formel I' bereitgestellt werden: In a manner analogous to the method described here, it is also possible to provide compounds of the formula I ':
worin R1, R2, R3, R6, R7, R8, R9 und R10 die zuvor genannten Bedeutungen, insbesondere eine der als bevorzugt genannten Bedeutungen aufweisen, R4c für Wasserstoff oder eine Schutzgruppe steht und R5c eine der für R5 angegebenen Bedeutungen hat oder für eine Schutzgruppe steht. Bevorzugte Schutzgruppen sind die zuvor genannten Acylgruppen der Formel R52C(O)-, worin R52 eine der für R51 angegebenen Bedeutungen hat und insbesondere für Ci-C4-AIkVl z.B. Methyl steht.wherein R 1 , R 2 , R 3 , R 6 , R 7 , R 8 , R 9 and R 10 have the abovementioned meanings, in particular one of the meanings mentioned as preferred, R 4c is hydrogen or a protective group and R 5c is a has the meanings given for R 5 or is a protective group. Preferred protective groups are the abovementioned acyl groups of the formula R 52 C (O) -, in which R 52 has one of the meanings given for R 51 and, in particular, for C 1 -C 4 -alkyl, for example methyl.
Sofern R4c und/oder R5c in Formel I' für eine Schutzgruppe stehen, wird man dieIf R 4c and / or R 5c in formula I 'are a protective group, the
Schutzgruppen R4c und/oder R5c entfernen. Auf diese Weise erhält man eine Verbindung I', worin R4c und gegebenenfalls R5c für Wasserstoff steht.Remove protecting groups R 4c and / or R 5c . In this way, a compound I ', wherein R 4c and optionally R 5c is hydrogen.
Diese Verbindung I', worin R4c für Wasserstoff steht, wird anschließend mit einem Alky- lierungsmittel der Formel R4-X1, vorzugsweise in Gegenwart einer Base, umgesetzt.This compound I ', in which R 4c is hydrogen, is then reacted with an alkylating agent of the formula R 4 -X 1 , preferably in the presence of a base.
Sofern R5c für Wasserstoff steht, wird die Verbindung I' mit einem Alkylierungsmittel der Formel R5-X1 oder einem Acylierungsmittel der Formel R5-X2, vorzugsweise in Gegenwart einer Base, umgesetzt. Für die Umsetzung von Verbindung I' mit den Alkylie- rungsmitteln X1-R4a, X1-R5, bzw. X2-R5 gilt das zuvor für die Schritte ii) und iii) Gesagte in analoger Weise.If R 5c is hydrogen, the compound I 'is reacted with an alkylating agent of the formula R 5 -X 1 or an acylating agent of the formula R 5 -X 2 , preferably in the presence of a base. For the reaction of compound I 'with the alkylating agents X 1 -R 4a , X 1 -R 5 or X 2 -R 5 , the statements made above for the steps ii) and iii) apply analogously.
Die Herstellung der Verbindung I' gelingt in Analogie zur Herstellung von Verbindung Il durch Aldoladdition von Verbindung III mit einer Verbindung IVa mit nachfolgender EIi- minerung von Wasser oder vorzugsweise durch Umsetzung von III mit einer Verbin- düng IVa unter den Bedingungen einer Aldolkondensation:The preparation of the compound I 'succeeds analogously to the preparation of compound II by aldol addition of compound III with a compound IVa with subsequent elimination of water or, preferably, by reacting III with a compound IVa under the conditions of an aldol condensation:
(III) (IVa) In diesem Schema haben die Varbiablen R1, R2, R3, R4c, R5c, R6, R7, R8, R9 und R10 die zuvor genannten Bedeutungen.(III) (IVa) In this scheme, the variables R 1 , R 2 , R 3 , R 4c , R 5c , R 6 , R 7 , R 8 , R 9 and R 10 have the meanings given above.
Der Aldehyd III ist entweder kommerziell erhältlich oder kann gemäß bekannten Ver- fahren zur Herstellung von Aldehyden synthetisiert werden.The aldehyde III is either commercially available or can be synthesized according to known methods for the preparation of aldehydes.
Die Verbindungen der Formel IV bzw. IVa können durch intramolekulare Cyclisierung von Verbindungen der allgemeinen Formel V bzw. Va in Analogie zu weiteren literaturbekannten Verfahren, beispielsweise nach T. Kawasaki et al., Org. Lett. 2(19) (2000), 3027-3029, Igor L. Rodionov et al., Tetrahedron 58(42) (2002), 8515-8523 oder A. L. Johnson et al., Tetrahedron 60 (2004), 961-965 hergestellt werden.The compounds of the formula IV or IVa can be prepared by intramolecular cyclization of compounds of the general formula V or Va in analogy to other methods known from the literature, for example according to T. Kawasaki et al., Org. Lett. 2 (19) (2000), 3027-3029, Igor L. Rodionov et al., Tetrahedron 58 (42) (2002), 8515-8523 or AL Johnson et al., Tetrahedron 60 (2004), 961-965 ,
Gegebenenfalls erfolgt im Anschluss an die Cyclisierung die Einführung einer von Wasserstoff verschiedenen Gruppe R4a bzw. R4c, R5a bzw. R5c, wenn R4a bzw. R4c und/oder R5b in den Formeln V bzw. Va für Wasserstoff stehen.Optionally, following the cyclization, the introduction of a group R 4a or R 4c , R 5a or R 5c which is different from hydrogen takes place when R 4a or R 4c and / or R 5b in the formulas V or Va are hydrogen ,
In Formel V haben die Variablen R4a, R7, R8, R9 und R10 die zuvor genannten Bedeutungen. R5b steht für Wasserstoff, Ci-C4-Alkyl, C3-C4-Alkenyl oder C3-C4-Al kinyl. Rx ist hierbei z.B. Ci-Cβ-Alkyl, insbesondere Methyl, Ethyl oder Phenyl-Ci-Cβ-alkyl, z.B. Ben- zyl. In Formel Va haben die Variablen R4c, R7, R8, R9 und R10 die zuvor genannten Bedeutungen. R5b steht für Wasserstoff, Ci-C4-Alkyl, C3-C4-Alkenyl oder C3-C4-Al kinyl. Rx ist hierbei z.B. Ci-C6-Alkyl, insbesondere Methyl, Ethyl oder Phenyl-d-Ce-alkyl, z.B. Benzyl.In formula V, the variables R 4a , R 7 , R 8 , R 9 and R 10 have the meanings given above. R 5b represents hydrogen, Ci-C 4 alkyl, C 3 -C 4 alkenyl or C 3 -C 4 -alkyl kinyl. Here, R x is, for example, C 1 -C 6 -alkyl, in particular methyl, ethyl or phenyl-C 1 -C 6 -alkyl, for example benzyl. In formula Va, the variables R 4c , R 7 , R 8 , R 9 and R 10 have the meanings given above. R 5b represents hydrogen, Ci-C 4 alkyl, C 3 -C 4 alkenyl or C 3 -C 4 -alkyl kinyl. Here, R x is, for example, C 1 -C 6 -alkyl, in particular methyl, ethyl or phenyl-d-ce-alkyl, for example benzyl.
Die Cyclisierung der Verbindungen der Formel V bzw. Va kann in Gegenwart einer Base erfolgen. Die Reaktion erfolgt dann in der Regel bei Temperaturen im Bereich von 00C bis zum Siedepunkt der Reaktionsmischung, bevorzugt von 100C bis 500C, insbesondere bevorzugt von 15°C bis 35°C. Die Umsetzung kann in einem Lösungsmittel durchgeführt werden, bevorzugt in einem inerten organischen Lösungsmittel.The cyclization of the compounds of formula V or Va can be carried out in the presence of a base. The reaction is then usually carried out at temperatures in the range of 0 0 C to the boiling point of the reaction mixture, preferably from 10 0 C to 50 0 C, more preferably from 15 ° C to 35 ° C. The reaction can be carried out in a solvent, preferably in an inert organic solvent.
Geeignete inerte organische Lösungsmittel umfassen aliphatische Kohlenwasserstoffe wie Pentan, Hexan, Cyclohexan und Gemische von Cs-Cs-Al kanen, aromatische Kohlenwasserstoffe wie Toluol, o-, m- und p-Xylol, halogenierte Kohlenwasserstoffe wie Dichlormethan, Dichlorethan, Chloroform und Chlorbenzol, Ether wie Diethylether, Dii- sopropylether, tert.-Butylmethylether, Dioxan, Anisol und Tetrahydrofuran, Nitrile wie Acetonitril und Propionitril, Ketone wie Aceton, Methylethylketon, Diethylketon und tert- Butylmethylketon, Alkohole wie Methanol, Ethanol, n-Propanol, Isopropanol, n-Butanol, 2-Butanol, Isobutanol, tert.-Butanol, Wasser sowie Dimethylsulfoxid, Dimethylformamid und Dimethylacetamid sowie Morpholin und N-Methylmorpholin. Es können auch Gemische der genannten Lösungsmittel verwendet werden. Bevorzugtes Lösungsmittel ist ein Tetrahydrofuran - Wasser Gemisch mit einem Mischungsverhältnis von 1 : 10 bis 10 : 1.Suitable inert organic solvents include aliphatic hydrocarbons such as pentane, hexane, cyclohexane and mixtures of Cs-Cs-alkanes, aromatic hydrocarbons such as toluene, o-, m- and p-xylene, halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform and chlorobenzene, ethers such as diethyl ether, diisopropyl ether, tert-butyl methyl ether, dioxane, anisole and tetrahydrofuran, nitriles such as acetonitrile and propionitrile, ketones such as acetone, methyl ethyl ketone, diethyl ketone and tert-butyl methyl ketone, alcohols such as methanol, ethanol, n-propanol, isopropanol, n- Butanol, 2-butanol, isobutanol, tert-butanol, water and dimethyl sulfoxide, dimethylformamide and dimethylacetamide and morpholine and N-methylmorpholine. It is also possible to use mixtures of the solvents mentioned. The preferred solvent is a tetrahydrofuran-water mixture with a mixing ratio of 1:10 to 10: 1.
Geeignete Basen sind z.B. anorganische Verbindungen wie Alkalimetall- und Erdalkalimetallhydroxide wie Lithiumhydroxid, Natriumhydroxid, Kaliumhydroxid oder Calcium- hydroxid, wässrige Lösung von Ammoniak, Alkalimetall- oder Erdalkalimetalloxide wie Lithiumoxid, Natriumoxid, Calciumoxid und Magnesiumoxid, Alkalimetall- und Erdalkalimetallhydride wie Lithiumhydrid, Natriumhydrid, Kaliumhydrid und Calciumhydrid, Al- kalimetallamide wie Lithiumamid, beispielsweise Lithiumdiisopropylamid, Natriumamid und Kaliumamid, Alkalimetall- und Erdalkalimetallcarbonate wie Lithiumcarbonat, KaIi- umcarbonat, Cäsiumcarbonat und Calciumcarbonat sowie Alkalimetallhydrogencarbo- nate wie Natriumhydrogencarbonat, metallorganische Verbindungen, insbesondereSuitable bases are e.g. inorganic compounds such as alkali metal and alkaline earth metal hydroxides such as lithium hydroxide, sodium hydroxide, potassium hydroxide or calcium hydroxide, aqueous solution of ammonia, alkali metal or alkaline earth metal oxides such as lithium oxide, sodium oxide, calcium oxide and magnesium oxide, alkali metal and alkaline earth metal hydrides such as lithium hydride, sodium hydride, potassium hydride and calcium hydride, Al alkali metal amides, such as lithium amide, for example lithium diisopropylamide, sodium amide and potassium amide, alkali metal and alkaline earth metal carbonates, such as lithium carbonate, potassium carbonate, cesium carbonate and calcium carbonate, and also alkali metal bicarbonates, such as sodium bicarbonate, organometallic compounds, in particular
Alkalimetallalkyle wie Methyllithium, Butyllithium und Phenyllithium, Alkylmagnesiumha- logenide wie Methylmagnesiumchlorid sowie Alkalimetall- und Erdalkalimetallalkohola- te wie Natriummethanolat, Natriumethanolat, Kaliumethanolat, Kalium- tert.-Butanolat, Kalium-tert.-Pentanolat und Dimethoxymagnesium, außerdem organische Basen, z.B. tertiäre Amine wie Trimethylamin, Triethylamin, Diisopropylethylamin, 2-Hydroxypyridin und N-Methylpiperidin, Pyridin, substituierte Pyridine wie Collidin, Lutidin und 4- Dimethylaminopyridin sowie bicyclische Amine. Selbstverständlich kann auch eine Mischung verschiedener Basen verwendet werden. Bevorzugt sind insbesondere Kalium- tert-butanolat, 2-Hydroxypyridin oder eine wässrige Lösung von Ammoniak oder einer Mischung dieser Basen. Bevorzugt wird nur eine dieser Basen verwendet. In einer besonders bevorzugten Ausführungsform wird die Reaktion in Gegenwart einer wässri- gen Lösung von Ammoniak, die beispielsweise von 10 bis 50 w/v %ig sein kann, durchgeführt. In einer anderen, besonders bevorzugten Ausführungsform erfolgt die Cyclisie- rung in einer Mischung umfassend n-Butanol oder ein Butanolisomerengemisch (z.B. ein Gemisch aus n-Butanol mit 2-Butanol und/oder Isobutanol) und N-Methyl- Morpholin, vorzugsweise unter Rückflussbedingungen. Die Cyclisierung von V bzw. Va kann auch unter sauerer Katalyse, in Gegenwart aktivierender Verbindungen oder thermisch erfolgen. Die Umsetzung von V in Gegenwart einer Säure erfolgt üblicherweise bei Temperaturen im Bereich von 100C bis zum Sie- depunkt der Reaktionsmischung, bevorzugt von 500C bis zum Siedepunkt, insbesondere bevorzugt beim Siedepunkt unter Rückfluss. In der Regel wird die Umsetzung in einem Lösungsmittel vorgenommen, bevorzugt in einem inerten organischen Lösungsmittel.Alkali metal alkyls such as methyllithium, butyllithium and phenyllithium, alkylmagnesium halides such as methylmagnesium chloride and also alkali metal and alkaline earth metal alkoxides such as sodium methoxide, sodium ethanolate, potassium ethanolate, potassium tert-butoxide, potassium tert-pentoxide and dimethoxy magnesium, as well as organic bases, eg tertiary amines such as trimethylamine, triethylamine, diisopropylethylamine, 2-hydroxypyridine and N-methylpiperidine, pyridine, substituted pyridines such as collidine, lutidine and 4-dimethylaminopyridine as well as bicyclic amines. Of course, a mixture of different bases can be used. Particularly preferred are potassium tert-butoxide, 2-hydroxypyridine or an aqueous solution of ammonia or a mixture of these bases. Preferably, only one of these bases is used. In a particularly preferred embodiment, the reaction is carried out in the presence of an aqueous solution of ammonia, which may for example be from 10 to 50 w / v%. In another particularly preferred embodiment, the cyclization takes place in a mixture comprising n-butanol or a mixture of butanol isomers (for example a mixture of n-butanol with 2-butanol and / or isobutanol) and N-methyl-morpholine, preferably under reflux conditions. The cyclization of V or Va can also be carried out under acidic catalysis, in the presence of activating compounds or thermally. The reaction of V in the presence of an acid is usually effected at temperatures in the range of 10 0 C to the boiling point of the reaction mixture, preferably from 50 0 C to the boiling point, particularly preferably at the boiling point under reflux. In general, the reaction is carried out in a solvent, preferably in an inert organic solvent.
Als Lösungsmittel kommen prinzipiell diejenigen in Betracht, die auch für die basische Cyclisierung verwendet werden können, insbesondere Alkohole. In einer bevorzugten Ausführungsform wird die Reaktion in n-Butanol oder einem Gemisch verschiedener Butanolisomere(z.B. ein Gemisch aus n-Butanol mit 2-Butanol und/oder Isobutanol) durchgeführt.Suitable solvents are, in principle, those which can also be used for the basic cyclization, in particular alcohols. In a preferred embodiment, the reaction is carried out in n-butanol or a mixture of different butanol isomers (e.g., a mixture of n-butanol with 2-butanol and / or isobutanol).
Als Säuren für die Cyclisierung von V bzw. Va kommen grundsätzlich sowohl Brönstedt- als auch Lewis-Säuren in Betracht. Insbesondere können anorganische Säuren, z.B. Halogenwasserstoffsäuren wie Fluorwasserstoffsäure, Salzsäure, Bromwasserstoffsäure, anorganische Oxosäuren wie Schwefelsäure und Perchlorsäure, weiterhin anorganische Lewis-Säuren wie Bortrifluorid, Aluminiumtrichlorid, Eisen-Ill- chlorid, Zinn-IV-chlorid, Titan-IV-chlorid und Zink-ll-chlorid, sowie organische Säuren, beispielsweise Carbonsäuren und Hydroxycarbonsäuren wie Ameisensäure, Essigsäure, Propionsäure, Oxalsäure, Zitronensäure und Trifluoressigsäure, sowie organische Sulfonsäuren wie Toluolsulfonsäure, Benzolsulfonsäure, Camphersulfonsäure und dergleichen, Verwendung finden. Selbstverständlich kann auch eine Mischung verschiedener Säuren eingesetzt werden.Suitable acids for the cyclization of V or Va are in principle both Bronstedt and Lewis acids into consideration. In particular, inorganic acids, e.g. Hydrohalic acids such as hydrofluoric acid, hydrochloric acid, hydrobromic acid, inorganic oxo acids such as sulfuric acid and perchloric acid, furthermore inorganic Lewis acids such as boron trifluoride, aluminum trichloride, ferric chloride, tin IV chloride, titanium (IV) chloride and zinc (II) chloride, and organic acids, for example carboxylic acids and hydroxycarboxylic acids such as formic acid, acetic acid, propionic acid, oxalic acid, citric acid and trifluoroacetic acid, as well as organic sulfonic acids such as toluenesulfonic acid, benzenesulfonic acid, camphorsulfonic acid and the like, find use. Of course, a mixture of different acids can be used.
In einer Ausführungsform des erfindungsgemäßen Verfahrens wird die Reaktion in Gegenwart von organischen Säuren durchgeführt, beispielsweise in Gegenwart von Carbonsäuren wie Ameisensäure, Essigsäure oder Trifluoressigsäure oder einer Mischung dieser Säuren. Bevorzugt wird nur eine dieser Säuren verwendet. In einer bevorzugten Ausführungsform wird die Reaktion in Essigsäure durchgeführt.In one embodiment of the process according to the invention, the reaction is carried out in the presence of organic acids, for example in the presence of carboxylic acids such as formic acid, acetic acid or trifluoroacetic acid or a mixture of these acids. Preferably, only one of these acids is used. In a preferred embodiment, the reaction is carried out in acetic acid.
In einer besonders bevorzugten Ausführungsform erfolgt die saure Cyclisierung in ei- ner Mischung umfassend n-Butanol oder ein Butanolisomerengemisch (z.B. ein Gemisch aus n-Butanol mit 2-Butanol und/oder Isobutanol), N-Methyl-Morpholin und Essigsäure, vorzugsweise unter Rückflussbedingungen.In a particularly preferred embodiment, the acid cyclization takes place in a mixture comprising n-butanol or a mixture of butanol isomers (for example a mixture of n-butanol with 2-butanol and / or isobutanol), N-methyl-morpholine and acetic acid, preferably under reflux conditions ,
In einer weiteren Ausführungsform der Erfindung wird die Umsetzung von V bzw. Va durch Behandlung mit einem Aktivierungsmittel in Gegenwart einer Base durchgeführt. Rx steht dann für Wasserstoff. Beispiel für ein geeignetes Aktivierungsmittel ist Di-(N- succinimidinyl)carbonat. Geeignete Aktivierungsmittel sind außerdem polystyrol- oder nicht polystyrolgebundenes Dicyclohexylcarbodiimid (DCC), Diisopropylcarbodiimid, 1- Ethyl-3-(dimethylaminopropyl)carbodiimid (EDAC), Carbonyldiimidazol, Chlorkohlensäureester wie Methylchloroformiat, Ethylchloroformiat, Isopropylchloroformiat, Isobu- tylchloroformiat, sec-Butylchloroformiat oder Allylchloroformiat, Pivaloylchlorid, PoIy- phosphorsäure, Propanphosphonsäureanhydrid, Bis(2-oxo-3-oxazolidinyl)- phosphorylchlorid (BOPCI) oder Sulfonylchloride wie Methansulfonylchlorid, Toluolsul- fonylchlorid oder Benzolsulfonylchlorid. Geeignete Basen sind die für die basische Cyc- lisierung zitierten Verbindungen. In einer Ausführungsform werden als Base Triethyla- min oder N-Ethyldiisopropylamin oder deren Mischungen, besonders bevorzugt N- Ethyldiisopropylamin verwendet.In a further embodiment of the invention, the reaction of V or Va is carried out by treatment with an activating agent in the presence of a base. R x then stands for hydrogen. An example of a suitable activating agent is di (N-succinimidinyl) carbonate. Suitable activating agents are also polystyrene or non-polystyrene-bonded dicyclohexylcarbodiimide (DCC), diisopropylcarbodiimide, 1-ethyl-3- (dimethylaminopropyl) carbodiimide (EDAC), carbonyldiimidazole, chloroformate such as methyl chloroformate, ethyl chloroformate, isopropyl chloroformate, isobutyl chloroformate, sec-butyl chloroformate or allyl chloroformate, pivaloyl chloride, polyphosphoric acid, propanephosphonic anhydride , Bis (2-oxo-3-oxazolidinyl) -phosphoryl chloride (BOPCI) or sulfonyl chlorides such as methanesulfonyl chloride, toluenesulfonyl chloride or benzenesulfonyl chloride. Suitable bases are the compounds cited for the basic cyclization. In one embodiment, the base used is triethylamine or N-ethyldiisopropylamine or mixtures thereof, particularly preferably N-ethyldiisopropylamine.
In einer weiteren Ausführungsform der Erfindung wird die Umsetzung von V bzw. Va ausschließlich durch Erhitzen der Reaktionsmischung durchgeführt (thermische Cycli- sierung). Die Umsetzung erfolgt hierbei üblicherweise bei Temperaturen im Bereich von 10°C bis zum Siedepunkt der Reaktionsmischung, bevorzugt von 50°C bis zumIn a further embodiment of the invention, the reaction of V or Va is carried out exclusively by heating the reaction mixture (thermal cyclization). The reaction is usually carried out at temperatures in the range of 10 ° C to the boiling point of the reaction mixture, preferably from 50 ° C to
Siedepunkt der Reaktionsmischung, insbesondere bevorzugt beim Siedepunkt der Reaktionsmischung unter Rückfluss. In der Regel wird die Umsetzung in einem Lösungsmittel vorgenommen, bevorzugt in einem inerten organischen Lösungsmittel.Boiling point of the reaction mixture, particularly preferably at the boiling point of the reaction mixture under reflux. In general, the reaction is carried out in a solvent, preferably in an inert organic solvent.
Als Lösungsmittel kommen prinzipiell diejenigen in Betracht, die bei der basischen Cyc- lisierung verwendet werden. Bevorzugt werden polar aprotische Lösungsmittel, z.B. Dimethylsulfoxid oder Dimethylformamid oder deren Mischungen. In einer bevorzugten Ausführungsform wird die Reaktion in Dimethylsulfoxid durchgeführt.Suitable solvents are, in principle, those which are used in the basic cyclization. Preferred are polar aprotic solvents, e.g. Dimethyl sulfoxide or dimethylformamide or mixtures thereof. In a preferred embodiment, the reaction is carried out in dimethyl sulfoxide.
Sofern in Verbindung V bzw. Va einer oder beide Reste R4a bzw. R4c und/oder R5b für Wasserstoff stehen, können die Piperazinstickstoffe anschließend zur Einführung der Reste R4a bzw. R4c und/oder R5a bzw. R5c durch Umsetzung mit einem Alkylierungsmit- tel R4a-X1, R5a-X1, R4c-X1 bzw. R5c-X1 alkyliert oder durch Umsetzung mit einem Acylie- rungsmittel R4a-X2, R5a-X2, R4c-X2 bzw. R5c-X2 mit einer Schutzgruppe versehen wer- den. Hierbei haben R4a, R4c, R5a, R5c, X1 und X2 die zuvor angegebenen Bedeutungen.If one or both R 4a and R 4c and / or R 5b is hydrogen in compound V or Va, the piperazine nitrogens can subsequently be used to introduce the radicals R 4a or R 4c and / or R 5a or R 5c Reaction with an alkylating agent R 4a -X 1 , R 5a -X 1 , R 4c -X 1 or R 5c -X 1 alkylated or by reaction with an acylating agent R 4a -X 2 , R 5a -X 2 , R 4c -X 2 or R 5c -X 2 are provided with a protective group. Here, R 4a , R 4c , R 5a , R 5c , X 1 and X 2 have the meanings given above.
Die Verbindungen der Formel V bzw. Va können ihrerseits nach der im folgenden Schema dargestellten Synthese in Analogie zu literaturbekannten Verfahren hergestellt werden, beispielsweise nach Wilford L. Mendelson et al., Int. J. Peptide & Protein Re- search 35(3), (1990), 249-57, Glenn L. Stahl et al., J. Org. Chem. 43(1 1), (1978), 2285-6. oder A. K. Ghosh et al., Org. Lett. 3(4), (2001), 635-638. The compounds of formula V or Va in turn can be prepared according to the synthesis shown in the following scheme in analogy to literature methods, for example according to Wilford L. Mendelson et al., Int. J. Peptide & Protein Research 35 (3), (1990), 249-57, Glenn L. Stahl et al., J. Org. Chem. 43 (11), (1978), 2285-6. or AK Ghosh et al., Org. Lett. 3 (4), (2001), 635-638.
In dem Schema haben die Variablen Rx, R4a, R4c, R5b, R6, R7, R8, R9 und R10 die für Formel V angegebenen Bedeutungen. Die Synthese umfasst in einem ersten Schritt die Kupplung von Glycinesterverbindungen der Formel VII mit Boc-geschützten Pheny- lalaninverbindungen VIII bzw. Villa in Gegenwart eines Aktivierungsreagenz. Anstelle von Boc kann auch eine andere Aminoschutzgruppe eingesetzt werden.In the scheme, the variables R x, R 4a, R 4c, R 5b, R 6, R 7, R 8, R 9 and R 10 have the meanings given for formula V. In a first step, the synthesis comprises the coupling of glycine ester compounds of the formula VII with Boc-protected phenylalanine compounds VIII or Villa in the presence of an activating reagent. Instead of Boc, another amino protecting group can also be used.
Die Umsetzung einer Verbindung der Formel VII mit einer Verbindung der Formel VIII bzw. Villa erfolgt üblicherweise bei Temperaturen im Bereich von -300C bis zum Siedepunkt der Reaktionsmischung, bevorzugt von 00C bis 500C, insbesondere bevorzugt von 200C bis 35°C. Die Reaktion kann in einem Lösungsmittel durchgeführt werden, bevorzugt in einem inerten organischen Lösungsmittel.The reaction of a compound of formula VII with a compound of formula VIII or Villa is usually carried out at temperatures in the range of -30 0 C to the boiling point of the reaction mixture, preferably from 0 0 C to 50 0 C, particularly preferably from 20 0 C to 35 ° C. The reaction may be carried out in a solvent, preferably in an inert organic solvent.
Im Allgemeinen erfordert die Umsetzung die Anwesenheit eines Aktivierungsreagenzes. Geeignete Aktivierungsreagenzien sind Kondensationsmittel wie z.B. polystyrol- oder nicht polystyrolgebundenes Dicyclohexylcarbodiimid (DCC), Diisopropylcarbodii- mid, Carbonyldiimidazol (CDI), 1-Ethyl-3-(dimethylaminopropyl)carbodiimid (EDAC), Chlorkohlensäureester wie Methylchloroformiat, Ethylchloroformiat, Isopropylchloro- formiat, Isobutylchloroformiat, sec-Butylchloroformiat oder Allylchloroformiat, Piva- loylchlorid, Polyphosphorsäure, Propanphosphonsäureanhydrid, Bis(2-oxo-3- oxazolidinyl)-phosphorylchlorid (BOPCI) oder Sulfonylchloride wie Methansulfonylchlo- rid, Toluolsulfonylchlorid oder Benzolsulfonylchlorid. Nach einer Ausführungsform werden als Aktivierungsreagenz EDAC oder DCC bevorzugt.In general, the reaction requires the presence of an activating reagent. Suitable activating reagents are condensing agents, e.g. polystyrene- or non-polystyrene-bonded dicyclohexylcarbodiimide (DCC), diisopropylcarbodiimide, carbonyldiimidazole (CDI), 1-ethyl-3- (dimethylaminopropyl) carbodiimide (EDAC), chloroformate such as methyl chloroformate, ethyl chloroformate, isopropyl chloroformate, isobutyl chloroformate, sec-butyl chloroformate or allyl chloroformate , Polyvinyl chloride, polyphosphoric acid, propanephosphonic anhydride, bis (2-oxo-3-oxazolidinyl) -phosphoryl chloride (BOPCI) or sulfonyl chlorides such as methanesulfonyl chloride, toluenesulfonyl chloride or benzenesulfonyl chloride. In one embodiment, EDAC or DCC are preferred as the activating reagent.
Vorzugsweise erfolgt die Umsetzung von VII mit VIII bzw. Villa in Gegenwart einer Base. Geeignete Basen sind die Cyclisierung des Dipeptids V zum Piperazin IV zitierten Verbindungen. In einer Ausführungsform werden als Base Triethylamin oder N- Ethyldiisopropylamin oder deren Mischungen, besonders bevorzugt N-Ethyl- diisopropylamin verwendet. Das Entschützen der Verbindungen VI bzw. VIa zur Verbindung V bzw. Va kann nach üblichen Verfahren erfolgen, wie beispielsweise nach Glenn L. Stahl et al., J. Org. Chem. 43(1 1), (1978), 2285-6. oder A. K. Ghosh et al., Org. Lett. 3(4), (2001), 635-638. Das Entschützen erfolgt typischerweise durch Behandlung mit einer Säure. Als Säuren kommen sowohl Brönstedt- als auch Lewis-Säuren in Betracht, vorzugsweise organischen Carbonsäuren, beispielsweise Ameisensäure, Essigsäure oder Trifluoressigsäu- re oder deren Mischungen in betracht. In einer bevorzugten Ausführungsform wird die Reaktion in Gegenwart von Trifluoressigsäure durchgeführt.Preferably, the reaction of VII with VIII or Villa takes place in the presence of a base. Suitable bases are the cyclization of the dipeptide V to piperazine IV cited compounds. In one embodiment, the base used is triethylamine or N-ethyldiisopropylamine or mixtures thereof, particularly preferably N-ethyldiisopropylamine. The deprotection of the compounds VI or VIa to compound V or Va can be carried out by customary processes, for example as described by Glenn L. Stahl et al., J. Org. Chem. 43 (11), (1978), 2285-6 , or AK Ghosh et al., Org. Lett. 3 (4), (2001), 635-638. Deprotection is typically by treatment with an acid. Suitable acids are both Brönstedt and Lewis acids, preferably organic carboxylic acids, for example formic acid, acetic acid or trifluoroacetic acid or mixtures thereof. In a preferred embodiment, the reaction is carried out in the presence of trifluoroacetic acid.
Die Umsetzung erfolgt üblicherweise bei Temperaturen im Bereich von -300C bis zum Siedepunkt der Reaktionsmischung, bevorzugt von 00C bis 500C, insbesondere bevorzugt von 200C bis 35°C. Die Reaktion kann in einem Lösungsmittel, bevorzugt in einem inerten organischen Lösungsmittel ausgeführt werden.The reaction is usually carried out at temperatures in the range from -30 0 C to the boiling point of the reaction mixture, preferably from 0 0 C to 50 0 C, particularly preferably from 20 0 C to 35 ° C. The reaction may be carried out in a solvent, preferably in an inert organic solvent.
Als Lösungsmittel kommen prinzipiell die zuvor im Zusammenhang mit der basischen Cyclisierung von V zu IV genannten Lösungsmittel in Betracht, insbesondere Tetra- hydrofuran oder Dichlormethan oder deren Mischungen. In einer bevorzugten Ausführungsform wird die Reaktion in Dichlormethan durchgeführt.Suitable solvents are, in principle, the solvents mentioned above in connection with the basic cyclization of V to IV, in particular tetrahydrofuran or dichloromethane or mixtures thereof. In a preferred embodiment, the reaction is carried out in dichloromethane.
Wenn anstelle von Boc eine andere Schutzgruppe eingesetzt wird, so wird selbstverständlich ein für die jeweilige Schutzgruppe geeignetes Entschützungsverfahren angewendet.When a different protecting group is used instead of Boc, it will be understood that a deprotection method suitable for the particular protecting group is used.
Sofern in den Verbindungen IV bzw. IVa die Gruppen R4a und R5a bzw. R4c und R5c für Wasserstoff stehen, kann man die Verbindungen IV bzw. IVa auch durch intermolekulare Cyclisierung eines Glycinester-Derivats VIIa mit einer Phenylalanin-Verbindung VIIIb bzw. VIIIc gemäß den folgenden Schemata darstellen:If the groups R 4a and R 5a or R 4c and R 5c in the compounds IV or IVa are hydrogen, the compounds IV or IVa can also be prepared by intermolecular cyclization of a glycine ester derivative VIIa with a phenylalanine compound VIIIb or VIIIc according to the following schemes:
(VIIa) (VIIIb) (IV: R4a = R5a = H) (VIIa) (VIIIc) (IVa: R4c = R5c = H) In den Schemata haben Rx, R6, R7, R8, R9 und R10 die zuvor angegebenen Bedeutungen. Ry steht für Alkyl, z.B. Methyl oder Ethyl. Die intermolekulare Cyclisierung kann z.B. durch eine Base, z.B. Ammoniak bewirkt werden. Die Verbindungen VIIa und/oder VIIIb bzw. VIIIc können auch in Form ihrer Säureadditionssalze, z.B. als Hydrochloride eingesetzt werden. (VIIa) (VIIIb) (IV: R 4a = R 5a = H) (VIIa) (VIIIc) (IVa: R 4c = R 5c = H) In the schemes, R x , R 6 , R 7 , R 8 , R 9 and R 10 have the meanings given above. R y is alkyl, for example methyl or ethyl. The intermolecular cyclization can be effected, for example, by a base, for example ammonia. The compounds VIIa and / or VIIIb or VIIIc can also be used in the form of their acid addition salts, for example as hydrochlorides.
Gemäß einer anderen Ausführungsform (im Folgenden als Verfahren B bezeichnet) umfasst die Herstellung der Verbindungen IAccording to another embodiment (hereinafter referred to as process B), the preparation of the compounds I comprises
i) die Bereitstellung einer Verbindung der allgemeinen Formel IXi) the provision of a compound of general formula IX
worin R1, R2, R3, R4 und R6 die zuvor genannten Bedeutungen aufweisen, und R5a eine der für R5 angegebenen, von Wasserstoff verschiedenen Bedeutungen aufweist oder für eine Schutzgruppe steht;wherein R 1 , R 2 , R 3 , R 4 and R 6 have the abovementioned meanings, and R 5a has one of the meanings given for R 5 other than hydrogen or is a protective group;
ii) Umsetzung der Verbindung IX mit einer Benzylverbindung der Formel Xii) reaction of the compound IX with a benzyl compound of the formula X.
worin R7, R8, R9 und R10 die zuvor angegebenen Bedeutungen aufweisen und X für eine nucleophil verdrängbare Abgangsgruppe steht, in Gegenwart einer Base; und wherein R 7 , R 8 , R 9 and R 10 have the meanings given above and X is a nucleophilically displaceable leaving group, in the presence of a base; and
iii) wenn R5a für einen Schutzgruppe steht, Entfernen der Schutzgruppe.iii) when R 5a is a protecting group, deprotecting.
In Formel IX hat R5a vorzugsweise eine für R5 angegebene, von Wasserstoff verschiedene Bedeutung. In Formel X hat die Variable X vorzugsweise eine der folgenden Bedeutungen: Halogen, insbesondere Chlor, Brom oder lod oder O-Sθ2-Rm mit Rm in der Bedeutung von Ci-C4-AIkVl oder Aryl, welche gegebenenfalls durch Halogen, C1-C4- Alkyl oder Halo-Ci-C4-alkyl substituiert sind. Geeignete Schutzgruppen für die Stick- stoffatome des Piperazinrings in IX sind insbesondere die zuvor genannten Reste C(O)R51, z.B. der Acetylrest.In formula IX, R 5a preferably has a meaning other than hydrogen given for R 5 . In formula X, the variable X preferably has one of the following meanings: halogen, in particular chlorine, bromine or iodine or O-SO 2 -R m with R m in the meaning of Ci-C 4 -AlkVl or aryl, which is optionally substituted by halogen, C1 C4 alkyl or halo-Ci-C4-alkyl are substituted. Suitable protective groups for the embroidery Substance atoms of the piperazine ring in IX are in particular the abovementioned radicals C (O) R 51 , for example the acetyl radical.
Die Umsetzung der Verbindung IX mit der Verbindung X in Schritt ii) kann in Analogie zu der in Verfahren A, Schritt iv) beschriebenen Methode erfolgen oder z.B. nach der in J. Am. Chem. Soc. 105, 1983, 3214 beschriebenen Methode. In einer bevorzugten Ausführungsform erfolgt die Umsetzung in Gegenwart von Natriumhydrid als Base in N-Methylpyrrolidon als Lösungsmittel.The reaction of the compound IX with the compound X in step ii) can be carried out in analogy to the method described in process A, step iv) or, e.g. after in J. Am. Chem. Soc. 105, 1983, 3214. In a preferred embodiment, the reaction takes place in the presence of sodium hydride as base in N-methylpyrrolidone as solvent.
Die Bereitstellung der Verbindungen IX kann z.B. durch Umsetzung der Verbindung Xl mit einer Benzaldehyd-Verbindung XII, wie in dem folgenden Schema erläutert, erfolgen.The provision of the compounds IX can e.g. by reacting compound XI with a benzaldehyde compound XII, as explained in the following scheme.
(Xl) (XII)(XI) (XII)
Hierin weisen R1, R2, R3, R5a und R6 die zuvor genannten Bedeutungen auf. R4a hat eine der für R4 angegebenen Bedeutungen oder steht für eine Schutzgruppe. Geeignete Schutzgruppen für die Stickstoffatome des Piperazinrings in Xl sind insbesondere die zuvor genannten Reste C(O)R51, z.B. der Acetylrest. Insbesondere stehen R4a und R5a für einen der zuvor genannten Reste C(O)R52, z.B. für Acetylreste.Herein, R 1 , R 2 , R 3 , R 5a and R 6 have the meanings given above. R 4a has one of the meanings given for R 4 or is a protective group. Suitable protecting groups for the nitrogen atoms of the piperazine ring in XI are in particular the abovementioned radicals C (O) R 51 , for example the acetyl radical. In particular, R 4a and R 5a represent one of the abovementioned radicals C (O) R 52 , for example acetyl radicals.
Die Umsetzung von Xl mit XII kann unter den Bedingungen einer Aldolkondensation erfolgen, wie bereits für die Umsetzung von III mit IV bzw. IVa beschrieben. Solche Aldolkondensationen können analog zu den in J. Org. Chem. 2000, 65 (24), 8402- 8405, Synlett 2006, 677, J. Heterocycl. Chem. 1988, 25, 591 beschriebenen Verfahren durchgeführt werden, worauf hiermit in vollem Umfang Bezug genommen wird.The reaction of XI with XII can be carried out under the conditions of an aldol condensation, as already described for the reaction of III with IV or IVa. Such aldol condensations can be carried out analogously to those described in J. Org. Chem. 2000, 65 (24), 8402-8405, Synlett 2006, 677, J. Heterocycl. Chem. 1988, 25, 591, to which reference is hereby fully made.
Die Umsetzung erfolgt in der Regel in Gegenwart einer Base. Als Base verwendet man vorzugsweise ein Alkalimetall- oder Erdalkalimetallcarbonat, z.B. Natriumcarbonat, Kaliumcarbonat oder Cäsiumcarbonat oder deren Gemische.The reaction is usually carried out in the presence of a base. As the base, it is preferable to use an alkali metal or alkaline earth metal carbonate, e.g. Sodium carbonate, potassium carbonate or cesium carbonate or mixtures thereof.
Vorzugsweise erfolgt die Umsetzung in einem inerten, vorzugsweise aprotischen organischen Lösungsmittel. Beispiele für geeignete Lösungsmittel sind insbesondere Dich- lormethan, Dichlorethan, Chlorbenzol, Ether wie Diethylether, Diisopropylether, tert- Butylmethylether, Dioxan, Anisol und Tetrahydrofuran, Nitrile wie Acetonitril und Propi- onitril, sowie Dimethylsulfoxid, Dimethylformamid, N-Methylpyrrolidon und Dimethyla- cetamidPreferably, the reaction is carried out in an inert, preferably aprotic organic solvent. Examples of suitable solvents are, in particular, dichloromethane, dichloroethane, chlorobenzene, ethers, such as diethyl ether, diisopropyl ether, tert-butyl methyl ether, dioxane, anisole and tetrahydrofuran, nitriles, such as acetonitrile and propylene onitrile, and dimethyl sulfoxide, dimethylformamide, N-methylpyrrolidone and dimethylacetamide
Vorzugsweise erfolgt die Umsetzung von solchen Verbindungen Xl, worin R4a und R5a für eine Schutzgruppe und insbesondere einen Acylrest R52C(O)- (R52 = Ci-C4-AIkVl), z.B. einen Acetylrest, stehen. Dementsprechend schließt sich im Anschluss an die Kondensationreaktion in der Regel eine Entfernung der Schutzgruppen an. Die Entfernung einer Schutzgruppe R4a, R5a kann in Analogie zu bekannten Verfahren der Schutzgruppenchemie erfolgen, z.B. nach der in Green, Wuts, Protective Groups in Organic Synthesis, 3rd ed. 1999, John Wiley and Sons, S. 553 beschriebenen Methode. Eine anschließende Alkylierung zur Einführung der Reste R4 bzw. R5 kann auf die zuvor bei Verfahren A für die Schritte ii) bzw. iii) angegebene Methode erfolgen.Preferably, the reaction of such compounds Xl, wherein R 4a and R 5a is a protective group and in particular an acyl radical R 52 C (O) - (R 52 = Ci-C 4 -AlkVl), for example an acetyl radical, are. Accordingly, removal of the protective groups usually follows the condensation reaction. The removal of a protective group R 4a , R 5a can be carried out in analogy to known methods of protecting group chemistry, for example according to the method described in Green, Wuts, Protective Groups in Organic Synthesis, 3rd ed. 1999, John Wiley and Sons, p. A subsequent alkylation to introduce the radicals R 4 or R 5 can be carried out in the manner previously indicated in process A for the steps ii) or iii).
Die Verbindungen Xl sind bekannt. Ihre Herstellung kann in Analogie zur Herstellung der oben beschriebenen Verbindungen V gemäß dem im Folgenden gezeigten Schema erfolgen:The compounds XI are known. Their preparation can be carried out analogously to the preparation of the compounds V described above according to the scheme shown below:
In diesem Schema haben R4a, R5a und R6 die zuvor genannten Bedeutungen. Rx steht vorzugsweise für CrC4-AIkVl oder Benzyl. Boc steht für einen tert.-Butoxycarbonyl- Rest.In this scheme, R 4a , R 5a and R 6 have the meanings given above. R x is preferably C 1 -C 4 -alkyl or benzyl. Boc is a tert-butoxycarbonyl radical.
Bezüglich weiterer Details für den ersten Reaktionsschritt wird auf die Umsetzung von Verbindung VII mit der Verbindung VIII bzw. Villa bzw. auf die Umsetzung von VIIa mit VIIIb bwz. VIIIc verwiesen. Die anschließende Entfernung der boc-Schutzgruppe kann in Analogie zur Umsetzung der Verbindung VI zur Verbindung V erfolgen. Die Cyclisie- rung der dabei erhaltenen entschützten Verbindung kann nach den für die Cyclisierung der Verbindung V genannten Methoden erfolgen. Sofern R4a und R5a für eine Schutz- gruppe, z.B. einen Rest C(O)R51 steht, kann die Einführung dieser Schutzgruppen in Analogie zu bekannten Verfahren der Schutzgruppenchemie erfolgen, z.B. durch Umsetzung mit Anhydriden der Formel (R51C(O))2θ, z.B. nach der in Green, Wuts, Protec- tive Groups in Organic Synthesis, 3rd ed. 1999, John Wiley and Sons, S. 553 beschriebenen Methode.With regard to further details for the first reaction step, reference is made to the reaction of compound VII with compound VIII or Villa or to the reaction of VIIa with VIIIb bwz. Referenced VIIIc. The subsequent removal of the boc protective group can be carried out analogously to the reaction of compound VI to compound V. The cyclization of the resulting deprotected compound can be carried out according to the methods mentioned for the cyclization of compound V. If R 4a and R 5a is a protective group, for example a radical C (O) R 51 , the introduction of these protective groups in By analogy with known methods of protecting group chemistry, for example by reaction with anhydrides of the formula (R 51 C (O)) 2θ, for example according to the in Green, Wuts, Protective Groups in Organic Synthesis, 3rd ed. 1999, John Wiley and Sons , P. 553.
Die Verbindungen der Formel I mit R5 * H können auch dadurch hergestellt werden, dass man eine Piperazinverbindung der Formel I, worin R5 für Wasserstoff steht, mit einem Alkylierungsmittel oder Acylierungsmittel, das den von Wasserstoff verschiedenen Rest R5 enthält, umsetzt. Derartige Umsetzungen können in Analogie zu denjeni- gen Methoden durchgeführt werden, die im Zusammenhang mit Verfahren A Schritte ii), iii) und v) erläutert wurden. Enstrechende Alkylierungen können auch auf den Stufen der Verbindungen VII, VIIa, VIII, Villa, VIIIb und VIIIc vorgenommen werden.The compounds of the formula I where R 5 * H can also be prepared by reacting a piperazine compound of the formula I in which R 5 is hydrogen with an alkylating agent or acylating agent which contains the radical R 5 other than hydrogen. Such reactions can be carried out analogously to those methods which have been explained in connection with method A steps ii), iii) and v). Competing alkylations can also be carried out at the stages of compounds VII, VIIa, VIII, VIIIa, VIIIb and VIIIc.
Hierzu wird die Piperazinverbindung der Formel I mit R5 = Wasserstoff mit einem ge- eigneten Alkylierungsmittel, im Folgenden Verbindung X1-R5, oder Acylierungsmittel, im Folgenden Verbindung X2-R5, umgesetzt, wobei man eine Piperazinverbindung der Formel I mit R5 * Wasserstoff erhält.For this purpose, the piperazine compound of the formula I is reacted with R 5 = hydrogen with a suitable alkylating agent, hereinafter compound X 1 -R 5 , or acylating agent, hereinafter compound X 2 -R 5 , to give a piperazine compound of the formula I ## STR4 ## R 5 * receives hydrogen.
In den Alkylierungsmitteln X1-R5 kann X1 Halogen oder O-SO2-R111 mit Rm in der Bedeu- tung von Ci-C4-AIkVl oder Aryl, welche gegebenenfalls durch Halogen, CrC4-AIkVl oder Halo-Ci-C4-alkyl substituiert sind, bedeuten. In Acylierungsmitteln X2-R5 kann X2 Halogen, insbesondere Cl bedeuten. R5 steht dabei für einen Rest (CO)R51.In the alkylating agents X 1 -R 5 X can 1 is halogen or O-SO2-R 111 with R m in the importance of Ci-C 4 -alkyl or aryl, which are optionally substituted by halogen, -C 4 -alkyl or halo-C -C 4 alkyl substituted. In acylating agents X 2 -R 5 , X 2 may be halogen, in particular Cl. R 5 stands for a radical (CO) R 51 .
Die Umsetzung erfolgt üblicherweise bei Temperaturen im Bereich von -78°C bis zum Siedepunkt der Reaktionsmischung, bevorzugt von -500C bis 65°C, insbesondere bevorzugt von -300C bis 65°C. In der Regel wird die Umsetzung in einem Lösungsmittel vorgenommen, bevorzugt in einem inerten organischen Lösungsmittel.The reaction is usually carried out at temperatures in the range of -78 ° C to the boiling point of the reaction mixture, preferably from -50 0 C to 65 ° C, particularly preferably from -30 0 C to 65 ° C. In general, the reaction is carried out in a solvent, preferably in an inert organic solvent.
Geeignete Lösungsmittel sind die bei der Cyclisierung des Dipeptids V zum Piperazin IV genannten Verbindungen, unter anderem Toluol, Dichlormethan, Tetrahydrofuran oder Dimethylformamid oder deren Mischungen.Suitable solvents are the compounds mentioned in the cyclization of the dipeptide V to the piperazine IV, including toluene, dichloromethane, tetrahydrofuran or dimethylformamide or mixtures thereof.
In einer bevorzugten Ausführungsform wird die Verbindung I mit R5 = H mit dem Alky- lierungs- bzw. Acylierungsmittel in Gegenwart einer Base umgesetzt. Geeignete Basen sind die bei der Cyclisierung des Dipeptids V zum Piperazin IV genannten Verbindungen. Die Basen werden im Allgemeinen äquimolar eingesetzt. Sie können auch im Ü- berschuss oder selbst als Lösungsmittel verwendet werden. In einer bevorzugten Ausführungsform wird die Base in äquimolarer Menge oder im Wesentlichen äquimolarer Menge zugesetzt. In einer weiteren bevorzugten Ausführungsform wird Natriumhydrid als Base verwendet. Die Alkylierung bzw. Acylierung der Gruppe NR5, worin R5 für H steht, kann alternativ auch in den Vorstufen erfolgen. So können z.B. Verbindungen II, IV, V, VI, VIII, in denen R5a bzw. R5b für H steht, wie zuvor beschrieben N-alkyliert oder N-acyliert werden. In gleicher Weise können Vorstufen II, IV, V, VI, VII, in denen der mit R4 bzw. R4a be- zeichnete Rest für Wasserstoff steht, alkyliert werden.In a preferred embodiment, the compound I is reacted with R 5 = H with the alkylating or acylating agent in the presence of a base. Suitable bases are the compounds mentioned in the cyclization of the dipeptide V to the piperazine IV. The bases are generally used equimolar. They can also be used in excess or even as a solvent. In a preferred embodiment, the base is added in equimolar amount or substantially equimolar amount. In another preferred embodiment, sodium hydride is used as the base. The alkylation or acylation of the group NR 5 , in which R 5 is H, can alternatively also be carried out in the precursors. Thus, for example, compounds II, IV, V, VI, VIII in which R 5a or R 5b is H can be N-alkylated or N-acylated as described above. In the same way, precursors II, IV, V, VI, VII, in which the radical denoted by R 4 or R 4a is hydrogen, can be alkylated.
Die Verbindungen der Formel I können außerdem an der Gruppe R1 modifiziert werden. So können beispielweise Verbindungen der Formel I, in denen R1 für CN, gegebenenfalls substituiertes Phenyl oder für einen gegebenenfalls substituierten hetero- cyclischen Rest steht, ausgehend von Verbindungen I, worin R1 für Halogen wie Chlor, Brom oder Jod steht, durch Umwandlung des Substituenten R1 hergestellt werden, z.B. in Analogie zu den von J. Tsuji, Top. Organomet. Chem. (14) (2005), 332 pp., J. Tsuji, Organic Synthesis with Palladium Compounds, (1980), 207 pp., Tetrahedron Lett. 42, 2001 , S.7473 oder Org. Lett. 5, 2003, 1785 beschriebenen Methoden.The compounds of the formula I can also be modified on the group R 1 . Thus, for example, compounds of the formula I in which R 1 is CN, optionally substituted phenyl or an optionally substituted heterocyclic radical, starting from compounds I, wherein R 1 is halogen, such as chlorine, bromine or iodine, by conversion of the Substituents R 1 are prepared, for example in analogy to those of J. Tsuji, Top. Organomet. Chem. (14) (2005), 332 pp., J. Tsuji, Organic Synthesis with Palladium Compounds, (1980), 207 pp., Tetrahedron Lett. 42, 2001, p. 7473 or Org. Lett. 5, 2003, 1785.
Hierzu wird eine Piperazinverbindung der Formel I, die als Substituenten R1 ein Halogenatom wie Chlor, Brom oder lod aufweist, durch Umsetzung mit einem Kupplungspartner, der eine Gruppe R1 enthält (Verbindung R1-X3), in ein anderes Piperazinderivat der Formel I überführt. In analoger Weise können auch Verbindungen Ia, Il und IIa um- gesetzt werden.For this purpose, a piperazine compound of formula I, which as substituent R 1 has a halogen atom such as chlorine, bromine or iodine, by reaction with a coupling partner containing a group R 1 (compound R 1 -X 3 ), in another piperazine derivative of the formula I convicted. Analogously, it is also possible to convert compounds Ia, II and IIa.
Die Umsetzung erfolgt üblicherweise in Gegenwart eines Katalysators, bevorzugt in Gegenwart eines Übergangsmetallkatalysators. In der Regel findet die Reaktion in Gegenwart einer Base statt.The reaction is usually carried out in the presence of a catalyst, preferably in the presence of a transition metal catalyst. In general, the reaction takes place in the presence of a base.
Als Kupplungspartner X3-R1 kommen insbesondere solche Verbindungen in Betracht, worin X3 im Falle von R1 in der Bedeutung von Phenyl oder heterocyclischer Rest (He- terocyclyl) für eine der folgenden Gruppen steht:Suitable coupling partners X 3 -R 1 are, in particular, those compounds in which X 3 in the case of R 1 in the meaning of phenyl or heterocyclic radical (heterocyclyl) represents one of the following groups:
- Zn-R1 mit R1 in der Bedeutung von Halogen, Phenyl oder Heterocyclyl;- Zn-R 1 with R 1 in the meaning of halogen, phenyl or heterocyclyl;
B(ORm)2, mit Rm in der Bedeutung von H oder Ci-Cβ-Alkyl, wobei zwei Alkyl- substituenten zusammen eine C2-C4-Alkylenkette bilden können; oder SnRn3, mit Rn in der Bedeutung von Ci-Cβ-Alkyl bedeutet.B (OR m ) 2, where R m is H or C 1 -C 6 -alkyl, where two alkyl substituents can together form a C 2 -C 4 -alkylene chain; or SnR n 3, with R n in the meaning of Ci-Cβ-alkyl.
Diese Umsetzungen erfolgt üblicherweise bei Temperaturen im Bereich von -78°C bis zum Siedepunkt der Reaktionsmischung, bevorzugt von -300C bis 65°C, insbesondere bevorzugt bei Temperaturen von 300C bis 65°C. In der Regel wird die Umsetzung in einem inerten organischen Lösungsmittel in Gegenwart einer Base durchgeführt.These reactions are usually carried out at temperatures ranging from -78 ° C to the boiling point of the reaction mixture, preferably from -30 0 C to 65 ° C, particularly preferably at temperatures of 30 0 C to 65 ° C. In general, the reaction is carried out in an inert organic solvent in the presence of a base.
Geeignete Lösungsmittel sind die bei der Cyclisierung des Dipeptids IV zum Piperazin V genannten Verbindungen. In einer Ausführungsform des erfindungsgemäßen Verfah- rens wird Tetrahydrofuran mit einer katalytischen Menge Wasser verwendet; in einer anderen Ausführungsform wird nur Tetrahydrofuran eingesetzt.Suitable solvents are the compounds mentioned in the cyclization of the dipeptide IV to the piperazine V. In one embodiment of the method according to the invention rens, tetrahydrofuran is used with a catalytic amount of water; In another embodiment, only tetrahydrofuran is used.
Geeignete Basen sind die die bei der Cyclisierung des Dipeptids IV zum Piperazin V genannten Verbindungen.Suitable bases are the compounds mentioned in the cyclization of the dipeptide IV to the piperazine V.
Die Basen werden im Allgemeinen äquimolar eingesetzt. Sie können auch im Über- schuss oder selbst als Lösungsmittel verwendet werden.The bases are generally used equimolar. They can also be used in excess or even as a solvent.
In einer bevorzugten Ausführungsform des erfindungsgemäßen Verfahrens wird die Base in äquimolarer Menge zugesetzt. In einer weiteren bevorzugten Ausführungsform werden Triethylamin oder Cäsiumcarbonat als Base verwendet, besonders bevorzugt Cäsiumcarbonat.In a preferred embodiment of the process according to the invention, the base is added in equimolar amount. In a further preferred embodiment, triethylamine or cesium carbonate are used as the base, particularly preferably cesium carbonate.
Als Katalysatoren für das erfindungsgemäße Verfahren sind prinzipiell Verbindungen der Übergangsmetalle Ni, Fe, Pd, Pt, Zr oder Cu geeignet. Es ist möglich, organische oder anorganische Verbindungen einzusetzen. Beispielhaft seien genannt: Pd(PPh3^CI2, Pd(OAc)2, PdCI2, oder Na2PdCI4. Ph steht hierbei für Phenyl; Ac für Ace- tyl.In principle, compounds of the transition metals Ni, Fe, Pd, Pt, Zr or Cu are suitable as catalysts for the process according to the invention. It is possible to use organic or inorganic compounds. By way of example, mention may be made of: Pd (PPh 3) Cl 2 , Pd (OAc) 2 , PdCl 2 or Na 2 PdCl 4. Ph stands for phenyl; Ac for acetyl.
Die verschiedenen Katalysatoren können sowohl einzeln als auch als Gemische eingesetzt werden. In einer bevorzugten Ausführungsform der Erfindung wird Pd(PPhi3)2CI2 verwendet.The various catalysts can be used both individually and as mixtures. In a preferred embodiment of the invention, Pd (PPhi3) 2 Cl 2 is used.
Zur Herstellung der Verbindung I, worin R1 für CN steht, kann man die Verbindung Ia, worin L für Chlor, Brom oder lod steht, auch mit Kupfercyanid in Analogie zu bekannten Verfahren umsetzen (siehe beispielsweise Organikum, 21. Auflage, 2001 , Wiley, S. 404, Tetrahedron Lett. 42, 2001 , S.7473 oder Org. Lett. 5, 2003, 1785 und dort zitierte Literatur).For the preparation of the compound I in which R 1 is CN, the compound Ia in which L is chlorine, bromine or iodine can also be reacted with copper cyanide in analogy to known processes (see, for example, Organikum, 21st Edition, 2001, Wiley 404, Tetrahedron Lett. 42, 2001, p.7473 or Org. Lett. 5, 2003, 1785 and literature cited therein).
Diese Umsetzungen erfolgt üblicherweise bei Temperaturen im Bereich von 1000C bis zum Siedepunkt der Reaktionsmischung, bevorzugt von 1000C bis 250°C. In der Regel wird die Umsetzung in einem inerten organischen Lösungsmittel durchgeführt. Geeignete Lösungsmittel sind insbesondere aprotisch polare Lösungsmittel, z.B. Dimethyl- formamid, N-Methylpyrrolidon, N,N'-Dimethylimidazolidin-2-on und Dimethylacetamid..These reactions are usually carried out at temperatures in the range of 100 0 C to the boiling point of the reaction mixture, preferably from 100 0 C to 250 ° C. In general, the reaction is carried out in an inert organic solvent. Suitable solvents are in particular aprotic polar solvents, for example dimethylformamide, N-methylpyrrolidone, N, N'-dimethylimidazolidin-2-one and dimethylacetamide.
Die Umwandlung der Gruppe R1 kann alternativ auch bei den Vorstufen der Verbindung I erfolgen. So können z.B. Verbindungen Il in denen R1 für ein Halogenatom wie Chlor, Brom oder lod steht, der zuvor beschriebenen Umsetzung unterworfen werden. Die Alkylierung bzw. Acylierung der Gruppe NR4a, NR5a, worin R4a bzw. R5a für H steht, kann alternativ auch in den Vorstufen erfolgen. So können z.B. Verbindungen II, IV, V, VI, VIII, in denen R5a bzw. R5b für H steht, wie zuvor beschrieben N-alkyliert oder N- acyliert werden. In gleicher Weise können Vorstufen II, IV, V, VI, VII, in denen der mit R4 bzw. R4a bezeichnete Rest für Wasserstoff steht, alkyliert werden.The conversion of the group R 1 can alternatively also take place in the precursors of the compound I. Thus, for example, compounds II in which R 1 is a halogen atom such as chlorine, bromine or iodine, be subjected to the reaction described above. The alkylation or acylation of the group NR 4a , NR 5a , wherein R 4a and R 5a is H, can alternatively be carried out in the precursors. Thus, for example, compounds II, IV, V, VI, VIII in which R 5a or R 5b is H can be N-alkylated or N-acylated as described above. In the same way, precursors II, IV, V, VI, VII, in which the radical denoted by R 4 or R 4a is hydrogen, can be alkylated.
Die Verbindungen I und deren landwirtschaftlich brauchbaren Salze eignen sich - sowohl als Isomerengemische als auch in Form der reinen Isomeren - als Herbizide. Sie eignen sich als solche oder als entsprechend formuliertes Mittel. Die herbiziden Mittel, die die Verbindung I oder Ia enthalten, bekämpfen Pflanzenwuchs auf Nichtkulturflächen sehr gut, besonders bei hohen Aufwandmengen. In Kulturen wie Weizen, Reis, Mais, Soja und Baumwolle wirken sie gegen Unkräuter und Schadgräser, ohne die Kulturpflanzen nennenswert zu schädigen. Dieser Effekt tritt vor allem bei niedrigen Aufwandmengen auf.The compounds I and their agriculturally useful salts are suitable - both as mixtures of isomers and in the form of pure isomers - as herbicides. They are suitable as such or as appropriately formulated agent. The herbicidal compositions containing compound I or Ia control plant growth on nonculture areas very well, especially at high application rates. In crops such as wheat, rice, corn, soybeans and cotton, they act against weeds and grass weeds without significantly damaging the crops. This effect occurs especially at low application rates.
In Abhängigkeit von der jeweiligen Applikationsmethode können die Verbindungen I oder Ia bzw. sie enthaltende Mittel noch in einer weiteren Zahl von Kulturpflanzen zur Beseitigung unerwünschter Pflanzen eingesetzt werden. In Betracht kommen beispielsweise folgende Kulturen:Depending on the particular application method, the compounds I or Ia or agents containing them can be used in a further number of crop plants for the removal of undesirable plants. For example, the following cultures may be considered:
Allium cepa, Ananas comosus, Arachis hypogaea, Asparagus officinalis, Avena sativa, Beta vulgaris spec. altissima, Beta vulgaris spec. rapa, Brassica napus var. napus, Brassica napus var. napobrassica, Brassica rapa var. silvestris, Brassica oleracea, Brassica nigra, Camellia sinensis, Carthamus tinctorius, Carya illinoinensis, Citrus Ii- mon, Citrus sinensis, Coffea arabica (Coffea canephora, Coffea liberica), Cucumis sa- tivus, Cynodon dactylon, Daucus carota, Elaeis guineensis, Fragaria vesca, Glycine max, Gossypium hirsutum, (Gossypium arboreum, Gossypium herbaceum, Gossypium vitifolium), Helianthus annuus, Hevea brasiliensis, Hordeum vulgäre, Humulus lupulus, Ipomoea batatas, Juglans regia, Lens culinaris, Linum usitatissimum, Lycopersicon lycopersicum, Malus spec, Manihot esculenta, Medicago sativa, Musa spec, Nicotiana tabacum (N.rustica), Olea europaea, Oryza sativa, Phaseolus lunatus, Phaseolus vulgaris, Picea abies, Pinus spec, Pistacia vera, Pisum sativum, Prunus avium, Prunus persica, Pyrus communis, Prunus armeniaca, Prunus cerasus, Prunus dulcis und prunus domestica, Ribes sylvestre, Ricinus communis, Saccharum officinarum, Seeale cereale, Sinapis alba, Solanum tuberosum, Sorghum bicolor (s. vulgäre), Theobroma cacao, Trifolium pratense, Triticum aestivum, Triticale, Triticum durum, Vicia faba, Vitis vinifera, Zea mays.Allium cepa, pineapple comosus, Arachis hypogaea, Asparagus officinalis, Avena sativa, Beta vulgaris spec. altissima, Beta vulgaris spec. rapeseed, Brassica napus var. napus, Brassica napus var. napobrassica, Brassica rapa var. silvestris, Brassica oleracea, Brassica nigra, Camellia sinensis, Carthamus tinctorius, Carya illinoinensis, Citrus monon, Citrus sinensis, Coffea arabica (Coffea canephora, Coffea Liberica), Cucumis sativus, Cynodon dactylon, Daucus carota, Elaeis guineensis, Fragaria vesca, Glycine max, Gossypium hirsutum, (Gossypium arboreum, Gossypium herbaceum, Gossypium vitifolium), Helianthus annuus, Hevea brasiliensis, Hordeum vulgare, Humulus lupulus, Ipomoea batatas, Juglans regia, Lens culinaris, Linum usitatissimum, Lycopersicon lycopersicum, Malus spec., Manihot esculenta, Medicago sativa, Musa spec., Nicotiana tabacum (N.rustica), Olea europaea, Oryza sativa, Phaseolus lunatus, Phaseolus vulgaris, Picea abies, Pinus Priscus vera, Pisum sativum, Prunus avium, Prunus persica, Pyrus communis, Prunus armeniaca, Prunus cerasus, Prunus dulcis and Prunus domestica, Ribes sylvestre, Ricinus communis, p accharum officinarum, Seeale cereale, Sinapis alba, Solanum tuberosum, Sorghum bicolor (s. vulgaris), Theobroma cacao, Trifolium pratense, Triticum aestivum, Triticale, Triticum durum, Vicia faba, Vitis vinifera, Zea mays.
Vorzugsweise kommen die folgenden Kulturen in Betracht: Arachis hypogaea, Beta vulgaris spec. altissima, Brassica napus var. napus, Brassica oleracea, Citrus limon, Citrus sinensis, Coffea arabica (Coffea canephora, Coffea liberica), Cynodon dactylon, Glycine max, Gossypium hirsutum, (Gossypium arboreum, Gossypium herbaceum, Gossypium vitifolium), Helianthus annuus, Hordeum vulgäre, Juglans regia, Lens culi- naris, Linum usitatissimum, Lycopersicon lycopersicum, Malus spec, Medicago sativa, Nicotiana tabacum (N.rustica), Olea europaea, Oryza sativa , Phaseolus lunatus, Pha- seolus vulgaris, Pistacia vera, Pisum sativum, Prunus dulcis, Saccharum officinarum, Seeale cereale, Solarium tuberosum, Sorghum bicolor (s. vulgäre), Triticale, Triticum aestivum, Triticum durum, Vicia faba, Vitis vinifera und Zea mays.Preferably, the following cultures are contemplated: Arachis hypogaea, Beta vulgaris spec. altissima, Brassica napus var. napus, Brassica oleracea, Citrus limon, Citrus sinensis, Coffea arabica (Coffea canephora, Coffea liberica), Cynodon dactylon, Glycine max, Gossypium hirsutum, (Gossypium arboreum, Gossypium herbaceum, Gossypium vitifolium), Helianthus annuus, Hordeum vulgaris, Juglans regia, Lens culinaris, Linum usitatissimum, Lycopersicon lycopersicum, Malus spec., Medicago sativa, Nicotiana tabacum (N.rustica), Olea europaea, Oryza sativa, Phaseolus lunatus, Phasolus Vulgaris, Pistacia vera, Pisum sativum, Prunus dulcis, Saccharum officinarum, Seeale cereale, Solarium tuberosum, Sorghum bicolor (see vulgaris), Triticale, Triticum aestivum, Triticum durum, Vicia faba, Vitis vinifera and Zea mays.
Darüber hinaus können die Verbindungen I auch in Kulturen, die durch Züchtung einschließlich gentechnischer Methoden gegen die Wirkung von Herbiziden tolerant sind, verwandt werden.In addition, the compounds I can also be used in cultures that are tolerant to herbicides by breeding including genetic engineering methods.
Darüber hinaus können die Verbindungen I auch in Kulturen, die durch Züchtung einschließlich gentechnischer Methoden gegen Insekten oder Pilzbefall tolerant sind, verwendet werden.In addition, the compounds I can also be used in cultures which are tolerant by breeding, including genetic engineering against insects or fungal attack.
Des Weiteren wurde gefunden, dass die Verbindungen der Formel I auch zur Defoliati- on und/oder Desikkation von Pflanzenteilen geeignet ist, wofür Kulturpflanzen wie Baumwolle, Kartoffel, Raps, Sonnenblume, Sojabohne oder Ackerbohnen, insbesondere Baumwolle, in Betracht kommen. Diesbezüglich wurden Mittel zur Desikkation und /oder Defoliation von Pflanzen, Verfahren zur Herstellung dieser Mittel und Verfahren zur Desikkation und/oder Defoliation von Pflanzen mit der Verbindungen der Formel I gefunden.Furthermore, it has been found that the compounds of the formula I are also suitable for the defoliation and / or desiccation of plant parts, for which crop plants such as cotton, potato, oilseed rape, sunflower, soybean or field beans, in particular cotton, come into consideration. In this regard, compositions for the desiccation and / or defoliation of plants, processes for the preparation of these agents and methods for the desiccation and / or defoliation of plants with the compounds of formula I have been found.
Als Desikkantien eignet sich die Verbindungen der Formel I insbesondere zur Aus- trocknung der oberirdischen Teile von Kulturpflanzen wie Kartoffel, Raps, Sonnenblume und Sojabohne aber auch Getreide. Damit wird ein vollständig mechanisches Be- ernten dieser wichtigen Kulturpflanzen ermöglicht.As desiccants, the compounds of the formula I are particularly suitable for drying out the aerial parts of crop plants such as potato, rape, sunflower and soybean, but also cereals. This enables a completely mechanical harvesting of these important crops.
Von wirtschaftlichem Interesse ist ferner die Ernteerleichterung, die durch das zeitlich konzentrierte Abfallen oder Vermindern der Haftfestigkeit am Baum bei Zitrusfrüchten, Oliven oder bei anderen Arten und Sorten von Kern-, Stein- und Schalenobst ermöglicht wird. Derselbe Mechanismus, d.h., die Förderung der Ausbildung von Trenngewebe zwischen Frucht- oder Blatt- und Sprossteil der Pflanzen ist auch für ein gut kontrollierbares Entblättern von Nutzpflanzen, insbesondere Baumwolle, wesentlich.Of economic interest is also the harvest relief, which is made possible by the time-concentrated dropping or reducing the adhesion to the tree in citrus fruits, olives or other types and varieties of pome, stone and peel fruit. The same mechanism, i.e., promotion of the formation of release tissue between the fruit or leaf and shoot part of the plants, is also essential for a well controllable defoliation of crops, especially cotton.
Außerdem führt die Verkürzung des Zeitintervalls, in dem die einzelnen Baumwollpflanzen reif werden, zu einer erhöhten Qualität der Faser nach der Ernte.In addition, shortening the time interval in which the individual cotton plants ripen results in increased fiber quality after harvest.
Die Verbindungen I bzw. die sie enthaltenden herbiziden Mittel können beispielsweise in Form von direkt versprühbaren wässrigen Lösungen, Pulvern, Suspensionen, auch hochprozentigen wässrigen, öligen oder sonstigen Suspensionen oder Dispersionen, Emulsionen, Öldispersionen, Pasten, Stäubemitteln, Streumitteln oder Granulaten durch Versprühen, Vernebeln, Verstäuben, Verstreuen, Gießen oder Behandlung des Saatgutes bzw. Mischen mit dem Saatgut angewendet werden. Die Anwendungsformen richten sich nach den Verwendungszwecken; sie sollten in jedem Fall möglichst die feinste Verteilung der erfindungsgemäßen Wirkstoffe gewährleisten.The compounds I or the herbicidal compositions containing them can be used, for example, in the form of directly sprayable aqueous solutions, powders, suspensions, and also high-percentage aqueous, oily or other suspensions or dispersions, Emulsions, oil dispersions, pastes, dusts, scattering agents or granules by spraying, atomizing, dusting, scattering, pouring or treatment of the seed or mixing with the seed can be applied. The forms of application depend on the intended use; In any case, they should ensure the finest possible distribution of the active compounds according to the invention.
Die herbiziden Mittel enthalten eine herbizid wirksame Menge mindestens einer Verbindung der Formel I oder eines landwirtschaftlich brauchbaren Salzes von I und für die Formulierung von Pflanzenschutzmitteln übliche Hilfsstoffe.The herbicidal compositions contain a herbicidally effective amount of at least one compound of the formula I or an agriculturally useful salt of I and auxiliaries customary for the formulation of pesticides.
Beispiele für die Formulierung von Pflanzenschutzmitteln übliche Hilfsmittel sind inerte Hilfsstoffe, feste Trägerstoffe, oberflächenaktive Stoffe (wie Dispergiermittel Schutzkolloide, Emulgatoren, Netzmittel und Haftmittel), organische und anorganische Verdicker, Bakterizide, Frostschutzmittel, Entschäumer ggf. Farbstoffe und für Saatgutformulie- rungen Kleber.Examples of the Formulation of Plant Protection Agents Usual auxiliaries are inert auxiliaries, solid carriers, surface-active substances (such as dispersants, protective colloids, emulsifiers, wetting agents and adhesives), organic and inorganic thickeners, bactericides, antifreeze agents, defoamers, if appropriate, dyes and for seed formulations adhesives.
Beispiele für Verdicker (d.h. Verbindungen, die der Formulierung ein modifiziertes Fließverhalten verleihen, d.h. hohe Viskosität im Ruhezustand und niedrige Viskosität im bewegten Zustand) sind Polysaccharide wie Xanthan Gum (Kelzan® der Fa. Kelco), Rhodopol® 23 (Rhone Poulenc) oder Veegum® (Firma RT. Vanderbilt) sowie organische und anorganische Schichtmineralien wie Attaclay® (Firma Engelhardt).Examples of thickeners (ie, compounds which impart modified flowability to the formulation, ie, high-level at low viscosity and low viscosity in the agitated state) are polysaccharides such as xanthan gum (Kelzan® from Kelco), Rhodopol® 23 (Rhone Poulenc) or Veegum ® (company RT Vanderbilt) and organic and inorganic layer minerals such as Attaclay® (Engelhardt).
Beispiele für Antischaummittel sind Silikonemulsionen (wie z. Bsp. Silikon® SRE, Firma Wacker oder Rhodorsil® der Firma Rhodia ), langkettige Alkohole, Fettsäuren, Salze von Fettsäuren, fluororganische Verbindungen und deren Gemische.Examples of antifoam agents are silicone emulsions (such as, for example, Silikon® SRE, Wacker or Rhodorsil® from Rhodia), long-chain alcohols, fatty acids, salts of fatty acids, organofluorine compounds and mixtures thereof.
Bakterizide können zur Stabilisierung der wäßrigen Herbizid-Formulierung zugesetzt werden. Beispiele für Bakterizide sind Bakterizide basierend auf Diclorophen und Ben- zylalkoholhemiformal (Proxel® der Fa. ICI oder Acticide® RS der Fa. Thor Chemie und Kathon® MK der Firma Rohm & Haas) sowie Isothiazolinonderivaten wie Alkylisothia- zolinonen und Benzisothiazolinonen (Acticide MBS der Fa. Thor Chemie)Bactericides may be added to stabilize the aqueous herbicidal formulation. Examples of bactericides are bactericides based on diclorophene and benzyl alcohol hemiformal (Proxel® from ICI or Acticide® RS from Thor Chemie and Kathon® MK from Rohm & Haas) as well as isothiazolinone derivatives such as alkylisothiazolinones and benzisothiazolinones (Acticide MBS der Fa. Thor Chemie)
Beispiele für Frostschutzmittel sind Ethylenglycol, Propylenglycol, Harnstoff oder GIy- cerin.Examples of antifreeze agents are ethylene glycol, propylene glycol, urea or glycerol.
Beispiele für Farbmittel sind sowohl in Wasser wenig lösliche Pigmente als auch in Wasser lösliche Farbstoffe. Als Beispiele genannt seien die unter den Bezeichnungen Rhodamin B, Cl. Pigment Red 1 12 und Cl. Solvent Red 1 bekannten Farbstoffe, sowie pigment blue 15:4, pigment blue 15:3, pigment blue 15:2, pigment blue 15:1 , pigment blue 80, pigment yellow 1 , pigment yellow 13, pigment red 1 12, pigment red 48:2, pigment red 48:1 , pigment red 57:1 , pigment red 53:1 , pigment orange 43, pigment orange 34, pigment orange 5, pigment green 36, pigment green 7, pigment white 6, pigment brown 25, basic violet 10, basic violet 49, acid red 51 , acid red 52, acid red 14, acid blue 9, acid yellow 23, basic red 10, basic red 108.Examples of colorants are both water-insoluble pigments and water-soluble dyes. Examples which may be mentioned under the names rhodamine B, Cl. Pigment Red 1 12 and Cl. Solvent Red 1 known dyes, as well as pigment blue 15: 4, pigment blue 15: 3, pigment blue 15: 2, pigment blue 15: 1, pigment blue 80, pigment yellow 1, pigment yellow 13, pigment red 1 12, pigment red 48: 2, pigment red 48: 1, pigment red 57: 1, pigment red 53: 1, pigment orange 43, pigment orange 34, pigment orange 5, pigment green 36, pigment green 7, pigment white 6, pigment brown 25, basic violet 10, basic violet 49, acid red 51, acid red 52, acid red 14, acid blue 9, acid yellow 23, basic red 10, basic red 108.
Beispiele für Kleber sind Polyvinylpyrrolidon, Polyvinylacetat, Polyvinylalkohol und Ty- lose.Examples of adhesives are polyvinylpyrrolidone, polyvinyl acetate, polyvinyl alcohol and Tylose.
Als inerte Zusatzstoffe kommen beispielsweise in Betracht:Suitable inert additives are, for example:
Mineralölfraktionen von mittlerem bis hohem Siedepunkt, wie Kerosin oder Dieselöl, ferner Kohlenteeröle sowie Öle pflanzlichen oder tierischen Ursprungs, aliphatische, cyclische und aromatische Kohlenwasserstoffe, z.B. Paraffin, Tetrahydronaphthalin, alkylierte Naphthaline oder deren Derivate, alkylierte Benzole oder deren Derivate, Alkohole wie Methanol, Ethanol, Propanol, Butanol, Cyclohexanol, Ketone wie Cyclo- hexanon oder stark polare Lösungsmittel, z. B. Amine wie N-Methylpyrrolidon oder Wasser.Mineral oil fractions of medium to high boiling point, such as kerosene or diesel oil, coal tar oils and oils of vegetable or animal origin, aliphatic, cyclic and aromatic hydrocarbons, e.g. Paraffin, tetrahydronaphthalene, alkylated naphthalenes or their derivatives, alkylated benzenes or their derivatives, alcohols such as methanol, ethanol, propanol, butanol, cyclohexanol, ketones such as cyclohexanone or strongly polar solvents, eg. As amines such as N-methylpyrrolidone or water.
Feste Trägerstoffe sind Mineralerden wie Kieselsäuren, Kieselgele, Silikate, Talkum, Kaolin, Kalkstein, Kalk, Kreide, Bolus, Löß, Ton, Dolomit, Diatomeenerde, Calcium- und Magnesiumsulfat, Magnesiumoxid, gemahlene Kunststoffe, Düngemittel, wie Am- moniumsulfat, Ammoniumphosphat, Ammoniumnitrat, Harnstoffe und pflanzliche Produkte wie Getreidemehl, Baumrinden-, Holz- und Nußschalenmehl, Cellulosepulver oder andere feste Trägerstoffe.Solid carriers are mineral earths such as silicic acids, 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.
Als oberflächenaktive Stoffe (Adjuvantien, Netz-, Haft-, Dispergier- sowie Emulgiermit- tel) kommen die Alkali-, Erdalkali-, Ammoniumsalze von aromatischen Sulfonsäuren, z.B. Ligninsulfonsäuren (z.B. Borrespers-Typen, Borregaard), Phenolsulfonsäuren, Naphthalinsulfonsäuren (Morwet-Typen, Akzo Nobel) und Dibutylnaphthalinsulfonsäure (Nekal-Typen, BASF AG), sowie von Fettsäuren, Alkyl- und Alkylarylsulfonaten, Alkyl-, Laurylether- und Fettalkoholsulfaten, sowie Salze sulfatierter Hexa-, Hepta- und Octa- decanolen sowie von Fettalkoholglykolether, Kondensationsprodukte von sulfoniertem Naphthalin und seiner Derivate mit Formaldehyd, Kondensationsprodukte des Naphthalins bzw. der Naphthalinsulfonsäuren mit Phenol und Formaldehyd, Polyoxyethyle- noctylphenolether, ethoxyliertes Isooctyl-, Octyl- oder Nonylphenol, Alkylphenyl-, Tribu- tylphenylpolyglykolether, Alkylarylpolyetheralkohole, Isotridecylalkohol, Fettalkoholethy- lenoxid-Kondensate, ethoxyliertes Rizinusöl, Polyoxyethylenalkylether oder Polyo- xypropylenalkylether, Laurylalkoholpolyglykoletheracetat, Sorbitester, Lignin- Sulfitablaugen sowie Proteine, denaturierte Proteine, Polysaccharide (z.B. Methylcellu- lose), hydrophob modifizierte Stärken, Polyvinylalkohol (Mowiol typen Clariant), PoIy- carboxylate (BASF AG, Sokalan-Typen), Polyalkoxylate, Polyvinylamin (BASF AG, Lupamin-Typen), Polyethylenimin (BASF AG, Lupasol-Typen) , Polyvinylpyrrolidon und deren Copolymere in Betracht. Pulver-, Streu- und Stäubemittel können durch Mischen oder gemeinsames Vermählen der wirksamen Substanzen mit einem festen Trägerstoff hergestellt werden.Suitable surface-active substances (adjuvants, wetting agents, adhesives, dispersants and emulsifiers) are the alkali metal, alkaline earth metal, ammonium salts of aromatic sulfonic acids, eg lignosulfonic acids (eg Borrespers types, Borregaard), phenolsulfonic acids, naphthalenesulfonic acids (Morwet types , Akzo Nobel) and dibutylnaphthalenesulfonic acid (Nekal types, BASF AG), as well as fatty acids, alkyl and alkylarylsulfonates, alkyl, lauryl ether and fatty alcohol sulfates, as well as salts of sulfated hexa-, hepta- and octadecanols and of fatty alcohol glycol ethers, condensation products of sulfonated naphthalene and its derivatives with formaldehyde, condensation products of naphthalene or naphthalenesulfonic acids with phenol and formaldehyde, polyoxyethyl tocylphenol ethers, ethoxylated isooctyl, octyl or nonylphenol, alkylphenyl, tributylphenyl polyglycol ethers, alkylaryl polyether alcohols, isotridecyl alcohol, fatty alcohol-ethylene oxide condensates, ethoxylated castor oil, polyoxyethylene alkyl lether or polyoxypropylene alkyl ethers, lauryl alcohol polyglycol ether acetate, sorbitol esters, lignin liquors and proteins, denatured proteins, polysaccharides (eg methyl cellulose), hydrophobically modified starches, polyvinyl alcohol (Mowiol types Clariant), polycarboxylates (BASF AG, Sokalan types), Polyalkoxylates, polyvinylamine (BASF AG, Lupamin types), polyethyleneimine (BASF AG, Lupasol types), polyvinylpyrrolidone and copolymers thereof. Powders, dispersants and dusts may be prepared by mixing or co-grinding the active substances with a solid carrier.
Granulate, z.B. Umhüllungs-, Imprägnierungs- und Homogengranulate können durch Bindung der Wirkstoffe an feste Trägerstoffe hergestellt werden.Granules, e.g. Coating, impregnation and homogeneous granules can be prepared by binding the active compounds to solid carriers.
Wässrige Anwendungsformen können aus Emulsionskonzentraten, Suspensionen, Pasten, netzbaren Pulvern oder wasserdispergierbaren Granulaten durch Zusatz von Wasser bereitet werden. Zur Herstellung von Emulsionen, Pasten oder Öldispersionen können die Verbindungen der Formel I oder Ia als solche oder in einem Öl oder Lösungsmittel gelöst, mittels Netz-, Haft-, Dispergier- oder Emulgiermittel in Wasser homogenisiert werden. Es können aber auch aus wirksamer Substanz, Netz-, Haft-, Dispergier- oder Emulgiermittel und eventuell Lösungsmittel oder Öl bestehende Konzentrate hergestellt werden, die zur Verdünnung mit Wasser geeignet sind.Aqueous application forms can be prepared from emulsion concentrates, suspensions, pastes, wettable powders or water-dispersible granules by adding water. To prepare emulsions, pastes or oil dispersions, the compounds of the formula I or Ia, as such or dissolved in an oil or solvent, can be homogenized in water by means of wetting agents, tackifiers, dispersants or emulsifiers. However, it is also possible to prepare concentrates consisting of active substance, wetting, adhesion, dispersing or emulsifying agent and possibly solvent or oil, which are suitable for dilution with water.
Die Konzentrationen der Verbindungen der Formel I in den anwendungsfertigen Zubereitungen können in weiten Bereichen variiert werden. Die Formulierungen enthalten im Allgemeinen 0,001 bis 98 Gew.-%, vorzugsweise 0,01 bis 95 Gew.-%, mindestens eines Wirkstoffs. Die Wirkstoffe werden dabei in einer Reinheit von 90% bis 100%, vor- zugsweise 95% bis 100% (nach NMR-Spektrum) eingesetzt.The concentrations of the compounds of the formula I in the ready-to-use formulations can be varied within wide limits. The formulations generally contain from 0.001 to 98% by weight, preferably from 0.01 to 95% by weight, of at least one active ingredient. The active compounds are used in a purity of 90% to 100%, preferably 95% to 100% (according to NMR spectrum).
Die erfindungsgemäßen Verbindungen I können beispielsweise wie folgt formuliert werden:The compounds I according to the invention can be formulated, for example, as follows:
1. Produkte zur Verdünnung in Wasser1. Products for dilution in water
A Wasserlösliche KonzentrateA Water-soluble concentrates
10 Gew.-Teile Wirkstoff werden mit 90 Gew.-Teilen Wasser oder einem wasserlöslichen Lösungsmittel gelöst. Alternativ werden Netzmittel oder andere Hilfsmittel zuge- fügt. Bei der Verdünnung in Wasser löst sich der Wirkstoff. Man erhält auf diese Weise eine Formulierung mit 10 Gew.-% Wirkstoffgehalt.10 parts by weight of active compound are dissolved with 90 parts by weight of water or a water-soluble solvent. Alternatively, wetting agents or other auxiliaries are added. When diluted in water, the active ingredient dissolves. This gives a formulation with 10 wt .-% active ingredient content.
B Dispergierbare KonzentrateB Dispersible concentrates
20 Gew.-Teile Wirkstoff werden in 70 Gew.-Teilen Cyclohexanon unter Zusatz von 10 Gew.-Teilen eines Dispergiermittels z.B. Polyvinylpyrrolidon gelöst. Bei Verdünnung in Wasser ergibt sich eine Dispersion. Der Wirkstoffgehalt beträgt 20 Gew.-%20 parts by weight of active compound are dissolved in 70 parts by weight of cyclohexanone with the addition of 10 parts by weight of a dispersant, e.g. Polyvinylpyrrolidone dissolved. Dilution in water gives a dispersion. The active ingredient content is 20% by weight
C Emulgierbare KonzentrateC Emulsifiable concentrates
15 Gew.-Teile Wirkstoff werden in 75 Gew.-Teilen eines organisches Lösungsmittel (z.B. Alkylaromaten)-unter Zusatz von Ca-Dodecylbenzolsulfonat und Ricinusölethoxy- lat (jeweils 5 Gew.-Teile) gelöst. Bei der Verdünnung in Wasser ergibt sich eine Emulsion. Die Formulierung hat 15 Gew.-% Wirkstoffgehalt. D Emulsionen15 parts by weight of active compound are dissolved in 75 parts by weight of an organic solvent (for example alkylaromatics) with the addition of calcium dodecylbenzenesulfonate and castor oil ethoxylate (in each case 5 parts by weight). Dilution in water results in an emulsion. The formulation has 15% by weight active ingredient content. D emulsions
25 Gew.-Teile Wirkstoff werden in 35 Gew.-Teilen eines organisches Lösungsmittel (z.B. Alkylaromaten) unter Zusatz von Ca-Dodecylbenzolsulfonat und Ricinusölethoxy- lat (jeweils 5 Gew.-Teile) gelöst. Diese Mischung wird mittels einer Emulgiermaschine (z.B. Ultraturax) in 30 Gew.Teile Wasser gegeben und zu einer homogenen Emulsion gebracht. Bei der Verdünnung in Wasser ergibt sich eine Emulsion. Die Formulierung hat einen Wirkstoffgehalt von 25 Gew.-%.25 parts by weight of active compound are dissolved in 35 parts by weight of an organic solvent (for example alkylaromatics) with addition of calcium dodecylbenzenesulfonate and castor oil ethoxylate (in each case 5 parts by weight). This mixture is added to water by means of an emulsifying machine (e.g., Ultraturax) in 30 parts by weight and made into a homogeneous emulsion. Dilution in water results in an emulsion. The formulation has an active ingredient content of 25% by weight.
E SuspensionenE suspensions
20 Gew.-Teile Wirkstoff werden unter Zusatz von 10 Gew.-Teilen Dispergier- und Netzmitteln und 70 Gew.-Teilen Wasser oder einem organischen Lösungsmittel in einer Rührwerkskugelmühle zu einer feinen Wirkstoffsuspension zerkleinert. Bei der Verdünnung in Wasser ergibt sich eine stabile Suspension des Wirkstoffs. Der Wirk- stoffgehalt in der Formulierung beträgt 20 Gew.-%.20 parts by weight of active compound are comminuted with the addition of 10 parts by weight dispersing and wetting agents and 70 parts by weight of water or an organic solvent in a stirred ball mill to a fine active substance suspension. Dilution in water results in a stable suspension of the active ingredient. The active ingredient content in the formulation is 20% by weight.
F Wasserdispergierbare und wasserlösliche Granulate 50 Gew.-Teile Wirkstoff werden unter Zusatz von 50 Gew-Teilen Dispergier- und Netzmitteln fein gemahlen und mittels technischer Geräte (z.B. Extrusion, Sprühturm, Wirbelschicht) als wasserdispergierbare oder wasserlösliche Granulate hergestellt. Bei der Verdünnung in Wasser ergibt sich eine stabile Dispersion oder Lösung des Wirkstoffs. Die Formulierung hat einen Wirkstoffgehalt von 50 Gew.-%.F Water-dispersible and water-soluble granules 50 parts by weight of active compound are finely ground with the addition of 50 parts by weight of dispersing and wetting agents and prepared by means of industrial equipment (for example extrusion, spray tower, fluidized bed) as water-dispersible or water-soluble granules. Dilution in water results in a stable dispersion or solution of the active ingredient. The formulation has an active ingredient content of 50% by weight.
G Wasserdispergierbare und wasserlösliche Pulver 75 Gew.-Teile Wirkstoff werden unter Zusatz von 25 Gew.-Teilen Dispergier- undG Water-dispersible and water-soluble powders 75 parts by weight of active compound are dispersed with the addition of 25 parts by weight of dispersing and
Netzmitteln sowie Kieselsäuregel in einer Rotor-Strator Mühle vermählen. Bei der Verdünnung in Wasser ergibt sich eine stabile Dispersion oder Lösung des Wirkstoffs. Der Wirkstoffgehalt der Formulierung beträgt 75 Gew.-%.Wetting agents and silica gel in a rotor-Strator mill. Dilution in water results in a stable dispersion or solution of the active ingredient. The active ingredient content of the formulation is 75% by weight.
H GelformulierungenH gel formulations
In einer Kugelmühle werden 20 Gew.-Teile Wirkstoff, 10 Gew.-Teile Dispergiermittel, 1 Gew.-Teil Geliermittel und 70 Gew.-Teile Wasser oder eines organischen Lösungsmittels zu einer feinen Suspension vermählen. Bei der Verdünnung mit Wasser ergibt sich eine stabile Suspension mit 20 Gew.-% Wirkstoffgehalt.In a ball mill, 20 parts by weight of the active ingredient, 10 parts by weight of the dispersant, 1 part by weight of the gelling agent and 70 parts by weight of water or an organic solvent are ground to a fine suspension. Dilution with water results in a stable suspension with 20% by weight active ingredient content.
2. Produkte für die Direktapplikation2. Products for direct application
I StäubeI dusts
5 Gew.-Teile Wirkstoff werden fein gemahlen und mit 95 Gew.-Teilen feinteiligem Kao- Nn innig vermischt. Man erhält dadurch ein Stäubemittel mit 5 Gew.-% Wirkstoffgehalt. J Granulate (GR, FG, GG, MG)5 parts by weight of active compound are finely ground and intimately mixed with 95 parts by weight of finely divided KaOnn. This gives a dust with 5 wt .-% active ingredient content. J Granules (GR, FG, GG, MG)
0,5 Gew-Teile Wirkstoff werden fein gemahlen und mit 99,5 Gewichtsteilen Trägerstoffe verbunden. Gängige Verfahren sind dabei die Extrusion, die Sprühtrocknung oder die Wirbelschicht. Man erhält dadurch ein Granulat für die Direktapplikation mit 0,5 Gew.-% Wirkstoffgehalt.0.5 parts by weight of active compound are finely ground and combined with 99.5 parts by weight of carriers. Common processes are extrusion, spray drying or fluidized bed. This gives a granulate for direct application with 0.5 wt .-% active ingredient content.
K ULV- Lösungen (UL)K ULV solutions (UL)
10 Gew.-Teile Wirkstoff werden in 90 Gew.-Teilen eines organischen Lösungsmittel z.B. XyIoI gelöst. Dadurch erhält man ein Produkt für die Direktapplikation mit 10 Gew.- % Wirkstoffgehalt.10 parts by weight of active compound are dissolved in 90 parts by weight of an organic solvent, e.g. XyIoI solved. This gives a product for direct application with 10% by weight of active ingredient content.
Die Applikation der Verbindungen I oder der sie enthaltenden herbiziden Mittel kann im Vorauflauf-, im Nachauflaufverfahren oder zusammen mit dem Saatgut einer Kulturpflanze erfolgen. Es besteht auch die Möglichkeit, die herbiziden Mittel bzw. Wirkstoffe dadurch zu applizieren, dass mit den herbiziden Mitteln bzw. Wirkstoffen vorbehandeltes Saatgut einer Kulturpflanze ausgebracht wird. Sind die Wirkstoffe für gewisse Kulturpflanzen weniger verträglich, so können Ausbringungstechniken angewandt werden, bei welchen die herbiziden Mittel mit Hilfe der Spritzgeräte so gespritzt werden, dass die Blätter der empfindlichen Kulturpflanzen nach Möglichkeit nicht getroffen werden, während die Wirkstoffe auf die Blätter darunter wachsender unerwünschter Pflanzen oder die unbedeckte Bodenfläche gelangen (post-directed, lay-by).The application of the compounds I or the herbicidal compositions containing them can be carried out in the pre-emergence, postemergence or together with the seed of a crop. It is also possible to apply the herbicidal compositions or active ingredients characterized in that with the herbicidal agents or active ingredients pretreated seed of a crop plant is applied. If the active ingredients are less compatible with certain crops, then application techniques may be used whereby the herbicidal agents are sprayed with the sprayers so as not to hit the leaves of the sensitive crop if possible, while the active ingredients affect the leaves of growing undesirable plants or the uncovered floor surface (post-directed, lay-by).
In einer weiteren Ausführungsform kann die Applikation der Verbindungen der Formel I bzw. der herbiziden Mittel durch Behandlung von Saatgut erfolgen.In a further embodiment, the application of the compounds of the formula I or of the herbicidal compositions can be carried out by treating seed.
Die Behandlung von Saatgut umfasst im Wesentlichen alle dem Fachmann geläufigen Techniken (seed dressing, seed coating, seed dusting, seed soaking, seed film coa- ting, seed multilayer coating, seed encrusting, seed dripping, und seed pelleting) basierend auf den erfindungsgemäßen Verbindungen der Formel I bzw. daraus hergestellten Mitteln. Hierbei können die herbiziden Mittel verdünnt oder unverdünnt aufgetragen werden.The treatment of seed comprises essentially all techniques familiar to the skilled worker (seed dressing, seed coating, seed dusting, seed soaking, seed film coating, seed multilayer coating, seed encrusting, seed dripping, and seed pelleting) based on the compounds according to the invention of the formula I or agents produced therefrom. Here, the herbicidal agents can be diluted or applied undiluted.
Der Begriff Saatgut umfasst Saatgut aller Arten, wie z.B. Körner, Samen, Früchte, Knollen, Stecklinge und ähnliche Formen. Bevorzugt beschreibt der Begriff Saatgut hier Körner und Samen.The term seed includes seeds of all kinds, e.g. Grains, seeds, fruits, tubers, cuttings and similar forms. The term seed preferably describes grains and seeds here.
Als Saatgut kann Saatgut der oben erwähnten Nutzpflanzen aber auch das Saatgut transgener oder durch herkömmliche Züchtungsmethoden erhaltener Pflanzen eingesetzt werden.Seeds of the abovementioned crops but also the seeds of transgenic or obtained by conventional breeding methods plants can be used as seeds.
Die Aufwandmengen an Wirkstoff betragen je nach Bekämpfungsziel, Jahreszeit, Zielpflanzen und Wachstumsstadium 0,001 bis 3,0, vorzugsweise 0,01 bis 1 ,0 kg/ha aktive Substanz (a. S.)- Zur Saatgutbehandlung werden die Verbindungen I üblicherweise in Mengen von 0,001 bis 10 kg pro 100 kg Saatgut eingesetzt.Depending on the control target, season, target plants and growth stage, the application rates of active ingredient are 0.001 to 3.0, preferably 0.01 to 1.0 kg / ha active Substance (supra) - For seed treatment, the compounds I are usually used in amounts of 0.001 to 10 kg per 100 kg of seed.
Zur Verbreiterung des Wirkungsspektrums und zur Erzielung synergistischer Effekte können die Verbindungen der Formel I mit zahlreichen Vertretern anderer herbizider oder wachstumsregulierender Wirkstoffgruppen oder mit Safenern gemischt und gemeinsam ausgebracht werden. Beispielsweise kommen als Vertreter anderer herbizider oder wachstumsregulierender Wirkstoffgruppen 1 ,2,4-Thiadiazole, 1 ,3,4- Thiadiazole, Amide, Aminophosphorsäure und deren Derivate, Aminotriazole, Anilide, Aryloxy-/Heteroaryloxyalkansäuren und deren Derivate, Benzoesäure und deren Derivate, Benzothiadiazinone, 2-(Hetaroyl/Aroyl)-1 ,3-cyclohexandione, Heteroaryl-Aryl- Ketone, Benzylisoxazolidinone, meta-CF3-Phenylderivate, Carbamate, Chinolincarbon- säure und deren Derivate, Chloracetanilide, Cyclohexenonoximetherderivate, Diazine, Dichlorpropionsäure und deren Derivate, Dihydrobenzofurane, Dihydrofuran-3-one, Dinitroaniline, Dinitrophenole, Diphenylether, Dipyridyle, Halogencarbonsäuren und deren Derivate, Harnstoffe, 3-Phenyluracile, Imidazole, Imidazolinone, N-Phenyl- 3,4,5,6-tetrahydrophthalimide, Oxadiazole, Oxirane, Phenole, Aryloxy- und Heteroary- loxyphenoxypropionsäureester, Phenylessigsäure und deren Derivate, 2- Phenylpropionsäure und deren Derivate, Pyrazole, Phenylpyrazole, Pyridazine, Pyri- dincarbonsäure und deren Derivate, Pyrimidylether, Sulfonamide, Sulfonylharnstoffe, Triazine, Triazinone, Triazolinone, Triazolcarboxamide, Uracile sowie Phenylpyrazoline und Isoxazoline und deren Derivate in Betracht.To widen the spectrum of action and to achieve synergistic effects, the compounds of formula I can be mixed with numerous representatives of other herbicidal or growth-regulating active ingredient groups or with safeners and applied together. For example, 1, 2,4-thiadiazoles, 1, 3,4-thiadiazoles, amides, aminophosphoric acid and its derivatives, aminotriazoles, anilides, aryloxy / Heteroaryloxyalkansäuren and their derivatives, benzoic acid and derivatives thereof, benzothiadiazinones as representatives of other herbicidal or growth-regulating active ingredient groups , 2- (Hetaroyl / aroyl) -1, 3-cyclohexanediones, heteroaryl-aryl ketones, benzylisoxazolidinones, meta-CF3-phenyl derivatives, carbamates, quinolinecarboxylic acid and its derivatives, chloroacetanilides, cyclohexenone oxime ether derivatives, diazines, dichloropropionic acid and its derivatives, dihydrobenzofurans , Dihydrofuran-3-ones, dinitroanilines, dinitrophenols, diphenyl ethers, dipyridyls, halocarboxylic acids and their derivatives, ureas, 3-phenyluracils, imidazoles, imidazolinones, N-phenyl-3,4,5,6-tetrahydrophthalimides, oxadiazoles, oxiranes, phenols, Aryloxy and heteroaryloxyphenoxypropionic acid esters, phenylacetic acid and its derivatives, 2-phenylpropionic acid and its derivatives, pyrazoles, P henylpyrazoles, pyridazines, pyridinecarboxylic acid and derivatives thereof, pyrimidyl ethers, sulfonamides, sulfonylureas, triazines, triazinones, triazolinones, triazolecarboxamides, uracils and also phenylpyrazolines and isoxazolines and derivatives thereof.
Es kann auch von Vorteil sein, die Verbindungen der Formel I in Kombination mit Safe- nern zu verwenden. Safener sind chemische Verbindungen, die Schaden an Nutzpflanzen verhindern oder reduzieren, ohne die herbizide Wirkung der Verbindungen der Formel I auf unerwünschte Pflanzen wesentlich zu beeinflussen. Sie können sowohl vor der Aussaat (beispielsweise bei Saatgutbehandlungen, bei Stecklingen, oder bei Setzlingen) als auch im Vor- oder Nachauflauf der Nutzpflanze verwendet werden. Die Safener und die Verbindungen der Formel I können gleichzeitig oder nacheinander verwendet werden. Geeignete Safener sind beispielsweise (Chinolin-8- oxy)essigsäuren, 1 -Phenyl-5-haloalkyl-1 H-1 ,2,4-triazol-3-carbonsäuren, 1 -Phenyl-4,5- dihydro-5-alkyl-1 H-pyrazol-3,5-dicarbonsäuren, 4,5-Dihydro-5,5-diaryl-3- isoxazolcarbonsäuren, Dichloroacetamide, alpha-Oximinophenylacetonitrile, Ace- tophenonoxime, 4,6-Dihalo-2-phenylpyrimidine, N-[[4-(Aminocarbonyl)phenyl]sulfonyl]- 2-benzoesäureamide, 1 ,8-Naphthalsäureanhydrid, 2-Halo-4-(haloalkyl)-5- thiazolcarbonsäuren, Phosphorthiolate und N-Alkyl-O-phenylcarbamate sowie ihre landwirtschaftlich brauchbaren Salze, und vorausgesetzt sie haben eine Säurefunktion, ihre landwirtschaftlich brauchbaren Derivate, wie Amide, Ester und Thioester.It may also be advantageous to use the compounds of the formula I in combination with safeners. Safeners are chemical compounds that prevent or reduce damage to crops without significantly affecting the herbicidal activity of the compounds of formula I on undesirable plants. They can be used both before sowing (for example, in seed treatments, in cuttings, or in seedlings) as well as in the pre- or post-emergence of the crop. The safeners and the compounds of formula I can be used simultaneously or sequentially. Suitable safeners are, for example, (quinoline-8-oxy) acetic acids, 1-phenyl-5-haloalkyl-1H-1, 2,4-triazole-3-carboxylic acid, 1-phenyl-4,5-dihydro-5-alkyl- 1 H-pyrazole-3,5-dicarboxylic acids, 4,5-dihydro-5,5-diaryl-3-isoxazolecarboxylic acids, dichloroacetamides, alpha-oximinophenylacetonitriles, acetophenone oximes, 4,6-dihalo-2-phenylpyrimidines, N- [ [4- (aminocarbonyl) phenyl] sulfonyl] -2-benzoic acid amides, 1,8-naphthalic anhydride, 2-halo-4- (haloalkyl) -5-thiazolecarboxylic acids, phosphorothiolates and N-alkyl-O-phenylcarbamates and their agriculturally useful salts, and provided they have an acid function, their agriculturally useful derivatives such as amides, esters and thioesters.
Außerdem kann es von Nutzen sein, die Verbindungen I allein oder in Kombination mit anderen Herbiziden oder auch noch mit weiteren Pflanzenschutzmitteln gemischt, ge- meinsam auszubringen, beispielsweise mit Mitteln zur Bekämpfung von Schädlingen oder phytopathogenen Pilzen bzw. Bakterien. Von Interesse ist ferner die Mischbarkeit mit Mineralsalzlösungen, welche zur Behebung von Ernährungs- und Spurenelementmängeln eingesetzt werden. Es können auch weitere Additive wie nicht phytotoxische Öle und Ölkonzentrate zugesetzt werden.In addition, it may be useful to mix the compounds I alone or in combination with other herbicides or else with other crop protection agents. common use, for example with agents for controlling pests or phytopathogenic fungi or bacteria. Also of interest is the miscibility with mineral salt solutions, which are used for the elimination of nutritional and trace element deficiencies. Other additives such as non-phytotoxic oils and oil concentrates may also be added.
Im Folgenden wird die Herstellung von Piperazinverbindungen der Formel I anhand von Beispielen erläutert ohne dabei den Gegenstand der vorliegenden Erfindung auf die gezeigten Beispiele zu begrenzen.In the following, the preparation of piperazine compounds of the formula I is explained by way of examples without limiting the subject matter of the present invention to the examples shown.
BeispieleExamples
Die Charakterisierung der im Folgenden gezeigten Produkte erfolgte durch Bestimmung des Schmelzpunktes, durch NMR-Spektroskopie oder anhand der durch HPLC-MS-Spektrometrie ermittelten Massen ([m/z]) oder Retentionszeit (RT; [min.]).The characterization of the products shown below was carried out by determining the melting point, by NMR spectroscopy or by the masses ([m / z]) or retention time (RT, [min.]) Determined by HPLC-MS spectrometry.
[HPLC-MS = High Performance Liquid Chromatographie kombiniert mit Massen Spektrometrie; HPLC-Säule: RP-18 Säule (Chromolith Speed ROD von Merck KGaA, Deutschland), 50*4,6 mm; Eluent: Acetonitril + 0,1 % Trifluoressigsäure (TFA)/ Wasser + 0,1 % TFA, mit einem Gradienten von 5 : 95 bis 100 : 0 in 5 Minuten bei 400C, Flussrate 1 ,8 ml/min; MS: Quadrupol Elektrospray-Ionisation, 80 V (Positiv-Modus).][HPLC-MS = High Performance Liquid Chromatography combined with mass spectrometry; HPLC column: RP-18 column (Chromolith Speed ROD from Merck KGaA, Germany), 50 * 4.6 mm; Eluent: acetonitrile + 0.1% trifluoroacetic acid (TFA) / water + 0.1% TFA, with a gradient of 5: 95 to 100: 0 in 5 minutes at 40 0 C, flow rate 1, 8 ml / min; MS: Quadrupole electrospray ionization, 80V (positive mode).]
I. HerstellungsbeispieleI. Preparation Examples
Beispiel 1 : 3-Benzyl-6-(2-brombenzyliden)-1 ,3,4-trimethyl-piperazin-2,5-dionExample 1: 3-Benzyl-6- (2-bromobenzylidene) -1,3,4-trimethyl-piperazine-2,5-dione
1.1 Herstellung von (2-tert-Butoxycarbonylamino-3-phenyl-propionylamino)- essigsäuremethylester1.1 Preparation of (2-tert-Butoxycarbonylamino-3-phenyl-propionylamino) - acetic acid methyl ester
Zu einer Lösung von Glycinmethylester-Hydrochlorid (100 g, 0,8 mol) in Tetra- hydrofuran (THF, 1000 ml) wurde bei 0 0C Ethyldiisopropylamin (259 g, 2,0 mol), N-tert-Butoxycarbonyl-L-phenylalanin (212 g, 0,8 mol) und 1-Ethyl-3- (3'-dimethylaminopropyl)carbodiimid (EDAC, 230 g, 1 ,2 mol) gegeben. Anschlie- ßend wurde das Reaktionsgemisch 24 h bei Raumtemperatur gerührt. Das erhaltene Reaktionsgemisch wurde unter vermindertem Druck von flüchtigen Bestandteilen befreit und der so erhaltene Rückstand wurde in Wasser (1000 ml) aufgenommen. Die wässrige Phase wurde mehrmals mit CH2CI2 extrahiert. Die so erhaltenen organischen Phasen wurden vereint, mit Wasser gewaschen, über Na2SO4 getrocknet, filtriert und unter vermindertem Druck vom Lösungsmittel befreit. (2-tert-Butoxycarbonylamino-3-phenyl-propionylamino)-essigsäure- methylester wurde als gelbes Öl in einer Menge von 300 g erhalten. Das erhaltene Rohprodukt wurde ohne weitere Aufreinigung weiter umgesetzt.To a solution of glycine methyl ester hydrochloride (100 g, 0.8 mol) in tetrahydrofuran (THF, 1000 ml) was added at 0 0 C ethyldiisopropylamine (259 g, 2.0 mol), N-tert-butoxycarbonyl-L- phenylalanine (212 g, 0.8 mol) and 1-ethyl-3- (3'-dimethylaminopropyl) carbodiimide (EDAC, 230 g, 1.2 mol). Subsequently, the reaction mixture was stirred for 24 h at room temperature. The resulting reaction mixture was devolatilized under reduced pressure and the resulting residue was taken up in water (1000 ml). The aqueous phase was extracted several times with CH 2 Cl 2. The organic phases thus obtained were combined, washed with water, dried over Na 2 SO 4, filtered and freed from the solvent under reduced pressure. (2-tert-butoxycarbonylamino-3-phenyl-propionylamino) -acetic acid methyl ester was obtained as a yellow oil in an amount of 300 g. The crude product obtained was reacted further without further purification.
1.2 Herstellung von 3-Benzylpiperazin-2,5-dion1.2 Preparation of 3-benzylpiperazine-2,5-dione
Zu einer Lösung von (2-tert-Butoxycarbonylamino-3-phenyl-propionylamino)- essigsäuremethylester (300 g, ca. 0,8 mol) in CH2CI2 wurde bei Raumtemperatur Trifluoressigsäure (342 g, 3 mol) getropft. Das erhaltene Reaktionsgemisch wurde für 24 h bei Raumtemperatur gerührt und anschließend unter vermindertem Druck eingeengt. Der erhaltene Rückstand wurde in THF (500 ml) aufgenommen und langsam mit einer wässrigen Ammoniak-Lösung (25%ig, 500 ml) versetzt. Das Reaktionsgemisch wurde weitere 72 h bei Raumtemperatur gerührt. Der ausgefallene Feststoff wurde durch Filtrieren isoliert und mit Wasser gewaschen. 3-Benzylpiperazin-2,5-dion wurde in einer Menge von 88 g (Ausbeute 54 %) er- halten.To a solution of (2-tert-butoxycarbonylamino-3-phenyl-propionylamino) - acetic acid methyl ester (300 g, about 0.8 mol) in CH 2 Cl 2, trifluoroacetic acid (342 g, 3 mol) was added dropwise at room temperature. The resulting reaction mixture was stirred for 24 h at room temperature and then concentrated under reduced pressure. The resulting residue was taken up in THF (500 ml) and slowly added with an aqueous ammonia solution (25%, 500 ml). The reaction mixture was stirred at room temperature for a further 72 h. The precipitated solid was isolated by filtration and washed with water. 3-Benzylpiperazine-2,5-dione was obtained in an amount of 88 g (yield 54%).
1.3 Herstellung von 1 ,4-Diacetyl-3-benzyl-piperazin-2,5-dion1.3 Preparation of 1,4-diacetyl-3-benzyl-piperazine-2,5-dione
Eine Lösung von 3-Benzylpiperazin-2,5-dion (20,4 g, 0,1 mol) in Essigsäurean- hydrid (200 ml) wurde unter Rückflussbedingungen für 4 h gerührt. Das erhalteneA solution of 3-benzylpiperazine-2,5-dione (20.4 g, 0.1 mol) in acetic anhydride (200 mL) was stirred at reflux for 4 h. The obtained
Reaktionsgemisch wurde unter vermindertem Druck eingeengt. Der Rückstand wurde in CH2CI2 aufgenommen, nacheinander mit einer wässrigen NaHCθ3- Lösung und Wasser gewaschen, über Na2SO4 getrocknet, filtriert und unter vermindertem Druck vom Lösungsmittel befreit. 1 ,4-Diacetyl-3-benzyl-piperazin-2,5- dion wurde als gelbes Öl in einer Menge von 28,5 g (quantitativ) erhalten und alsReaction mixture was concentrated under reduced pressure. The residue was taken up in CH 2 Cl 2, washed successively with an aqueous NaHCO 3 solution and water, dried over Na 2 SO 4, filtered and freed from the solvent under reduced pressure. 1, 4-Diacetyl-3-benzyl-piperazine-2,5-dione was obtained as a yellow oil in an amount of 28.5 g (quantitative) and as
Rohprodukt weiter umgesetzt. HPLC-MS [m/z]: 289.1 [M+1]+.Raw product further implemented. HPLC-MS [m / z]: 289.1 [M + 1] + .
1.4 Herstellung von 1-Acetyl-6-benzyl-3-(2-brombenzyliden)-piperazin-2,5-dion1.4 Preparation of 1-acetyl-6-benzyl-3- (2-bromobenzylidene) -piperazine-2,5-dione
Zu einer Lösung von 1 ,4-Diacetyl-3-benzyl-piperazin-2,5-dion (17,4 g, 0,06 mol) in Dimethylformamid (DMF, 100 ml) wurde Brombenzaldehyd (5,55 g, 0,03 mol) und CS2CO3 (9,8 g, 0,03 mol) gegeben. Das Reaktionsgemisch wurde für 36 h bei Raumtemperatur gerührt, anschließend mit Wasser (500 ml) und Zitronen- säure (10 g) versetzt und mehrmals mit CH2CI2 extrahiert. Die so erhaltenen organischen Phasen wurden vereint, mit Wasser gewaschen, über Na2SÜ4 getrocknet, filtriert und unter vermindertem Druck vom Lösungsmittel befreit. 1- Acetyl-6-benzyl-3-(2-brombenzyliden)-piperazin-2,5-dion wurde nach säulechro- matographischer Reinigung (CH2CI2 als Eluent) als gelbes Öl in einer Menge von 12 g (Ausbeute 48 %) erhalten.To a solution of 1,4-diacetyl-3-benzyl-piperazine-2,5-dione (17.4 g, 0.06 mol) in dimethylformamide (DMF, 100 ml) was added bromobenzaldehyde (5.55 g, 0; 03 mol) and CS2CO3 (9.8 g, 0.03 mol). The reaction mixture was stirred for 36 h at room temperature, then treated with water (500 ml) and citric acid (10 g) and extracted several times with CH 2 Cl 2. The organic phases thus obtained were combined, washed with water, dried over Na 2 SO 4, filtered and freed from the solvent under reduced pressure. 1-Acetyl-6-benzyl-3- (2-bromobenzylidene) -piperazine-2,5-dione was obtained after purification by column chromatography (CH 2 Cl 2 as eluent) as a yellow oil in an amount of 12 g (48% yield).
HPLC-MS [m/z]: 413.9 [M+1]+ 1.5 Herstellung von 3-Benzyl-6-(2-brombenzyliden)-piperazin-2,5-dionHPLC-MS [m / z]: 413.9 [M + 1] + 1.5 Preparation of 3-benzyl-6- (2-bromobenzylidene) -piperazine-2,5-dione
Zu einer Lösung von 1-Acetyl-6-benzyl-3-(2-brombenzyliden)-piperazin-2,5-dion (12 g, 0,03 mol) in THF (50 ml) wurde verdünnte wässrige Salzsäure (5%ig, 250 ml) gegeben. Das Reaktionsgemisch wurde 8 h unter Rückflussbedingungen gerührt. Nach Abkühlen der Reaktionslösung wurde der ausgefallene Feststoff durch Filtrieren isoliert. Der so erhaltene Feststoff wurde mit Wasser und THF gewaschen. 3-Benzyl-6-(2-brombenzyliden)-piperazin-2,5-dion wurde als farbloser Feststoff in einer Menge von 8.3 g (Ausbeute 75 %) erhalten. HPLC-MS [m/z]: 371.2 [M]+.To a solution of 1-acetyl-6-benzyl-3- (2-bromobenzylidene) -piperazine-2,5-dione (12 g, 0.03 mol) in THF (50 ml) was added dilute aqueous hydrochloric acid (5% , 250 ml). The reaction mixture was stirred for 8 hours under reflux conditions. After cooling the reaction solution, the precipitated solid was isolated by filtration. The resulting solid was washed with water and THF. 3-Benzyl-6- (2-bromobenzylidene) -piperazine-2,5-dione was obtained as a colorless solid in an amount of 8.3 g (75% yield). HPLC-MS [m / z]: 371.2 [M] + .
1.6 3-Benzyl-6-(2-brombenzyliden)-1 ,3,4-trimethyl-piperazin-2,5-dion1.6 3-Benzyl-6- (2-bromobenzylidene) -1,3,4-trimethyl-piperazine-2,5-dione
Zu einer Lösung von 3-Benzyl-6-(2-brombenzyliden)-piperazin-2,5-dion (2,00 g, 5,4 mmol) in DMF (50 ml) wurde bei 0 0C NaH (0,85 g, 60%ig, 21 mmol) gegeben. Das Reaktionsgemisch wurde 2 h bei 0 0C gerührt und anschließend mit Methyliodid (5.,0 g, 35 mmol) versetzt. Das Reaktionsgemisch wurde für weitere 18 h bei Raumtemperatur gerührt und anschließend mit Wasser versetzt. Es wurde mehrfach mit Methyl-tert-butylether extrahiert. Die so erhaltenen organi- sehen Phasen wurden vereint, mit Wasser gewaschen, über Na2SÜ4 getrocknet, filtriert und unter vermindertem Druck vom Lösungsmittel befreit. 3-Benzyl-6-(2- brombenzyliden)-1 ,3,4-trimethyl-piperazin-2,5-dion wurde nach säulenchroma- tographischer Reinigung in einer Menge von 1 ,6 g (Ausbeute 72 %) erhalten. HPLC-MS [m/z]: 413.0 [M]+.To a solution of 3-benzyl-6- (2-bromobenzylidene) piperazine-2,5-dione (2.00 g, 5.4 mmol) in DMF (50 mL) was added (at 0 0 C 0.85 NaH g, 60%, 21 mmol). The reaction mixture was stirred for 2 h at 0 0 C and then treated with methyl iodide (5. 0 g, 35 mmol). The reaction mixture was stirred for a further 18 h at room temperature and then treated with water. It was extracted several times with methyl tert-butyl ether. The resulting organic phases were combined, washed with water, dried over Na 2 SO 4, filtered and freed from the solvent under reduced pressure. 3-Benzyl-6- (2-bromobenzylidene) -1,3,4-trimethyl-piperazine-2,5-dione was obtained after column chromatography purification in an amount of 1.6 g (yield 72%). HPLC-MS [m / z]: 413.0 [M] + .
Beispiel 2: 2-(5-Benzyl-1 ,4,5-trimethyl-3,6-dioxo-piperazin-2-ylidenmethyl)-benzonitrilExample 2: 2- (5-Benzyl-1, 4,5-trimethyl-3,6-dioxo-piperazin-2-ylidenemethyl) -benzonitrile
Zu einer Lösung von 3-Benzyl-6-(2-brombenzyliden)-1 ,3,4-trimethyl-piperazin- 2,5-dion (1 ,5 g, 3,6 mmol) in N-Methylpyrrolidin (NMP, 25 ml) wurde CuCN (0,7 g, 7,8 mmol) gegeben. Das Reaktionsgemisch wurde 16 h bei 155 0C gerührt und nach Abkühlung auf Raumtemperatur in Essigester eingebracht. Das Reaktionsgemisch wurde mit Methyl-tert-butylether verdünnt. Die so erhaltene organische Phase wurde mit Wasser gewaschen, über Na2SÜ4 getrocknet, filtriert und unter vermindertem Druck vom Lösungsmittel befreit. Nach säulenchroma- tographischer Reinigung wurde 2-(5-Benzyl-1 ,4,5-trimethyl-3,6-dioxo-piperazin-2- ylidenmethyl)-benzonitril in einer Menge von 0,79 g (Ausbeute 61 %) erhalten. HPLC-MS [m/z]: 360.5 [M+1]+.To a solution of 3-benzyl-6- (2-bromobenzylidene) -1,3,4-trimethyl-piperazine-2,5-dione (1, 5 g, 3.6 mmol) in N-methylpyrrolidine (NMP, 25 ml) was added CuCN (0.7 g, 7.8 mmol). The reaction mixture was stirred at 155 ° C. for 16 h and, after cooling to room temperature, introduced into ethyl acetate. The reaction mixture was diluted with methyl tert-butyl ether. The organic phase thus obtained was washed with water, dried over Na 2 SO 4, filtered and freed from the solvent under reduced pressure. After column chromatography, 2- (5-benzyl-1, 4,5-trimethyl-3,6-dioxo-piperazin-2-ylidenemethyl) -benzonitrile was obtained in an amount of 0.79 g (yield 61%). HPLC-MS [m / z]: 360.5 [M + 1] + .
Beispiel 3: 2-(5-Benzyl-5-ethyl-1 ,4-dimethyl-3,6-dioxo-piperazin-2-ylidenmethyl)- benzonitrilExample 3: 2- (5-Benzyl-5-ethyl-1,4-dimethyl-3,6-dioxo-piperazin-2-ylidene-methyl) -benzonitrile
3.1 Herstellung von 3-Benzyl-6-(2-brombenzyliden)-1 ,4-dimethyl-piperazin-2,5-dion Zu einer Lösung von 3-Benzyl-6-(2-brombenzyliden)-piperazin-2,5-dion (3,71 g, 0,01 mol) in DMF (50 ml) wurde bei 0 0C NaH (0,8 g, 60%ig, 0,02 mol) gegeben. Es wurde 1 h bei 0 0C nachgerührt und dann mit Methyliodid (14,2 g, 0,1 mol) versetzt. Das erhaltene Reaktionsgemisch wurde weitere 18 h bei Raumtemperatur gerührt und anschließend in eine Wasser (500 ml)/Zitronensäure (5 g)-Lösung eingebracht. Das erhaltene Reaktionsgemisch wurde mehrmals mit CH2CI2 extrahiert. Die so erhaltenen organischen Phasen wurden vereint, mit Wasser gewaschen, über Na2SO4 getrocknet, filtriert und unter vermindertem Druck vom Lösungsmittel befreit. 3-Benzyl-6-(2-brombenzyliden)-1 ,4-dimethyl-piperazin-2,5- dion wurde nach Ausrühren mit Diisopropylehter in einer Menge von 2 g (Ausbeute 50 %) erhalten. HPLC-MS [m/z]: 401.4 [M+1]+.3.1 Preparation of 3-Benzyl-6- (2-bromobenzylidene) -1,4-dimethyl-piperazine-2,5-dione To a solution of 3-benzyl-6- (2-bromobenzylidene) piperazine-2,5-dione (3.71 g, 0.01 mol) in DMF (50 ml) at 0 0 C. NaH (0.8 g, 60%, 0.02 mol). The mixture was stirred for 1 h at 0 0 C and then treated with methyl iodide (14.2 g, 0.1 mol). The resulting reaction mixture was stirred at room temperature for an additional 18 hours and then introduced into a water (500 ml) / citric acid (5 g) solution. The resulting reaction mixture was extracted several times with CH 2 Cl 2. The organic phases thus obtained were combined, washed with water, dried over Na 2 SO 4, filtered and freed from the solvent under reduced pressure. 3-Benzyl-6- (2-bromobenzylidene) -1,4-dimethyl-piperazine-2,5-dione was obtained after stirring with diisopropyl ether in an amount of 2 g (yield 50%). HPLC-MS [m / z]: 401.4 [M + 1] + .
3.2 Herstellung von 2-(5-Benzyl-1 ,4-dimethyl-3,6-dioxo-piperazin-2-ylidenmethyl)- benzonitril3.2 Preparation of 2- (5-Benzyl-1,4-dimethyl-3,6-dioxo-piperazin-2-ylidenemethyl) benzonitrile
Zu einer Lösung von 3-Benzyl-6-(2-brombenzyliden)-1 ,4-dimethyl-piperazin-2,5- dion (2 g, 0.005 mol) in NMP (20 ml) wurde CuCN (0,9 g, 0,1 mol) gegeben. Das Reaktionsgemisch wurde für 18 h bei 150 0C gerührt und anschließend in eine wässrige NaCN-Lösung (6%ig, 50 ml) eingebracht. Das Reaktionsgemisch wurde mehrfach mit CH2CI2 extrahiert. Die so erhaltenen organischen Phasen wurden vereint, mit Wasser gewaschen, über Na2SC"4 getrocknet, filtriert und unter vermindertem Druck vom Lösungsmittel befreit. 2-(5-Benzyl-1 ,4-dimethyl-3,6-dioxo- piperazin-2-ylidenmethyl)-benzonitril wurde nach säulenchromatographischerTo a solution of 3-benzyl-6- (2-bromobenzylidene) -1,4-dimethyl-piperazine-2,5-dione (2 g, 0.005 mol) in NMP (20 ml) was added CuCN (0.9 g, 0.1 mol). The reaction mixture was stirred for 18 h at 150 0 C and then introduced into an aqueous NaCN solution (6%, 50 ml). The reaction mixture was extracted several times with CH 2 Cl 2. The organic phases thus obtained were combined, washed with water, dried over Na 2 SC 4, filtered and freed from the solvent under reduced pressure. 2- (5-Benzyl-1,4-dimethyl-3,6-dioxopiperazine-2- ylidenemethyl) benzonitrile was purified by column chromatography
Reinigung und Ausrühren mit Diisopropylether als beiger Feststoff in einer Menge von 1 ,2 g (Ausbeute 67 %) erhalten. HPLC-MS [m/z]: 346.4 [M+1]+.Purification and trituration with diisopropyl ether as a beige solid in an amount of 1, 2 g (yield 67%). HPLC-MS [m / z]: 346.4 [M + 1] + .
3.3 Herstellung von 2-(5-Benzyl-5-ethyl-1 ,4-dimethyl-3, 6-dioxo-piperazin-2-yliden- methyl)-benzonitril3.3 Preparation of 2- (5-benzyl-5-ethyl-1,4-dimethyl-3,6-dioxo-piperazin-2-ylidene-methyl) -benzonitrile
Zu einer Lösung von 2-(5-Benzyl-1 ,4-dimethyl-3,6-dioxo-piperazin-2-yliden- methyl)-benzonitril (1 ,04 g, 3,0 mmol) in DMF (10 ml) wurde bei 0 0C NaH (0,12 g, 60%ig, ca. 3 mmol) gegeben. Das Reaktiongemisch wurde 1 h bei 0 0C nachgerührt und dann mit lodethan (0,47 g, 3,1 mmol) versetzt. Das erhaltene Reaktionsgemisch wurde 18 h bei Raumtemperatur gerührt und anschließend in Wasser (100 ml) eingetragen und angesäuert. Man extrahierte 3-mal mit Dichlor- methan, wusch die vereinigten organischen Phasen mit Wasser und trocknete über Natriumsulfat. Nach einengen der getrockneten organischen Phase erhielt man 1 ,2 g der Titelverbindung als Rohprodukt. Das Rohprodukt wurde zunächst mit n-Hexan und anschließend mit heißem Ethylacetat behandelt. Der feste Rückstand wurde mittels Flash-Chromatographie unter Verwendung von Ethyl- acetat als Eluens gereinigt. Auf diese Weise erhielt man 200 mg der Titelverbindung als einen weißen Feststoff (200 mg, Z-Isomer, Schmelzpunkt 1410C). Aufarbeitung der beim Ausrühren mit Ethylacetat erhaltenen Mutterlauge lieferte weitere 400 mg der Titelverbindung als E/Z-Isomerengemisch mit einem Schmelzpunkt von 1200C (E/Z etwa 1 :1 ).To a solution of 2- (5-benzyl-1,4-dimethyl-3,6-dioxo-piperazin-2-ylidene-methyl) -benzonitrile (1. 04 g, 3.0 mmol) in DMF (10 mL). (about 3 mmol 0.12 g, 60%,) was added at 0 0 C. NaH added. The reaction mixture was stirred for 1 h at 0 0 C and then with iodoethane (0.47 g, 3.1 mmol) was added. The resulting reaction mixture was stirred for 18 h at room temperature and then added to water (100 ml) and acidified. It was extracted 3 times with dichloromethane, and the combined organic phases were washed with water and dried over sodium sulfate. After narrowing the dried organic phase gave 1, 2 g of the title compound as a crude product. The crude product was treated first with n-hexane and then with hot ethyl acetate. The solid Residue was purified by flash chromatography using ethyl acetate as eluent. In this way, 200 mg of the title compound were obtained as a white solid (200 mg, Z-isomer, m.p .: 141 ° C.). Working up of the mother liquor obtained on stirring with ethyl acetate yielded a further 400 mg of the title compound as an E / Z isomer mixture having a melting point of 120 ° C. (E / Z about 1: 1).
Die Herstellung der in den Tabellen 1 , 2 und 3 zusammengestellten Verbindungen der Formel I (Beispiele 4 bis 190) erfolgte in Analogie zu den zuvor gezeigten Beispielen 1 bis 3.The preparation of the compounds of the formula I (Examples 4 to 190) compiled in Tables 1, 2 and 3 was carried out in analogy to Examples 1 to 3 shown above.
Tabelle 1 : Verbindungen der allgemeinen Formel I, worin R4 für CH3 steht und R7, R8, R9 und R10 jeweils für Wasserstoff stehen (Verbindungen der Formel l.b)Table 1: Compounds of the general formula I in which R 4 is CH 3 and R 7 , R 8 , R 9 and R 10 are each hydrogen (compounds of the formula Ib)
*) Diese Angabe bezieht sich auf die Stereochemie der Doppelbindung am Piperazin- gerüst. * ) This data refers to the stereochemistry of the double bond on the piperazine skeleton.
0) HPLC-Säule: RP-18 Säule (XTerra MS 5 mm von Waters) Eluent: Acetonitril +0 ) HPLC column: RP-18 column (XTerra MS 5 mm from Waters) eluent: acetonitrile +
0,1 % Ameisensäure (A)/ Wasser + 0,1 % Ameisensäure (B) mit einem Gradienten von0.1% formic acid (A) / water + 0.1% formic acid (B) with a gradient of
5:95 (A/B) zu 100:0 (A/B) in 8 Minuten bei Raumtemperatur.5:95 (A / B) to 100: 0 (A / B) in 8 minutes at room temperature.
MS: Quadrupol Electrospray Ionisation, 80 V Positiv-Modus)MS: quadrupole electrospray ionization, 80 V positive mode)
Mit Ausnahme der mit **) gekennzeichneten Verbindungen handelt es sich jeweils um racemische Verbindungen bezüglich des Stereozentrums am Piperazingerüst. Die mit **» gekennzeichneten Verbindung leiten sich vom L-Phenylalanin ab und weisen somit an diesem Stereozentrum S-Konfiguration auf.With the exception of the compounds marked **) , these are in each case racemic compounds with respect to the stereocenter on the piperazine skeleton. The compounds marked with * * »are derived from L-phenylalanine and thus have an S configuration at this stereocenter.
Tabelle 2: Verbindungen der allgemeinen Formel I, worin R4 für CH3 steht und R7 und R8 jeweils für Wasserstoff stehen (Verbindungen der Formel l.c).Table 2: Compounds of the general formula I in which R 4 is CH 3 and R 7 and R 8 are each hydrogen (compounds of the formula Ic).
*) Diese Angabe bezieht sich auf die Stereochemie der Doppelbindung am Piperazin- gerüst. Bei den hergestellten Verbindungen handelt es sich jeweils um das Racemat. * ) This data refers to the stereochemistry of the double bond on the piperazine skeleton. The compounds prepared are each the racemate.
Tabelle 3: Verbindungen der allgemeinen Formel I, worin R7, R8, R9 und R10 jeweils für Wasserstoff stehen (Verbindungen der Formel l.d).Table 3: Compounds of the general formula I in which R 7 , R 8 , R 9 and R 10 are each hydrogen (compounds of the formula Id).
*) Diese Angabe bezieht sich auf die Stereochemie der Doppelbindung am Piperazin- gerüst. Bei den hergestellten Verbindungen handelt es sich jeweils um das Racemat. * ) This data refers to the stereochemistry of the double bond on the piperazine skeleton. The compounds prepared are each the racemate.
II: AnwendungsbeispieleII: Application examples
Die herbizide Wirkung der Verbindungen der Formel I ließ sich durch Gewächshaus- versuche zeigen:The herbicidal activity of the compounds of the formula I was demonstrated by greenhouse experiments:
Als Kulturgefäße dienten Plastiktöpfe mit lehmigem Sand mit etwa 3,0 % Humus als Substrat. Die Samen der Testpflanzen wurden nach Arten getrennt eingesät. Bei Vorauflaufbehandlung wurden die in Wasser suspendierten oder emulgierten Wirkstoffe direkt nach Einsaat mittels fein verteilender Düsen aufgebracht. Die Gefäße wurden leicht beregnet, um Keimung und Wachstum zu fördern, und anschließend mit durchsichtigen Plastikhauben abgedeckt, bis die Pflanzen angewachsen waren. Diese Abdeckung bewirkt ein gleichmäßiges Keimen der Testpflanzen, sofern dies nicht durch die Wirkstoffe beeinträchtigt wurde.The culture vessels used were plastic pots with loamy sand with about 3.0% humus as substrate. The seeds of the test plants were sown separately by species. In pre-emergence treatment, the active ingredients suspended or emulsified in water were applied directly after sowing by means of finely distributing nozzles. The jars were lightly rained to promote germination and growth and then covered with clear plastic hoods until the plants had grown. This cover causes a uniform germination of the test plants, if it was not affected by the active ingredients.
Zum Zweck der Nachauflaufbehandlung wurden die Testpflanzen je nach Wuchsform erst bis zu einer Wuchshöhe von 3 bis 15 cm angezogen und dann mit den in Wasser suspendierten oder emulgierten Wirkstoffen behandelt. Die Testpflanzen wurden dafür entweder direkt gesät und in den gleichen Gefäßen aufgezogen oder sie wurden erst als Keimpflanzen getrennt angezogen und einige Tage vor der Behandlung in die Versuchsgefäße verpflanzt.For the postemergence treatment, the test plants were grown depending on the growth form only to a height of from 3 to 15 cm and then treated with the suspended or emulsified in water agents. For this purpose, 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.
Die Pflanzen wurden artenspezifisch bei Temperaturen von 10 - 25°C bzw. 20 - 35°C gehalten. Die Versuchsperiode erstreckte sich über 2 bis 4 Wochen. Während dieser Zeit wurden die Pflanzen gepflegt, und ihre Reaktion auf die einzelnen Behandlungen wurde ausgewertet.The plants were kept species-specific at temperatures of 10 - 25 ° C and 20 - 35 ° C, respectively. The trial period lasted for 2 to 4 weeks. During this time, the plants were cared for, and their response to each treatment was evaluated.
Bewertet wurde nach einer Skala von 0 bis 100. Dabei bedeutet 100 kein Aufgang der Pflanzen bzw. völlige Zerstörung zumindest der oberirdischen Teile und 0 keine Schädigung oder normaler Wachstumsverlauf. Eine gute herbizide Aktivität ist bei Werten von wenigstens 70 und eine sehr gute herbizide Aktivität ist bei Werten von wenigstens 85 gegeben.The rating was based on a scale of 0 to 100. 100 means no emergence of the plants or complete destruction of at least the above-ground parts and 0 no damage or normal growth course. A good herbicidal activity is at values of at least 70 and a very good herbicidal activity is given at values of at least 85.
Die in den Gewächshausversuchen verwendeten Pflanzen setzten sich aus folgenden Arten zusammen:The plants used in the greenhouse experiments were composed of the following species:
Die Verbindungen der Beispiele 3, 6, 7, 11 , 12, 13, 16, 18, 24, 26, 39, 43, 44, 47, 55, 56 und 138 zeigen bei einer Aufwandmenge von 0,5 kg/ha im Nachauflauf gegen AMARE eine gute bis sehr gute herbizide Wirkung. The compounds of Examples 3, 6, 7, 11, 12, 13, 16, 18, 24, 26, 39, 43, 44, 47, 55, 56 and 138 post-emerge at a rate of 0.5 kg / ha against AMARE a good to very good herbicidal action.
Die Verbindung des Beispiels 43 zeigt bei einer Aufwandmenge von 0,5 kg/ha im Nachauflauf gegen APESV eine gute herbizide Wirkung.The compound of Example 43 shows at a rate of 0.5 kg / ha postemergence against APESV a good herbicidal action.
Die Verbindungen der Beispiele 3, 7, 11 , 12, 13, 14, 16, 18, 25, 39 und 55 zeigen bei einer Aufwandmenge von 0,5 kg/ha im Nachauflauf gegen CHEAL eine gute bis sehr gute herbizide Wirkung.The compounds of Examples 3, 7, 11, 12, 13, 14, 16, 18, 25, 39 and 55 show at a rate of 0.5 kg / ha postemergence against CHEAL a good to very good herbicidal activity.
Die Verbindungen der Beispiele 44 und 47 zeigen bei einer Aufwandmenge von 0,5 kg/ha im Nachauflauf gegen ECHCG eine sehr gute herbizide Wirkung.The compounds of Examples 44 and 47 show at a rate of 0.5 kg / ha postemergence against ECHCG a very good herbicidal activity.
Die Verbindung des Beispiels 137 zeigt bei einer Aufwandmenge von 0,5 kg/ha im Nachauflauf gegen GALAP eine gute herbizide Wirkung.The compound of Example 137 shows at a rate of 0.5 kg / ha postemergence against GALAP a good herbicidal action.
Die Verbindung des Beispiels 10 zeigt bei einer Aufwandmenge von 0,5 kg/ha im Nachauflauf gegen LOLMU eine gute herbizide Wirkung.The compound of Example 10 shows at a rate of 0.5 kg / ha postemergence against LOLMU a good herbicidal action.
Die Verbindungen der Beispiele 6, 7, 10, 1 1 , 12, 13, 14, 16, 18, 25, 26, 29, 39, 44, 47, 55, 56 und 138 zeigen bei einer Aufwandmenge von 0,5 kg/ha im Nachauflauf gegen SETVI eine gute bis sehr gute herbizide Wirkung.The compounds of Examples 6, 7, 10, 11, 12, 13, 14, 16, 18, 25, 26, 29, 39, 44, 47, 55, 56 and 138 show at a rate of 0.5 kg / ha postemergence against SETVI a good to very good herbicidal effect.
Die Verbindungen der Beispiele 24, 29, 43 und 137 zeigen bei einer Aufwandmenge von 0,5k g/ha im Vorauflauf gegen APESV eine sehr gute herbizide Wirkung.The compounds of Examples 24, 29, 43 and 137 show at a rate of application of 0.5 k g / ha in pre-emergence against APESV a very good herbicidal activity.
Die Verbindung des Beispiels 25 zeigt bei einer Aufwandmenge von 0,5 kg/ha im Vor- auflauf gegen CHEAL eine gute herbizide Wirkung.The compound of Example 25 shows at a rate of 0.5 kg / ha in the pre-emergence against CHEAL a good herbicidal action.
Die Verbindung des Beispiels 25 zeigt bei einer Aufwandmenge von 0,5 kg/ha im Vorauflauf gegen SETVI eine gute herbizide Wirkung. The compound of Example 25 shows at a rate of 0.5 kg / ha in the pre-emergence against SETVI a good herbicidal action.

Claims

Patentansprüche: claims:
Piperazinverbindungen der FormelPiperazine compounds of the formula
worin R1 ausgewählt ist unter Halogen, Cyano, Nitro, Z-C(=O)-R11, Phenyl und einem 5- oder 6-gliedrigen heterocyclischen Rest, der 1 , 2, 3 oder 4 Hetero- atome, ausgewählt unter O, N und S als Ringatome aufweist, worin Phenyl und der heterocyclische Rest unsubstituiert sind oder 1 , 2, 3 oder 4 Substi- tuenten R1a aufweisen können, die unabhängig voneinander unter Halogen, CN, NO2, Ci-C4-AIkVl, Ci-C4-Haloalkyl, Ci-C4-Alkoxy und Ci-C4-Haloalkoxy ausgewählt sind, und worinwherein R 1 is selected from halogen, cyano, nitro, ZC (= O) -R 11, phenyl and a 5- or 6-membered heterocyclic radical, of the atoms 1, 2, 3 or 4 hetero selected from O, N and S as ring atoms, in which phenyl and the heterocyclic radical are unsubstituted or may have 1, 2, 3 or 4 substituents R 1a which are independently of one another halogen, CN, NO 2 , C 1 -C 4 -alkyl, C 4 haloalkyl, C 1 -C 4 alkoxy and C 1 -C 4 haloalkoxy are selected, and wherein
Z für eine kovalente Bindung oder eine CH2-Gruppe steht; R11 Wasserstoff, d-Ce-Alkyl, C3-C6-Cycloalkyl, C2-C6-Al kenyl, C5-C6-Z is a covalent bond or a CH 2 group; R 11 is hydrogen, C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, C 2 -C 6 -alkynyl, C 5 -C 6 -
Cycloalkenyl, C2-C6-Al kinyl, Hydroxy, Ci-C6-Alkoxy, C3-C6-Alkenyloxy, C3-C6-Alkinyloxy, Amino, Ci-C6-Alkylamino, [Di-(Ci-C6)-alkyl]amino, Ci-C6-Alkoxyamino, Ci-C6-Alkylsulfonylamino, CrC6- Alkylaminosulfonylamino, [Di-(Ci-C6)-alkylamino]sulfonylamino, C3- C6-Alkenylamino, C3-C6-Alkinylamino, N-(C2-C6-Alkenyl)-N-(Ci-C6- alkyl)-amino, N-(C2-C6-Alkinyl)-N-(Ci-C6-alkyl)-amino, N-(CrC6- Alkoxy)-N-(Ci-C6-alkyl)-amino, N-(C2-C6-Alkenyl)-N-(Ci-C6-alkoxy)- amino, N-(C2-C6-Alkinyl)-N-(Ci-C6-alkoxy)-amino, Phenyl, Phenoxy oder Phenylamino bedeutet; wobei die Alkylteile in den unter R11 aufgeführten Resten teileweise oder vollständig halogeniert sein können und die Phenylteile in den unter R11 aufgeführten Resten 1 , 2, 3 oder 4 Substituenten R11a tragen können, die unter Halogen, CN, NO2, Ci-C4-Alkyl, Ci-C4-Haloalkyl, Ci-C4-Alkoxy und Ci-C4-Haloalkoxy ausgewählt sind;Cycloalkenyl, C 2 -C 6 -alkyl kinyl, hydroxy, Ci-C6 alkoxy, C3-C6 alkenyloxy, C3-C6 alkynyloxy, amino, Ci-C 6 -alkylamino, [di- (Ci-C 6) alkyl] amino, Ci-C 6 -Alkoxyamino, Ci-C 6 alkylsulfonylamino, CrC 6 - Alkylaminosulfonylamino, [di- (Ci-C6) -alkylamino] sulfonylamino, C 3 - C 6 alkenylamino, C 3 -C 6 -alkynylamino, N- (C 2 -C 6 alkenyl) -N- (Ci-C 6 - alkyl) amino, N- (C 2 -C 6 alkynyl) -N- (Ci-C 6 alkyl) amino, N- (CrC 6 - alkoxy) -N- (Ci-C 6 alkyl) amino, N- (C 2 -C 6 alkenyl) -N- (Ci-C 6 alkoxy) - amino, N- (C 2 -C 6 alkynyl) (alkoxy Ci-C 6) amino, phenyl, phenoxy or phenylamino -N-; where the alkyl moieties in the radicals listed under R 11 can be partially or completely halogenated and the phenyl moieties in the radicals listed under R 11 can carry 1, 2, 3 or 4 substituents R 11a which are halogen, CN, NO 2 , C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy and C 1 -C 4 haloalkoxy are selected;
R2 Wasserstoff, Halogen, Cyano, Nitro, Ci-C4-Alkyl, Ci-C4-Haloalkyl, C2-C4- Alkenyl, Ci-C4-Alkoxy, Ci-C4-Haloalkoxy, Benzyl oder eine Gruppe S(O)nR21 bedeutet, worin R21 für Ci-C4-Alkyl oder Ci-C4-Haloalkyl steht und n für 0, 1 oder 2 steht;R2 is hydrogen, halogen, cyano, nitro, Ci-C4-alkyl, Ci-C 4 haloalkyl, C 2 -C 4 - alkenyl, Ci-C 4 alkoxy, Ci-C4-haloalkoxy, benzyl or a group S (O) n R 21, wherein R 21 4 -alkyl or C is 4 -haloalkyl is C and n is 0, 1 or 2;
R3 Wasserstoff oder Halogen bedeutet; R4 Ci-C4-Alkyl, C3-C4-Alkenyl oder C3-C4-Alkinyl bedeutet; R5 Wasserstoff, Ci-C4-Alkyl, C3-C4-Alkenyl, C3-C4-Alkinyl oder eine GruppeR 3 is hydrogen or halogen; R 4 is C 1 -C 4 -alkyl, C 3 -C 4 -alkenyl or C 3 -C 4 -alkynyl; R 5 is hydrogen, Ci-C 4 alkyl, C 3 -C 4 alkenyl, C 3 -C 4 alkynyl or a group
C(=O)R51 bedeutet, worin R51 für Wasserstoff, Ci -C4-Al kyl, Ci-C4-Haloalkyl,C (= O) R 51 in which R 51 is hydrogen, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl,
Ci-C4-Alkoxy oder Ci-C4-Haloalkoxy steht;C 1 -C 4 alkoxy or C 1 -C 4 haloalkoxy;
R6 für d-C4-Alkyl, Ci-C4-Hydroxyalkyl oder Ci-C4-Haloalkyl steht; R7, R8 unabhängig voneinander für Wasserstoff, OH, Ci-C4-Alkoxy, Ci-C4-R 6 is C 1 -C 4 -alkyl, C 1 -C 4 -hydroxyalkyl or C 1 -C 4 -haloalkyl; R 7 , R 8 independently of one another represent hydrogen, OH, C 1 -C 4 -alkoxy, C 1 -C 4 -
Haloalkyoxy, Ci-C4-Alkyl oder Ci-C4-Haloalkyl stehen; R9, R10 unabhängig voneinander ausgewählt sind unter Wasserstoff, Halogen,Haloalkoxy, C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl; R 9 , R 10 are independently selected from hydrogen, halogen,
CN, NO2, d-C4-Alkyl, Ci-C4-Haloalkyl, C2-C4-Al kenyl, Ci -C4-Al koxy und d-CN, NO 2, dC 4 alkyl, Ci-C 4 haloalkyl, C 2 -C 4 -alkenyl -alkyl, Ci -C 4 -alkyl -alkoxy and d-
C4-Haloalkoxy; sowie die landwirtschaftlich geeigneten Salze dieser Verbindungen.C 4 haloalkoxy; and the agriculturally suitable salts of these compounds.
2. Piperazinverbindungen gemäß Anspruch 1 , worin R1 für Cyano, Nitro oder einen 5- oder 6-gliedrigen heteroaromatischen Rest steht, der entweder 1 , 2 oder 3 Stickstoffatome oder 1 Sauerstoff oder 1 Schwefelatom und gegebenenfalls 1 oder 2 Stickstoffatome als Ringlieder aufweist und der unsubstituiert ist oder 1 oder 2 unter R1a ausgewählte Substituenten aufweisen kann.2. piperazine compounds according to claim 1, wherein R 1 is cyano, nitro or a 5- or 6-membered heteroaromatic radical having either 1, 2 or 3 nitrogen atoms or 1 oxygen or 1 sulfur atom and optionally 1 or 2 nitrogen atoms as ring members, and which is unsubstituted or may have 1 or 2 substituents selected from R 1a .
3. Piperazinverbindungen gemäß Anspruch 1 , worin R1 für Halogen, insbesondere für Chlor oder Brom, steht.3. piperazine compounds according to claim 1, wherein R 1 is halogen, in particular chlorine or bromine.
4. Piperazinverbindungen gemäß einem der vorhergehenden Ansprüche, worin R2 in ortho-Position zur Bindungsstelle des Phenylrings angeordnet ist, wenn R2 von Wasserstoff verschieden ist.4. piperazine compounds according to any one of the preceding claims, wherein R 2 is arranged in ortho position to the binding site of the phenyl ring, when R 2 is different from hydrogen.
5. Piperazinverbindungen gemäß einem der vorhergehenden Ansprüche, worin R2 für Wasserstoff, Fluor, Chlor, Ci-C2-Alkyl, Ci-C2-Fluoralkyl, Ethenyl, Ci-C2-Alkoxy oder Ci-C2-Fluoralkoxy steht.5. piperazine compounds according to any one of the preceding claims, wherein R 2 is hydrogen, fluorine, chlorine, C 1 -C 2 -alkyl, C 1 -C 2 -fluoroalkyl, ethenyl, C 1 -C 2 -alkoxy or C 1 -C 2 -fluoroalkoxy.
6. Piperazinverbindungen gemäß Anspruch 5, worin R2 Fluor oder Chlor bedeutet und in ortho-Position zur Bindungsstelle des Phenylrings angeordnet ist.6. piperazine compounds according to claim 5, wherein R 2 is fluorine or chlorine and is arranged in the ortho position to the binding site of the phenyl ring.
7. Piperazinverbindungen gemäß einem der vorhergehenden Ansprüche, worin R4 für Methyl steht.7. piperazine compounds according to any one of the preceding claims, wherein R 4 is methyl.
8. Piperazinverbindungen gemäß einem der vorhergehenden Ansprüche, worin R5 für Wasserstoff, Methyl oder Ethyl steht.8. piperazine compounds according to any one of the preceding claims, wherein R 5 is hydrogen, methyl or ethyl.
9. Piperazinverbindungen gemäß einem der Ansprüche 1 bis 8, worin R5 C(=O)R51 bedeutet, worin R51 für Wasserstoff, Ci-C4-Alkyl oder Ci-C4-Haloalkyl steht.9. piperazine compounds according to any one of claims 1 to 8, wherein R 5 is C (= O) R 51 , wherein R 51 is hydrogen, Ci-C 4 alkyl or Ci-C 4 haloalkyl.
10. Piperazinverbindungen gemäß einem der vorhergehenden Ansprüche, worin R6 für Methyl oder Ethyl steht. 10. piperazine compounds according to any one of the preceding claims, wherein R 6 is methyl or ethyl.
1 1. Piperazinverbindungen gemäß einem der vorhergehenden Ansprüche, worin R7 und R8 Wasserstoff bedeuten.1 1. piperazine compounds according to any one of the preceding claims, wherein R 7 and R 8 is hydrogen.
12. Piperazinverbindungen gemäß einem der vorhergehenden Ansprüche, worin R9 in para-Position zur Gruppe CR7R8 angeordnet ist, wenn R9 Halogen bedeutet.12. piperazine compounds according to any one of the preceding claims, wherein R 9 is arranged in the para position to the group CR 7 R 8 , when R 9 is halogen.
13. Piperazinverbindungen gemäß einem der vorhergehenden Ansprüche, worin R9 Halogen oder Wasserstoff bedeutet.13. piperazine compounds according to any one of the preceding claims, wherein R 9 is halogen or hydrogen.
14. Piperazinverbindungen gemäß einem der vorhergehenden Ansprüche, worin R10 Wasserstoff bedeutet.14. piperazine compounds according to any one of the preceding claims, wherein R 10 is hydrogen.
15. Piperazinverbindungen gemäß einem der vorhergehenden Ansprüche in Form des Enantiomers der allgemeinen Formel I-S, worin R1, R2, R3, R4, R5, R6, R7, R8,15. Piperazine compounds according to one of the preceding claims in the form of the enantiomer of the general formula IS, in which R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 ,
R9 und R10 eine der zuvor angegebenen Bedeutungen aufweisen, oder einer Enantiomerenmischung, die einen Enantiomerenüberschuss bezüglich des Enantiomers der Formel I-S aufweist:R 9 and R 10 have one of the meanings given above, or an enantiomeric mixture which has an enantiomeric excess with respect to the enantiomer of the formula IS:
sowie die landwirtschaftlich geeigneten Salze dieser Verbindungen. and the agriculturally suitable salts of these compounds.
16. Piperazinverbindungen gemäß einem der vorhergehenden Ansprüche der allgemeinen Formel Ia, worin R1, R2, R3, R4, R5, R6 und R9 eine der zuvor angegebenen Bedeutungen aufweisen:16. piperazine compounds according to any one of the preceding claims of the general formula Ia, wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 9 have one of the meanings given above:
sowie die landwirtschaftlich geeigneten Salze dieser Verbindungen. and the agriculturally suitable salts of these compounds.
17. Piperazinverbindungen gemäß Anspruch 16 in Form des Enantiomers der allgemeinen Formel I-S.a, worin R1, R2, R3, R4, R5, R6 und R9 eine der zuvor angegebenen Bedeutungen aufweisen, oder einer Enantiomerenmischung, die einen Enantiomerenüberschuss bezüglich des Enantiomers der Formel I-S.a aufweist:17. piperazine compounds according to claim 16 in the form of the enantiomer of the general formula IS.a, wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 9 have one of the meanings given above, or an enantiomeric mixture, the has an enantiomeric excess with respect to the enantiomer of formula IS.a:
sowie die landwirtschaftlich geeigneten Salze dieser Verbindungen. and the agriculturally suitable salts of these compounds.
18. Piperazinverbindungen gemäß Anspruch 16 oder 17, worin18. piperazine compounds according to claim 16 or 17, wherein
R1 für Cyano oder Nitro steht;R 1 is cyano or nitro;
R2 für Wasserstoff, Fluor, Chlor, Ci-C2-Alkyl, Ethenyl oder Ci-C2-Alkoxy steht;R 2 is hydrogen, fluorine, chlorine, C 1 -C 2 -alkyl, ethenyl or C 1 -C 2 -alkoxy;
R3 Fluor oder Wasserstoff bedeutet;R 3 is fluorine or hydrogen;
R4 für Methyl steht;R 4 is methyl;
R5 für Wasserstoff, Methyl oder Ethyl steht;R 5 is hydrogen, methyl or ethyl;
R6 für Methyl oder Ethyl steht; undR 6 is methyl or ethyl; and
R9 Wasserstoff oder Halogen bedeutet.R 9 is hydrogen or halogen.
19. Piperazinverbindungen gemäß Anspruch 1 , ausgewählt unter:19. piperazine compounds according to claim 1, selected from:
2-[5-Benzyl-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-benzonitril,2- [5-Benzyl-1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -benzonitrile,
2-[5-Benzyl-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-fluorbenzonitril,2- [5-Benzyl-1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-fluorobenzonitrile,
2-[5-Benzyl-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-methoxy- benzonitril,2- [5-Benzyl-1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-methoxybenzonitrile,
2-[5-Benzyl-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3,4-difluor- benzonitril,2- [5-Benzyl-1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3,4-difluoro-benzonitrile,
2-[5-Benzyl-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-methyl- benzonitril,2- [5-Benzyl-1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-methylbenzonitrile,
2-[5-Benzyl-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-ethenyl- benzonitril,2- [5-Benzyl-1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-ethenylbenzonitrile,
2-[5-Benzyl-1 ,5-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-benzonitril,2- [5-Benzyl-1,5-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -benzonitrile,
2-[5-Benzyl-1 ,5-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-fluorbenzonitril,2- [5-Benzyl-1, 5-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-fluorobenzonitrile,
2-[5-Benzyl-1 ,5-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-methoxy- benzonitril,2- [5-Benzyl-1,5-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-methoxybenzonitrile,
2-[5-Benzyl-1 ,5-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3,4-difluorbenzonitril,2- [5-Benzyl-1,5-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3,4-difluorobenzonitrile,
2-[5-Benzyl-1 ,5-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-methylbenzonitril,2- [5-Benzyl-1, 5-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-methylbenzonitrile,
2-[5-Benzyl-1 ,5-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-ethenylbenzonitril,2- [5-Benzyl-1, 5-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-ethenylbenzonitrile,
2-[5-Benzyl-5-ethyl-1 ,4-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-benzonitril 2-[5-Benzyl-5-ethyl-1 ,4-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-fluor- benzonitril,2- [5-Benzyl-5-ethyl-1,4-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] benzonitrile 2- [5-benzyl-5-ethyl-1,4-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-fluorobenzonitrile,
2-[5-Benzyl-5-ethyl-1 ,4-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-methoxy- benzonitril, 2-[5-Benzyl-5-ethyl-1 ,4-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3,4-difluor- benzonitril,2- [5-Benzyl-5-ethyl-1,4-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-methoxybenzonitrile, 2- [5-benzyl-5-ethyl-1,4-dimethyl 3,6-dioxopiperazin-2-ylidenemethyl] -3,4-difluoro-benzonitrile,
2-[5-Benzyl-5-ethyl-1 ,4-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-methyl- benzonitril,2- [5-benzyl-5-ethyl-1,4-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-methylbenzonitrile,
2-[5-Benzyl-5-ethyl-1 ,4-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-ethenyl- benzonitril,2- [5-benzyl-5-ethyl-1,4-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-ethenylbenzonitrile,
2-[5-Benzyl-5-ethyl-1-methyl-3,6-dioxopiperazin-2-ylidenmethyl]-benzonitril,2- [5-benzyl-5-ethyl-1-methyl-3,6-dioxopiperazin-2-ylidenemethyl] -benzonitrile,
2-[5-Benzyl-5-ethyl-1-methyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-fluor- benzonitril,2- [5-benzyl-5-ethyl-1-methyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-fluoro-benzonitrile,
2-[5-Benzyl-5-ethyl-1-methyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-methoxy- benzonitril,2- [5-benzyl-5-ethyl-1-methyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-methoxybenzonitrile,
2-[5-Benzyl-5-ethyl-1-methyl-3,6-dioxopiperazin-2-ylidenmethyl]-3,4-difluor- benzonitril,2- [5-benzyl-5-ethyl-1-methyl-3,6-dioxopiperazin-2-ylidenemethyl] -3,4-difluoro-benzonitrile,
2-[5-Benzyl-5-ethyl-1-methyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-methyl- benzonitril, 2-[5-Benzyl-5-ethyl-1-methyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-ethenyl- benzonitril,2- [5-Benzyl-5-ethyl-1-methyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-methylbenzonitrile, 2- [5-benzyl-5-ethyl-1-methyl-3,6 dioxopiperazin-2-ylidenemethyl] -3-ethenylbenzonitrile,
3-Benzyl-6-[1-(2-nitrophenyl)-methyliden]-1 ,3,4-trimethylpiperazin-2,5-dion,3-Benzyl-6- [1- (2-nitrophenyl) -methylidene] -1,3,4-trimethyl-piperazine-2,5-dione,
3-Benzyl-6-[1-(2-fluor-6-nitrophenyl)-methyliden]-1 ,3,4-trimethylpiperazin-2,5- dion, 3-Benzyl-6-[1 -(2,3-difluor-6-nitrophenyl)-methyliden]-1 ,3,4-trimethylpiperazin-2,5- dion,3-Benzyl-6- [1- (2-fluoro-6-nitrophenyl) -methylidene] -1,3,4-trimethyl-piperazine-2,5-dione, 3-benzyl-6- [1 - (2,3- difluoro-6-nitrophenyl) methylidene] -1, 3,4-trimethylpiperazine-2,5-dione,
3-Benzyl-6-[1-(2-methoxy-6-nitrophenyl)-methyliden]-1 ,3,4-trimethylpiperazin-2,5- dion,3-Benzyl-6- [1- (2-methoxy-6-nitrophenyl) methylidene] -1,3,4-trimethylpiperazine-2,5-dione,
3-Benzyl-6-[1-(2-methyl-6-nitrophenyl)-methyliden]-1 ,3,4-trimethylpiperazin-2,5- dion,3-Benzyl-6- [1- (2-methyl-6-nitrophenyl) -methylidene] -1,3,4-trimethyl-piperazine-2,5-dione,
3-Benzyl-6-[1-(2-ethenyl-6-nitrophenyl)-methyliden]-1 ,3,4-trimethylpiperazin-2,5- dion,3-Benzyl-6- [1- (2-ethenyl-6-nitrophenyl) -methylidene] -1,3,4-trimethyl-piperazine-2,5-dione,
3-Benzyl-6-[1-(2-nitrophenyl)-methyliden]-1 ,3-dimethylpiperazin-2,5-dion,3-Benzyl-6- [1- (2-nitrophenyl) -methylidene] -1,3-dimethylpiperazine-2,5-dione,
3-Benzyl-6-[1-(2-fluor-6-nitrophenyl)-methyliden]-1 ,3-dimethylpiperazin-2,5-dion, 3-Benzyl-6-[1 -(2,3-difluor-6-nitrophenyl)-methyliden]-1 ,3-dimethylpiperazin-2,5- dion,3-Benzyl-6- [1- (2-fluoro-6-nitrophenyl) -methylidene] -1,3-dimethylpiperazine-2,5-dione, 3-benzyl-6- [1- (2,3-difluoro- 6-nitrophenyl) methylidene] -1,3-dimethylpiperazine-2,5-dione,
3-Benzyl-6-[1-(2-methoxy-6-nitrophenyl)-methyliden]-1 ,3-dimethylpiperazin-2,5- dion,3-Benzyl-6- [1- (2-methoxy-6-nitrophenyl) -methylidene] -1,3-dimethylpiperazine-2,5-dione,
3-Benzyl-6-[1-(2-methyl-6-nitrophenyl)-methyliden]-1 ,3-dimethylpiperazin-2,5- dion,3-Benzyl-6- [1- (2-methyl-6-nitrophenyl) methylidene] -1,3-dimethylpiperazine-2,5-dione,
3-Benzyl-6-[1-(2-ethenyl-6-nitrophenyl)-methyliden]-1 ,3-dimethylpiperazin-2,5- dion, 3-Benzyl-6-[1-(2-nitrophenyl)-methyliden]-3-ethyl-1 ,4-dimethylpiperazin-2,5-dion,3-Benzyl-6- [1- (2-ethenyl-6-nitrophenyl) -methylidene] -1,3-dimethylpiperazine-2,5-dione, 3-Benzyl-6- [1- (2-nitrophenyl) methylidene] -3-ethyl-1,4-dimethylpiperazine-2,5-dione,
3-Benzyl-6-[1-(2-fluor-6-nitrophenyl)-methyliden]-3-ethyl-1 ,4-dimethylpiperazin-3-Benzyl-6- [1- (2-fluoro-6-nitrophenyl) -methylidene] -3-ethyl-1,4-dimethylpiperazine
2,5-dion,2,5-dione,
3-Benzyl-6-[1-(2,3-difluor-6-nitrophenyl)-methyliden]-3-ethyl-1 ,4- dimethylpiperazin-2,5-dion,3-Benzyl-6- [1- (2,3-difluoro-6-nitrophenyl) -methylidene] -3-ethyl-1, 4-dimethylpiperazine-2,5-dione,
3-Benzyl-6-[1-(2-methoxy-6-nitrophenyl)-methyliden]-3-ethyl-1 ,4-dimethyl- piperazin-2,5-dion,3-Benzyl-6- [1- (2-methoxy-6-nitrophenyl) methylidene] -3-ethyl-1,4-dimethyl-piperazine-2,5-dione,
3-Benzyl-6-[1-(2-methyl-6-nitrophenyl)-methyliden]-3-ethyl-1 ,4-dimethylpiperazin-3-Benzyl-6- [1- (2-methyl-6-nitrophenyl) methylidene] -3-ethyl-1,4-dimethylpiperazine
2,5-dion, 3-Benzyl-6-[1 -(2-ethenyl-6-nitrophenyl)-methyliden]-3-ethyl-1 ,4-dimethyl- piperazin-2,5-dion,2,5-dione, 3-benzyl-6- [1- (2-ethenyl-6-nitrophenyl) -methylidene] -3-ethyl-1,4-dimethyl-piperazine-2,5-dione,
3-Benzyl-6-[1-(2-nitrophenyl)-methyliden]-3-ethyl-1-methylpiperazin-2,5-dion,3-Benzyl-6- [1- (2-nitrophenyl) methylidene] -3-ethyl-1-methylpiperazine-2,5-dione,
3-Benzyl-6-[1-(2-fluor-6-nitrophenyl)-methyliden]-3-ethyl-1-methylpiperazin-2,5- dion, 3-Benzyl-6-[1 -(2,3-difluor-6-nitrophenyl)-methyliden]-3-ethyl-1 -methylpiperazin-3-Benzyl-6- [1- (2-fluoro-6-nitrophenyl) -methylidene] -3-ethyl-1-methylpiperazine-2,5-dione, 3-benzyl-6- [1 - (2,3- difluoro-6-nitrophenyl) methylidene] -3-ethyl-1-methylpiperazine
2,5-dion,2,5-dione,
3-Benzyl-6-[1-(2-methoxy-6-nitrophenyl)-methyliden]-3-ethyl-1-methylpiperazin-3-Benzyl-6- [1- (2-methoxy-6-nitrophenyl) methylidene] -3-ethyl-1-methylpiperazin-
2,5-dion,2,5-dione,
3-Benzyl-6-[1-(2-methyl-6-nitrophenyl)-methyliden]-3-ethyl-1-methylpiperazin-2,5- dion,3-Benzyl-6- [1- (2-methyl-6-nitrophenyl) methylidene] -3-ethyl-1-methylpiperazine-2,5-dione,
3-Benzyl-6-[1-(2-ethenyl-6-nitrophenyl)-methyliden]-3-ethyl-1-methylpiperazin-3-Benzyl-6- [1- (2-ethenyl-6-nitrophenyl) methylidene] -3-ethyl-1-methylpiperazin-
2,5-dion2,5-dione
2-[5-(4-Fluorbenzyl)-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]- benzonitril, 2-[5-(4-Fluorbenzyl)-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3- fluorbenzonitril,2- [5- (4-fluorobenzyl) -1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -benzonitrile, 2- [5- (4-fluorobenzyl) -1, 4,5-trimethyl 3,6-dioxopiperazin-2-ylidenemethyl] -3-fluorobenzonitrile,
2-[5-(4-Fluorbenzyl)-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3- methoxybenzonitril,2- [5- (4-fluorobenzyl) -1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-methoxybenzonitrile,
2-[5-(4-Fluorbenzyl)-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3,4- difluorbenzonitril,2- [5- (4-fluorobenzyl) -1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3,4-difluorobenzonitrile,
2-[5-(4-Fluorbenzyl)-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-methyl- benzonitril,2- [5- (4-fluorobenzyl) -1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-methylbenzonitrile,
2-[5-(4-Fluorbenzyl)-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-ethenyl- benzonitril, 2-[5-(4-Fluorbenzyl)-1 ,5-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-benzonitril,2- [5- (4-fluorobenzyl) -1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-ethenylbenzonitrile, 2- [5- (4-fluorobenzyl) -1, 5 dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -benzonitrile,
2-[5-(4-Fluorbenzyl)-1 ,5-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3- fluorbenzonitril,2- [5- (4-fluorobenzyl) -1,5-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-fluorobenzonitrile,
2-[5-(4-Fluorbenzyl)-1 ,5-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-methoxy- benzonitril, 2-[5-(4-Fluorbenzyl)-1 ,5-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3,4-difluor- benzonitril, 2-[5-(4-Fluorbenzyl)-1 ,5-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-methyl- benzonitril,2- [5- (4-fluorobenzyl) -1, 5-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-methoxybenzonitrile, 2- [5- (4-fluorobenzyl) -1, 5-dimethyl 3,6-dioxopiperazin-2-ylidenemethyl] -3,4-difluoro-benzonitrile, 2- [5- (4-fluorobenzyl) -1, 5-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-methylbenzonitrile,
2-[5-(4-Fluorbenzyl)-1 ,5-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-ethenyl- benzonitril, 2-[5-(4-Fluorbenzyl)-5-ethyl-1 ,4-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]- benzonitril2- [5- (4-fluorobenzyl) -1, 5-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-ethenylbenzonitrile, 2- [5- (4-fluorobenzyl) -5-ethyl-1 , 4-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] benzonitrile
2-[5-(4-Fluorbenzyl)-5-ethyl-1 ,4-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3- fluorbenzonitril2- [5- (4-fluorobenzyl) -5-ethyl-1,4-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-fluorobenzonitrile
2-[5-(4-Fluorbenzyl)-5-ethyl-1 ,4-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3- methoxybenzonitril2- [5- (4-fluorobenzyl) -5-ethyl-1,4-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-methoxybenzonitrile
2-[5-(4-Fluorbenzyl)-5-ethyl-1 ,4-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3,4- difluorbenzonitril,2- [5- (4-fluorobenzyl) -5-ethyl-1,4-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3,4-difluorobenzonitrile,
2-[5-(4-Fluorbenzyl)-5-ethyl-1 ,4-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3- methylbenzonitril, 2-[5-(4-Fluorbenzyl)-5-ethyl-1 ,4-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3- ethenylbenzonitril,2- [5- (4-fluorobenzyl) -5-ethyl-1,4-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-methylbenzonitrile, 2- [5- (4-fluorobenzyl) -5-ethyl -1, 4-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-ethenylbenzonitrile,
2-[5-(4-Fluorbenzyl)-5-ethyl-1-methyl-3,6-dioxopiperazin-2-ylidenmethyl]- benzonitril,2- [5- (4-fluorobenzyl) -5-ethyl-1-methyl-3,6-dioxopiperazin-2-ylidenemethyl] -benzonitrile,
2-[5-(4-Fluorbenzyl)-5-ethyl-1-methyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-fluor- benzonitril,2- [5- (4-fluorobenzyl) -5-ethyl-1-methyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-fluorobenzonitrile,
2-[5-(4-Fluorbenzyl)-5-ethyl-1-methyl-3,6-dioxopiperazin-2-ylidenmethyl]-3- methoxybenzonitril,2- [5- (4-fluorobenzyl) -5-ethyl-1-methyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-methoxybenzonitrile,
2-[5-(4-Fluorbenzyl)-5-ethyl-1-methyl-3,6-dioxopiperazin-2-ylidenmethyl]-3,4- difluorbenzonitril, 2-[5-(4-Fluorbenzyl)-5-ethyl-1-methyl-3,6-dioxopiperazin-2-ylidenmethyl]-3- methylbenzonitril,2- [5- (4-fluorobenzyl) -5-ethyl-1-methyl-3,6-dioxopiperazin-2-ylidenemethyl] -3,4-difluorobenzonitrile, 2- [5- (4-fluorobenzyl) -5-ethyl 1-methyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-methylbenzonitrile,
2-[5-(4-Fluorbenzyl)-5-ethyl-1-methyl-3,6-dioxopiperazin-2-ylidenmethyl]-3- ethenylbenzonitril,2- [5- (4-fluorobenzyl) -5-ethyl-1-methyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-ethenylbenzonitrile,
3-(4-Fluorbenzyl)-6-[1-(2-nitrophenyl)-methyliden]-1 ,3,4-trimethylpiperazin-2,5- dion,3- (4-fluorobenzyl) -6- [1- (2-nitrophenyl) methylidene] -1,3,4-trimethylpiperazine-2,5-dione,
3-(4-Fluorbenzyl)-6-[1-(2-fluor-6-nitrophenyl)-methyliden]-1 ,3,4- trimethylpiperazin-2,5-dion,3- (4-fluorobenzyl) -6- [1- (2-fluoro-6-nitrophenyl) -methylidene] -1,3,4-trimethyl-piperazine-2,5-dione,
3-(4-Fluorbenzyl)-6-[1-(2,3-difluor-6-nitrophenyl)-methyliden]-1 ,3,4- trimethylpiperazin-2,5-dion, 3-(4-Fluorbenzyl)-6-[1 -(2-methoxy-6-nitrophenyl)-methyliden]-1 ,3,4- trimethylpiperazin-2,5-dion,3- (4-fluorobenzyl) -6- [1- (2,3-difluoro-6-nitrophenyl) -methylidene] -1,3,4-trimethyl-piperazine-2,5-dione, 3- (4-fluorobenzyl) - 6- [1- (2-methoxy-6-nitrophenyl) methylidene] -1,3,4-trimethylpiperazine-2,5-dione,
3-(4-Fluorbenzyl)-6-[1-(2-methyl-6-nitrophenyl)-methyliden]-1 ,3,4- trimethylpiperazin-2,5-dion,3- (4-fluorobenzyl) -6- [1- (2-methyl-6-nitrophenyl) methylidene] -1,3,4-trimethylpiperazine-2,5-dione,
3-(4-Fluorbenzyl)-6-[1-(2-ethenyl-6-nitrophenyl)-methyliden]-1 ,3,4- trimethylpiperazin-2,5-dion,3- (4-fluorobenzyl) -6- [1- (2-ethenyl-6-nitrophenyl) methylidene] -1,3,4-trimethylpiperazine-2,5-dione,
3-(4-Fluorbenzyl)-6-[1-(2-nitrophenyl)-methyliden]-1 ,3-dimethylpiperazin-2,5-dion, 3-(4-Fluorbenzyl)-6-[1-(2-fluor-6-nitrophenyl)-methyliden]-1 ,3-dimethylpiperazin-3- (4-fluorobenzyl) -6- [1- (2-nitrophenyl) methylidene] -1,3-dimethylpiperazine-2,5-dione, 3- (4-fluorobenzyl) -6- [1- (2-fluoro-6-nitrophenyl) -methylidene] -1,3-dimethylpiperazine
2,5-dion,2,5-dione,
3-(4-Fluorbenzyl)-6-[1-(2,3-difluor-6-nitrophenyl)-methyliden]-1 ,3- dimethylpiperazin-2,5-dion, 3-(4-Fluorbenzyl)-6-[1 -(2-methoxy-6-nitrophenyl)-methyliden]-1 ,3- dimethylpiperazin-2,5-dion,3- (4-fluorobenzyl) -6- [1- (2,3-difluoro-6-nitrophenyl) methylidene] -1,3-dimethylpiperazine-2,5-dione, 3- (4-fluorobenzyl) -6- [1- (2-methoxy-6-nitrophenyl) methylidene] -1,3-dimethylpiperazine-2,5-dione,
3-(4-Fluorbenzyl)-6-[1-(2-methyl-6-nitrophenyl)-methyliden]-1 ,3- dimethylpiperazin-2,5-dion,3- (4-fluorobenzyl) -6- [1- (2-methyl-6-nitrophenyl) methylidene] -1,3-dimethylpiperazine-2,5-dione,
3-(4-Fluorbenzyl)-6-[1-(2-ethenyl-6-nitrophenyl)-methyliden]-1 ,3- dimethylpiperazin-2,5-dion,3- (4-fluorobenzyl) -6- [1- (2-ethenyl-6-nitrophenyl) methylidene] -1,3-dimethylpiperazine-2,5-dione,
3-(4-Fluorbenzyl)-6-[1-(2-nitrophenyl)-methyliden]-3-ethyl-1 ,4-dimethylpiperazin-3- (4-fluorobenzyl) -6- [1- (2-nitrophenyl) methylidene] -3-ethyl-1,4-dimethylpiperazine
2,5-dion,2,5-dione,
3-(4-Fluorbenzyl)-6-[1-(2-fluor-6-nitrophenyl)-methyliden]-3-ethyl-1 ,4- dimethylpiperazin-2,5-dion, 3-(4-Fluorbenzyl)-6-[1 -(2,3-difluor-6-nitrophenyl)-methyliden]-3-ethyl-1 ,4- dimethylpiperazin-2,5-dion,3- (4-fluorobenzyl) -6- [1- (2-fluoro-6-nitrophenyl) methylidene] -3-ethyl-1,4-dimethylpiperazine-2,5-dione, 3- (4-fluorobenzyl) - 6- [1- (2,3-difluoro-6-nitrophenyl) methylidene] -3-ethyl-1,4-dimethylpiperazine-2,5-dione,
3-(4-Fluorbenzyl)-6-[1-(2-methoxy-6-nitrophenyl)-methyliden]-3-ethyl-1 ,4- dimethylpiperazin-2,5-dion,3- (4-fluorobenzyl) -6- [1- (2-methoxy-6-nitrophenyl) methylidene] -3-ethyl-1,4-dimethylpiperazine-2,5-dione,
3-(4-Fluorbenzyl)-6-[1-(2-methyl-6-nitrophenyl)-methyliden]-3-ethyl-1 ,4- dimethylpiperazin-2,5-dion,3- (4-fluorobenzyl) -6- [1- (2-methyl-6-nitrophenyl) methylidene] -3-ethyl-1,4-dimethylpiperazine-2,5-dione,
3-(4-Fluorbenzyl)-6-[1-(2-ethenyl-6-nitrophenyl)-methyliden]-3-ethyl-1 ,4-dimethyl- piperazin-2,5-dion,3- (4-fluorobenzyl) -6- [1- (2-ethenyl-6-nitrophenyl) methylidene] -3-ethyl-1,4-dimethyl-piperazine-2,5-dione,
3-(4-Fluorbenzyl)-6-[1-(2-nitrophenyl)-methyliden]-3-ethyl-1-methylpiperazin-2,5- dion, 3-(4-Fluorbenzyl)-6-[1 -(2-fluor-6-nitrophenyl)-methyliden]-3-ethyl-1 - methylpiperazin-2,5-dion,3- (4-fluorobenzyl) -6- [1- (2-nitrophenyl) methylidene] -3-ethyl-1-methylpiperazine-2,5-dione, 3- (4-fluorobenzyl) -6- [1 - ( 2-fluoro-6-nitrophenyl) methylidene] -3-ethyl-1-methylpiperazine-2,5-dione,
3-(4-Fluorbenzyl)-6-[1-(2,3-difluor-6-nitrophenyl)-methyliden]-3-ethyl-1- methylpiperazin-2,5-dion,3- (4-fluorobenzyl) -6- [1- (2,3-difluoro-6-nitrophenyl) methylidene] -3-ethyl-1-methylpiperazine-2,5-dione,
3-(4-Fluorbenzyl)-6-[1-(2-methoxy-6-nitrophenyl)-methyliden]-3-ethyl-1-methyl- piperazin-2,5-dion,3- (4-fluorobenzyl) -6- [1- (2-methoxy-6-nitrophenyl) methylidene] -3-ethyl-1-methylpiperazine-2,5-dione,
3-(4-Fluorbenzyl)-6-[1-(2-methyl-6-nitrophenyl)-methyliden]-3-ethyl-1- methylpiperazin-2,5-dion,3- (4-fluorobenzyl) -6- [1- (2-methyl-6-nitrophenyl) methylidene] -3-ethyl-1-methylpiperazine-2,5-dione,
3-(4-Fluorbenzyl)-6-[1-(2-ethenyl-6-nitrophenyl)-methyliden]-3-ethyl-1-methyl- piperazin-2,5-dion, 2-[5-Benzyl-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-brombenzonitπl,3- (4-fluorobenzyl) -6- [1- (2-ethenyl-6-nitrophenyl) methylidene] -3-ethyl-1-methylpiperazine-2,5-dione, 2- [5-benzyl-1 , 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-brombenzonitπl,
2-[5-Benzyl-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-isophthalonitπl,2- [5-Benzyl-1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -isophthalonitrile,
3-Benzyl-6-[1-(2,3-difluor-6-nitrophenyl)-methyliden]-1 ,3,4-trimethylpiperazin-2,5- dion,3-Benzyl-6- [1- (2,3-difluoro-6-nitrophenyl) -methylidene] -1,3,4-trimethyl-piperazine-2,5-dione,
3-Benzyl-6-[1-(2-nitro-5-methoxyphenyl)-methyliden]-1 ,3,4-trimethylpiperazin-2,5- dion,3-Benzyl-6- [1- (2-nitro-5-methoxyphenyl) methylidene] -1,3,4-trimethylpiperazine-2,5-dione,
2-[5-Benzyl-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-nitrobenzonitril, 3-Benzyl-6-[1-(2-ethenyl-6-nitrophenyl)-methyliden]-1 ,3,4-trimethylpiperazin-2,5- dion,2- [5-Benzyl-1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -3-nitrobenzonitrile, 3-Benzyl-6- [1- (2-ethenyl-6-nitrophenyl) -methylidene] -1,3,4-trimethyl-piperazine-2,5-dione,
3-Benzyl-6-[1-(3-chlor-2-nitrophenyl)-methyliden]-1 ,3,4-trimethylpiperazin-2,5- dion, 3-Benzyl-6-[1 -(2-nitro-6-trifluormethylphenyl)-methyliden]-1 ,3,4- trimethylpiperazin-2,5-dion,3-Benzyl-6- [1- (3-chloro-2-nitrophenyl) -methylidene] -1,3,4-trimethyl-piperazine-2,5-dione, 3-benzyl-6- [1- (2-nitro-) 6-trifluoromethylphenyl) methylidene] -1,3,4-trimethylpiperazine-2,5-dione,
2-[5-Benzyl-1 ,5-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-benzonitπl,2- [5-Benzyl-1, 5-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -benzonitrile,
3-Benzyl-6-[1-(2-methoxy-6-nitrophenyl)-methyliden]-1 ,3,4-trimethylpiperazin-2,5- dion, 2-[5-Benzyl-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-4-fluorbenzonitπl,3-Benzyl-6- [1- (2-methoxy-6-nitrophenyl) -methylidene] -1,3,4-trimethyl-piperazine-2,5-dione, 2- [5-benzyl-1, 4,5-trimethyl -3,6-dioxo-piperazine-2-ylidene] -4-fluorbenzonitπl,
2-[5-Benzyl-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-5- methylbenzonitril,2- [5-Benzyl-1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -5-methylbenzonitrile,
2-[5-Benzyl-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-6-fluorbenzonitπl,2- [5-Benzyl-1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -6-fluorobenzonitrile,
3-Benzyl-1 ,3,4-trimethyl-6-[2-(1 -methyl-1 H-pyrrol-2-yl)-benzyliden]-piperazin-2,5- dion,3-Benzyl-1,3,4-trimethyl-6- [2- (1-methyl-1H-pyrrol-2-yl) -benzylidene] -piperazine-2,5-dione,
3-Benzyl-6-(2-furan-2-yl-benzyliden)-1 ,3,4-trimethylpiperazin-2,5-dion,3-Benzyl-6- (2-furan-2-yl-benzylidene) -1, 3,4-trimethyl-piperazine-2,5-dione,
2-[5-Benzyl-5-fluormethyl-1 ,4-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]- benzonitril,2- [5-Benzyl-5-fluoromethyl-1,4-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -benzonitrile,
3-Benzyl-1 ,3,4-trimethyl-6-(4-methyl-2-nitrobenzyliden)-piperazin-2,5-dion, 2-[5-Benzyl-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-4- methoxybenzonitril,3-Benzyl-1, 3,4-trimethyl-6- (4-methyl-2-nitrobenzylidene) -piperazine-2,5-dione, 2- [5-benzyl-1, 4,5-trimethyl-3,6 dioxopiperazin-2-ylidenemethyl] -4-methoxybenzonitrile,
3-Benzyl-6-[2-(2-chlorpyrimidin-5-yl)-benzyliden]-1 ,3,4-trimethylpiperazin-2,5- dion,3-Benzyl-6- [2- (2-chloropyrimidin-5-yl) -benzylidene] -1,3,4-trimethyl-piperazine-2,5-dione,
3-Benzyl-6-[2-(6-fluorpyridin-2-yl)-benzyliden]-1 ,3,4-trimethylpiperazin-2,5-dion, 2-[5-Benzyl-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-4-fluorbenzonitπl,3-Benzyl-6- [2- (6-fluoropyridin-2-yl) -benzylidene] -1,3,4-trimethyl-piperazine-2,5-dione, 2- [5-benzyl-1, 4,5-trimethyl -3,6-dioxo-piperazine-2-ylidene] -4-fluorbenzonitπl,
2-[5-Benzyl-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-4- trifluormethylbenzonitril,2- [5-Benzyl-1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -4-trifluoromethylbenzonitrile,
3-Benzyl-1 ,3,4-trimethyl-6-[2-(1 -methyl-1 H-imidazol-2-yl)-benzyliden]-piperazin-3-Benzyl-1, 3,4-trimethyl-6- [2- (1-methyl-1H-imidazol-2-yl) -benzylidene] -piperazine
2,5-dion, 3-Benzyl-3-fluormethyl-1 ,4-dimethyl-6-(2-nitrobenzyliden)-piperazin-2,5-dion,2,5-dione, 3-benzyl-3-fluoromethyl-1, 4-dimethyl-6- (2-nitrobenzylidene) -piperazine-2,5-dione,
3-Benzyl-6-(5-brom-2-nitrobenzyliden)-1 ,3,4-trimethylpiperazin-2,5-dion,3-Benzyl-6- (5-bromo-2-nitrobenzylidene) -1, 3,4-trimethylpiperazine-2,5-dione,
2-[5-Benzyl-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-4- difluormethoxybenzonitril,2- [5-Benzyl-1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -4-difluoromethoxybenzonitrile,
2-[5-Benzyl-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-4- methansulfonylbenzonitril,2- [5-Benzyl-1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -4-methanesulfonylbenzonitrile,
2-[5-Benzyl-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-4- methansulfinylbenzonitril,2- [5-Benzyl-1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -4-methanesulfinylbenzonitrile,
2-[5-Benzyl-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-4- methylsulfanylbenzonitril, 2-[5-Benzyl-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-3-fluor-4- methoxybenzonitril, 2-[5-Benzyl-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-4,6- difluorbenzonitril,2- [5-Benzyl-1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -4-methylsulfanylbenzonitrile, 2- [5-Benzyl-1, 4,5-trimethyl-3,6-dioxopiperazine 2-ylidenemethyl] -3-fluoro-4-methoxybenzonitrile, 2- [5-Benzyl-1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -4,6-difluorobenzonitrile,
3-Benzyl-1 ,3,4-trimethyl-6-[2-(2-methyl-2H-pyrazol-3-yl)-benzyliden]-piperazin-3-Benzyl-1, 3,4-trimethyl-6- [2- (2-methyl-2H-pyrazol-3-yl) -benzylidene] -piperazine
2,5-dion, 3-Benzyl-1 ,3,4-trimethyl-6-[2-(5-methyl-thiophen-2-yl)-benzyliden]-piperazin-2,5- dion,2,5-dione, 3-benzyl-1, 3,4-trimethyl-6- [2- (5-methyl-thiophen-2-yl) -benzylidene] -piperazine-2,5-dione,
3-Benzyl-1 ,3,4-trimethyl-6-[2-(3-methyl-thiophen-2-yl)-benzyliden]-piperazin-2,5- dion,3-Benzyl-1,3,4-trimethyl-6- [2- (3-methyl-thiophen-2-yl) -benzylidene] -piperazine-2,5-dione,
2-[5-Benzyl-4-ethyl-1 ,5-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-benzonitril, 2-[5-Benzyl-4-isopropyl-1 ,5-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]- benzonitril,2- [5-Benzyl-4-ethyl-1,5-dimethyl-3,6-dioxopiperazin-2-ylidene-methyl] -benzonitrile, 2- [5-benzyl-4-isopropyl-1, 5-dimethyl-3,6 dioxopiperazin-2-ylidenemethyl] benzonitrile,
2-[5-Benzyl-4-butyl-1 ,5-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-benzonitril,2- [5-benzyl-4-butyl-1,5-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -benzonitrile,
2-[4-Allyl-5-benzyl-1 ,5-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-benzonitril,2- [4-allyl-5-benzyl-1, 5-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -benzonitrile,
2-[5-Benzyl-5-trifluormethyl-1 ,4-dimethyl-3,6-dioxopiperazin-2-ylidenmethyl]- benzonitril,2- [5-Benzyl-5-trifluoromethyl-1,4-dimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -benzonitrile,
3-Benzyl-6-[1-(2-nitrophenyl)-methyliden]-1 ,4-dimethyl-3-trifluormethylpiperazin-3-Benzyl-6- [1- (2-nitrophenyl) -methylidene] -1,4-dimethyl-3-trifluoromethylpiperazine
2,5-dion,2,5-dione,
3-Benzyl-6-[2-(6-chlorpyridin-3-yl)-benzyliden]-1 ,3,4-trimethylpiperazin-2,5-dion,3-Benzyl-6- [2- (6-chloropyridin-3-yl) -benzylidene] -1,3,4-trimethyl-piperazine-2,5-dione,
2-[5-Benzyl-1 ,5-dimethyl-4-prop-2-inyl-3,6-dioxopiperazin-2-ylidenmethyl]- benzonitril,2- [5-Benzyl-1, 5-dimethyl-4-prop-2-ynyl-3,6-dioxopiperazin-2-ylidenemethyl] benzonitrile,
3-(3-Fluorbenzyl)-6-[1-(2-nitrophenyl)-methyliden]-1 ,3,4-trimethylpiperazin-2,5- dion,3- (3-fluorobenzyl) -6- [1- (2-nitrophenyl) methylidene] -1,3,4-trimethylpiperazine-2,5-dione,
3-(3,5-Difluorbenzyl)-6-[1-(2-nitrophenyl)-methyliden]-1 ,3,4-trimethylpiperazin-2,5- dion, 2-[5-(2,3-Difluorbenzyl)-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]- benzonitril,3- (3,5-Difluorobenzyl) -6- [1- (2-nitrophenyl) methylidene] -1,3,4-trimethylpiperazine-2,5-dione, 2- [5- (2,3-difluorobenzyl) -1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] - benzonitrile,
2-[5-(2,5-Difluorbenzyl)-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]- benzonitril,2- [5- (2,5-difluorobenzyl) -1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] benzonitrile,
2-[5-(2,6-Difluorbenzyl)-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]- benzonitril,2- [5- (2,6-difluorobenzyl) -1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -benzonitrile,
2-[5-(2-Difluormethoxybenzyl)-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]- benzonitril,2- [5- (2-Difluoromethoxybenzyl) -1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] benzonitrile,
2-[5-(3-Difluormethoxybenzyl)-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]- benzonitril, 2-[5-(3-Trifluormethylbenzyl)-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]- benzonitril,2- [5- (3-Difluoromethoxybenzyl) -1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -benzonitrile, 2- [5- (3-trifluoromethylbenzyl) -1, 4,5-trimethyl 3,6-dioxopiperazin-2-ylidenemethyl] -benzonitrile,
3-(3-Fluorbenzyl)-6-[1-(2-nitrophenyl)-methyliden]-1 ,3,4-trimethylpiperazin-2,5- dion,3- (3-fluorobenzyl) -6- [1- (2-nitrophenyl) methylidene] -1,3,4-trimethylpiperazine-2,5-dione,
2-[5-(2-Cyanobenzyl)-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]- benzonitril,2- [5- (2-cyanobenzyl) -1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -benzonitrile,
2-[5-(3-Cyanobenzyl)-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]- benzonitril, 2-[5-(3,5-Difluorbenzyl)-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]- benzonitril,2- [5- (3-cyanobenzyl) -1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -benzonitrile, 2- [5- (3,5-difluorobenzyl) -1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] benzonitrile,
2-[5-(3-Nitrobenzyl)-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]-benzonitril,2- [5- (3-nitrobenzyl) -1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -benzonitrile,
2-[5-(4-Fluor-3-methylbenzyl)-1 ,4,5-trimethyl-3,6-dioxopiperazin-2-ylidenmethyl]- benzonitril,2- [5- (4-fluoro-3-methylbenzyl) -1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -benzonitrile,
2-[5-(4-Fluor-3-methoxybenzyl)-1 ,4,5-trimethyl-3,6-dioxopiperazin-2- ylidenmethyl]-benzonitril,2- [5- (4-fluoro-3-methoxybenzyl) -1, 4,5-trimethyl-3,6-dioxopiperazin-2-ylidenemethyl] -benzonitrile,
1-Allyl-3-benzyl-3,4-dimethyl-6-[1-(2-nitrophenyl)-methyliden]-piperazin-2,5-dion und1-allyl-3-benzyl-3,4-dimethyl-6- [1- (2-nitrophenyl) -methylidene] -piperazine-2,5-dione and
3-Benzyl-6-[1-(2-nitrophenyl)-methyliden]-1-prop-2-inyl-3,4-dimethylpiperazin-2,5- dion.3-Benzyl-6- [1- (2-nitrophenyl) -methylidene] -1-prop-2-ynyl-3,4-dimethylpiperazine-2,5-dione.
20. Piperazinverbindungen gemäß einem der vorhergehenden Ansprüche, wobei die exo-Doppelbindung am Piperazinring die (Z)-Konfiguration aufweist.20. piperazine compounds according to any one of the preceding claims, wherein the exo-double bond on the piperazine ring has the (Z) configuration.
21. Verwendung von Piperazinverbindungen der Formel I bzw. Ia gemäß einem der Ansprüche 1 bis 20 und deren landwirtschaftlich geeignete Salze als Herbizide.21. Use of piperazine compounds of the formula I or Ia according to any one of claims 1 to 20 and their agriculturally suitable salts as herbicides.
22. Mittel, enthaltend eine herbizid wirksame Menge mindestens einer Piperazinver- bindung der Formel I bzw. Ia oder eines landwirtschaftlich geeigneten Salzes von I bzw. Ia nach einem der Ansprüche 1 bis 20 und für die Formulierung von Pflanzenschutzmitteln übliche Hilfsmittel.22. A composition comprising a herbicidally effective amount of at least one piperazine compound of the formula I or Ia or an agriculturally suitable salt of I or Ia according to any one of claims 1 to 20 and for the formulation of pesticides usual auxiliaries.
23. Verfahren zur Bekämpfung von unerwünschtem Pflanzenwuchs, dadurch ge- kennzeichnet, dass man eine herbizid wirksame Menge mindestens einer Pipe- razinverbindung der Formel I bzw. Ia oder eines landwirtschaftlich brauchbaren Salzes von I bzw. Ia nach einem der Ansprüche 1 bis 20 auf Pflanzen, deren Samen und/oder deren Lebensraum einwirken lässt.23. A method for controlling undesired plant growth, characterized in that a herbicidally effective amount of at least one piperazine compound of the formula I or Ia or an agriculturally useful salt of I or Ia according to any one of claims 1 to 20 on plants whose seeds and / or their habitat act.
24. Verfahren zur Herstellung einer Verbindung der allgemeinen Formel I gemäß einem der Ansprüche 1 bis 20, umfassend:24. A process for the preparation of a compound of general formula I according to any one of claims 1 to 20, comprising:
i) die Bereitstellung einer Verbindung der allgemeinen Formel Ili) the provision of a compound of general formula II
worin R1, R2, R3, R7, R8, R9 und R10 die zuvor genannten Bedeutungen, insbesondere eine der als bevorzugt genannten Bedeutungen aufweisen, R4a für Wasserstoff oder eine Schutzgruppe steht oder eine der für R4 angegebenen Bedeutungen hat und R5a eine der für R5 angegebenen Bedeutungen hat oder für eine Schutzgruppe steht; wherein R 1, R 2, R 3, R 7, R 8, R 9 and R 10 are as defined above, in particular have one of the preferred meanings mentioned, R 4a is hydrogen or a protecting group or one of the given for R 4 Has meanings and R 5a has one of the meanings given for R 5 or is a protective group;
ii) gegebenenfalls Umsetzung der Verbindung II, worin R4a für Wasserstoff steht mit einem Alkylierungsmittel der Formel R4-X1 worin R4 die zuvor angegebenen Bedeutungen aufweist und X1 für eine nucleophil verdrängbare Abgangsgruppe steht, in Gegenwart einer Base;ii) optionally reacting the compound II, wherein R 4a is hydrogen with an alkylating agent of the formula R 4 -X 1 in which R 4 has the meanings given above and X 1 is a nucleophilically displaceable leaving group, in the presence of a base;
iii) gegebenenfalls Umsetzung der Verbindung II, worin R5a für Wasserstoff steht mit einem Alkylierungsmittel der Formel R5-X1 oder einem Acylie- rungsmittel der Formel R5-X2, worin R5 die zuvor angegebenen, von Wasserstoff verschiedenen Bedeutungen aufweist und X1 und X2 für eine nucleophil verdrängbare Abgangsgruppe stehen, in Gegenwart einer Base;iii) if appropriate, reaction of the compound II in which R 5a is hydrogen with an alkylating agent of the formula R 5 -X 1 or an acylating agent of the formula R 5 -X 2 , in which R 5 has the meanings indicated above, other than hydrogen, and X 1 and X 2 are a nucleophilically displaceable leaving group, in the presence of a base;
iv) Umsetzung der Verbindung Il mit einem Alkylierungsmittel der Formel R6-X worin R6 die zuvor angegebenen Bedeutungen aufweist und X für eine nucleophil verdrängbare Abgangsgruppe steht, in Gegenwart einer Base; undiv) reacting the compound II with an alkylating agent of the formula R 6 -X in which R 6 has the meanings given above and X is a nucleophilically displaceable leaving group, in the presence of a base; and
v) wenn R4a und/oder R5a für einen Schutzgruppe steht, Entfernen derv) when R 4a and / or R 5a is a protecting group, removing the
Schutzgruppe, und gegebenenfalls Umsetzung der dabei erhaltenen Verbindung II, worin R4a und/oder R5a für Wasserstoff steht mit einem Alkylierungsmittel der Formel R4-X1, und/oder R5-X1 oder einem Acylierungsmittel R5-X2, worin R4 bzw. R5 die zuvor angegebenen, von Wasserstoff verschiedenen Bedeutungen aufweisen und X1 und X2 für eine nucleophil verdrängbare Abgangsgruppe stehen, in Gegenwart einer Base.Protecting group, and optionally reacting the compound II thus obtained wherein R 4a and / or R 5a is hydrogen with an alkylating agent of the formula R 4 -X 1, and / or R 5 -X 1 or an acylating agent R 5 -X 2, wherein R 4 and R 5 have the meanings given above, other than hydrogen and X 1 and X 2 are a nucleophilically displaceable leaving group, in the presence of a base.
25. Verfahren nach Anspruch 24, wobei die Bereitstellung der Verbindung Il in Schritt i) die Umsetzung einer Verbindung der Formel III mit einer Verbindung der Formel IV in Gegenwart einer Base umfasst:25. The method of claim 24, wherein the preparation of compound II in step i) comprises reacting a compound of formula III with a compound of formula IV in the presence of a base:
worin R1, R2, R3, R4a, R5a, R7, R8, R9 und R10 die zuvor genannten Bedeutungen aufweisen. wherein R 1 , R 2 , R 3 , R 4a , R 5a , R 7 , R 8 , R 9 and R 10 have the meanings given above.
26. Verfahren zur Herstellung einer Verbindung der allgemeinen Formel I gemäß einem der Ansprüche 1 bis 20, umfassend:26. A process for the preparation of a compound of general formula I according to any one of claims 1 to 20, comprising:
i) die Bereitstellung einer Verbindung der allgemeinen Formel I'i) the provision of a compound of general formula I '
worin R1, R2, R3, R6, R7, R8, R9 und R10 die zuvor genannten Bedeutungen, insbesondere eine der als bevorzugt genannten Bedeutungen aufweisen, R4c für Wasserstoff oder eine Schutzgruppe steht und R5c eine der für R5 angegebenen Bedeutungen hat oder für eine Schutzgruppe steht;wherein R 1 , R 2 , R 3 , R 6 , R 7 , R 8 , R 9 and R 10 have the abovementioned meanings, in particular one of the meanings mentioned as preferred, R 4c is hydrogen or a protective group and R 5c is a has the meanings given for R 5 or is a protective group;
ii) gegebenenfalls Entfernen der Schutzgruppen R4c und/oder R5c;ii) optionally removing the protecting groups R 4c and / or R 5c ;
iii) Umsetzung der Verbindung Ia, worin R4c für Wasserstoff steht, mit einem Alkylierungsmittel der Formel R4-X1 worin R4 die zuvor angegebenen Bedeutungen aufweist und X1 für eine nucleophil verdrängbare Abgangsgruppe steht, in Gegenwart einer Base; undiii) reacting the compound Ia, wherein R 4c is hydrogen, with an alkylating agent of the formula R 4 -X 1 in which R 4 has the meanings given above and X 1 is a nucleophilically displaceable leaving group, in the presence of a base; and
iv) gegebenenfalls Umsetzung der Verbindung Ia, worin R5c für Wasserstoff steht mit einem Alkylierungsmittel der Formel R5-X1 oder einem Acylie- rungsmittel der Formel R5-X2, worin R5 die zuvor angegebenen Bedeutungen, von Wasserstoff verschiedenen Bedeutungen aufweist und X1 und X2 für eine nucleophil verdrängbare Abgangsgruppe stehen, in Gegenwart einer Base.iv) if appropriate, reaction of the compound Ia in which R 5c is hydrogen with an alkylating agent of the formula R 5 -X 1 or an acylating agent of the formula R 5 -X 2 , where R 5 has the meanings given above, other than hydrogen and X 1 and X 2 are a nucleophilically displaceable leaving group, in the presence of a base.
27. Verfahren nach Anspruch 26, wobei die Bereitstellung der Verbindung Ia in27. The method of claim 26, wherein the provision of the compound Ia in
Schritt i) die Umsetzung einer Verbindung der Formel III mit einer Verbindung der Formel IVa in Gegenwart einer Base umfasst: Step i) comprises reacting a compound of the formula III with a compound of the formula IVa in the presence of a base:
worin R1, R2, R3, R4c, R5c, R7, R8, R9 und R10 die zuvor genannten Bedeutungen aufweisen.wherein R 1 , R 2 , R 3 , R 4c , R 5c , R 7 , R 8 , R 9 and R 10 have the meanings given above.
28. Verfahren zur Herstellung einer Verbindung der allgemeinen Formel I gemäß einem der Ansprüche 1 bis 20, umfassend:28. A process for the preparation of a compound of general formula I according to any one of claims 1 to 20, comprising:
i) die Bereitstellung einer Verbindung der allgemeinen Formel IXi) the provision of a compound of general formula IX
worin R1, R2, R3, R4 und R6 die zuvor genannten Bedeutungen aufweisen, und R5a eine der für R5 angegebenen, von Wasserstoff verschiedenen Bedeutungen aufweist oder für eine Schutzgruppe steht;wherein R 1 , R 2 , R 3 , R 4 and R 6 have the abovementioned meanings, and R 5a has one of the meanings given for R 5 other than hydrogen or is a protective group;
ii) Umsetzung der Verbindung IX mit einer Benzylverbindung der Formel Xii) reaction of the compound IX with a benzyl compound of the formula X.
worin R7, R8, R9 und R10 die zuvor angegebenen Bedeutungen aufweisen und X für eine nucleophil verdrängbare Abgangsgruppe steht, in Gegenwart einer Base; und wherein R 7 , R 8 , R 9 and R 10 have the meanings given above and X is a nucleophilically displaceable leaving group, in the presence of a base; and
iii) wenn R5a für einen Schutzgruppe steht, Entfernen der Schutzgruppe. iii) when R 5a is a protecting group, deprotecting.
29. Verfahren nach Anspruch 28, wobei die Bereitstellung der Verbindung IX in29. The method of claim 28, wherein providing the compound IX in
Schritt i) die Umsetzung der Verbindung der Formel Xl mit einer Verbindung der Formel XII in Gegenwart einer Base umfasst:Step i) comprises reacting the compound of the formula XI with a compound of the formula XII in the presence of a base:
(Xl) (XII)(XI) (XII)
worin R1, R2, R3, R5a und R6 die zuvor genannten Bedeutungen aufweisen, und R4a eine der für R4 angegebenen Bedeutungen aufweist oder für eine Schutzgruppe steht. wherein R 1 , R 2 , R 3 , R 5a and R 6 have the meanings given above, and R 4a has one of the meanings given for R 4 or is a protective group.
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