[go: up one dir, main page]

EP2064188A1 - Pyridazines fongicides, leur procédé de fabrication et leur utilisation pour lutter contre les champignons parasites et agent les contenant - Google Patents

Pyridazines fongicides, leur procédé de fabrication et leur utilisation pour lutter contre les champignons parasites et agent les contenant

Info

Publication number
EP2064188A1
EP2064188A1 EP08736575A EP08736575A EP2064188A1 EP 2064188 A1 EP2064188 A1 EP 2064188A1 EP 08736575 A EP08736575 A EP 08736575A EP 08736575 A EP08736575 A EP 08736575A EP 2064188 A1 EP2064188 A1 EP 2064188A1
Authority
EP
European Patent Office
Prior art keywords
compounds
formula
row
alkyl
compound corresponds
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Withdrawn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
EP08736575A
Other languages
German (de)
English (en)
Inventor
Jochen Dietz
Marianna Vrettou
Bernd Müller
Jens Renner
Sarah Ulmschneider
Jan Klaas Lohmann
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 EP08736575A priority Critical patent/EP2064188A1/fr
Publication of EP2064188A1 publication Critical patent/EP2064188A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
    • C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
    • C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D237/12—Halogen atoms or nitro radicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
    • C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
    • C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D237/14—Oxygen atoms
    • C07D237/16—Two oxygen atoms

Definitions

  • Fungicidal pyridazines process for their preparation and their use to control harmful fungi and agents containing them
  • the present invention relates to pyridazines of the formula I.
  • R 1 , R 4 are independently halogen, cyano, Ci-Cs-alkyl or Ci-Cs-alkoxy;
  • R 2 Ci-Ci2-alkyl, Ci-Cio-haloalkyl, C 2 -Cio-alkenyl, C 2 -Cio-haloalkenyl, C 2 -C 0 - alkynyl, C 2 -Cio-haloalkynyl, C 3 -C 6 cycloalkyl , C 3 -C 8 cycloalkenyl, C 3 -C 2 - cycloalkenyl, C 3 -C 6 halocycloalkyl, C3-Ci 2 halocycloalkenyl, aryl or aromatic heterocycle containing besides carbon atoms one to four nitrogen atoms or one to three nitrogen atoms and one Sulfur or oxygen as ring members, wherein the aromatic groups are five-, six-, seven-, eight-, nine
  • R a is cyano, nitro, hydroxy, carboxyl, Ci -C 6 -alkyl, C 2 -C 6 -alkyl kinyl, C 3 -C 6 -CyCIo- alkyl, C 3 -C 8 cycloalkenyl, C 6 - alkoxy, C 2 -C 6 kenyloxy -alkyl, C 3 -C 6 -alkyl kinyl- oxy, Cs-Ce-cycloalkoxy, C 3 -C 6 -cycloalkenyloxy, C (O) R ⁇ , C (O) OR ⁇ , C (S) OR ⁇ , C (O) SR ⁇ , C (S) SR ⁇ , OC (O) OR ⁇ , d-C ⁇ alkylthio, amino, -C 6 - alkylamino, di-Ci-C 6 -alkylamino, C 1 -C 6 -alkylene, oxy-
  • R a and R ⁇ are in turn partially halogenated or fully halogenated and / or can carry one, two or three groups R b :
  • R b is halogen, cyano, nitro, hydroxy, mercapto , Amino, carboxyl, alkyl,
  • Haloalkyl alkenyl, alkoxy, haloalkoxy, alkenyloxy, alkynyloxy, alkylthio, alkylamino, dialkylamino, formyl, alkylcarbonyl, alkylsulfonyl, alkylsulfoxyl, alkoxycarbonyl, alkylcarbonyloxy, alkoxycarbonyloxy, aminocarbonyl, aminothiocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkylaminothiocarbonyl, dialkylaminothiocarbonyl, wherein the alkyl groups in these groups contain 1 to 6 carbon atoms and said alkenyl or alkynyl groups in these groups contain 2 to 8 carbon atoms; Cycloalkyl, cycloalkoxy, heterocyclyl, heterocyclyloxy, wherein the cyclic systems contain 3 to 10 ring members; Aryl, aryloxy, arylthio,
  • R 3 is phenyl or a 5- or 6-membered heteroaromatic group containing in addition to carbon atoms 1, 2, 3 or 4 heteroatoms selected from O, S and N as ring members, wherein phenyl or the heteroaromatic group has a substituent L 1, and optionally substituent L contributes m;
  • T 2 is O, S or NR h ;
  • R h is independently h is hydrogen or has one of the meanings mentioned for R ⁇ ; and R 1 , R "independently of one another represent one of the groups mentioned for R a ; independently of one another halogen, hydroxy, mercapto (SH), cyanato (OCN), cyano, nitro, C 1 -C 8 -alkyl, C 1 -C 4 -alkyl 8 haloalkyl, C 2 -C 0 - alkenyl, C 2 -C 0 haloalkenyl, C 2 -C 0 alkynyl, C 3 -C 6 cycloalkyl, C 3 -C 6 - halocycloalkyl, Cs-C ⁇ cycloalkenyl, Ci-Cs-alkoxy, Ci-Cs-oxy halogenoAlk-, C 2 -C 0 alkenyl
  • the invention relates to processes and intermediates for the preparation of these compounds, compositions containing them and their use for controlling phytopathogenic harmful fungi.
  • the invention relates to the use of pyridazines for the manufacture of a medicament for the treatment of cancer.
  • the object of the present invention is to provide compounds with improved activity and / or broadened spectrum of activity.
  • Pyridazines of formula I, R 1 and R 4 are in the two groups represents halogen, in particular chlorine, are advantageously accessible by halogenation of the compounds of the formula II with a halogenating agent [HAL] in the following way. They correspond to the formula 1.1, in which Hal is halogen, preferably bromine or chlorine, in particular chlorine.
  • halogenating agents are chlorinating or brominating agents, such as phosphorus oxybromide, phosphorus oxychloride, thionyl chloride, thionyl bromide or sulfonyl. chloride, in particular phosphorus oxychloride in question.
  • the reaction may be carried out neat or in the presence of a solvent.
  • the halogenating agent is generally used in equimolar amounts. It can also be used in excess or as a solvent.
  • Suitable solvents are aliphatic hydrocarbons such as pentane, hexane, cyclohexane and petroleum ether, aromatic hydrocarbons such as toluene, o-, m- and p-xylene, halogenated hydrocarbons such as methylene chloride, 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, iso
  • This reaction is usually carried out at temperatures of from -3O 0 C to 15O 0 C, preferably 5O 0 C to 12O 0 C, in an inert organic solvent or in suitable inorganic or organic acids, and water instead of [cp. Eur J Org Chem, 2004, 2797-2804; J Chem Soc, 1970, 1316; WO 2006/032518; Heteroatom Chem, 16 (4), 298-307, 2005; HeIv Chim Acta, 85 (7), 2195-2213, 2002].
  • Suitable solvents are ethers such as diethyl ether, diisopropyl ether, tert-butyl methyl ether, dioxane, anisole and tetrahydrofuran, alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol and tert-butanol. It is also possible to use mixtures of the solvents mentioned.
  • the acids used are inorganic acids such as hydrofluoric acid, hydrochloric acid, hydrobromic acid, sulfuric acid and perchloric acid, and organic acids such as formic acid, acetic acid, propionic acid, oxalic acid, toluenesulfonic acid, benzenesulfonic acid, camphorsulfonic acid, citric acid and trifluoroacetic acid.
  • the starting materials are generally reacted with one another in equimolar amounts. It may be advantageous for the yield to use hydrazine or hydrazine hydrate in an excess of up to 5 molar equivalents based on III.
  • the furandions of the formula III are advantageously obtained by oxidative cyclization of esters of the formula IV.
  • This reaction is usually carried out at temperatures from -3O 0 C to + 100 0 C, preferably +1 0 0 C to + 5O 0 C, in an inert organic solvent in the presence a base [cf. Synlett, 2002, (6), 947-951; Bioorg Med Chem Lett, 2003, 13, 1 195].
  • a base cf. Synlett, 2002, (6), 947-951; Bioorg Med Chem Lett, 2003, 13, 1 195].
  • the oxidizing agent is, for example, oxygen in question.
  • Suitable solvents are aliphatic hydrocarbons such as pentane, hexane, cyclohexane and petroleum ether, aromatic hydrocarbons such as toluene, o-, m- and p-xylene, halogenated hydrocarbons such as methylene chloride, 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 and tert-butanol, as well as Dimethyl sulfoxide
  • Bases are generally inorganic compounds such as alkali metal and alkaline earth metal hydroxides such as lithium hydroxide, sodium hydroxide, potassium hydroxide and calcium hydroxide, alkali metal and 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, sodium amide and potassium amide, alkali metal and alkaline earth metal carbonates such as lithium carbonate, potassium 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 phenyl lithium, alkylmagnesium halides such as methylmagnesium chloride and also alkali metal and alkaline earth metal alcoholates.
  • alkali metal and alkaline earth metal hydroxides such as lithium hydro
  • te as sodium methoxide, sodium ethoxide, potassium, potassium tert-butoxide and Dimethoxymagnesium
  • organic bases eg tertiary amines such as trimethylamine, triethylamine, diisopropylethylamine and N-methylpiperidine, pyridine, substituted pyridines such as collidine, lutidine and 4-dimethylaminopyridine as well as bicyclic amines such as 1, 8-diazabicyclo [5.4.0] undec-7 -en (DBU).
  • DBU 1, 8-diazabicyclo [5.4.0] undec-7 -en
  • the bases are generally used in catalytic amounts, but they can also be used equimolar, in excess or optionally as a solvent.
  • the starting materials are generally reacted with one another in equimolar amounts. It may be advantageous for the yield to use the base in about 3 molar equivalents based on IV.
  • esters of the formula IV are obtainable by condensation of carboxylic acids of the formula V or their sodium or potassium salts, with halides of the formula VI, in which X is a halogen, such as iodine, chlorine or bromine, preferably chlorine or bromine.
  • This reaction is usually carried out at temperatures of - 5O 0 C to 100 0 C, preferably 25 0 C to 100 0 C, in an inert organic solvent in the presence or absence of a base [see. Bioorg Med Chem Lett, 2003, 13, 1195; Synth. Commun., 25 (12), 1681-1686, 2005, Org Prep and Proc Int, 20 (5), 527-532, 1988; Synth Commun, 16 (14), 1777-1780, 1986].
  • Suitable solvents are water, aliphatic hydrocarbons such as pentane, hexane, cyclohexane and petroleum ether, aromatic hydrocarbons such as toluene, o-, m- and p-xylene, halogenated hydrocarbons such as methylene chloride, 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 and tert-butanol, as well as Dimethylsulfoxide
  • Bases generally include inorganic compounds such as alkali metal and alkaline earth metal hydroxides such as lithium hydroxide, sodium hydroxide, potassium hydroxide and calcium hydroxide, alkali metal and alkaline earth metal oxides such as lithium oxide, sodium oxide, calcite 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, sodium amide and potassium amide, alkali metal and alkaline earth metal carbonates such as lithium carbonate, potassium 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 phenyl lithium, alkylmagnesium halides such as methylmagnesium chloride and also alkali metal and alkaline earth metal alcoholates.
  • alkali metal and alkaline earth metal hydroxides such as
  • te as sodium methoxide, sodium ethoxide, potassium, potassium tert-butoxide and Dimethoxymagnesium
  • organic bases eg tertiary amines such as trimethylamine, triethylamine, diisopropylethylamine, trisdioxaheptylamine (TDA) and N-methylpiperidine, pyridine, substituted pyridines such as collidine, lutidine and 4-dimethylaminopyridine and also bicyclic amines.
  • bases such as potassium carbonate and TDA.
  • the bases are generally used in catalytic amounts, but they can also be used equimolar, in excess or optionally as a solvent.
  • Halides of the formula VI, in which X is a halogen, such as iodine, bromine or chlorine, in particular chlorine or bromine, are accessible by halogenation of ketones of the formula VII.
  • halogenating agents are elemental halogens such as chlorine or bromine, in particular bromine, or other common halogenating agents such as N-bromosuccinimide, thionyl chloride, sulfuryl chloride, Cu (2) bromide or benzyltrimethylammonium tribromide.
  • Suitable solvents are ethers such as diethyl ether, diisopropyl ether, tert-butyl methyl ether, dioxane, anisole and tetrahydrofuran (THF), particularly preferably THF or halogenated hydrocarbons such as methylene chloride, chloroform and carbon tetrachloride, but also further solvents such as, for example, ethyl acetate ,
  • the acids used are organic acids such as formic acid, acetic acid, propionic acid, oxalic acid, toluenesulfonic acid, benzenesulfonic acid, camphorsulfonic acid, citric acid and trifluoroacetic acid. It is also possible to use mixtures of the solvents mentioned.
  • This reaction is usually carried out at temperatures of from 0 C to 15O 0 C, preferably 0 ° C to 5O 0 C, in an inert organic solvent in the presence of a base and of a catalyst [see. Tetrahedron Lett, 47 (2006), 2107-2109].
  • Suitable solvents are aliphatic hydrocarbons such as pentane, hexane, cyclohexane and petroleum ether, aromatic hydrocarbons such as toluene, o-, m- and p-xylene, halogenated hydrocarbons such as methylene chloride, 1, 2-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 and tert.
  • Bases are generally inorganic compounds such as alkali metal and alkaline earth metal hydroxides such as lithium hydroxide, sodium hydroxide, potassium hydroxide and calcium hydroxide, alkali metal and 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, sodium amide and potassium amide, alkali metal and alkaline earth metal carbonates such as lithium carbonate, potassium 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 phenyl lithium, alkylmagnes
  • tertiary amines such as trisodium methylamine, triethylamine, tributylamine, di-isopropylethylamine and N-methylpiperidine, pyridine, substituted pyridines such as collidine, lutidine and 4-dimethylaminopyridine and bicyclic amines into consideration.
  • tributylamine Especially preferred is tributylamine.
  • the bases are generally used in catalytic amounts, but they can also be used equimolar, in excess or optionally as a solvent.
  • Acids and acid catalysts are Lewis acids such as boron trifluoride, aluminum trichloride, ferric chloride, tin IV chloride, titanium-IV chloride and zinc-II chloride, preferably titanium-IV chloride use.
  • ⁇ -Ketocarbonklareester of formula VIII are preferably accessible under Grignard conditions from the corresponding (hetero) aryl halides, in particular (hetero) aryl bromides R 3 -X of the formula X in which X is halogen, such as chlorine or bromine, especially bromine , and the corresponding oxalic acid dialkyl esters of the formula XI, in particular
  • This reaction usually takes place in the first step at temperatures of
  • Preferred Grignard salts are C 1 -C 4 -alkylmagnesium chlorides, in particular isopropylmagnesium chloride.
  • Suitable solvents are the oxalic acid of the formula XI, aliphatic hydrocarbons such as pentane, hexane, cyclohexane and petroleum ether, aromatic hydrocarbons such as toluene, o-, m- and p-xylene, halogenated hydrocarbons such as methylene chloride, chloroform and chlorobenzene, ethers such as diethyl ether, diisopropyl ether, tert-butyl methyl ether, dioxane, anisole and tetrahydrofuran (THF), 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 and tert-butanol, and dimethyl sulfoxide, dimethylformamide and dimethylacetamide, particularly preferred are ethers such as Diethyl ether or THF. It is also possible to use mixtures of the solvents mentioned.
  • the reaction of the Grignard compound formed in the first step with the oxalic acid esters is usually carried out at temperatures from -78 0 C to + 100 0 C, preferably +1 0 0 C to + 5O 0 C, in an inert organic solvent [cf. Ref. J Med Chem, 49, (4), 1271-1281, 2006; JOC, 68 (10), 3990-3998, 2003].
  • Suitable solvents are aliphatic hydrocarbons such as pentane, hexane, cyclohexane and petroleum ether, aromatic hydrocarbons such as toluene, o-, m- and p-xylene, halogenated hydrocarbons such as methylene chloride, 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, methylethyl ketone, diethyl ketone and tert-butyl methyl ketone, alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol and tert-butanol, and also dimethyl sulfoxide, di
  • ⁇ -ketocarboxylic esters of the formula VIII can be prepared directly from oxalic esters of the formula XI and the corresponding aryl halides of the formula X in the presence of a base [cf. JACS, 125 (30), 9032-9034, 2003; Synthesis, 9, 1241-1242, 1998]
  • Bases used are generally inorganic compounds such as alkali metal and alkaline earth metal hydroxides such as lithium hydroxide, sodium hydroxide, potassium hydroxide and calcium hydroxide, alkali metal and alkaline earth metal oxides such as lithium oxide, sodium oxide, calic 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, sodium amide and potassium amide, alkali metal and alkaline earth metal carbonates such as lithium carbonate, potassium carbonate and calcium carbonate and alkali metal hydrogencarbonates such as sodium hydrogencarbon
  • tertiary amines such as trimethylamine, triethylamine, tributylamine, di-isopropyl-ethylamine and N-methylpiperidine, pyridine, substituted pyridines such as collidine, lutidine and 4-dimethylaminopyridine and bicyclic amines into consideration.
  • the bases are generally used in catalytic amounts, but they can also be used equimolar, in excess or optionally as a solvent.
  • This reaction is usually carried out at temperatures of from 0 C to 12O 0 C, preferably 25 0 C to 100 0 C, in an inert organic solvent [cf.. Tetrahedron, 60 (36), 7983-7994, 2004; Synthesis, (7), 1 163-1 168, 1999].
  • Suitable solvents are aliphatic hydrocarbons such as pentane, hexane, cyclohexane and petroleum ether, aromatic hydrocarbons such as toluene, o-, m- and p- XyIoI, ketones such as acetone, methyl ethyl ketone, diethyl ketone and tert-butyl methyl ketone, alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol and tert-butanol, and dimethyl sulfoxide, dimethylformamide and dimethylacetamide, particularly preferably alcohols such as methanol, ethanol , n-propanol, isopropanol, n-butanol and tert-butanol, especially methanol. It is also possible to use mixtures of the solvents mentioned.
  • the starting materials are generally reacted with one another in equimolar amounts. It may be advantageous for the yield to use Y + M- in an excess based on 1.1.
  • Compounds of the formula I in which both groups R 1 and R 4 are alkoxy correspond to the formula I.4. They are obtainable by reacting the compounds of the formula 1.1 with the corresponding alkoxide [Y + M "], where M is a cation, usually an alkali metal or alkaline earth metal cation.
  • Suitable solvents are aliphatic hydrocarbons such as pentane, hexane, cyclohexane and petroleum ether, aromatic hydrocarbons such as toluene, o-, m- and p-xylene, ketones such as acetone, methyl ethyl ketone, diethyl ketone and tert-butyl methyl ketone, alcohols such as methanol, ethanol, n-butyl Propanol, isopropanol, n-butanol and tert-butanol, and dimethyl sulfoxide, dimethylformamide and dimethylacetamide, particularly preferably alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol and tert-butanol, in particular methanol. It is also possible to use mixtures of the solvents mentioned.
  • the starting materials are generally reacted with one another in equimolar amounts. It may be advantageous for the yield to use Y + M "in an excess based on 1.1.
  • Compounds of the formula I in which one group of R 1 and R 4 is cyano and the respective other group is halogen, in particular chlorine , or both groups of R 1 and R 4 are cyano, correspond to the formulas 1.5, 1.6, and 1.7, respectively, and are accessible according to the selected boundary conditions from compounds of the formula 1.1 by reaction with cyanides.
  • This reaction is usually carried out at temperatures of 5O 0 C to 15O 0 C, preferably 8O 0 C to 100 0 C, in an inert organic solvent optionally in the presence of a catalyst such as p-toluenesulfonic acid sodium salt [cf.. Heterocycles, 39 (1), 345-56; 1994].
  • a catalyst such as p-toluenesulfonic acid sodium salt [cf.. Heterocycles, 39 (1), 345-56; 1994].
  • alkali or Erdalkalicyanide preferably potassium cyanide in question.
  • Suitable solvents are aliphatic hydrocarbons such as pentane, hexane, cyclohexane and petroleum ether, aromatic hydrocarbons such as toluene, o-, m- and p-xylene, halogenated hydrocarbons such as methylene chloride, 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 and tert-butanol , and dimethyl sulfoxide, di
  • the starting materials are generally reacted with one another in equimolar amounts. It may be advantageous for the yield to use the cyanide in an excess based on 1.1.
  • the compounds of the formula I are obtainable by oxidation of 4,5-dihydropyridines of the formula XII.
  • the oxidation is usually carried out at temperatures of from 2O 0 C to 100 0 C, preferably 4O 0 C to 8O 0 C, in an inert organic solvent in the presence of an oxidizing agent and / or a catalyst such as preferably Pt or Pd, or oxides or peroxides, such as H2O2 [Ref: Coprehensive Organic Reactions, RC Larock, Chapter 5.1 Aromatization - Dehydrogenation, page 93, VCH, 1989; J Het, Chem, 26 (3), 717-719, 1989].
  • Suitable solvents are aliphatic hydrocarbons such as pentane, hexane, cyclohexane and petroleum ether, aromatic hydrocarbons such as toluene, o-, m- and p-xylene, halogenated hydrocarbons such as methylene chloride, 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.
  • aliphatic hydrocarbons such as pentane, hexane, cyclohexane and petroleum ether
  • aromatic hydrocarbons such as toluene, o-, m- and p-xylene
  • Butyl methyl ketone alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol and tert-butanol, and dimethyl sulfoxide, dimethylformamide and dimethylacetamide. It is also possible to use mixtures of the solvents mentioned.
  • the oxidizing agent is usually used in equimolar amounts, based on the compound of formula XII. It may be advantageous for the yield to use the oxidizing agent in equimolar amounts or in an excess of up to 5 molar equivalents based on XII.
  • dihydropyridazines can be obtained by chlorination or bromination and subsequent elimination of HCl or HBr. This reaction is usually carried out at temperatures from -3O 0 C to 100 0 C, preferably 0 0 C to 8O 0 C, in an inert organic solvent or in organic acids such as acetic acid [cf. Ref. Synthesis, 1995, (10), 240-242; Syn Comm, 23 (21), 2957-2964, 1993].
  • 4,5-Dihydropyridazines of the formula XII are advantageous from 1, 2-diketones of the formula
  • This reaction is usually carried out at temperatures from -3O 0 C to 100 0 C, preferably 0 0 C to 8O 0 C, in an inert organic solvent [see. Lit. Syn Comm, 31 (5), 645-651, 2001; Heterocycles, 57 (1), 39-46, 2002].
  • Suitable solvents are ethers, such as diethyl ether, diisopropyl ether, dimethoxyethane, tert-butyl methyl ether, dioxane, anisole and tetrahydrofuran, alcohols, such as methanol, ethanol, n-propanol, isopropanol, n-butanol and tert-butanol, particularly preferably alcohols. It is also possible to use mixtures of the solvents mentioned.
  • the starting materials are generally reacted with one another in equimolar amounts. It may be advantageous for the yield to use hydrazine or hydrazine hydrate in an excess of up to 5 molar equivalents based on XIII.
  • Diketones of the formula XIII can be prepared by reacting compounds of the formulas
  • the reaction of the compounds XIV and XV is usually carried out at temperatures from -3O 0 C to 100 0 C, preferably 2O 0 C to 4O 0 C, in bulk or in an inert organic solvent [cf. Tetrahedron, 45 (17), 5667-5678, 1989].
  • the reaction is preferably carried out in bulk.
  • the reaction of the intermediate XIIIa is usually carried out at temperatures of from -30 0 C to 8O 0 C, preferably 0 0 C to 3O 0 C, in an aqueous organic solution medium, in an acidic medium, preferably at a pH of about 2 [cf. Tetrahedron, 45 (17), 5667-5678, 1989; Tetrahedron, 45 (7), 2099-2108, 1989.
  • Suitable solvents are water and ethers such as diethyl ether, diisopropyl ether, tert-butyl methyl ether, dioxane, anisole and tetrahydrofuran, alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol and tert-butanol, more preferably ethanol. It is also possible to use mixtures of the solvents mentioned.
  • ethers such as diethyl ether, diisopropyl ether, tert-butyl methyl ether, dioxane, anisole and tetrahydrofuran
  • alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol and tert-butanol, more preferably ethanol. It is also possible to use mixtures of the solvents mentioned.
  • Acids and acidic catalysts include inorganic acids such as hydrofluoric acid, hydrochloric acid, hydrobromic acid, sulfuric acid and perchloric acid, Lewis acids such as boron trifluoride, aluminum trichloride, ferric chloride, tin IV chloride, titanium IV chloride and zinc II chloride, and organic acids such as formic acid, acetic acid, propionic acid, oxalic acid, toluenesulfonic acid, benzenesulfonic acid, camphorsulfonic acid, citric acid and trifluoroacetic acid, preferably hydrochloric acid use.
  • inorganic acids such as hydrofluoric acid, hydrochloric acid, hydrobromic acid, sulfuric acid and perchloric acid
  • Lewis acids such as boron trifluoride, aluminum trichloride, ferric chloride, tin IV chloride, titanium IV chloride and zinc II chloride
  • organic acids such as formic acid, acetic acid, propionic acid,
  • the acids are generally used in catalytic amounts, but they can also be used equimolar, in excess or optionally as a solvent.
  • the compounds of formula I can be obtained from substituted hydrazone ketones of formula XVI.
  • This reaction is usually carried out at temperatures of from 0 C to 12O 0 C, preferably upstream 5O 0 C to 100 0 C, in an inert organic solvent in the presence of a base [cp. Ref. J Chem Res. 3, 187-189, 2005].
  • Suitable solvents are ethers such as diethyl ether, diisopropyl ether, tert-butyl methyl ether, dimethoxyethane, dioxane, anisole and tetrahydrofuran, alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol and tert-butanol, more preferably ethanol. It is also possible to use mixtures of the solvents mentioned.
  • Bases are generally inorganic compounds such as alkali metal and alkaline earth metal hydroxides such as lithium hydroxide, sodium hydroxide, potassium hydroxide and calcium hydroxide, alkali metal and 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, sodium amide and potassium amide, alkali metal and alkaline earth metal carbonates such as lithium carbonate, potassium 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 phenyl lithium, alkylmagnesium halides such as methylmagnesium chloride and also alkali metal and alkaline earth metal alcoholates.
  • alkali metal and alkaline earth metal hydroxides such as lithium hydro
  • te as sodium methoxide, sodium ethoxide, potassium, potassium tert-butoxide and Dimethoxymagnesium
  • organic bases such as tertiary amines such as tri- ethylamine, triethylamine, di-isopropylethylamine and N-methylpiperidine, pyridine, substituted pyridines such as collidine, lutidine and 4-Dimethylaminopy ⁇ idin and bicyclic A- mine into consideration.
  • teritäre- amines such as triethylamine.
  • the bases are generally used in catalytic amounts, but they can also be used equimolar, in excess, preferably up to 2 molar equivalents, or optionally as a solvent.
  • the hydrazone ketones of the formula XVI are obtainable by reacting compounds of the formulas XVII and XVIII.
  • This reaction is usually carried out at temperatures of from 0 C to 15O 0 C, preferably upstream 2O 0 C and 12O 0 C, in an inert organic solvent in the presence or absence of a base or an acid catalyst [cp. Ref. J for Prakt Chem, 328 (4), 551-557, 1986; J for Prakt Chem, 327 (1), 109-116, 1985; Synthesis, (5), 691-694, 2003].
  • Suitable solvents are aliphatic hydrocarbons such as pentane, hexane, cyclohexane and petroleum ether, aromatic hydrocarbons such as toluene, o-, m- and p-xylene, benzene, more preferably benzene, halogenated hydrocarbons such as methylene chloride, chloroform and chlorobenzene, more preferably dichloromethane, ethers such as Diethyl ether, diisopropyl ether, tert-butyl methyl ether, dioxane, anisole and tetrahydrofuran, particularly preferably dioxane, 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, Isopropan
  • Acids and acidic catalysts include inorganic acids such as hydrofluoric acid, hydrochloric acid, hydrobromic acid, sulfuric acid and perchloric acid, Lewis acids such as boron trifluoride, aluminum trichloride, ferric chloride, tin IV chloride, titanium IV chloride and zinc II chloride, and organic acids such as formic acid, acetic acid, propionic acid, oxalic acid, citric acid, trifluoroacetic acid and sulfonic acids such as toluenesulfonic acid, benzenesulfonic acid, camphorsulfonic acid, particularly preferably p-toluenesulfonic acid, use.
  • inorganic acids such as hydrofluoric acid, hydrochloric acid, hydrobromic acid, sulfuric acid and perchloric acid
  • Lewis acids such as boron trifluoride, aluminum trichloride, ferric chloride, tin IV chloride, titanium IV chloride and zinc II chloride
  • Bases are generally inorganic compounds such as alkali metal and alkaline earth metal hydroxides such as lithium hydroxide, sodium hydroxide, potassium hydroxide and calcium hydroxide, alkali metal and 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 mid, sodium amide and potassium amide, alkali metal and alkaline earth metal carbonates such as lithium carbonate, potassium 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
  • Sodium ethoxide, potassium, potassium tert-butoxide and Dimethoxymagnesium also organic bases, for example tertiary amines such as trimethylamine, triethylamine, di-isopropylethylamine and N-methylpiperidine, pyridine, substituted pyridines such as collidine, lutidine and 4-dimethylaminopyridine and bicyclic A - mine in consideration.
  • tertiary amines such as trimethylamine, triethylamine, di-isopropylethylamine and N-methylpiperidine
  • pyridine substituted pyridines such as collidine, lutidine and 4-dimethylaminopyridine and bicyclic A - mine in consideration.
  • alkali metal hydrogencarbonates such as sodium bicarbonate.
  • the bases are generally used in catalytic amounts, but they can also be used equimolar, in excess, preferably up to 2 molar equivalents, or optionally as a solvent.
  • the starting materials are generally reacted with one another in equimolar amounts. It may be advantageous for the yield to use XVII in about 0.8 to 1.3 mol equivalents based on XVIII.
  • the hydrazonoketones of the formula XVIII are accessible from the reaction of diketones of the formula XIX with hydrazine or hydrazine hydrate.
  • This reaction is usually carried out at temperatures from -3O 0 C to 12O 0 C, preferably 0 0 C to 8O 0 C, in an inert organic solvent [see. J Med Chem, 48 (22), 6843-6854, 2005].
  • Suitable solvents include alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol and tert-butanol, more preferably ethanol. It is also possible to use mixtures of the solvents mentioned.
  • the starting materials are generally reacted with one another in equimolar amounts. It may be advantageous for the yield to use the hydrazine or hydrazine hydrate in a molar ratio of 0.8 to 1.3 based on XIX.
  • Compounds of formula I are provided in which R 1 and / or R 4 represents alkyl, are prepared from the compounds 1.1, preferably from the compounds 1.1 in which are both "Jaws" represents chlorine, accessible.
  • compounds 1.8, 1.9 and 1.10 are available with different selectivity on the following routes:
  • R 1 'and R 4 ' are alkyl, especially Compounds of formulas 1.8, 1.9 and 1.10 can be obtained by reacting the compounds of formula 1.1 with alkylmagnesium halides.
  • This reaction is usually carried out at temperatures of from -3O 0 C to 25 0 C, preferably 0 ° C to 2O 0 C in an inert organic solvent in the presence of a catalyst [see. JACS, 124 (46), 13856-13863].
  • Suitable solvents are ethers such as diethyl ether, diisopropyl ether, tert-butyl methyl ether, dioxane, anisole and tetrahydrofuran, and N-methylpyrrolidone (NMP), more preferably THF and NMP.
  • the catalyst used is advantageously Fe (acac) 3 or Fe (salen) Cl in catalytic amounts, such as, for example, 5 mol%.
  • the starting materials are generally reacted with one another in equimolar amounts. It may be advantageous for the yield to use the alkylmagnesium halides in a slight excess based on the pyridazine.
  • the compounds of formulas 1.8, 1.9 and 1.10 can also be prepared by reacting the compounds of formula 1.1 with alkylzinc halides at temperatures of 0 0 C to 12O 0 C, preferably 2O 0 C to 6O 0 C, in an inert organic solvent in the presence of a catalyst [see. Tetrahedron Letters, 46 (8), 1303-1305 (2005)].
  • Suitable solvents are ethers, such as diethyl ether, diisopropyl ether, tert-butyl methyl ether, dioxane, anisole and tetrahydrofuran.
  • the catalyst used is advantageously a Pd (0) catalyst, more preferably Pd (PPh ⁇ ) 4 used in amounts of about 5 mol%.
  • the starting materials are generally reacted with one another in equimolar amounts in order to obtain the monosubstituted products. If the zinc reagent is used in large quantities (1.6 eq.), Disubstituted product is already obtained as minor component. If the reaction temperature is increased from 20 ° to 60 0 C, so mainly disubstituted product is obtained.
  • the group L 1 can be introduced at the pyridazine level of formula XIX by nucleophilic substitution according to the synthesis shown below.
  • LG 1 is a nucleophilically unburnuchbare group such as halogen, for example fluorine, and ⁇ - ⁇ phenyl or a 5- or 6-membered heteroaromatic group, which 1, 2, 3 or 4 heteroatoms selected from O, S and N as ring members.
  • the reaction of XIX with HL 1 is carried out, for example, according to the method described in WO 2005/030775 and is advantageously carried out in the presence of strong bases.
  • suitable bases are alkali metal hydroxides, such as sodium hydroxide or potassium hydroxide, alkali metal carbonates, such as sodium carbonate or potassium carbonate, alkaline earth metal carbonates, such as calcium or magnesium carbonate, or alkali metal hydrides, such as lithium or sodium hydride.
  • the reaction can be carried out in the presence of a solvent.
  • Suitable solvents are aprotic solvents, for example N, N-disubstituted amides, such as N, N-dimethylformamide, N, N-dimethylacetamide or N-methylpyrrolidone, sulfoxides, such as dimethyl sulfoxide, or ethers, such as diethyl ether, diisopropyl ether, tert-butyl ether, 1, 2 -Dimethoxyethane, tetrahydrofuran, dioxane or anisole.
  • the reaction is usually carried out at temperatures ranging from 0 ° C. to the boiling point of the solvent.
  • T in the group L 1 is OH or a primary or secondary amino group, it is advantageous to protect the hydroxyl group or the amino group.
  • a suitable protecting group for the hydroxy group is, for example, the benzyl group which optionally bears a methoxy group in the 4-position of the phenyl ring.
  • the protective group for the hydroxy group can be removed, for example, by catalytic hydrogenolysis or by means of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ).
  • a suitable protective group for primary and secondary amino groups is, for example, the tert-butoxycarbonyl group (Boc), which is usually removed again with trifluoroacetic acid or p-toluenesulfonic acid.
  • Pyridazines of the formula XIX can be represented by a modification of the precursors with respect to the embodiment of R 3 analogous to the above synthesis routes.
  • Compounds HL 1 are generally commercially available or can be prepared by literature methods.
  • the compound XX is reacted with a Lewis acid such as aluminum trichloride or iron (III) chloride to obtain the phenolic compound XXa around.
  • a Lewis acid such as aluminum trichloride or iron (III) chloride
  • the ether cleavage takes place in an organic solvent, for example in an aromatic hydrocarbon such as benzene, toluene or xylene.
  • the introduction of the group L 1 is carried out by nucleophilic substitution of the hydroxy group under basic conditions as described above.
  • Pyridazines of the formula XX can be represented by a modification of the precursors with respect to the design of R 3 analogous to the above synthesis routes.
  • Formulas XXb and XXI have the variables and the meanings given above.
  • Compounds of formula I in which L 1 represents a group bonded through nitrogen group DAR can advantageously be prepared from precursors whose group ⁇ - ⁇ carries an amino group which is obtained from the corresponding nitro-substituted compounds by reduction, if necessary.
  • the reaction mixtures are worked up in the usual way, e.g. by mixing with water, separation of the phases and optionally chromatographic purification of the crude products.
  • the intermediate and end products are z.T. in the form of colorless or pale brownish, viscous oils, which are freed or purified under reduced pressure and at moderately elevated temperature from volatile constituents. If the intermediate and end products are obtained as solids, the purification can also be carried out by recrystallization or trituration.
  • halogen fluorine, chlorine, bromine and iodine
  • Alkyl saturated, straight-chain or branched hydrocarbon radicals having 1 to 4, 6 or 8 carbon atoms, e.g.
  • C 1 -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-methylpropy
  • Haloalkyl straight-chain or branched alkyl groups having 1 to 2, 4 or 6 carbon atoms (as mentioned above), in which groups the hydrogen atoms may be partially or completely replaced by halogen atoms as mentioned above: in particular C 1 -C 2 -haloalkyl, such as chloromethyl, Bromomethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 1-chloroethyl, 1-bromoethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2- Trifluoroethyl, 2-chloro-2-fluoroethyl, 2-chloro-2,2-difluoroethyl, 2,2-dichloro-2-fluoroethyl, 2,2,2-trichloroeth
  • Alkynyl straight-chain or branched hydrocarbon groups having 2 to 4, 6 or 8 carbon atoms and one or two triple bonds in any position, for example 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-pentyny
  • Aryl mono-, bi- or tricyclic aromatic hydrocarbon groups containing 6, 8, 10, 12 or 14 ring members, such as phenyl, naphthyl or anthracenyl, preferably phenyl or naphthyl, in particular phenyl; a five- or six-membered saturated, partially unsaturated or aromatic heterocycle containing one, two, three or four heteroatoms from the group O, N and S: nonaromatic saturated or partially unsaturated 5- or 6-membered heterocyclyl containing one bis three nitrogen atoms and / or an oxygen or sulfur atom or one or two oxygen and / or sulfur atoms, for example 2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-tetrahydrothienyl, 3-tetrahydrothienyl, 2-pyrrolidinyl, 3-pyrrolidinyl, 3-isoxazolidinyl, 4-isoxazolidinyl, 5-isoxazolidinyl, 3-iso
  • Alkylene divalent unbranched chains of 2 to 8 Chb groups, eg CH 2 CH 2, CH 2 CH 2 CH 2 , CH 2 CH 2 CH 2 CH 2 , CH 2 CH 2 CH 2 CH 2 CH 2 , CH 2 CH 2 CH 2 CH 2 CH 2 , CH 2 CH 2 CH 2 CH 2 CH 2 , CH 2 CH 2 CH 2 CH 2 CH 2 and CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 ;
  • Oxyalkylene divalent unbranched chains of 2 to 4 Chb groups, wherein a valency is bonded to the skeleton via an oxygen atom, for example OCH 2 CH 2 , OCH 2 CH 2 CH 2 and OCH 2 CH 2 CH 2 CH 2 ;
  • Oxyalkylenoxy divalent unbranched chains of 1 to 3 Chb groups, both valences being bonded to the skeleton via an oxygen atom, for example OCH 2 O, OCH 2 CH 2 O and OCH 2 CH 2 CH 2 O;
  • suitable agriculturally acceptable salts are, in particular, the salts of those cations or the acid addition salts of those acids whose cations or anions do not adversely affect the pesticidal activity of the pyrimidines according to the invention.
  • Suitable agriculturally useful salts are, in particular, the salts of those cations or the acid addition salts of those acids whose cations or anions do not adversely affect the fungicidal activity of the compounds I.
  • Anions of useful acid addition salts are primarily chloride, bromide, fluoride, hydrogen sulfate, sulfate, dihydrogen phosphate, hydrogen phosphate, phosphate, nitrate, bicarbonate, carbonate, hexafluorosilicate, hexafluorophosphate, benzoate, and the anions of C 1 -C 4 alkanoic acids, preferably formate, acetate , Propionate and butyrate. They may be formed by reaction of I with an acid of the corresponding anion, preferably hydrochloric, hydrobromic, sulfuric, phosphoric or nitric acid.
  • Suitable pharmaceutically acceptable salts are, in particular, physiologically tolerated salts of compound I, in particular the acid addition salts with physiologically tolerated acids.
  • suitable organic and inorganic acids are hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, C 1 -C 4 -alkyl sulfonic acids, such as methanesulfonic acid, aromatic sulfonic acids, such as benzene sulfonic acid.
  • fonic acid and toluenesulfonic acid oxalic acid, maleic acid, fumaric acid, lactic acid, tartaric acid, adipic acid and benzoic acid.
  • suitable acids are described, for example, in Fort Whitney der Arzneistoffforschung, Volume 10, pages 224 et seq., Birkhäuser Verlag, Basel and Stuttgart, 1966, to which reference is hereby made in their entirety.
  • Hindered rotation of unsymmetrically substituted groups may give atropisomers of compounds of the formula I. They are also the subject of the invention.
  • One embodiment relates to compounds I in which R 1 and R 4 are halogen, in particular chlorine. These compounds correspond to the formula 1.1.
  • a further embodiment relates to compounds I in which R 1 is halogen, in particular chlorine and R 4 is C 1 -C 6 -alkoxy, such as methoxy, ethoxy, n-propoxy, isopropoxy, in particular methoxy. These compounds correspond to the formula 1.2.
  • a further embodiment relates to compounds I in which R 1 is C 1 -C 6 -alkoxy, such as methoxy, ethoxy, n-propoxy, isopropoxy, in particular methoxy, and R 4 is halogen, in particular chlorine. These compounds correspond to the formula 1.3.
  • a further embodiment relates to compounds I in which R 1 and R 4 are C 1 -C 6 -alkoxy, such as methoxy, ethoxy, n-propoxy, isopropoxy, in particular methoxy. These compounds correspond to the formula 1.4.
  • a further embodiment relates to compounds I in which R 1 is halogen, in particular chlorine and R 4 is cyano. These compounds correspond to the formula
  • a further embodiment relates to compounds I in which R 1 is cyano and R 4 is halogen, in particular chlorine. These compounds correspond to the formula 1.5.
  • Another embodiment relates to compounds I in which R 1 and R 4 are cyano. These compounds correspond to the formula 1.7.
  • a further embodiment relates to compounds I in which R 1 is halogen, in particular chlorine and R 4 is alkyl, in particular methyl. These compounds correspond to the formula 1.8, in which R 4 'has the abovementioned meaning.
  • a further embodiment relates to compounds I in which R 1 is alkyl, in particular methyl and R 4 is halogen, in particular chlorine. These compounds correspond to the formula 1.9, in which R 1 'has the abovementioned meaning.
  • a further embodiment relates to compounds I in which R 1 and R 4 are alkyl, in particular methyl. These compounds correspond to the formula 1.10 in which R 1 'and R 4 ' have the abovementioned meaning.
  • R 2 in the compounds of the invention Ci-Cio-alkyl, Ci-Cio-haloalkyl, C 2 -Cio-alkenyl, C 2 -Cio-haloalkenyl, C 2 -Cio-alkynyl, C 2 -C 0 - haloalkynyl, C3 Ci2 cycloalkyl (including, in particular Cs-Cs-cycloalkyl and / or C9-Ci2 cycloalkyl), C3-Ci 2 halocycloalkyl, C3-Ci2 cycloalkenyl, C3-Ci 2-halo-cycloalkenyl, naphthyl or halonaphthyl or a five, six, seven, eight, Nine or ten membered saturated, partially unsaturated or aromatic carbon-bonded heterocycle containing one, two, three or four heteroatoms selected from the group consisting of oxygen, nitrogen and sulfur, more preferably
  • R 2 is an aliphatic group which is unsubstituted or, as defined above , substituted by R a .
  • R 2 is C 1 -C 10 -alkyl, C 1 -C 10 -haloalkyl, C 2 -C 10 -alkenyl, C 2 -C 10 -haloalkenyl, C 2 -C 10 -alkynyl, C 2 -C 10 -alkoxy
  • Haloalkynyl, C3-Ci2-cycloalkyl, C3-Ci2-halocycloalkyl, C3-Ci2-cycloalkenyl, C3-Ci2-halocycloalkenyl means.
  • R 2 is C 1 -C 8 -alkyl, in particular branched C 3 -C 8 -alkyl, C 1 -C 6 -haloalkyl, C 1 -C 8 -alkenyl, in particular branched C 3 -C 8 -alkenyl, C 5 -C 8 -Cycloalkyl, which may have a Ci-C4-alkyl group, or C5-C6-cycloalkenyl, which may have a Ci-C4-alkyl group is.
  • a further embodiment relates to compounds Ia in which R 2 is C 3 -C 12 -cycloalkyl, in particular C 6 -C 8 -cycloalkyl.
  • a further embodiment relates to compounds Ia in which R 2 is C 1 -C 10 -alkyl, in particular C 1 -C 8 -alkyl, which is optionally substituted by one, two or three R a .
  • R a is preferably selected from halogen, cyano, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 1 -C 6 -alkoxycarbonyl, C 1 -C 6 -alkoximino, C 2 -C 6 -alkenyloximino, C 2 -C 6 - Alkinyloximino, Cs-C ⁇ -cycloalkyl or Cs-C ⁇ -cycloalkenyl, wherein the aliphatic and / or alicyclic groups may in turn be substituted by one, two or three groups R b .
  • R b represents C 2 preferably each independently halogen, cyano, d-Ce-alkyl, C 2 -C 6 alkenyl, C 6 -C -Al kinyl, Ci-C 6 alkoxy, d-Ce-alkylcarbonyl or Ci-C ⁇ haloalkylcarbonyl.
  • R 2 is C 1 -C 10 -haloalkyl, in particular C 1 -C 8 -haloalkyl.
  • a further embodiment relates to compounds Ia in which R 2 is C 2 -C 10 alkenyl, in particular C 5 -C 8 alkenyl, which is optionally substituted by one, two or three R a , as defined herein.
  • a further embodiment relates to compounds Ia in which R 2 is C 2 -C 10 -alkynyl, in particular C 3 -C 8 -alkynyl, which is optionally substituted by one, two or three R a , as defined herein.
  • a further embodiment relates to compounds Ia in which R 2 is C 3 -C 12 -CCCl 10 -alkenyl, in particular C 1 -C 10 -cycloalkenyl, especially C 5 -C 6 -cycloalkenyl, optionally substituted by one, two or three R a as defined herein.
  • the cycoalkenyl group is one, two or three times by Ci-C4-alkyl, such as methyl and / or ethyl, substituted.
  • R 2 is a five, six, seven, eight, nine or ten membered saturated, partially unsaturated or aromatic heterocycle bonded via carbon to the pyridazine skeleton, containing one, two, three or four Heteroatoms from the group consisting of oxygen, nitrogen and sulfur, wherein the heterocycle is unsubstituted or substituted by one, two, three or four identical or different substituents R a as defined herein.
  • R 2 is a substituted or unsubstituted five- or six-membered saturated or aromatic heterocycle bonded via carbon to the pyridazine skeleton.
  • R 2 carries one, two, three or four, preferably one, two or three, identical or different groups R a
  • R a is preferably chosen from halogen, cyano, Ci-C 6 alkyl, C 2 -C 6 - alkenyl, C 2 -C 6 -alkyl kinyl, Ci-C 6 alkoxy, Ci-C 6 alkoxycarbonyl, Ci-C ⁇ -alkoximino, C2-C6-Alkenyloximino, C2-C6-Alkinyloximino, Cs-C ⁇ cycloalkyl, C5 -C 6 -cycloalkenyl, where the aliphatic or alicyclic groups in turn may be partially or fully halogenated or NEN one, two or three groups R b nen wear.
  • R b 2 2 6 provided that R a R bears at least one group b, then is preferably chosen from halogen, cyano, Ci-C 6 alkyl, Ci-C 6 haloalkyl, C -C 6 alkenyl, C -C -Al kinyl, Ci-C ⁇ -alkylcarbonyl, Ci-C ⁇ -haloalkylcarbonyl and Ci-C ⁇ -alkoxy.
  • R 2 is Ci-Cio-alkyl, in particular Cs-Cs-alkyl, which is optionally substituted by one, two or three R a .
  • R a is preferably selected from halogen, cyano, Ci-C ⁇ alkyl, C 2 -C 6 alkenyl, C 2 - C ⁇ -alkynyl, Ci-C ⁇ -alkoxycarbonyl, Ci-C ⁇ -alkoximino, C2-C6 Alkenyloximino, C 2 -C e -alkynyloximino, C 5 -C 6 -cycloalkyl or C 5 -C 6 -cycloalkenyl, where the aliphatic and / or alicyclic groups may in turn be substituted by one, two or three groups R b .
  • R b represents C 2 preferably each independently halogen, cyano, d-Ce-alkyl, C 2 -C 6 alkenyl, C 6 -C -Al kinyl, Ci-C 6 alkoxy, d-Ce-alkylcarbonyl or Ci-C ⁇ haloalkylcarbonyl.
  • R 2 is Ci-Cio-haloalkyl, in particular Cs-Cs-haloalkyl.
  • a further embodiment relates to compounds I in which R 2 is an aryl group which is unsubstituted or substituted as defined above by R a , such as phenyl or naphthyl, in particular a phenyl group.
  • a further embodiment relates to compounds I in which R 2 is a heteroaryl group bonded via carbon, which is unsubstituted or as defined above. N, is substituted by R a .
  • R 2 is a heteroaryl group bonded via carbon, which is unsubstituted or as defined above. N, is substituted by R a .
  • Preferred compounds of the formula Ic have, in position R 2, a group selected from pyridin-3-yl and pyridin-4-yl.
  • a further embodiment relates to compounds I in which R 2 is a nitrogen-bonded heteroaryl group which is unsubstituted or, as defined above , substituted by R a . These compounds correspond to formula Id.
  • R 2 is not optionally substituted phenyl.
  • R 2 is not C ⁇ -Cs-cycloalkyl, more preferably not C 3 -C 12 -cycloalkyl.
  • R 2 is not C ⁇ -Cs-cycloalkyl, more preferably not C 3 -C 12 -cycloalkyl.
  • R 2 is C 2 -C 10 alkenyl, in particular C 5 -C 8 alkenyl, which is optionally substituted by one, two or three R a , as defined herein.
  • R 2 is C 2 -C 10 -alkynyl, in particular C 5 -C 8 -alkynyl, which is optionally substituted by one, two or three R a , as defined herein.
  • R 2 is C3-Ci2-cycloalkenyl, in particular Cs-do-cycloalkenyl, especially C5- or C ⁇ -cycloalkenyl, which is optionally by one, two or three R a substituted as defined herein.
  • the cycoalkenyl group is monosubstituted, disubstituted or trisubstituted by C 1 -C 4 -alkyl, such as, for example, methyl and / or ethyl.
  • R 2 is a saturated, partially unsaturated, unsaturated or aromatic heterocycle bonded via carbon to the pyridazine skeleton containing five, six, seven, eight, nine or ten members containing one, two, three or ten four heteroatoms selected from the group consisting of oxygen, nitrogen and sulfur, wherein the heterocycle is unsubstituted or substituted by one, two, three or four identical or different substituents R a as defined herein.
  • a further embodiment relates to compounds I in which R 3 is an aryl group which is unsubstituted or as defined above , substituted by R a , such as phenyl or naphthyl, in particular a phenyl group. These compounds correspond to formula IA
  • R 3 is phenyl which, in addition to a group L 1 in ortho position to the bond to the pyridazine skeleton, carries at least one further group L m .
  • R 3 is phenyl which is substituted by only one group L 1 in ortho position to the bond to the pyridazine backbone.
  • R 3 is phenyl which, in addition to two groups L 1, carries at least one further group L m in both ortho positions to the bond to the pyridazine skeleton.
  • R 3 is phenyl, which is substituted by only two groups L 1 in both ortho positions to the bond to the pyridine zingrundgerüst.
  • a further embodiment relates to compounds I in which R 3 is a heteroaryl group bonded via carbon which is unsubstituted or substituted by R a as defined above. These compounds correspond to Formula IB
  • a further embodiment relates to compounds I in which R 3 is a nitrogen-bonded heteroaryl group which is unsubstituted or substituted as defined above, by R a . These compounds correspond to formula I.
  • R 3 is phenyl, pyridinyl, for example 2-, 3- or 4-pyridinyl, pyrimidinyl, for example 2-, A- or 5-pyrimidinyl, pyrazinyl, for example, 2-pyrazinyl, pyridazinyl, for example 3- or 4-pyridazinyl, triazinyl, furyl, for example 2- or 3-furyl, thienyl, for example 2- or 3-thienyl, pyrrolyl, for example 2- or 3-pyrrolyl, pyrazolyl , for example 1-, 3-, 4- or 5-pyrazolyl, imidazolyl, for example 1-, 2-, 4- or 5-imidazolyl, oxazolyl, for example 2-, 4- or 5-o
  • R 3 is particularly preferably phenyl, pyridinyl, for example 2-, 3- or 4-pyridinyl, pyrimidinyl, especially A- or 5-pyrimidinyl, pyrazinyl, for example 2-pyrazinyl, pyridazinyl, for example 3- or 4-pyridazinyl , Furyl, for example 2- or 3-furyl, thienyl, for example 2- or 3-thienyl, pyrazolyl, especially 1- or 5-pyrazolyl, imidazolyl, especially 1-, 2- or 5-imidazolyl, oxazolyl, for example 2 -, A- or 5-oxazolyl, isoxazolyl, for example 3-, A- or ⁇ -soxazolyl, thiazolyl, for example 2-, A- or 5-thiazolyl, isothiazolyl, for example 3-, A- or 5-isothiazolyl, or triazolyl , Above all 1- [1, 2,4] -1
  • R 3 is phenyl which is substituted by a group L 1 and 0, 1, 2, 3 or 4 radicals L.
  • L halogen, such as fluorine or chlorine; cyano; nitro; alkoxycarbonyl; aminocarbonyl; C 1 -C 4 -alkyl, such as methyl; CrC 4 -
  • Haloalkyl such as trifluoromethyl
  • CrC is like methoxy
  • Embodiments of R 3 relate in particular phenyl groups which may have in addition to the group L 1, the following substitution: Position 2: fluorine, chlorine, methyl; Position 3: hydrogen, fluorine, methoxy; Position 4: hydrogen, fluorine, chlorine, methyl, methoxy, cyano, nitro, alkoxycarbonyl, aminocarbonyl, haloalkyl, particularly preferably fluorine, chlorine, methyl, methoxy, cyano; Position 5: hydrogen, fluorine, chlorine, methyl; particularly preferably hydrogen, fluorine; Position 6: hydrogen, fluorine, chlorine, methyl; particularly preferably hydrogen, fluorine.
  • the group L 1 is preferably in the positions 3, 4 or 5.
  • R 3 is one of the groups A1 or A2 (
  • L m preferably represents one of the following substituent combinations:
  • L m is one of the following substituent combinations: 2-F; 2-CI; 2-CH 3 ; 2,6-F 2 ; 2-F, 6-Cl; 2-F, 6-CH 3 .
  • R 3 is a 5-membered heteroaryl which is substituted by L 1 and, if appropriate, by 1, 2 or 3 groups L.
  • the 5-membered heteroaryl ring is preferably selected from thienyl, for example 2- or 3-thienyl, pyrazolyl, for example 1-, 3-, 4- or 5-pyrazolyl, and thiazolyl, for example 2-, 4- or 5-thiazolyl ,
  • R 3 is a 6-membered heteroaryl which is substituted by a group L 1 and optionally by 1, 2 or 3 groups L and contains one to three nitrogen atoms.
  • the 6-membered heteroaryl ring is preferably pyridinyl, for example 2-, 3- or 4-pyridinyl, pyrimidinyl, for example 2-, 4- or 5-pyrimidinyl, pyrazinyl, for example 2-pyrazinyl and pyridazinyl, for example 3- or 4- Pyridazinyl, selected.
  • R 3 is pyridyl which is bonded to the pyridazine ring in the 2, 3 or 4 position and can carry 1, 2 or 3 identical or different substituents L, which are preferably fluorine, chlorine, Bromine, cyano, nitro, methyl, ethyl, methoxy, methylthio, hydroximinomethyl, hydroxi- minoethyl, methoximinomethyl, methoximinoethyl and trifluoromethyl are selected.
  • substituents L which are preferably fluorine, chlorine, Bromine, cyano, nitro, methyl, ethyl, methoxy, methylthio, hydroximinomethyl, hydroxi- minoethyl, methoximinomethyl, methoximinoethyl and trifluoromethyl are selected.
  • substituents L are preferably fluorine, chlorine, Bromine, cyano, nitro, methyl, ethyl, methoxy, methyl
  • R 3 is pyrimidyl which is bonded to the pyridazine ring in the 2- or 4-position and can carry 1 or 2 identical or different substituents L, which are preferably fluorine, chlorine, bromine, cyano, Nitro, methyl, ethyl, methoxy, methylthio, hydroximinomethyl, hydroxi- minoethyl, methoximinomethyl, methoximinoethyl and trifluoromethyl are selected.
  • substituents L which are preferably fluorine, chlorine, bromine, cyano, Nitro, methyl, ethyl, methoxy, methylthio, hydroximinomethyl, hydroxi- minoethyl, methoximinomethyl, methoximinoethyl and trifluoromethyl are selected.
  • substituents L which are preferably fluorine, chlorine, bromine, cyano, Nitro, methyl, ethyl, methoxy, methylthio, hydro
  • R 3 is thienyl which is bonded to the pyridazine ring in the 2- or 3-position and can carry 1 or 2 identical or different substituents L, which are preferably fluorine, chlorine, bromine, cyano, Nitro, methyl, ethyl, methoxy, methylthio, hydroximinomethyl, hydroxi- minoethyl, methoximinomethyl, methoximinoethyl and trifluoromethyl are selected.
  • substituents L which are preferably fluorine, chlorine, bromine, cyano, Nitro, methyl, ethyl, methoxy, methylthio, hydroximinomethyl, hydroxi- minoethyl, methoximinomethyl, methoximinoethyl and trifluoromethyl are selected.
  • substituents L which are preferably fluorine, chlorine, bromine, cyano, Nitro, methyl, ethyl, methoxy, methylthio, hydrox
  • R 3 is thiazolyl which is bonded to the pyridazine ring in the 2-, 4- or 5-position and may carry a substituent L, which is preferably selected from fluorine, chlorine, bromine, cyano, nitro, Methyl, ethyl, methoxy, methylthio, hydroximinomethyl, hydroximinoethyl, methoximinomethyl, methoximinoethyl and trifluoromethyl.
  • substituent L is preferably selected from fluorine, chlorine, bromine, cyano, nitro, Methyl, ethyl, methoxy, methylthio, hydroximinomethyl, hydroximinoethyl, methoximinomethyl, methoximinoethyl and trifluoromethyl.
  • R 3 is imidazolyl which is bonded in the 4- or 5-position to the pyridazine ring and can carry 1 or 2 identical or different substituents L, which are preferably fluorine, chlorine, bromine, cyano, Nitro, methyl, ethyl, methoxy, methylthio, hydroximinomethyl, hydroxy minoethyl, methoximinomethyl, methoximinoethyl and trifluoromethyl are selected.
  • substituents L which are preferably fluorine, chlorine, bromine, cyano, Nitro, methyl, ethyl, methoxy, methylthio, hydroximinomethyl, hydroxy minoethyl, methoximinomethyl, methoximinoethyl and trifluoromethyl are selected.
  • substituents L which are preferably fluorine, chlorine, bromine, cyano, Nitro, methyl, ethyl, methoxy, methylthio, hydroximinomethyl
  • R 3 is pyrazolyl which is bonded to the pyridazine ring in the 1-, 3-, 4- or 5-position and can carry 1 or 2 identical or different substituents L, which are preferably fluorinated , Chloro, bromo, cyano, nitro, methyl, ethyl, methoxy, methylthio, hydroximino-methyl, hydroximinoethyl, methoximinomethyl, methoximinoethyl and trifluoromethyl.
  • substituents L which are preferably fluorinated , Chloro, bromo, cyano, nitro, methyl, ethyl, methoxy, methylthio, hydroximino-methyl, hydroximinoethyl, methoximinomethyl, methoximinoethyl and trifluoromethyl.
  • substituents L which are preferably fluorinated , Chloro, bromo, cyano, nitro, methyl
  • R 3 is oxazolyl which is bonded to the pyridazine ring in the 2-, 3- or 4-position and can carry a substituent L which is preferably selected from fluorine, chlorine, bromine, cyano, nitro, Methyl, ethyl, methoxy, methylthio, hydroximinomethyl, hydroximinoethyl, methoximinomethyl, methoximinoethyl and trifluoromethyl.
  • substituent L is preferably selected from fluorine, chlorine, bromine, cyano, nitro, Methyl, ethyl, methoxy, methylthio, hydroximinomethyl, hydroximinoethyl, methoximinomethyl, methoximinoethyl and trifluoromethyl.
  • R 3 is pyrazol-1-yl.
  • R 3 is pyrazol-1-yl, which may be monosubstituted to trisubstituted, identically or differently substituted in the 3-, 4- or 5-position by L 1 and, if appropriate, L m , which preferably chlorine, bromine and / or methyl.
  • L 1 and, if appropriate, L m , which preferably chlorine, bromine and / or methyl.
  • Embodiments of the compounds of the formula I relate to those of the formula I.C1 and IC
  • At least one group L is ortho to the point of attachment of the group R 3 with the pyridazine skeleton, in particular chlorine, fluorine or methyl.
  • a heteroatom of the heteroaromatic radical R 3 is ortho to the junction.
  • the index m is preferably from 1 to 4, where the groups L may be identical or different.
  • heteroaromatic groups R in addition to a group L 1 3 carry further substituents L, these are preferably selected from: fluorine, chlorine, methyl, methoxy, cyano, nitro, alkoxycarbonyl, amino carbonyl and haloalkyl.
  • the optional substituents L are selected from fluorine, chlorine, methyl and methoxy.
  • the optional substituents L are selected from chlorine, methyl and methoxy.
  • Another embodiment relates to heteroaromatic groups R 3 , which are substituted by chlorine in addition to a group L 1 .
  • R 3 is phenyl or pyridinyl, which carry a substituent L 1 and 0, 1, 2, 3 or 4, preferably 0, 1 or 2, in particular 1 or 2 substituents L, wherein L 1 and L are as above or as are defined below.
  • R 3 is phenyl or 2-pyridinyl
  • these rings preferably carry the substituent L 1 in the 3- or in particular 4-position (based on the 1-position of the bond to the pyridazine ring, ie L 1 is particularly preferably meta or especially para-linked to this binding site).
  • the phenyl or the 2-pyridinyl ring optionally have 1 or 2 further substituents L.
  • these are in the 2- and / or 6-position of the phenyl ring (based on the 1-position of the bond to the pyridazine ring), ie ortho-constantly to the point of attachment to the pyridazine ring, and in the 2-pyridine ring preferably in the 6-position (relative bonded to the 1-position of the bond to the pyridazine ring).
  • the substituent L 1 of the group R 3 is a group L 11 of the formula wherein
  • a ⁇ is C 1 -C 4 -alkylene
  • Y 0 " 1 , Y TM 2 independently of one another represent O, S or NR h ⁇ ;" T represents OR h ⁇ , SR h ⁇ or NR hCt R ' ⁇ ; each R h ⁇ and R ' ⁇ is independently hydrogen or C 1 -C 4 alkyl; and a is 1, 2, 3 or 4.
  • Ci-C 4 -alkylene in A ⁇ is preferably methylene, 1, 2-ethylene, 1, 2 or 1, 3-propylene or 1, 4-n-butylene.
  • a ⁇ is preferably methylene, 1, 2-ethylene, 1, 2-propylene or 1, 3-propylene and in particular methylene or 1, 2-ethylene.
  • Y TM 1 and Y TM 2 independently of one another preferably represent O or NR h ⁇ .
  • Y TM 1 is O
  • Y TM 2 is O.
  • T ⁇ for 0R hCt .
  • Y TM 1 stands for NR hCt R ' ⁇ and at the same time Y TM denotes 2 O, in this case T ⁇ preferably stands for 0R h ⁇ .
  • T ⁇ is preferably 0R hCt or NR hCt R ' ⁇ .
  • R h ⁇ and R ' ⁇ independently of one another preferably represent H, methyl or ethyl.
  • a is preferably 1, 2 or 3.
  • the substituent L 1 of the group R 3 is a group L 12 of the formula ⁇ .
  • a ß. T ß ß wherein Y is CH 2, O, S or NR HSS R LSS; A ß for d-Cs-alkylene; T SS for 0R HSS, HSS NR R LSS or OC ( O) -T is 3.beta.; T 3 ⁇ is R h ⁇ , OR h ⁇ or NR h ⁇ R l ⁇ ; and each R h and R l is independently H or C 1 -C 4 -alkyl.
  • Y ß is CH 2 or O, especially O.
  • a ⁇ is preferably C 1 -C 6 -alkylene, in particular C 1 -C 4 -alkylene.
  • T ß is preferably 0R hß or NR hß R lß .
  • R h ⁇ and R l ⁇ independently of one another preferably represent hydrogen, methyl or ethyl.
  • the substituent L 1 of the group R 3 is a group L 13 of the formula
  • Y 17 is -CON R h ⁇ or -COO;
  • a ⁇ is C 2 -C 6 alkylene;
  • the substituent L 1 of the group R 3 is a group L 14 of the formula
  • Ci-C 4 -alkylene in A ⁇ is preferably methylene, 1, 2-ethylene, 1, 2 or 1, 3-propylene or 1, 4-n-butylene.
  • a ⁇ is preferably methylene, 1, 2-ethylene, 1, 2-propylene or 1, 3-propylene and in particular methylene or 1, 2-ethylene.
  • Y ⁇ 1 and Y ⁇ 2 independently of one another preferably represent O or NR h ⁇ . If Y ⁇ 1 is O, preferably Y ⁇ 2 is O. In this case, moreover, preferably T ⁇ stands for 0R h ⁇ . If Y ⁇ 1 stands for NR h ⁇ R l ⁇ and at the same time Y ⁇ 2 denotes O, in this case T ⁇ is preferably 0R h ⁇ . T ⁇ is preferably 0R h ⁇ or NR h ⁇ R l ⁇ .
  • R h ⁇ and R l ⁇ independently of one another preferably represent H, methyl or ethyl.
  • a is preferably 1, 2 or 3.
  • the substituent L 1 of the group R 3 is a group L 15 of the formula C ⁇ CY ⁇ 1 -fA ⁇ -Y ⁇ 2 ⁇ a -A ⁇ -T ⁇ in which
  • a ⁇ is C 1 -C 4 -alkylene
  • Y ⁇ 1 , Y ⁇ 2 independently of one another represent O, S or NR h ⁇ ;
  • T ⁇ stands for 0R h ⁇ , SR h ⁇ or NR h ⁇ R ⁇ ; each R h ⁇ and R ⁇ is independently hydrogen or Ci-C 4 -AlkVl; and a is 1, 2, 3 or 4.
  • Ci-C 4 -alkylene in A ⁇ is preferably methylene, 1, 2-ethylene, 1, 2 or 1, 3-propylene or 1, 4-n-butylene.
  • a ⁇ preferably represents methylene, 1,2-ethylene, 1,2-propylene or 1,3-propylene and in particular methylene or 1,2-ethylene.
  • Y ⁇ 1 and Y ⁇ 2 independently of one another preferably represent O or NR h ⁇ . If Y ⁇ 1 is O, preferably Y ⁇ 2 is O. In this case, moreover, T ⁇ is preferably 0R h ⁇ . If Y ⁇ 1 stands for NR h ⁇ R ⁇ and at the same time Y ⁇ 2 O, T ⁇ in this case is preferably 0R h ⁇ . T ⁇ is preferably 0R h ⁇ or NR h ⁇ R ⁇ .
  • R h ⁇ and R ⁇ independently of one another preferably represent H, methyl or ethyl.
  • a is preferably 1, 2 or 3.
  • the substituent L 1 of the group R 3 particularly preferably represents a group L 11 or L 12 .
  • Lm is preferably independently selected from the herein for L m preferred meanings indicated, and it may furthermore be preferred that L is selected from halogen, nitro, cyano, Ci-C 4 alkyl, Ci-C4-haloalkyl, in particular C -C 2 -fluoroalkyl, C 1 -C 4 -alkoxy and C 1 -C 4 -alkoxycarbonyl, more preferably selected from nitro, cyano, fluorine, chlorine, bromine, methyl, ethyl, isopropyl, trifluoromethyl, fluoromethyl, methoxy and methoxycarbonyl.
  • Preferred L in the ortho position are fluorine, chlorine, bromine, C 1 -C 4 -alkyl, in particular methyl or ethyl, C 1 -C 2 -fluoroalkyl, such as trifluoromethyl, and C 1 -C 4 -alkoxy, in particular methoxy or ethoxy.
  • Halogen atoms in each case straight-chain or branched alkylamino, dialkylamino, alkylcarbonyl, alkylcarbonyloxy, alkoxycarbonyl, alkylsulfonyloxy, hydroximinoalkyl or alkoximinoalkyl having in each case 1 to 6 carbon atoms in the individual alkyl moieties; Cycloalkyl of 3 to 6 carbon atoms, 1,3-position linked 1,3-propanediyl, 1,4-butanediyl, methylenedioxy (-O-CH 2 -O-) or 1,2-ethylenedioxy (-O-CH 2 - CH 2 -O-), where these groups can be monosubstituted or polysubstituted by identical or different substituents
  • Halogen alkyl having 1 to 4 carbon atoms and / or haloalkyl having 1 to 4 carbon atoms and 1 to 9 identical or different halogen atoms.
  • Lm in particular the following groups are suitable: halogen, such as fluorine or chlorine; cyano; nitro; alkoxycarbonyl; C 1 -C 4 -alkyl, such as methyl; Ci-C4-haloalkyl, such as trifluoromethyl; CrC 4 -alkoxy, such as methoxy.
  • Examples of preferred compounds of the general formula I are those of the formulas Ia and Ib
  • Is -O-CH 2 CH 2 -NHCH 3 and R 2 for each compound corresponds to one row of Table A.
  • Is -O-CH 2 CH 2 CH 2 CH 2 -NHCH 3 and R 2 is a compound of one row each
  • Table A corresponds to Table 1 18
  • Table 1 19 Compounds of the formula La in which R 1 and R 4 are Cl, L 'and L' for F, L 1 for
  • Is -O-CH 2 CH 2 CH 2 -N (CH 3) 2 and R 2 is a compound of one row each of
  • Table A corresponds to Table 139
  • Is -O-CH 2 CH 2 CH 2 -NHCl 2 H 5 and R 2 is a compound of one row each of
  • Table A corresponds to Table 140 Compounds of the formula La, in which R 1 , R 4 , L 'for Cl and L "for F, L 1 for
  • Table A corresponds to Table 141
  • Table A corresponds to Table 142
  • Is -O-CH 2 CH 2 CH 2 -NHCH 3 and R 2 for each compound corresponds to one row of Table A.
  • Is -O-CH 2 CH 2 -NHCH 3 and R 2 for each compound corresponds to one row of Table A.
  • Table A corresponds to Table 234
  • Is -O-CH 2 CH 2 CH 2 -NHCl 2 H 5 and R 2 is a compound of one row each of
  • Table A corresponds to Table 236
  • Is -O-CH 2 CH 2 CH 2 -N (C 2 H 5 ) 2 and R 2 is a compound of one row each of
  • Table A corresponds to Table 237 Compounds of the formula La, in which R 1 and R 4 are each Cl, L 'and L "is CH 3, L 1 is
  • Is -O-CH 2 CH 2 CH 2 CH 2 -NHCH 3 and R 2 is a compound of one row each
  • Table A corresponds to Table 238
  • Is -O-CH 2 CH 2 CH 2 -NHCH 3 and R 2 for each compound corresponds to one row of Table A.
  • Is -O-CH 2 CH 2 CH 2 -NHCH 3 and R 2 is a compound of one line each
  • Table A corresponds to Table 330
  • Is -O-CH 2 CH 2 CH 2 -N (CH 3) 2 and R 2 is a compound of one row each of
  • Table A corresponds to Table 331 Compounds of the formula Ib in which R 1 and R 4 are each Cl, L 'is CH 3 , L 1 is
  • Is -O-CH 2 CH 2 CH 2 -NHCl 2 H 5 and R 2 is a compound of one row each of
  • Table A corresponds to Table 332
  • Table A corresponds to Table 333
  • the compounds I are suitable as fungicides. They are distinguished by outstanding activity against a broad spectrum of phytopathogenic fungi from the classes of the Ascomycetes, Deuteromycetes, Basidiomycetes and Peronospomycetes (Syn. Oomycetes). They are partially systemically effective and can be used in crop protection as foliar, pickling and soil fungicides.
  • fungi are particularly important for the control of a variety of fungi on various crops such as wheat, rye, barley, oats, rice, corn, grass, bananas, cotton, soy, coffee, sugar cane, wine, fruit and ornamental plants and vegetables such as cucumbers. Beans, tomatoes, potatoes and pumpkins, as well as the seeds of these plants. They may also be used in cultures tolerant of insect or fungal growth by breeding, including genetic engineering methods. In addition, they are suitable for the control of Botry- osphaeria species, Cylindrocarpon species, Eutypa lata, Neonectria liriodendri and Stereum hirsutum, which attack, inter alia, the wood or the roots of grapevines. In particular, they are suitable for controlling the following plant diseases:
  • Botrytis cinerea (gray mold) on strawberries, vegetables, flowers, vines and wheat (spike mold),
  • Drechslera species Pyrenophora species on maize, cereals, rice and turf, barley (e.g., D. teres) and wheat (e.g., D. tritici-repentis),
  • Fusarium and Verticillium species on different plants e.g. F. graminearum or F. culmorum (root rot) on cereals (e.g., wheat or barley) or e.g. F. oxysporum on tomatoes and Fusarium solani (stalk disease) on soybeans
  • Gaeumanomyces graminis root black on cereals (for example wheat or barley),
  • Gibberella species on cereals and rice e.g., Gibberella fujikuroi
  • Macrophomina phaseolina root rot
  • Michrodochium nivale sichrodochium nivale
  • cereals such as wheat or barley
  • Mycosphaerella species on cereals, bananas and peanuts e.g. M. graminicola on wheat or M. fijiensis on bananas,
  • Peronospora species on cabbage e.g., P. brassicae
  • bulbous plants e.g., P. destructor
  • Peronospora manshurica downy mildew
  • Phakopsara pachyrhizi (soybean rust) and Phakopsara meibomiae (soybean rust) on soybeans
  • Phytophthora species on various plants e.g. P. capsici on paprika, Phytophthora megasperma (leaf / stem rot) on soybeans, Phytophthora infestans on potatoes and tomatoes,
  • Pseudocercosporella herpotrichoides crushed straw
  • Pseudoperonospora on various plants, for example P. cubensis on cucumber or P. humili on hops,
  • Puccinia species on various plants e.g. P. triticina, P. striformins, P. hordei or P. graminis on cereals (e.g., wheat or barley) or asparagus (e.g., P. asparagi),
  • Ramularia collo-cygni (Ramularia / sunburn complex / Physiological leaf spots) on barley
  • Rhizoctonia species on cotton, rice, potatoes, turf, corn, oilseed rape, potatoes, sugar beets, vegetables and various other plants e.g. Rhizoctonia solani (root / stem rot) on soybeans or Rhizoctonia cerealis (pointed eye spot) on wheat or barley, Rhynchosporium secalis on barley (leaves), rye and triticale,
  • Venturia species scab
  • apples e.g., V. inaequalis
  • the compounds I are also suitable for controlling harmful fungi in the protection of materials (eg wood, paper, paint dispersions, fibers or fabrics) and in the protection of stored products.
  • harmful fungi Ascomycetes such as Ophiostoma spp., Ceratocystis spp., Aureobasidium pullulans, Sclerophoma spp., Chaetomium spp., Humicola spp., Petriella spp., Trichurus spp .; Basidiomycetes such as Coniophora spp., Coriolus spp., Gloeophyllum spp., Lentinus spp., Pleurotus spp., Poria spp., Serpula spp.
  • Tyromyces spp. Deuteromycetes such as Aspergillus spp., Cladosporium spp., Penicillium spp., Trichoderma spp., Alternaria spp., Paecilomyces spp. and Zygomycetes such as Mucor spp., moreover, in the protection of the following yeasts: Candida spp. and Saccharomyces cerevisae.
  • the compounds I are used by treating the fungi or the plants, seeds, materials or the soil to be protected against fungal attack with a fungicidally effective amount of the active ingredients.
  • the application can be done both before and after the infection of the materials, plants or seeds by the fungi.
  • the fungicidal compositions generally contain between 0.1 and 95, preferably between 0.5 and 90 wt .-% of active ingredient.
  • the application rates in the application in crop protection, depending on the nature of the desired effect between 0.01 and 2.0 kg of active ingredient per ha.
  • active ingredient in general, amounts of active ingredient of 1 to 1000 g / 100 kg, preferably 5 to 100 g / 100 kg of seed are needed.
  • the application rate of active ingredient depends on the type of application and the desired effect. Usual application rates are, for example, 0.001 g to 2 kg, preferably 0.005 g to 1 kg of active ingredient per cubic meter of material treated in the material protection.
  • the compounds of the formula I can be present in various crystal modifications, which may differ in their biological activity. They are also the subject of the present invention.
  • the compounds I can be converted into the usual formulations, e.g. Solutions, emulsions, suspensions, dusts, powders, pastes and granules.
  • the application form depends on the respective purpose; It should in any case ensure a fine and uniform distribution of the compound according to the invention.
  • the formulations are prepared in a known manner, e.g. by stretching the active compounds with solvents and carriers or solvents or carriers, if desired using further auxiliaries, such as emulsifiers or dispersants. Individual substances can also fulfill different functions. Suitable solvents, carriers or auxiliaries are essentially:
  • solvents for example Solvesso ® products, xylene
  • paraffins for example mineral oil fractions
  • alcohols for example methanol, butanol, pentanol, benzyl alcohol
  • ketones for example cyclohexanone, gamma-Butryolacton
  • pyrrolidones NMP, NOP
  • Acetates glycols, dimethyl fatty acid amides, fatty acids and fatty acid esters.
  • solvent mixtures can also be used.
  • Excipients such as ground natural minerals (e.g., kaolins, clays, talc, calks) or ground synthetic minerals (e.g., fumed silica, silicates);
  • ground natural minerals e.g., kaolins, clays, talc, calks
  • ground synthetic minerals e.g., fumed silica, silicates
  • Emulsifiers such as nonionic and anionic emulsifiers (eg polyoxyethylene) Fatty alcohol ethers, alkylsulfonates and arylsulfonates) and dispersants such as lignin liquors and methylcellulose.
  • nonionic and anionic emulsifiers eg polyoxyethylene Fatty alcohol ethers, alkylsulfonates and arylsulfonates
  • dispersants such as lignin liquors and methylcellulose.
  • compositions of the invention may be formulated in solid form or in liquid form.
  • the compositions according to the invention may also contain auxiliaries and / or carriers, as are customary in crop protection agents or in agents for the protection of materials.
  • the auxiliaries include, in particular, conventional surface-active substances and other additives customary in plant and material protection and carriers which may be solid or liquid.
  • Surface-active substances include, in particular, surfactants, in particular those which have wetting agent properties.
  • the other auxiliaries (additives) include, in particular, thickeners, defoamers, preservatives, antifreeze agents, stabilizers, anticaking agents or flow aids and buffers.
  • Principally useful conventional surfactants are anionic, nonionic and amphoteric surfactants, including polymer surfactants, wherein the molecular weight of the surfactants will typically not exceed a value of 2000 daltons, and more preferably 1000 daltons (number average).
  • the anionic surfactants include, for example, carboxylates, especially alkali, alkaline earth and ammonium salts of fatty acids, eg. Potassium stearate, which are commonly referred to as soaps; glutamates; Sarcosinates, e.g.
  • iso-tridecyl alcohol lauryl alcohol, oleyl alcohol or stearyl alcohol, and their C 1 -C 4 -alkyl ethers and C 1 -C 4 -alkyl esters e.g. their acetates; alkoxylated animal and / or vegetable fats and / or oils, for example corn oil ethoxylates, castor oil ethoxylates, tallow fat ethoxylates,
  • Glycerol esters such as glycerol monostearate, Alkylphenol alkoxylates, such as, for example, ethoxylated isooctyl, octyl or nonylphenol, tributylphenol polyoxyethylene ethers,
  • Alkyldimethylphosphine oxides such as, for example, tetradecyldimethylphosphine oxide.
  • the amphoteric surfactants include, for example, sulfobetaines, carboxybetaines and alkyldimethylamine oxides, e.g. B. tetradecyldimethylamine oxide.
  • surfactants which are to be mentioned here by way of example are perfluorosurfactants, silicone surfactants, phospholipids, such as lecithin or chemically modified lecithins, amino acid surfactants, eg. B. N-lauroylglutamate.
  • perfluorosurfactants silicone surfactants
  • phospholipids such as lecithin or chemically modified lecithins
  • amino acid surfactants eg. B. N-lauroylglutamate.
  • mineral oil fractions of medium to high boiling point such as kerosine or diesel oil, coal tar oils and oils of vegetable or animal origin, aliphatic, cyclic and aromatic hydrocarbons, e.g.
  • Powders, dispersants and dusts can be prepared by mixing or jointly grinding the active components A and B and, if present, further active ingredients with at least one solid carrier.
  • Granules, e.g. Coating, impregnation and homogeneous granules can be prepared by binding the active ingredients to at least one solid carrier.
  • Solid carriers are e.g.
  • Mineral earths such as silica gels, silicates, talc, kaolin, attaclay, 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 cornmeal, tree bark, wood and nut shell meal, cellulose powder and other solid carriers.
  • Mineral earths such as silica gels, silicates, talc, kaolin, attaclay, 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 cornmeal, tree bark, wood and nut shell
  • the formulations of the compounds according to the invention generally contain 0.01 to 95 wt .-%, preferably 0.1 to 90 wt .-% of the compounds I and II.
  • the active ingredients are preferably in a purity of 90% to 100%, preferably 95% to 100% used.
  • the formulations in question give, after dilution of from two to ten times, active compound concentrations of from 0.01 to 60% by weight, preferably from 0.1 to 40% by weight, in the ready-to-use preparations.
  • the formulations generally contain between 0.01 and 95 wt .-%, preferably between 0.1 and 90 wt .-% of the active ingredient.
  • the active ingredients are in a purity of 90% to 100%, preferably 95% to 100% (by NMR spectrum) used.
  • formulations are: 1. Products for dilution in water A Water-soluble concentrates (SL, LS) 10 parts by weight of the active ingredients are dissolved with 90 parts by weight of water or a water-soluble solvent. Alternatively, wetting agents or other adjuvants are added. When diluted in water, the active ingredient dissolves. This gives a formulation with 10 wt .-% active ingredient content.
  • DC Dispersible Concentrates
  • the active compounds 25 parts by weight of the active compounds are dissolved in 35 parts by weight of xylene 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 Suspensions 20 parts by weight of the active compounds are comminuted with the addition of 10 parts by weight of dispersing and wetting agents and 70 parts by weight of water or an organic solvent in a stirred ball mill to give 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 Water-dispersible and water-soluble granules (WG, SG)
  • the active ingredients are finely ground with the addition of 50 parts by weight of dispersants 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 substance.
  • the formulation has an active ingredient content of 50% by weight.
  • Water-dispersible and water-soluble powders 75 parts by weight of the active compounds are ground in a rotor-stator mill with the addition of 25 parts by weight of dispersing and wetting agents and silica gel. 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 Gel Formulations 20 parts by weight of the active ingredients, 10 parts by weight of dispersing agent are used in a ball mill. gelling agent and 70 parts by weight of water or of an organic solvent to a fine suspension.
  • LS water-soluble concentrates
  • FS suspensions
  • DS dusts
  • WS water-dispersible and water-soluble powders
  • ES emulsifiable concentrates
  • GF gel formulations
  • active compounds may be used as such, in the form of their formulations or the forms of use prepared therefrom, e.g. in the form of directly sprayable solutions, powders, suspensions or dispersions, emulsions, oil dispersions, pastes, dusts, scattering agents, granules by spraying, misting, dusting, scattering or pouring.
  • Aqueous application forms can be prepared from emulsion concentrates, pastes or wettable powders (wettable powders, oil dispersions) by adding water.
  • the substances, as such or dissolved in an oil or solvent can be homogenized in water by means of wetter, tackifier, dispersant or emulsifier. But it can also be made of effective substance wetting, adhesion, dispersing or emulsifying and possibly solvent or oil concentrates, which are suitable for dilution with water.
  • the active compound concentrations in the ready-to-use preparations can be varied within wide ranges. In general, they are between 0.0001 and 10%, preferably between 0.01 and 1%.
  • the active ingredients can also be used with great success in the ultra-low-volume (ULV) process, it being possible to apply formulations containing more than 95% by weight of active ingredient or even the active ingredient without additives.
  • UUV ultra-low-volume
  • oils of various types, wetting agents, adjuvants, herbicides, fungicides, other pesticides, bactericides, if appropriate also only immediately before use (tank mix), can be added.
  • These agents can be added to the compositions according to the invention in a weight ratio of 1: 100 to 100: 1, preferably 1:10 to 10: 1.
  • Suitable adjuvants in this sense are in particular: organically modified polysiloxanes, eg, Break Thru S 240® ; Alcohol alkoxylates, eg. As Atplus 245 ®, Atplus MBA 1303 ®, Plurafac LF 300 ® and Lutensol ON 30 ®; EO-PO block polymers, eg. B.
  • Pluronic RPE 2035 ® and Genapol B ® Alcohol ethoxylates, eg. As Lutensol XP 80 ®; and sodium dioctylsulfosuccinate, e.g. B. Leophen RA ®.
  • the agents according to the invention can also be present together with other active substances which, for example, can be mixed with herbicides, insecticides,
  • fungicides or with fertilizers.
  • the compounds (I) or the agents containing them with one or more further active compounds, in particular fungicides, for example, in many cases, the activity spectrum can be broadened or development of resistance can be prevented. In many cases, synergistic effects are obtained.
  • the fungicides are preferably selected from the following groups. Preferred representatives from these groups are listed in Table B.
  • carboxylic acid amides such as carboxylic anilides, carboxylic acid morpholides, benzoic acid amides, other carboxamides, azoles such as triazoles, imidazoles, benzimidazoles, others, nitrogen-containing heterocyclyl compounds such as pyridines, pyrimidines, pyrroles, morpholines, dicarboximides, other nitrogen-containing heterocyclyl compounds, thio- and dithiocarbamates, carbamates , Guanidines, antibiotics, nitrophenyl derivatives, organometallic compounds, sulfur-containing heterocyclyl compounds, organophosphorus compounds, organochlorine compounds, inorganic active substances, other fungicides.
  • carboxylic acid amides such as carboxylic anilides, carboxylic acid morpholides, benzoic acid amides, other carboxamides, azoles such as triazoles, imidazoles, benzimidazoles, others, nitrogen-containing heterocyclyl compounds
  • the present invention further relates to the compositions listed in Table B, wherein in each case one row of Table B corresponds to a fungicidal composition comprising a compound of formula I (component 1), which is preferably one of the compounds described herein as preferred, and the in each case indicated in the relevant line further active ingredient (component 2).
  • component 1 in each row of table B is in each case one of the compounds of the formula I which are specifically individualized in tables 1 to 336.
  • B-1 is a compound of formula I azoxystrobin
  • the active compounds II mentioned above as component 2 their preparation and their action against harmful fungi are generally known (cf.: http: //www.hci rss.demon.co.uk/index.html); they are commercially available.
  • the compounds named after IUPAC, their preparation and their fungicidal action are also known [cf. EP-A 226 917; EP-A 10 28 125; EP-A 10 35 122; EP-A 12 01 648; WO 98/46608; WO 99/24413; WO 03/14103; WO 03/053145; WO 03/066609; WO 04/049804].
  • the present invention relates to a pharmaceutical agent containing at least one pyridazine according to the invention and / or a pharmaceutically acceptable salt thereof and optionally at least one pharmaceutically acceptable carrier.
  • the invention also relates to the pharmaceutical use of the pyridazines of the formula I according to the invention, in particular the pyridazines of the formula I described in the preceding description, and / or the pharmaceutically acceptable salts thereof, in particular their use for the production of a medicament for the treatment of cancer ,
  • pyridazines of the formula I according to the invention in particular the pyridazines of the formula I according to the invention described in the preceding description, and / or their pharmaceutically acceptable salts, effectively inhibit the growth and / or proliferation of tumor cells, as in standard tests
  • Tumor cell lines such as HeLa, MCF-7 and COLO 205 can be shown.
  • pyrimidines of the invention of formula I generally show ICso values ⁇ 10 "6 mol / l (ie ⁇ 1 uM), preferably ICso-values ⁇ 10" 7 mol / l (ie ⁇ 100 nM) for ZeII- zyklusinhibitation in HeLa cells.
  • the pyridazines of the formula I according to the invention in particular the pyridazines according to the invention described as being preferred in the preceding description Formula I, and / or their pharmaceutically acceptable salts are useful for the treatment, inhibition or control of the growth and / or proliferation of tumor cells and associated diseases.
  • they are useful for the treatment of cancer in warm-blooded vertebrates, ie mammals and birds, in particular in humans, but also in other mammals, in particular useful and skin animals such as dogs, cats, pigs, ruminants (cattle, sheep, goat, Bison, etc.), horse and birds such as chicken, turkey, duck, goose, guinea fowl and the like.
  • the pyridazines of the formula I according to the invention in particular the pyridazines of the formula I according to the invention described in the preceding description, and / or their pharmaceutically acceptable salts are suitable for the treatment of cancer or cancerous diseases of the following organs: breast, lung, intestine , Prostate, skin (melanoma), kidney, bladder, mouth, larynx, esophagus, stomach, ovaries, pancreas, liver and brain.
  • the pharmaceutical compositions according to the invention contain, in addition to the pyridazine I according to the invention and / or its pharmaceutically acceptable salt, at least optionally a suitable carrier.
  • suitable carriers are, for example, the solvents, carriers, excipients, binders and the like commonly used for pharmaceutical formulations, which are described below by way of example for individual administration forms.
  • the compounds I according to the invention can be administered in the usual way, e.g. oral, intravenous, intramuscular or subcutaneous.
  • the active ingredient may be mixed with an inert diluent or with an edible carrier; it can be embedded in a hard or soft gelatin capsule, pressed into tablets or mixed directly with the food / feed.
  • the active ingredient may be mixed with excipients and administered in the form of indigestible tablets, buccal tablets, troches, pills, capsules, suspensions, juices, syrups and the like.
  • Such preparations should contain at least 0.1% active ingredient.
  • the composition of the preparation may of course vary. It usually contains from 2 to 60% by weight of active compound, based on the total weight of the particular preparation (dosage unit).
  • Preferred formulations of the compound I according to the invention contain 10 to 1000 mg of active ingredient per oral dosage unit.
  • the tablets, troches, pills, capsules and the like may also contain the following ingredients: excipients such as tragacanth, acacia, corn starch or gelatin, excipients such as dicalcium phosphate, disintegrants such as corn starch, potato starch, alginic acid and the like, lubricants such as magnesium stearate, sweetener, such as sucrose, lactose, or saccharin, and / or flavorants such as peppermint, vanilla, and the like.
  • Capsules may also contain a liquid carrier.
  • Other substances that change the nature of the dosing unit can also be used. For example, tablets, pills and capsules may be coated with shellac, sugar or mixtures thereof.
  • syrups or juices may also contain sugar (or other sweeteners), methyl or propylparaben Preservative, a dye and / or flavoring included.
  • sugar or other sweeteners
  • methyl or propylparaben Preservative a dye and / or flavoring included.
  • the ingredients of the active ingredient formulations in the amounts used must be pharmaceutically pure and non-toxic.
  • the active compounds can be formulated as preparations with controlled release of active ingredient, for example as sustained-release preparations.
  • the active substances can also be administered parenterally or intraperitoneally. Solutions or suspensions of the active compounds or their salts can be prepared with water using suitable wetting agents such as hydroxypropylcellulose. Dispersions can also be made with glycerin, liquid polyethylene glycols, and mixtures thereof in oils. Often these preparations also contain a preservative to prevent the growth of microorganisms.
  • Preparations for injections include sterile aqueous solutions and dispersions as well as sterile powders for the preparation of sterile solutions and dispersions.
  • the preparation must be sufficiently liquid so that it is injectable. It must be stable under the conditions of manufacture and storage and be protected against microbial contamination.
  • the carrier can be a solvent or a dispersion medium, e.g. water, ethanol, polyols (e.g., glycerin, propylene glycol, or liquid polyethylene glycol), mixtures thereof, and / or vegetable oils.
  • HPLC retention times (RT) in the following examples were determined using the RP-18 column Chromolith Speed ROD (from Merck KgaA, Germany) with the eluent acetonitrile + 0.1% trifluoroacetic acid (TFA) / water + 0.1%. TFA in a gradient from 5:95 to 95: 5 in 5 min at 40 0 C determined. Mass spectrometry was performed under Quadropol electrospray ionization, 80V (positive mode).
  • Step 1 4- [3-Chloro-5- (4-chlorophenyl) -6-methylpyridazin-4-yl) -3,5-difluoro-phenol 0.2g 3-chloro-5- (4-chlorophenyl) -4- (2,6-difluoro-4-methoxyphenyl) -6-methyl-pyridazine (see WO 2005/121 104) and 1 ml of 1 M BBr 3 solution in methylene chloride were stirred for about 6 hours at 20 to 25 ° C stirred. Subsequently, the reaction mixture was hydrolyzed with water and the aqueous phase was extracted with ethyl acetate. The combined organic phases were dried and freed from the solvent.
  • Step 2 (3- ⁇ 4- [3-chloro-5- (4-chlorophenyl) -6-methylpyridazin-4-yl] -3,5-difluoro-phenoxy ⁇ -propyl) -dimethylamine O, 2g 4- [3-Chloro-5- (4-chlorophenyl) -6-methylpyridazin-4-yl) -3,5-difluoro-phenol (from Step 1), 0.1 g dimethylaminopropanol and 0.3 g Triphenylphosphine in 5 ml of tetrahydrofuran were mixed with 0.2 g of diethyl azodicarboxylate and stirred for about 1 hour at 20 to 25 ° C.
  • the active compounds were separately prepared as a stock solution with 25 mg of active ingredient, which with a mixture of acetone and / or DMSO and the emulsifier Uniperol® EL (wetting agent with emulsifying and dispersing action based on ethoxylated alkylphenols) in the volume ratio solvent- Emulsifier from 99 to 1 ad 10 ml was filled. It was then made up to 100 ml with water. This stock solution was diluted with the described solvent-emulsifier-water mixture to the drug concentration given below. Alternatively, the active ingredients were used as a commercial ready-made formulation and with water to the specified Wirkstoffkonz. diluted.
  • Leaves of potted tomato plants were sprayed to drip point with an aqueous suspension in the drug concentration below. The following day, the leaves were inoculated with an aqueous sporangia suspension of Phytophthora infestans. Subsequently, the plants were placed in a water vapor-saturated chamber at temperatures between 18 and 20 0 C. After 6 days, the late blight on the untreated but infected control plants had developed so strongly that the infestation could be determined visually in%. In this test, the plants treated with 250 ppm of the active ingredient 1-1 showed no infestation, while the untreated plants were 80% infected.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne des pyridazines de formule (I) dans laquelle les substituants sont définis selon la description, des procédés et des produits intermédiaires pour la fabrication de ces composés, un agent les contenant et leur utilisation pour lutter contre les champignons parasites phytopathogènes. L'invention concerne également l'utilisation des pyridazines pour la fabrication d'un médicament pour le traitement du cancer.
EP08736575A 2007-05-02 2008-04-25 Pyridazines fongicides, leur procédé de fabrication et leur utilisation pour lutter contre les champignons parasites et agent les contenant Withdrawn EP2064188A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP08736575A EP2064188A1 (fr) 2007-05-02 2008-04-25 Pyridazines fongicides, leur procédé de fabrication et leur utilisation pour lutter contre les champignons parasites et agent les contenant

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP07107339 2007-05-02
EP08736575A EP2064188A1 (fr) 2007-05-02 2008-04-25 Pyridazines fongicides, leur procédé de fabrication et leur utilisation pour lutter contre les champignons parasites et agent les contenant
PCT/EP2008/055058 WO2008135413A1 (fr) 2007-05-02 2008-04-25 Pyridazines fongicides, leur procédé de fabrication et leur utilisation pour lutter contre les champignons parasites et agent les contenant

Publications (1)

Publication Number Publication Date
EP2064188A1 true EP2064188A1 (fr) 2009-06-03

Family

ID=39689283

Family Applications (1)

Application Number Title Priority Date Filing Date
EP08736575A Withdrawn EP2064188A1 (fr) 2007-05-02 2008-04-25 Pyridazines fongicides, leur procédé de fabrication et leur utilisation pour lutter contre les champignons parasites et agent les contenant

Country Status (6)

Country Link
US (1) US20100130359A1 (fr)
EP (1) EP2064188A1 (fr)
JP (1) JP2010525030A (fr)
CN (1) CN101679302A (fr)
BR (1) BRPI0810604A2 (fr)
WO (1) WO2008135413A1 (fr)

Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK1958948T3 (da) * 2005-12-07 2011-10-31 Sumitomo Chemical Co Pyridazinforbindelse og anvendelse deraf
GB0725059D0 (en) * 2007-12-21 2008-01-30 Syngenta Participations Ag Novel pyridazine derivatives
JP2013501715A (ja) * 2009-08-07 2013-01-17 イー・アイ・デュポン・ドウ・ヌムール・アンド・カンパニー 殺菌・殺カビ性ジフェニル−置換ピリダジン
JP2012056940A (ja) * 2010-08-10 2012-03-22 Sumitomo Chemical Co Ltd 植物病害防除組成物およびその用途
JP2012036143A (ja) * 2010-08-10 2012-02-23 Sumitomo Chemical Co Ltd 植物病害防除組成物およびその用途
JP2012056942A (ja) * 2010-08-10 2012-03-22 Sumitomo Chemical Co Ltd 植物病害防除組成物およびその用途
JP2013142065A (ja) 2012-01-10 2013-07-22 Sumitomo Chemical Co Ltd 植物病害防除組成物およびその用途
JP2013142063A (ja) * 2012-01-10 2013-07-22 Sumitomo Chemical Co Ltd 植物病害防除組成物およびその用途
JP2013142062A (ja) * 2012-01-10 2013-07-22 Sumitomo Chemical Co Ltd 植物病害防除組成物およびその用途
CN103800315B (zh) * 2012-11-09 2016-12-21 中国中化股份有限公司 苯腈类化合物作为制备抗肿瘤药物的应用
WO2014109375A1 (fr) * 2013-01-09 2014-07-17 日産化学工業株式会社 Composé pyridazine substitué, et fongicide agricole et horticole
JP6589697B2 (ja) * 2016-03-04 2019-10-16 住友化学株式会社 液状農薬
CN106588700B (zh) * 2016-12-06 2019-01-25 盐城辉煌化工有限公司 一种改进的霜脲氰合成方法
BR112021010152A2 (pt) * 2018-12-20 2021-11-09 Bayer Ag Heterociclil piridazina como compostos fungicidas
CN114404400A (zh) * 2022-01-24 2022-04-29 深圳承启生物科技有限公司 不占用核糖体资源的翻译抑制剂作为抗肿瘤药物

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6878709B2 (en) * 2002-01-04 2005-04-12 Schering Corporation 3,4-di-substituted pyridazinediones as CXC chemokine receptor antagonists
DE602005014359D1 (de) * 2004-06-09 2009-06-18 Sumitomo Chemical Co Pyridazinverbindung und deren verwendung
CN100586944C (zh) * 2004-06-25 2010-02-03 巴斯福股份公司 2,4,5,6-取代吡啶、它们的制备方法和它们在防治真菌中的用途
US7629342B2 (en) * 2005-06-17 2009-12-08 Bristol-Myers Squibb Company Azabicyclic heterocycles as cannabinoid receptor modulators
GB0614153D0 (en) * 2006-07-17 2006-08-23 Syngenta Participations Ag Novel pyridazine derivatives
BRPI0714872A2 (pt) * 2006-07-17 2013-03-19 Syngenta Participations Ag derivados de piridazina
EP1916240A1 (fr) * 2006-10-25 2008-04-30 Syngeta Participations AG Nouveaux derivés de pyridazine
BRPI0718022A2 (pt) * 2006-10-25 2013-11-12 Syngenta Participations Ag Derivados de piridazina
AR064962A1 (es) * 2007-01-22 2009-05-06 Syngenta Participations Ag Derivados de piridazina utiles como fungicidas

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2008135413A1 *

Also Published As

Publication number Publication date
JP2010525030A (ja) 2010-07-22
BRPI0810604A2 (pt) 2014-10-21
CN101679302A (zh) 2010-03-24
WO2008135413A1 (fr) 2008-11-13
US20100130359A1 (en) 2010-05-27

Similar Documents

Publication Publication Date Title
EP2064188A1 (fr) Pyridazines fongicides, leur procédé de fabrication et leur utilisation pour lutter contre les champignons parasites et agent les contenant
HUP0401488A2 (hu) Fungicid hatású 7-amino-triazolopirimidinek, előállításuk, alkalmazásuk és ilyeneket tartalmazó készítmények
WO2008037607A1 (fr) Composés hétérocycliques à teneur en groupe carbonyle et leur utilisation pour lutter contre des champignons phytopathogènes
EP2049498A1 (fr) Composés de pyrimidine pour la lutte contre les champignons nuisibles et le cancer
EP2010515A1 (fr) 2-(pyridine-2-yl)-pyrimidines utilisées comme fongicides
DE102008000872A1 (de) Fungizide Pyridazine, Verfahren zu ihrer Herstellung und ihre Verwendung zur Bekämpfung von Schadpilzen sowie sie enthaltende Mittel
WO2006114405A2 (fr) Utilisation de 5-alkyl-6-phenylalkyl-7-amino-azolopyrimidines, nouvelles azolopyrimidines, procede de fabrication et agents les contenant
EP1504009B1 (fr) Triazolopyrimidines fongicides, leurs procedes de production et leur utilisation pour la lutte contre des champignons nuisibles, et agents contenant ces composes
EP2046794A1 (fr) Azolopyrimidines fongicides, procédés de production associés, leur utilisation pour lutter contre des champignons nuisibles et agents les contenant
WO2007113136A1 (fr) Utilisation de triazolopyrimidines substituées dans la lutte contre des champignons phytopathogènes
WO2007116011A2 (fr) Triazolopyrimidines substituées, procédé de fabrication, utilisation dans la lutte contre des champignons parasites et agent contenant ces composés
EP1720879A2 (fr) Composes azolopyrimidine et leur utilisation pour lutter contre des champignons nuisibles
EP1585747B1 (fr) 5-alkyl-7-aminotriazolopyrimidines, procedes et produits intermediaires pour leur production, agents les contenant et leur utilisation pour lutter contre des champignons nocifs
EP1575957A1 (fr) Triazolopyrimidines substituees par un groupe mercapto en position 2, leurs procedes de production, leur utilisation pour lutter contre des champignons nuisibles et agents les contenant
WO2007101804A1 (fr) Pyrazolopyrimidines substituées, procédés de production associés et leur utilisation pour lutter contre des champignons nuisibles, et agents les contenant
EP1765824B1 (fr) 6-phenyl-7-amino-triazolopyrimidines substituees, procedes permettant de les produire et leur utilisation pour lutter contre des champignons nuisibles, et agents les contenant
WO2007012642A1 (fr) Composes de 7-amino-6-thiadiazolyl- et -oxadiazolyl- 1, 2, 4-triazolo [1, 5 -a] pyrimidine et leur utilisation pour lutter contre les champignons nuisibles
EP2117312A1 (fr) Utilisation d'azolopyrimidines pour la lutte contre des champignons parasites phytopathogenes
WO2007101859A1 (fr) Pyrazolopyrimidines substituées, procédés de production associés et leur utilisation pour lutter contre des champignons nuisibles, et agents les contenant
EP1931643A1 (fr) Hydroxylaminopyrimidines 2-substituees, procede permettant de les produire et leur utilisation comme pesticide
EP1697365B1 (fr) 6-(2-fluoro-4-alcoxyphenyl)-triazolopyrimidines, leurs procedes de fabrication, leur utilisation pour lutter contre les champignion nuisibles et agents les contenants
WO2007118844A1 (fr) Pyrazolopyrimidines substituées, leur procédé de préparation, leur utilisation pour lutter contre les champignons nuisibles, et agents les contenant
EP1758457A1 (fr) Composes de triazolopyrimidine et leur utilisation pour lutter contre des champignons nocifs
WO2007099092A1 (fr) 6-phenyl-7-amino-[1,2,4]-triazolo[1,5-a]pyrimidine substituee et son utilisation pour lutter contre les champignons parasites
EP1613605A1 (fr) Pyrimidine substituee en 2

Legal Events

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

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20090319

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MT NL NO PL PT RO SE SI SK TR

AX Request for extension of the european patent

Extension state: AL BA MK RS

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

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

18D Application deemed to be withdrawn

Effective date: 20111101