DE19544098A1 - Cycloalkylmethyl and cycloalkylidenemethyl pyridines, processes for their preparation, compositions containing them and their use as pesticides and fungicides - Google Patents

Abstract

The invention concerns compounds of formula (a) and their N-oxides and salts, Q meaning optionally substituted 4-pyridyl; R<1> and R<2> meaning H, alkyl, alkenyl, alkyl halide, alkenyl halide, aryl or aralkyl; R<3> meaning H; or R<1> + R<3> together being a bond and R<2> being defined as above; R<4> being alkyl, alkenyl, alkoxy, alkanoyloxy, alkenyloxy, acyl, alkoxycarbonyl, alkenyloxycarbonyl, alkyl halide, alkenyl halide, alkoxy halide, alkenyloxy halide, acyl halide, alkoxycarbonyl halide, aryl, aralkyl, heteroaryl or heteroarylalkyl; p being 2 to 7; and n being 1, 2 or 3. The invention further concerns processes for the production of these compounds and their use as pesticides and fungicides.

Description

The invention relates to new substituted pyridines, processes for their preparation and their use as pesticides, especially as Insecticides, acaricides and fungicides.

It is already known that certain substituted 4-aminopyridines and 4-hydroxypyridines show a fungicidal, acaricidal and insecticidal activity (cf. WO-A-93/05050). Furthermore, WO-A-93/04579 describes 4-aralkylpyridines known nematicidal effect. Finally, U.S. Patent 2,505,461 relates to Alkylcyclohexylmethylpyridines and their use as fungicides.

However, the biological action of these compounds is in particular: low application rates and concentrations not in all Areas of application satisfactory.

New substituted 4-cycloalkylmethyl and 4-cycloalkylidenemethyl Found pyridines of formula I, which are biologically active.

The invention therefore relates to compounds of the formula (I) and their N-oxides,

in which
R represents the same or different radicals selected from the series
(C₁-C₄) alkyl,
(C₂-C₄) alkenyl,
(C₂-C₄) alkynyl,
(C₂-C₄) alkoxy,
(C₂-C₄) alkenyloxy,
Halogen (C₁-C₄) alkyl,
Halogen (C₂-C₄) alkenyl,
Halogen (C₂-C₄) alkynyl,
Halogen (C₁-C₄) alkoxy,
Halogen (C₁-C₄) alkenyloxy,
R⁵-O-CH₂-,
R⁵-O-CO-,
R⁶-CO-,
Halogen (C₁-C₄) alkoxymethyl,
Halogen (C₁-C₄) alkoxycarbonyl,
Halogen (C₂-C₄) alkenyloxymethyl,
Halogen (C₂-C₄) alkenyloxycarbonyl,
(C₁-C₄) alkylthio,
(C₂-C₄) alkenylthio,
(C₁-C₄) alkylsulfinyl,
(C₂-C₄) alkenylsulfiny l,
(C₁-C₄) alkylsulfonyl,
(C₂-C₄) alkenylsulfonyl,
Aryl,
Aralkenyl,
substituted amino,
Cyano and
Halogen;
m represents 0, 1, 2, 3 or 4;
R¹ and R² are the same or different and are selected from the series hydrogen,
(C₁-C₄) alkyl,
(C₂-C₄) alkenyl,
Halogen (C₁-C₄) alkyl,
Halogen (C₂-C₄) alkenyl,
Aryl and
Aralkyl; and
R³ represents hydrogen; or
R¹ and R³ together represent a bond and
R² is as defined above;
p is an integer from 2 to 7, preferably 4 to 6, in particular 5;
R⁴ stands for the same or different radicals which are selected from the series
(C₅-C₁₀) alkyl,
(C₂-C₁₀) alkenyl,
(C₂-C₁₀) alkynyl,
(C₅-C₁₀) alkoxy,
(C₁-C₁₀) alkanoyloxy,
(C₂-C₁₀) alkenyloxy,
(C₅-C₁₀) acyl,
(C₁-C₁₀) alkoxy-carbonyl,
(C₂-C₁₀) alkenyloxycarbonyl,
Halogen (C₅-C₁₀) alkyl,
Halogen (C₅-C₁₀) alk enyl,
Halogen (C₅-C₁₀) alkoxy,
Halogen (C₂-C₁₀) alkenyloxy,
Halogen (C₂-C₁₀) acyl,
Halogen (C₂-C₁₀) alkoxy-carbonyl,
Halogen (C₂-C₁₀) alkenyloxycarbonyl,
Aryl,
Aralkyl,
Heteroaryl and
Heteroarylalkyl;
n represents 1, 2 or 3;
R⁵ (C₁-C₁₀) alkyl,
(C₂-C₁₀) alkenyl,
(C₂-C₁₀) alkynyl,
(C₃-C₈) cycloalkyl or
Aralkyl;
R⁶ is defined as R⁵ or
Halogen (C₁-C₁₀) alkyl,
Halogen (C₂-C₂₀) alkenyl or
Means aryl;
Aryl means phenyl, naphthyl or biphenyl, preferably phenyl, which are each optionally substituted;
Aralkyl is aryl (C₁-C₄) alkyl;
Heteroaryl is aryl, in which at least 1, preferably up to 4, in particular up to 2 CH, have been replaced by N and / or at least 1, preferably 1 -CH = CH unit has been replaced by NH, S or O, which may be as Aryl is substituted; and
Heteroarylalkyl means heteroaryl- (C₁-C₄) alkyl; or their salts.

In the above formula I, "halogen" means a fluorine, chlorine, bromine or iodine atom, preferably a fluorine, chlorine or bromine atom;
under the expression "(C₁-C₄) alkyl" an unbranched or branched hydrocarbon radical having 1 to 4 hydrocarbon atoms, such as. B. the methyl, ethyl, propyl, 1-methylethyl, 1-methylpropyl, 2-methylpropyl or 1,1-dimethylethyl radical;
under the expression "(C₅-C₁₀) alkyl" z. B. the pentyl, 2-methylbutyl or 1,1-dimethylpropyl radical, the hexyl, heptyl, octyl, 1,1,3,3-tetramethylbutyl, nonyl or decyl radical;
mono- or polyunsaturated residues derived from these alkyl residues under "alkenyl" and "alkynyl";
under the expression "(C₃-C₈) cycloalkyl" preferably cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl;
under the expression "halogen (C₁-C₄) alkyl" or "halogen (C₅-C₁₀) alkyl" one under the expression "(C₁-C₄) alkyl" or "(C₁-C₁₀) alkyl Said alkyl group in which one or more hydrogen atoms have been replaced by the above halogen atoms, preferably chlorine or fluorine, such as the trifluoromethyl group, the 2,2,2-trifluoroethyl group, the chloromethyl, fluoromethyl group, the difluoromethyl group, the 1,1, 2,2-tetrafluoroethyl group or the 1,1,2,2-tetrachlorohexyl group (the same applies to "haloalkenyl");
under "substituted aryl" an aryl radical which has one or more, preferably up to three identical or different substituents from the series halogen, (C₁-C₄) alkyl, halogen (C₁-C₄) alkyl, hydroxy- (C₁-C₄ ) alkyl, (C₁-C₄) alkoxy, halogen (C₂-C₄) alkoxy, phenoxy, phenyl, nitro, hydroxy, cyano, (C₁-C₄) alkanoyl, benzoyl, (C₁-C₄) alkanoyloxy and (C₁-C₄) alkoxycarbonyl; the same applies to aralkyl;
"Heteroaryl" means z. B. a residue of thiophene, furan, pyrrole, thiazole, oxazole, imidazole, isothiazole, isoxazole, pyrazole, 1,3,4-oxadiazole, 1,3,4-thiadiazole, 1,3,4-triazoo, 1,2 , 4-oxadiazole, 1,2,4-thiadiazole, 1,2,4-triazole, 1,2,3-triazole, 1,2,3,4-tetrazole, benzo [b] thiophene, benzo [b] furan , Indole, benzo [c] thiophene, benzo [c] furan, isoindole, benzoxazole, benzothiazole, benzimidazole, benzisoxazole, benzisothiazole, benzopyrazole, benzothidiazole, benzotriazole, dibenzofuran, dibenzothiophene, carbazole, pyridine, pyrazine, pyridine, 1,3-pyridine , 5-triazine, 1,2,4-triazine, 1,2,4,5-triazine, quinoline, isoquinoline, quinoxaline, quinazoline, cinnoline, 1,8-naphthyridine, 1,5-naphthyridine, 1,6-naphthyridine , 1,7-naphthyridine, phthalazine, pyridopyrimidine, purine, pteridine or 4H-quinolizine;
"substituted amino" means an amino group which is substituted by one or two (C₁-C₄) alkyl groups or by a (C₁-C₄) alkanoyl group;
under "(C₅-C₁₀) acyl" in particular a (C₅-C₁₀) alkanoyl radical or an aroxyl radical, such as valeryl, isovalerl, pivaloyl or benzoyl.

The explanations given above apply, unless otherwise specified defined correspondingly for residues derived therefrom, such as haloalkoxy, Alkylthio, alkylsulfinyl, alkylsulfonyl. They also apply to homologues.

Preferred compounds of formula I, their N-oxides and salts, in which
R represents the same or different radicals selected from the series
(C₁-C₄) alkyl,
(C₂-C₄) alkenyl,
(C₁-C₄) alkoxy,
(C₂-C₄) alkenyloxy,
Halogen (C₁-C₄) alkyl,
Halogen (C₂-C₄) alkenyl,
Halogen (C₁-C₄) alkoxy,
Halogen (C₁-C₄) alkenyloxy,
R⁵-O-CH₂-,
R⁵-O-CO-,
Halogen (C₁-C₄) alkoxymethyl,
Halogen (C₁-C₄) alkoxycarbonyl,
Halogen (C₂-C₄) alkenyloxymethyl,
Halogen (C₂-C₄) alkenyloxycarbonyl,
Cyano and
Halogen;
and the remaining radicals and variables are as defined above, especially those in which
R¹, R² and R³ are the same or different and are selected from the series hydrogen and (C₁-C₄) alkyl
or
R¹ and R³ together represent a bond and
R² is as defined above;
p is preferably 5.

If m = 2, the radicals R are preferably adjacent.

Also preferred are compounds of formula I, their N-oxides and salts, wherein
R⁴ stands for the same or different radicals which are selected from the series
(C₅-C₁₀) alkyl,
(C₂-C₁₀) alkenyl,
(C₅-C₁₀) alkoxy,
(C₁-C₁₀) alkanoyloxy,
(C₂-C₁₀) alkenyloxy,
(C₅-C₁₀) acyl,
(C₁-C₁₀) alkoxy-carbonyl,
(C₂-C₁₀) alkenyloxycarbonyl,
Halogen (C₅-C₁₀) alkyl,
Halogen (C₅-C₁₀) alkenyl,
Halogen (C₅- C₁₀) alkoxy,
Halogen (C₂-C₁₀) alkenyloxy,
Halogen (C₂-C₁₀) acyl,
Halogen (C₂-C₁₀) alkoxy-carbonyl,
Halogen (C₂-C₁₀) alkenyloxycarbonyl,
Aryl,
Aralkyl,
Heteroaryl and
Heteroarylalkyl;
and the remaining residues and variables are as defined above;
Compounds of the formula I are very particularly preferred, their N-oxide and salts, in which n = 1, in particular those in which p = 5 and R⁴ is in the 4-position of cyclohexyl or cyclohexylidene.

Compounds of formula I has at least one of the radicals R⁴ preferably the cis configuration with respect to the radicals R¹ and R² Carbon atom, unless R¹ and R³ together represent a bond.

The present invention relates to the compounds of formula I in the form of free base or a salt, especially acid addition salt. Acids that can be used for salt formation are inorganic acids, such as Hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid or organic acids such as formic acid, acetic acid, propionic acid, Malonic acid, oxalic acid, fumaric acid, adipic acid, stearic acid, oleic acid, Methanesulfonic acid, benzenesulfonic acid or toluenesulfonic acid.

Some of the compounds of the formula I have one or more asymmetrical compounds Carbon atoms. Racemates and diastereomers can therefore occur. The invention encompasses both the pure isomers and their mixtures. The Mixtures of diastereomers can by conventional methods, for. B. by selective crystallization from suitable solvents or by Chromatography can be separated into the components. Racemate can be separated into the enantiomers by conventional methods, for. B. by  Salt formation with an optically active acid, separation of the diastereomeric salts and release of the pure enantiomers using a base.

The invention also relates to a process for the preparation of compounds of the Formula I or its N-oxides, which is characterized in that

• a) for the preparation of a compound of formula I in which R¹ and R³ stand together for a bond,
• a₁) a compound of formula II, in which R⁴, n and p are as defined above,
  reacted in the presence of a base with a compound of formula III or formula IV in which R, R² and m are as defined above, R⁷ is aryl or (C₁-C₄) - alkoxy, R⁸ is aryl, aryl is as defined above and X⊖ is halide; or
• a₂) from a compound of formula V, in which R, R¹, R², R⁴, m, n and p are as defined above, in contrast to a basic or an acid catalyst, water is split off, or the hydroxyl group is split off after conversion to a leaving group to form the double bond, a compound of which Formula VI can arise in which R, R¹, R², R⁴, m, n and p are as defined above;
• b) for the preparation of a compound of the formula I in which R¹ and R³ are not together a bond,
  a compound of formula I in which R¹ and R³ together represent a bond and the remaining radicals and variables are as defined above, or a compound of formula VI as defined above under a₂) is hydrogenated; and optionally carries out one or more of the following steps: introduction of substituents on the pyridine;
  - Exchange or modification of reactive residues on the pyridine;
  - Conversion into the N-oxides with suitable oxidizing agents;
  - Transfer to their salts.

The methods of carbonyl olefination mentioned above under a 1) are as Horner or Wittig reaction known and in a number of reviews described in detail (see e.g. Chem. Rey. 74 [1974] 87 ff .; Org. React. 14 [1965] 270 ff.).

The olefination is normally carried out in a suitable solvent in the In the presence of a base. Examples of the solvent are ethers such as diethyl ether, tetrahydrofuran, dioxane and dimethoxyethane, aromatic Solvents such as benzene, toluene and xylene; and aprotic polar Solvents such as dimethylformamide and dimethyl sulfoxide. Preferred Solvents are tetrahydrofuran and dimethyl sulfoxide. Suitable bases are e.g. B. organic lithium compounds such as butyllithium, phenylithium; Lithium diisopropylamide, alkali metal hydrides such as sodium hydride, Alkali metal alcoholates such as sodium methylate and potassium tert-butoxide and Alkali metal amides such as sodium amide and potassium amide. Preferred base is Sodium hydride.

The amount of base used per mole of phosphorus compound can be 0.8 to 1.5 moles. Excesses of 5 to 10% base per mole are preferred Phosphorus compound. The reaction temperature depends on the reactivity of the both components and is in the range between -50 ° C and + 200 ° C. For a complete conversion of the phosphorus compounds will Carbonyl compound used in excess, the excess up to Can be 100%. Excesses of 10 to 20% are preferred.

The hydrogenation in the compounds of the formula I (R 1 + R 3 = bond) and (VI) the double bond can be carried out by the usual methods, such as. B. in Houben-Weyl are described (Houben-Weyl, reduction I and II, volumes 4 / 1c  and 4 / 1d, Thieme Verlag Stuttgart, New York 1980). The hydrogenation can be carried out in polar solvents such as B. aliphatic hydrocarbons or Ethers or esters can be carried out. Can also be used as a solvent polar aprotic or protic solvents can be used such. B. Alcohols and carboxylic acids. Furthermore, the hydrogenation in aqueous Mineral acids take place or in mixtures of the solvents described. The Hydrogenations can be carried out at normal pressure or under pressure. You can at temperatures between 0 ° C and 100 ° C. The is preferred Hydrogenation at ambient temperature. The usual catalysts Hydrogenation catalysts are used like nickel catalysts or precious metals catalysts here in particular platinum and palladium catalysts.

Depending on the olefin used, the hydrogenation can have different stereoisomers deliver. The type and proportion of the possible isomers depends on the hydrogenation system and can by appropriate choice of the solvent and the catalyst to be influenced. The hydrogenation of 2-ethynyl-3-methoxy-4 (4- phenyl-cyclohexylidene) methyl) pyridine in methanol with palladium on carbon largely the cis isomer. The selection of the catalyst must also under the Regarding whether other hydrogenable groups in the Molecule are present. So z. B. Halogen can be removed hydrolytically. The resulting isomers can be separated by chromatographic means Methods or by crystallization of salts with suitable acids.

Another preferred synthetic route is via variant a₂)

A cycloalkyl ketone is added to a 4-alkyl pyridine, with the  Alkyl group must be at least one hydrogen. This Reaction type is described in (O. F. Beumel, Jr., W.N. Smith v. B. Rybalka; Synthesis 1974, 43).

The reaction is carried out in ethers such as diethyl ether, tetrahydrofuran or dimethoxyethane. In addition, solvents such as dimethyl sulfoxide or liquid ammonia can also be used. Organic lithium compounds such as lithium butyl, lithium phenyl or lithium diisopropylamide can be used as bases. Alkali metal hydrides and alkali amides can also be used for this. The reaction runs at temperatures between -100 ° C and + 30 ° C, the activity of the base used and the stability of the intermediate carbanion determine the temperature limits. Lithium diisopropylamide in THF at -70 ° C has proven to be the preferred system. The carbonyl compound is preferably used in an equimolar amount in excess. Formed isomer mixtures can be separated by the usual methods, such as. B. chromatographic methods or z. B. by the crystallization of suitable acid addition salts. The alcohols are converted into the olefins by the customary methods (Houben-Weyl Alkene, Volume V / 1b page 62-104, Georg Thieme Verlag Stuttgart 1972). It takes place in the liquid phase and can be alkaline or acid catalyzed. Inorganic acids or organic acids such as e.g. B. sulfonic acids such. B. para-toluenesulfonic acid, or carboxylic acids such as. B. oxalic acid or trifluoroacetic acid. Other catalysts are Lewis acids, such as. B. BF₃ ^- etherate or zinc chloride. The reaction can be carried out at temperatures between 0 ° C and 200 ° C. To increase the reaction rate, the water can be used with a tractor such. B. xylene can be distilled off azeotropically or by a water-binding agent such as. B. anhydrides such as acetic anhydride or trifluoroacetic anhydride can be removed. Preferred reaction conditions are the elimination of the water with trifluoroacetic acid and trifluoroacetic anhydride and the azeotropic elimination with para-toluenesulfonic acid and xylene. Of course, the hydroxyl group can also be converted into a leaving group by derivatization, which can then be used for one of the known elimination reactions.

Various isomers are possible for the elimination. So you can Form compounds with an exocyclic or endocyclic double bond. she can be separated by the usual methods such. B. chromatographic methods or crystallization of the acid addition salts with suitable acids. For the hydrogenation of the olefins, what applies to the previous Hydrogenation of the olefins from the carbonyl olefinizations has been said.

Of course, there are other ways from alcohol to Hydrocarbon conceivable, such. B. an "ionic" hydrogenation of Hydroxygruppe (Kursanov, Synthesis, 633 (1974) or a reduction in the a leaving group converted hydroxy group z. B. Chin (tetrahedron; Asymetry, Vol. 6, No. 4, pp. 881-884, 1995). Another important one The reaction step is the modification of reactive groups and the exchange reactive groups on pyridine against suitable partners as follows Show reaction sequences

The exchange of the bromine for the methoxy group is described by Testaferri et al. (Tetrahedron Vol. 41, No. 7, 1373, 1985). He is in Dimethylformamide at 80 ° C with a fourfold excess Sodium methylate made. Of course, instead of  Sodium methylate also use other nucleophiles such as. B. alcoholates, Phenolates, mercaptides, azide, cyanide, halides, carboxylates.

C-C links can also be created in this way like that shows the above reduction, known as the Heck reaction. Your implementation is for pyridines described in T. Sakamoto et al. (Synthesis, 1983, 312). she is carried out in tertiary amines such as triethylamine or in secondary Amines such as diisopropylamine as a solvent and is catalyzed by Palladium and copper. Be particularly preferred Bistriphenylphosphine palladium dichloride and copper iodide. It is carried out at temperatures between 0 ° C and the boiling point of the solvent. in the In this case, temperatures between 20 and 50 ° C were preferred. Of course, substitution on the pyridine ring can also be on one other way z. B. by one of the methods described by D. Spitzner be referenced (Houben-Weyl, Hetarene II, Volume E 7b, 1992, page 568 to 659).

From the substituted 2-trimethylsilylethynylpyridine, the Trimethylsilyl group with acetic acid and sodium fluoride at room temperature split off. The other usual ones can of course also be used for this purpose Cleavage reagents for C-Si bonds can be used like Tetraalkylammonium fluoride, HF etc. The hydrogenation of the triple bond can with the usual systems for this. It can be protic Solvents such as alcohols or carboxylic acids or in aprotic Solvents such as ethers or esters are made by and for this usual catalysts such as platinum, palladium, nickel catalyzed.

Of course, it can also be carried out as a partial hydrogenation. The precursors for the preparation of the pyridines described here are partial for sale. The other part was synthesized according to known methods. For Preparation of the 2-bromo-3-methoxy-4-diethoxyphosphonomethylpyridin served following synthesis route:

The 2-bromo-3-methoxy-pyridine was compared with that described by Effenberger (Chem. Ber. 124 (1991) 2119) described method silylated. It was in Tetrahydrofuran at -70 ° C with trimethylsilyl chloride and lithium diisopropylamide implemented. After working up and column cleaning, it fell in 90% Yield at. The conversion of the silyl group to a formyl group is described by Effenberger (Chem. Ber. 118 (10) 3900 (1985)). That as DMF serving as a formyl source is also a solvent. As a source of fluoride served as a catalyst in a three-fold excess of cesium fluoride Tetrabutylammonium bromide.

The reduction of the formyl compound to the hydroxymethyl compound took place in the usual way of doing this with sodium borohydride in tetrahydrofuran.

The conversion of the hydroxymethyl compound to the chloromethyl compound happened in the usual way. It was done with thionyl chloride in Methylene chloride. DMF was used as a catalyst.

The conversion of the chloromethyl compound into the phosphonic acid ester happened through a Michaelis-Arbusov reaction as in G. M. Kosolapolff, (J. Am. Chem. Soc. 67, 2259 (1945)).  

Another important precursor was 4-ethyl-2,3-dichloropyridine manufactured in the following way.

Commercially available 2-amino-4-methyl-pyridine is chlorinated with chlorine. The exchange of the Amino group against chlorine occurs in a Sandmeyer reaction and is analogous to the regulation by Räth (Annalen 486, 100 (1931)). However, there is no need to add copper. The conversion of methyl into the ethyl group occurs through deprotonation of the methyl compound -70 ° C with lithium diisopropylamide and subsequent reaction with Methyl iodide. Of course, the others can also be used for deprotonation usual bases are used or other alkylating agents are used (D. Spitzner, Houben-Weyl, Hetarene II, Volume E 7b, 1992, page 659-660).

Another important reaction is the subsequent introduction of Substituents on pyridine z. B. in the following way:

The type of reaction is described in F. Minisci (Synthesis 1973, 1). As The alkylating agent is the carboxylic acid on which the alkyl radical is based used. Of course, other carboxylic acids such as Propionic acid and pivalic acid e.g. B. are used. The reaction is silver catalyzed. In addition to lead tetraacetate, a large number of oxidizing agents can be used  other oxidizing agents are used, such as ammonium peroxodisulfate, Diacyl peroxides, carbonic acid peresters or perborates. It can be in water, in Carboxylic acids and carried out in aromatic hydrocarbons and runs at temperatures between 0 and 100 ° C.

Another important reaction sequence is:

The formation of N-oxides of pyridines is comprehensively described by A. Albini u. S. Pietra (Heterocyclic N-Oxides, CRC-Press, Inc. Boca Raton, USA, 1991). It is possible with peracids such as peracetic acid or 3-chloroperbenzoic acid, can also be carried out with hydrogen peroxide in glacial acetic acid. The Reaction of the N-oxide to 2-cyanopyridine is described as a reaction type in Vorbrüggen (Synthesis 1983, 316). One uses as cyanide source Trimethylsilyl cyanide, however, is also the use of alkali cyanide and Trimethylsilyl chloride possible. The reaction of nitrile to the ketone represents one Addition of an organometallic compound to a nitrile with subsequent Hydrolysis. As an organometallic compound, z. B. lithium, Use magnesium, zinc or aluminum organyle to name just a few. The type of reaction is described in G. Sumrell (J. Org. Chem. 19, 817 (1954).  

The active compounds of the formula I are suitable for combating animal pests, in particular insects, arachnids, nematodes, helminths and molluscs, with very good plant tolerance and favorable warm-blood toxicity, very particularly preferably for combating insects and arachnids which are used in agriculture, in animal husbandry, in Forests, in the protection of stocks and materials and in the hygiene sector. They are effective against normally sensitive and resistant species as well as all or individual stages of development. The pests mentioned above include:
From the order of Acarina z. B. Acarus siro, Argas spp., Ornithodoros spp., Dermanyssus gallinae, Eriophyes ribis, Phyllocoptruta oleivora, Boophilus spp., Rhipicephalus spp., Amblyomma spp., Hyalomma spp., Ixodes spp., Psoroptes spp.,. Sarcoptes spp., Tarsonemus spp., Bryobia praetiosa, Panonychus spp., Tetranychus spp., Eotetranychus spp., Oligonychus spp., Eutetranychus spp.

From the order of the Isopoda z. B. Oniscus asselus, Armadium vulgar, Porcellio scaber.

From the order of the Diplopoda z. B. Blaniulus guttulatus.

From the order of the Chilopoda z. B. Geophilus carpophagus, Scutigera spp.

From the order of the Symphyla z. B. Scutigerella immaculata.

From the order of the Thysanura z. B. Lepisma saccharina.

From the order of the Collembola z. B. Onychiurus armatus.

From the order of Orthoptera z. B. Blatta orientalis, Periplaneta americana, Leucophaea madeirae, Blatella germanica, Acheta domesticus, Gryllotalpa spp., Locusta migratoria migratorioides, Melanoplus differentialis, Schistocerca gregaria.

From the order of the Isoptera z. B. Reticulitermes spp.

From the order of the Anoplura z. B. Phylloera vastatrix, Pemphigus spp., Pediculus humanus corporis, Haematopinus spp., Linognathus spp.

From the order of the Mallophaga z. B. Trichodectes pp., Damalinea spp.

From the order of the Thysanoptera z. B. Hercinothrips femoralis, Thrips tabaci.

From the order of Heteroptera z. B. Eurygaster spp., Dysdercus intermedius,  Piesma quadrata, Cimex lectularius, Rhodnius prolixus, Triatoma spp.

From the order of Homoptera z. B. Aleurodes brassicae, Bemisia tabaci, Trialeurodes vaporariorum, Aphis gossypii, Brevicoryne brassicae, Cryptomyzus ribis, Doralis fabae, Doralis pomi, Eriosoma lanigerum, Hyalopterus arundinis, Macrosiphum avenae, Myzus spp., Phorodon humuli, Rhopalosiphum padi, Empoasca spp., Euscelus bilobatus, Nephotettix cincticeps, Lecanium corni, Saissetia oleae, Laodelphax striatellus, Nilaparvata lugens, Aonidiella aurantii, Aspidiotus hederae, Pseudococcus spp., Psylla spp.

From the order of the Lepidoptera z. B. Pectinophora gossypiella, Bupalus piniarius, Cheimatobia brumata, Lithocolletis blancardella, Hyponomeuta padella, Plutella maculipennis, Malacosoma neustria, Euproctis chrysorrhoea, Lymantria spp., Bucculatrix thurberiella, Phyllocnistis citrella, Agrotis spp., Euxoa spp., Feltia spp., Earias insulana, Heliothis spp., Laphygma exigua, Mamestra brassicae, Panolis flammea, Prodenia litura, Spodoptera spp., Trichoplusia ni, Carpocapsa pomonella, Pieris spp., Chilo spp., Pyrausta nubilalis, Ephestia kuehniella, Galleria mellonella, Cacoecia podana, Capua reticulana, Choristoneura fumiferana, Clysia ambiguella, Homona magnanima, Tortrix viridana.

From the order of the Coleoptera z. B. Anobium punctatum, Rhizopertha dominica, Bruchidius obtectus, Acanthoscelides obtectus, Hylotrupes bajulus, Agelastica alni, Leptinotarsa decemlineata, Phaedon cochleariae, Diabrotica spp., Psylloides chrysocephala, Epilachna varivestis, Atomaria spp., Oryzaephilus surinamensis, Anthonumus spp., Sitophilus spp., Otiorrhynchus sulcatus, Cosmopolites sordidus, Ceuthorrynchus assimilis, Hypera postica, Dermestes spp., Trogoderma, Anthrenus spp., Attagenus spp., Lyctus spp., Meligethes aeneus, Ptinus spp., Niptus hololeucus, Gibbium psylloides, Tribolium spp., Tenebrio molitor, Agriotes spp., Conoderus spp., Melolontha melolontha, Amphimallon solstitialis, Costelytra zealandica.

From the order of the Hymenoptera z. B. Diprion spp., Hoplocampa spp., Lasius spp., Monomorium pharaonis, Vespa spp.  

From the order of the Diptera z. B. Aedes spp., Anopheles spp., Culex spp., Drosophila melanogaster, Musca spp., Fannia spp., Calliphora erythrocephala, Lucilia spp., Chrysomyia spp., Cuterebra spp., Gastrophilus spp., Hypobosca spp., Stomoxys spp., Oestrus spp., Hypoderma spp., Tabanus spp., Tannia spp., Bibio hortulanus, Oscinella frit, Phorbia spp., Pegomyia hyoscyami, Ceratitis capitata, Dacus oleae, Tipula paludosa.

From the order of the Siphonaptera z. B. Xenopsylla cheopsis, Ceratophyllus spp.

From the order of the Arachnida z. B. Scorpio maurus, Latrodectus mactans.

From the class of the Helminth z. B. Haemonchus, Trichostrongulus, Ostertagia, Cooperia, Chabertia, Strongyloides, Oesophagostomum, Hyostrongulus, Ancylostoma, Ascaris and Heterakis as well as Fasciola.

From the class of the Gastropoda z. B. Deroceras spp., Arion spp., Lymnaea spp., Galba spp., Succinea spp., Biomphalaria spp., Bulinus spp., Oncomelania spp.

From the class of the Bivalva z. B. Dreissena spp.

The plant-parasitic nematodes that can be controlled according to the invention include, for example, the root-parasitic soil nematodes, such as, for. For example, those of the genera Meloidogyne (root-knot nematodes such as Meloidogyne incognita, Meloidogyne hapla and Meloidogyne javanica), Heterodera and Globodera (cyst-forming nematodes, such as Globodera rostochiensis, Globodera pallida, Heterodera trifolii) and of the genera Radopholus, such as Radopholus similis, Pratylenchus such as Pratyglenchus neglectus, Pratylenchus penetrans and Pratylenchus curvitatus;
Tylenchulus such as Tylenchulus semipenetrans, Tylenchorhynchus, such as Tylenchorhynchus dubius and Tylenchorhynchus claytoni, Rotylenchus such as Rotylenchus robustus, Heliocotylenchus such as Haliocotylenchus multicinctus, Belonoaimus such as Belonoaimus Trachusususus longusus x longus.

Furthermore, with the compounds according to the invention Nematode genera Ditylenchus (stem parasites such as Ditylenchus dipsaci and Ditylenchus destructor), Aphelenchoides (leaf nematodes, such as Aphelenchoides ritzemabosi) and Anguina (flower nematodes, such as Anguina fight tritici).

The invention also relates to agents, in particular insecticidal and acaricidal agents, which the compounds of formula I in addition to suitable formulation auxiliaries contain.

The agents according to the invention contain the active ingredients of the formulas I in generally 1 to 95% by weight.

They can be formulated in different ways, depending on how it is specified by the biological and / or chemical-physical parameters. Possible formulations are therefore:
Wettable powder (WP), emulsifiable concentrates (EC), aqueous solutions (SL), emulsions, sprayable solutions, oil or water-based dispersions (SC), suspoemulsions (SE), dusts (DP), mordants, granules in the form of , Spray, elevator and adsorption granules, water-dispersible granules (WG), ULV formulations, microcapsules, waxes or baits.

These individual types of formulation are known in principle and are described, for example, in:
Winnacker-Küchler, "Chemical Technology", Volume 7, C. Hauser Verlag Munich, 4th ed. 1986; van Falkenberg, "Pesticides Formulations", Marcel Dekker NY, 2nd Ed. 1972-73; K. Martens, "Spray Drying Handbook", 3rd Ed. 1979, G. Goodwin Ltd. London.

The necessary formulation aids such as inert materials, surfactants, solvents and other additives are also known and are described, for example, in:
Watkins, "Handbook of Insecticide Dust Diluents and Garriers," 2nd Ed., Darland Books, Caldwell NJ; H. v. Olphen, "Introduction to Clay Colloid Chemistry", 2nd Ed., J. Wiley & Sons, NY; Marsden, Solvents Guide, 2nd Ed., Interscience, NY 1950; McCutcheon, s, "Detergents and Emulsifiers Annual", MC Publ. Corp., Ridgewood NJ; Sisley and Wood, "Encyclopedia of Surface Active Agents", Chem. Publ. Co. Inc., NY 1964; Schönfeldt, "Interface-active ethylene oxide adducts", Wiss. Publishing company, Stuttgart 1967; Winnacker-Küchler, "Chemical Technology", Volume 7, C. Hauser Verlag Munich, 4th ed. 1986.

Based on these formulations, combinations can also be made with other pesticidal substances, fertilizers and / or Produce growth regulators, e.g. B. in the form of a finished formulation or as Tank mix. Spray powders are preparations that are evenly dispersible in water in addition to the active ingredient, in addition to a diluent or inert Wetting agents, e.g. B. polyoxethylated alkylphenols, polyoxethylated fatty alcohols, Alkyl or alkylphenol sulfonates and dispersants, e.g. B. lignosulfonic acid Sodium, 2,2'-dinaphthylmethane-6,6'-disulfonic acid sodium. Emulsifiable concentrates are made by dissolving the active ingredient in one organic solvents, e.g. B. butanol, cyclohexanone, dimethylformamide, Xylene or even higher-boiling aromatics or hydrocarbons Addition of one or more emulsifiers produced. As emulsifiers can be used for example: alkylarylsulfonic acid calcium salts such as cadodecylbenzene sulfonate or nonionic emulsifiers such as Fatty acid polyglycol esters, alkylaryl polyglycol ethers, fatty alcohol polyglycol ethers, Propylene oxide-ethylene oxide condensation products, alkyl polyethers, Sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters or Polyoxethylene sorbitol ester.  

Dusts are obtained by grinding the active ingredient with finely divided solids, e.g. B. talc, natural clays such as kaolin, bentonite, pyrophillite or diatomaceous earth. Granules can be obtained either by spraying the Active ingredient can be produced on adsorbable, granulated inert material or by applying active ingredient concentrates using adhesives, e.g. B. Polyvinyl alcohol, polyacrylic acid sodium or mineral oils on which Surface of carriers such as sand, kaolinite or granulated Inert material. Suitable active ingredients can also be used in the production of Fertilizer granules in the usual way - if desired in a mixture with Fertilizers - be granulated.

In wettable powders, the active ingredient concentration is e.g. B. about 10 to 90% by weight the rest of 100% by weight consists of customary formulation components. At emulsifiable concentrates, the active ingredient concentration can be about 5 to Amount to 80% by weight. Dust-like formulations usually contain 5 to 20 wt .-% of active ingredient, sprayable solutions about 2 to 20 wt .-%. At Granules, the active ingredient content depends in part on whether the effective Connection is liquid or solid and what granulation aids, fillers etc. can be used.

In addition, the active ingredient formulations mentioned optionally contain the usual adhesive, wetting, dispersing, emulsifying, penetrating, Solvents, fillers or carriers.

The concentrates available in commercial form are used optionally diluted in a conventional manner, e.g. B. with wettable powders, emulsifiable Concentrates, dispersions and sometimes also with microgranules Water. Dust-like and granulated preparations as well as sprayable Solutions are usually no longer combined with other solutions before use inert substances diluted.  

With the external conditions such as temperature, humidity and. a. varies the required application rate. It can fluctuate within wide limits, e.g. B. between 0.0005 and 10.0 kg / ha or more of active substance, preferably however, it is between 0.001 and 5 kg / ha.

The active compounds according to the invention can be in their commercially available Formulations as well as those prepared from these formulations Application forms in mixtures with other active ingredients, such as insecticides, Attractants, sterilants, acaricides, nematicides, fungicides, growth regulating substances or herbicides.

Pesticides include, for example Phosphoric acid esters, carbamates, carboxylic acid esters, formamidines, Tin compounds, substances produced by microorganisms u. a.

Preferred mixing partners are

1. from the group of phosphorus compounds

Acephate, Azamethiphos, Azinphos-ethyl-, Azinphosmethyl, Bromophos, Bromophos-ethyl, Chlorfenvinphos, Chlormephos, Chlorpyrifos, Chlorpyrifos methyl, Demeton, Demeton-S-methyl, Demeton-S-methyl sulfphone, Dialifos, Diazinon, dichlorvos, dicrotophos, O, O-1,2,2,2-tetrachloroethyl phosphorothioates (SD 208 304), Dimethoate, Disulfoton, EPN, Ethion, Ethoprophos, Etrimfos, Famphur, Fenamiphos, Fenitriothion, Fensulfothion, Fenthion, Fonofos, Formothion, Heptenophos, Isozophos, Isothioate, Isoxathion, Malathion, Methacrifos, Methamidophos, Methidathion, Salithion, Mevinphos, Monocrotophos, Naled, Omethoate, Oxydemeton-methyl, Parathion, Parathion methyl, phenthoate, phorate, phosalone, phosfolan, phosmet, phosphamidon, Phoxim, Pirimiphos, Primiphos-ethyl, Pirimiphos-methyl, Profenofos, Propaphos, Proetamphos, Prothiofos, Pyraclofos, Pyridapenthion, Quinalphos, Sulprofos, Temephos, Terbufos, Tetrachlorvinphos, Thiometon, Triazophos, Trichlorphon, Vamidothione;  

2. from the group of carbamates

Aldicarb, 2-sec.-butylphenylmethylcarbamate (BPMC), carbaryl, carbofuran, Carbosulfan, cloethocarb, benfuracarb, ethiofencarb, furathiocarb, isoprocarb, Methomyl, 5-methyl-m-cumenylbutyryl (methyl) carbamate, oxamyl, pirimicarb, Propoxur, thiodicarb, thiofanox, ethyl-4,6,9-triaza-4-benzyl-6, 10-dimethyl-8- oxa-7-oxo-5,11-dithia-9-dodecenoate (OK 135), 1-methylthio (ethylideneamino) - N-methyl-N- (morpholinothio) carbamate (UC 51717).

3. from the group of carboxylic acid esters

Allethrin, alphametrin, 5-benzyl-3-furylmethyl- (E) - (1R) -cis, 2,2-dimethyl-3- (2- oxothiolan-3-ylidenemethyl) cyclopropanecarboxylate, bioallethrin, bioallethrin ((S) -cyclopentyl isomer), bioresmethrin, biphenates, (RS) -1-cyano-1 - (6-phenoxy- 2-pyridyl) methyl- (1RS) -trans-3- (4-tert-butylphenyl) -2, 2-dimethylcyclopropane carboxylate (NCI 85193), cycloprothrin, cyhalothrin, cythithrin, cypermethrin, Cyphenothrin, deltamethrin, empenthrin, Esfenvalerate, fenfluthrin, Fenpropathrin, fenvalerate, flucythrinate, flumethrin, fluvalinate (D-isomer), Permethrin, pheothrin ((R) -isomer), d-pralethrin, pyrethrins (natural Products), resmethrin, tefluthrin, tetramethrin, tralomethrin.

4. from the group of amidines

Amitraz, chlorordime form.

5. from the group of tin compounds

Cyhexatin, fenbutatin oxides.

6. Other

Abamectin, Bacillus thuringiensis, Bensultap, Binapacryl, Bromopropylate, Buprofezin, Camphechlor, Cartap, Chlorobenzilate, Chlorfluazuron, 2- (4-chlorophenyl) -4,5-diphenylthiophene (UBI-T 930), chlororfentezine, Cyclopropanecarboxylic acid (2-naphthylmethyl) ester (Ro 12-0470), cyromazine, N- (3,5-dichloro-4- (1,1,2,3,3,3-hexafluoro-1-propyloxy) phenyl) carbamoyl -) - 2-  chlorobenzcarboximidic acid ethyl ester, DDT, dicofol, N- (N- (3,5-di-chloro-4- (1,1,2,2-tetrafluoroethoxy) phenylamino) carbonyl) -2,6-difluorobenzamide (XRD 473), diflubenzuron, N- (2,3-dihydro-3-methyl-1,3-thiazol-2-ylidenes) -2,4- xylidine, dinobutone, dinocap, endosulfan, ethofenprox, (4-ethoxyphenyl) - (dimethyl) (3- (3-phenoxyphenyl) propyl) silane, (4-ethoxyphenyl) (3- (4-fluoro-3- phenoxyphenyl) propyl) dimethylsilane, fenoxycarb, 2-fluoro-5- (4- (4- ethoxyphenyl) -4-methyl-1-pentyl) diphenyl ether (MTI 800), granulosic and Nuclear polyhedron viruses, fenthiocarb, flubenzimine, flucycloxuron, flufenoxuron, Gamma-HCH, hexythiazox, hydramethylnon (AC 217300), ivermectin, 2-nitromethyl-4,5-dihydro-6H-thiazine (DS 52618), 2-nitromethyl-3,4- dihydrothiazole (SD 35651), 2-nitromethylene-1, 2-thiazinan-3-ylcarbamaldehydes (WL 108477), propargite, teflubenzuron, tetradifon, tetrasul, thiocyclam, Trifumuron, imidacloprid.

The active substance content of those prepared from the commercially available formulations Forms of use can range from 0.00000001 to 95% by weight of active ingredient, preferably between 0.00001 and 1% by weight.

The application takes place in a form adapted to the application forms usual way.

The active compounds according to the invention are also suitable for combating endo- and ectoparasites in the veterinary field animal husbandry.

The active compounds according to the invention are used here in a known manner Way like by oral use in the form of e.g. tablets, Capsules, drinkers, granules, in the form of dermal application for example diving (dipping), spraying (spraying), pouring (pour-on and spot-on) and powdering as well as by parenteral application in the form for example the injection.  

The new compounds of formula I according to the invention can accordingly also particularly advantageous in livestock farming (e.g. cattle, sheep, pigs and poultry such as chickens, geese, etc.). In a preferred one Embodiment of the invention, the animals the new compounds, if necessary in suitable formulations (see above) and if necessary with administered orally to drinking water or feed. Because an excretion in the feces in done effectively, development can be done very easily in this way prevent insects in the animal droppings. The appropriate dosages and formulations are particularly of the type and Stage of development of farm animals and also dependent on the infestation pressure and can be easily determined and determined using the usual methods. The new compounds in cattle z. B. in doses of 0.01 to 1 mg / kg body weight can be used.

The compounds of the formula I according to the invention are also notable for an excellent fungicidal effect. Already in the plant tissue Invaded fungal pathogens can be successfully curated fight. This is particularly important and advantageous for such Fungal diseases that occur after infection with the usual ones Fungicides can no longer be effectively combated. The Spectrum of action of the claimed compounds covers various economically important, phytopathogenic fungi, such as. B. Plasmopara viticola, Phytophthora infestans, Erysiphe graminis, Piricularia oryzae, Pyrenophora teres, Leptosphaerea nodorum and Pellikularia sasakii and Puccinia recondita.

The compounds of formula I according to the invention are therefore also suitable for Treating or coating seeds (seed dressers).  

The compounds of the invention are also suitable for use in technical areas, for example as wood preservatives, as Preservatives in paints, in cooling lubricants for the Metalworking or as a preservative in drilling and cutting oils.

The active compounds according to the invention can be in their commercially available Formulations either alone or in combination with other Fungicides known from the literature are used.

As fungicides known in the literature which, according to the invention, with the compounds of Formula I can be combined, for. B. to name the following products: Aldimorph, Andoprim, Anilazine, BAS 480F, BAS 450F, Benalaxyl, Benodanil, Benomyl, Binapacryl, Bitertanol, Bromuconazol, Buthiobate, Captafol, Captan, Carbendazim, carboxin, CGA 173506, cyprofuram, dichlofluanid, dichlomezin, Diclobutrazole, diethofencarb, difenconazole (CGA 169374), difluconazole, Dimethirimol, Dimethomorph, Diniconazole, Dinocap, Dithianon, Dodemorph, Dodine, Edifenfos, Ethirimol, Etridiazol, Fenarimol, Fenfuram, Fenpiclonil, Fenpropidin, fenpropimorph, fentin acetates, fentihydroxide, Ferimzone (TF164), Fluazinam, fluobenzimine, fluquinconazole, fluorimide, flusilazole, flutolanil, Flutriafol, Folpet, Fosetylaluminium, Fuberidazole, Fulsulfamide (MT-F 651), Furalaxyl, furconazole, furmecyclox, guazatine, hexaconazole, ICI A5504, Imazalil, Imibenconazole, Iprobefos, Iprodione, Isoprothiolane, KNF 317, Copper compounds such as Cu-oxychloride, Oxine-Cu, Cu-oxide, Mancozeb, Maneb, Mepanipyrim (KIF 3535), metconazole, mepronil, metalaxyl, methasulfocarb, Methfuroxam, MON 24000, myclobutanil, nabam, nitrothalidopropyl, nuarimol, Ofurace, Oxadixyl, Oxycarboxin, Penconazol, Pencycuron, PP 969, Probenazole, propineb, prochloraz, procymidone, propamocarb, propiconazole, Prothiocarb, pyracarbolide, pyrazophos, pyrifenox, pyroquilon, rabenzazole, RH7592, sulfur, tebuconazole, TF 167, thiabendazole, thicyofen, Thiofanatemethyl, Thiram, Tolclofos-methyl, Tolylfluanid, Triadimefon, Triadimenol, tricyclazole, tridemorph, triflumizole, triforine, validamycin,  Vinchlozolin, XRD 563, Zineb, sodium dodecyl sulfonate, sodium dodecyl sulfate, Sodium C13 / C15 alcohol ether sulfonate, sodium cetostearyl phosphate ester, Dioctyl sodium sulfosuccinate, sodium isopropyl naphthalenesulfonate, sodium methylenebisnaphthalene sulfonate, cetyl trimethyl ammonium chloride, salts of long-chain primary, secondary or tertiary amines, alkyl propylene amines, Lauryl pyrimidinium bromide, ethoxylated quaternized fatty amines, alkyl dimethyl benzyl ammonium chloride and 1-hydroxyethyl-2-alkyl imidazoline.

The combination partners mentioned above are known active ingredients that for the most part in Ch.R Worthing, S.B. Walker, The Pesticide Manual, 7th edition (1983), British Crop Protection Council. The active substance content of those prepared from the commercially available formulations Application forms can vary widely Drug concentration of use forms can range from 0.0001 to 95% by weight of active ingredient, preferably between 0.0001 and 1% by weight. The application takes place in a form adapted to the application forms usual way.

The following examples serve to illustrate the invention without this would be limited to this.  

A. Chemical examples example 1 2-bromo-3-methoxy-4-trimethylsilyl-pyridine

To a solution of 62 mmol lithium diisopropylamide in 100 ml abs. THF was dropped at -70 ° C a solution of 9.4 g of 2-bromo-3-methoxypyridine and 6.3 ml of chlorotrimethylsilane in 30 ml of abs. THF. After 5 hours at -70 ° C., the mixture was poured onto 100 ml of saturated ammonium chloride solution and extracted twice with ether. After concentration, the product was isolated by chromatography on silica gel with hexane / diisopropyl ether 1/1 as the eluent.
Yield: 10.1 g (= 90% of theory), syrup
1 H-NMR (100 MHz, CDCI₃)
8.1 (d, 2H), 7.3 (d, 1H), 3.9 (s, 3H), 0.3 (s, 9H) ppm.

Example 2 2-bromo-4-formyl-3-methoxy-pyridine

43.5 g dry CsF in 200 ml abs. DMF, 22.4 g of 2-bromo-3-methoxy-4-trimethylsilyl-pyridine (Example 1) and 38.5 g of tetrabutylammonium bromide were stirred at 10 to 20 ° C. until no starting material was visible in the thin layer chromatograph (eluent: diisopropyl ether ; Silica gel plates). The mixture was then poured into ice water and extracted exhaustively with ethyl acetate. The product was chromatographed on silica gel with CH₂Cl₂.
Yield: 16.2 g (= 86% of theory)
1 H-NMR (100 MHz, CDCl₃)
10.42 (s, 1H), 8.3 (d, 1H), 7.7 (d, 1H), 4.1 (s, 3H) ppm.

Example 3 2-bromo-4-hydroxymethyi-3-methoxy-pyridine

71 g of 2-bromo-4-formyl-3-methoxy-pyridine (Example 2) was dissolved in 600 ml of abs. THF stirred with 3.2 g of sodium borohydride for 3 hours. The excess sodium borohydride was then destroyed by adding methanol and glacial acetic acid. After concentration, the mixture was shaken with sodium bicarbonate solution and ethyl acetate. After drying over sodium sulfate, the organic phase was concentrated to a small volume, followed by crystallization.
Yield: 65 g (= 91% of theory)
1 H-NMR (100 MHz, CDCl₃)
8.2 (d, 1H), 7.4 (d, 1H), 4.8 (s, 2H), 4.0 (s, 3H) ppm.

Example 4 2-bromo-4-chloromethyl-3-methoxy-pyridine

To 5.2 g of 2-bromo-4-hydroxymethyl-3-methoxy-pyridine (Example 3) in 30 ml of abs. CH₂Cl₂ added dropwise after adding a drop of DMF 2.2 ml of thionyl chloride in 10 ml of CH₂Cl₂ so that the temperature remained at 20 to 25 ° C. After 2 hours the product was filtered off, washed with CH₂Cl₂ and dried.
Yield: 5.5 g (= 77% of theory)
1 H-NMR (100 MHz, CD₃OD)
8.2 (d, 1H), 7.6 (d, 1H), 5.0 (s, 2H), 4.0 (s, 3H) ppm.

Example 5 (2-bromo-3-methoxy-pyridin-4-yl) methylphosphonic acid diethyl ester

2.7 g of 2-bromo-4-chloromethyl-3-methoxy-pyridine hydrochloride (Example 4) were heated to 130 ° C. for 5 hours with 20 ml of triethyl phosphite. The excess triethyl phosphite was then distilled off in vacuo at 0.1 mm and 40 ° C. The product was purified by chromatography on silica gel (ethyl acetate). Syrup.
Yield: 3 g (= 99% of theory)
1 H-NMR (100 MHz, CDCl₃)
8.1 (d, 1H), 7.3 (q, 1H), 4.1 (m, 4H), 3.9 (s, 3H), 3.3 (d, 2H), 1.3 (t , 6H) ppm.

Example 6 Triphenyl- (pyridin-4-yl-methyl) phosphonium acetate hydrochloride

16 g of 4-chloromethylpyridine and 30 g of triphenylphosphine were boiled in 50 ml of glacial acetic acid for 6 hours. After cooling, 50 ml of ether were added to the solution and the mixture was left to crystallize with stirring. The product was filtered off with suction and washed well with ethyl acetate.
Yield: 42 g (= 93.4% of theory)
1 H-NMR (100 MHz, DMSO-d₆)
8.7 (d, 2H), 7.9 (m, 3H), 7.7-7.8 (m, 12H), 7.4 (m, 2H), 5.6 (d, 2H), 1 , 9 (s, 3H), ppm.

Example 7 4- (4-phenyl-cyclohexylidenemethyl) pyridine hydrochloride

170.4 g of triphenyl- (pyrid-4-yl-methyl) -phosphonium acetate hydrochloride (Example 6) were added to 92 g of potassium tert-butoxide in 1200 ml of o-xylene and the mixture was stirred for 30 minutes. Then 73.7 g of 4-phenylcyclohexanone were added to the solution and the mixture was stirred at 130 to 140 ° C. for 8 hours. The mixture was then poured into water and made alkaline with 2N NaOH. The xylene phase was separated and the aqueous phase was extracted several times with xylene. After concentration, the mixture was dissolved in ethyl acetate and the hydrochloride was precipitated with ethereal HCl. It was recrystallized from ethyl acetate / methanol.
Yield: 44 g (= 39% of theory)
1 H-NMR (100 MHz, CD₃OD)
8.7 (m, 2H), 7.9 (m, 2H), 7.1-7.3 (m, 5H), 6.6 (m, 1H), 3.0-3.1 (m, 1H), 2.8-3.0 (m, 1H), 2.5-2.7 (m, 2H), 2.3-2.4 (m, 1H), 2.0-2.2 ( m, 2H), 1.6-1.8 (m, 2H) ppm.

Example 8 2-bromo-3-methoxy-4- (4-phenylcyclohexlidenemethyl) pyridine

1.5 g of sodium hydride was dissolved in 135 ml of dry DMSO with heating. Thereafter, 17 g of diethyl 2-bromo-3-methoxy-pyridin-4-ylmethylphosphoate (Example 5) dissolved in 50 ml of THF and then 8 g of 4-phenylcyclohexanone in 45 ml of THF were added to the solution at room temperature. After 1 hour, the mixture was poured into sodium bicarbonate solution and extracted with ethyl acetate. Chromatography with ethyl acetate / hexane 1/6 on silica gel gave the product as a mixture of isomers.
Yield: 16 g (= 92% of theory); Mp .: 62 to 63 ° C
1 H-NMR (100 MHz, CDCl₃)
8.1 (d, 1H), 7.2-7.3 (m, 5H), 7.1 (d, 1H), 6.3 (m, 1H), 3.8 (s, 3H), 2 , 7-2.9 (m, 2H), 2.3-2.6 (m, 2H), 1.9-2.2 (m, 3H), 1.4-1.8 (m, 2H) ppm.

Example 9 2,3-dimethoxy-4- (4-phenylcyclohexylidenemethyl) pyridine hydrochloride

10.7 g of 2-bromo-3-methoxy-4- (4-phenyl-cyclohexylidene) methyl-pyridine (Example 8) were boiled together with 21.6 ml of 30% sodium ethylate solution in 30 ml of DMF. After three hours, the mixture was poured into sodium bicarbonate solution and extracted with ethyl acetate. The purification was carried out by chromatography with ethyl acetate / hexane 1/6 on silica gel.
Yield: 9 g (= 91% of theory)
1 H-NMR (100 MHz, CDCl₃)
7.8 (d, 1H), 7.1-7.3 (m, 5H), 6.7 (d, 1H), 5.5 (m, 1H), 4.0 (s, 3H), 3 , 8 (s, 3H), 2.8 (m, 1H), 1.6-2.4 (m, 8H) ppm.

Example 10 3-methoxy-4- (4-phenyl-cyclohexylidenemethyl) -2-trimethylsilylethynyl-pyridine

3.5 g of 2-bromo-3-methoxy-4- (4-phenyl-cyclohexylidenemethyl) pyridine (Example 8) in 20 ml of diisopropylamine were mixed with 1.7 ml of trimethylsilylacetylene, 0.1 g of CuJ and 0.2 g of palladium bis (triphenylphosphine) dichloride stirred at 60 ° C for 2 hours. The mixture was then poured into sodium bicarbonate solution and extracted with ethyl acetate. Chromatographic purification on silica gel with ethyl acetate / hexane 1/6 as eluent gave the pure product.
Yield: 3.2 g (= 88% of theory)
1 H-NMR (100 MHz, CDCl₃)
8.3 (d, 1H), 7.2-7.3 (m, 5H), 7.1 (d, 1H), 6.2 (s, 1H), 3.9 (s, 3H), 1 , 4-2.9 (multipletts, 9H), 1.3 (s, 9H) ppm.

Example 11 2-ethynyl-3-methoxy-4- (4-phenylcyclohexylidenemethyl) pyridine

10 g of 3-methoxy-4- (4-phenyl-cyclohexylidenemethyl) -2-trimethylsilylethynyl pyridine (Example 10) and 10 g of sodium fluoride were stirred for 17 hours in 100 ml of glacial acetic acid and 1 ml of acetic anhydride. After concentration, the residue was shaken with sodium bicarbonate solution and methylene chloride. The methylene chloride phase was chromatographed on silica gel. Ethyl acetate / hexane 1/7 served as eluent.
Yield: 6.3 g (= 88% of theory)
1 H-NMR (100 MHz, CDCl₃)
8.3 (d, 1H), 7.2-7.3 (m, 6H), 6.3 (s, 1H), 4.0 (s, 3H), 3.4 (s, 1H), 2nd , 7-2.9 (m, 2H), 2.5-2.6 (m, 1H), 2.4-2.5 (m, 1H), 2.0-2.2 (m, 3H) , 1.4-1.7 (m, 2H) ppm.

Example 12 3-methoxy-4- (4-phenyl-cyclohexylmethyl) pyridine

7 g of 2-bromo-3-methoxy-4- (4-phenyl-cyclohexylidenemethyl) pyridine (Example 8) in 70 ml of methanol were hydrogenated with 0.5 g of palladium / carbon (10%). After the hydrogen uptake had ended, the mixture was filtered and concentrated. The residue was shaken with sodium bicarbonate solution and methylene chloride. After drying over sodium sulfate, the organic phase was concentrated and dried.
Yield: 4.1 g (= 72.8% of theory); cis / trans mixture
A hydrochloride formed with HCl and was recrystallized from acetonitrile.
Mp .: 60 ° C (free base)
1 H-NMR (100 MHz, CD₃OD)
8.5 (s, 1H), 7.9 (d, 1H), 7.1-7.3 (m, 5H), 4.1 (s, 3H), 3.1 (d, 1H), 1 , 2-2.7 (multiplets, 10H) ppm.

Example 13 4- (4-cis-phenyl-cyclohexylmethyl) pyridine hydrochloride

22.9 g of 4- (4-phenyl-cyclohexylidenemethyl) pyridine hydrochloride (Example 7) were hydrogenated in 120 ml of methanol with 1.6 g of palladium on carbon (10%). After filtering, the solution was concentrated and the residue was repeatedly recrystallized from acetonitrile until the pure cis isomer was present.
Yield: 8.3 g (= 36% of theory); Mp: 65 ° C
1 H-NMR (100 MHz, CDCl₃)
8.5 (d 1 2H), 7.2-7.4 (m, 5H), 7.1 (d, 2H), 2.7 (d, 2H), 2.6-2.7 (m, 1H) ), 1.5-2.1 (multipletts, 9H) ppm.

Example 14 2,3-dimethoxy-4- (4-phenyl-cyclohexylmethyl) pyridine oxalate

6.5 g of 2,3-dimethoxy-4- (4-phenyl-cyclohexylidenemethyl) pyridine (Example 9) were hydrogenated in 50 ml of methanol with 0.5 g of palladium on activated carbon (10%). After filtering, the mixture was concentrated.
Yield: 5.5 g (= 84% of theory); cis / trans mixture
By adding 1 equivalent of oxalic acid, the oxalate was produced in methanol, which resulted in a pure trans product by repeated dissolution in ether and precipitation with hexane.
1 H-NMR (100 MHz, CDCl₃)
7.8 (d, 1H), 7.1-7.3 (m, 5H), 6.7 (d, 2H), 4.0 (s, 3H), 3.8 (s, 3H), 2nd , 6 (d, 2H), 2.4-2.6 (m, 1H), 1.1-2.0 (multipletts, 8H) ppm.

Example 15 3-methoxy-4- (4-phenyl-cyclohexylmethyl) -2- (2-trimethylsilyl-ethyl) -p-yridine

5 g of 3-methoxy-4- (4.phenyl-cyclohexylidenmethyl) -2-trimethylsilylethynyl-pyridine (Example 10) in 50 ml of methanol were hydrogenated with 0.5 g of palladium on carbon (10%). After filtering, the mixture was concentrated and the product was purified by column chromatography with ethyl acetate / hexane 1/6 on silica gel.
Yield: 3.9 g (= 64% of theory); cis / trans mixture
The cis isomer crystallized by dissolving in methanol, adding 1 g of oxalic acid and adding ether.
Yield: 2.9 g (= 38% of theory)
1 H-NMR (100 MHz, CDCl₃)
8.2 (d, 1H), 7.1-7.4 (m, 5H), 7.0 (d, 1H), 3.8 (s, 3H), 2.4-2.9 (multipletts, 5H), 2.1 (m, 1H), 1.4-1.9 (multipletts, 8H), 0.9-1.0 (m, 2H), 0.4 (s, 9H) ppm.

Example 16 2-ethyl-3-methoxy-4- (4-cis-phenyl-cyclohexylmethyl) pyridine hydrochloride

4.8 g of 2-ethynyl-3-methoxy-4- (4-phenyl-cyclohexylidenemethyl) pyridine (Example 11) were hydrogenated in 50 ml of methanol with 0.5 g of palladium on carbon (10%). After filtering, the mixture was concentrated and the syrup was dried in vacuo.
Yield: 4.5 g (= 100% of theory); cis / trans mixture of isomers
The substance was converted into the hydrochloride by dissolving in ether and adding ethereal HCl. The crystals were converted into the pure cis isomer by double recrystallization from ethyl acetate.
Yield: 2.4 g = 48%
1 H-NMR (100 MHz, CDCI₃)
8.4 (d, 1H), 7.5 (d, 1H), 7.2-7.4 (m, 5H), 3.9 (s, 3H), 3.2 (q, 2H), 3 , 0 (d, 2H), 2.6-2.8 (m, 1H), 2.1-2.2 (m, 1H), 1.5-1.9 (m, 8H), 1.5 (t, 3H) ppm.

By shaking the hydrochloride with sodium bicarbonate solution and Methylene chloride and subsequent evaporation of the methylene chloride extract you got the free base.

Example 17 1- (2,3-dichloropyridin-4-ylmethyl) -4-phenylcyclohexanol

3.2 g 2,3-dichloro-4-methyl-pyridine in 20 ml abs. THF were at -70 ° C 2 hours with 32 ml of a 1N solution of lithium diisopropylamide in THF touched. Then 11 g of 4-phenylcyclohexanone in 30 ml of THF were added dropwise and stirred at -70 ° C for 1 hour. Then 8.1 ml was added dropwise Trimethylsilyl chloride to the solution and left the mixture at room temperature come. It was poured into sodium bicarbonate solution and extracted with Methylene chloride. The column chromatography with ethylene acetate / hexane 1/4 on Silica gel gave 4.1 g (= 61% of theory) and 2.1 g (= 21% of theory) of isomer 2.

Isomer 1

1 H-NMR (100 MHz, CDCl₃)
8.2 (d, 1H), 7.2-7.4 (m, 5H), 7.3 (d, 1H), 3.0 (s, 2H), 2.5 (m, 1H), 1 , 4-1.9 (m, 8H) ppm.

Isomer 2

1 H-NMR (100 MHz, CDCl₃)
8.2 (d, 1H), 7.4 (d, 1H), 7.2-7.4 (m, 5H), 3.2 (s, 2H), 2.6-2.7 (m, 1H), 1.4-2.0 (m, 8H) ppm.

Example 18 1- (2-bromo-3-methoxy-pyridin-4-yl) ethyl-phosphonic acid diethyl ester

12 g potassium tert-butoxide in 100 ml abs. THF were with 33 g of diethyl 2-bromo-3-methoxy-pyridin-4-ylmethylphosphonate (Example 5) in 100 ml of abs. THF offset. After 10 minutes, 7.2 ml of methyl iodide were added dropwise to the solution while stirring. After 2 hours the THF was distilled off and the residue was shaken with sodium bicarbonate solution and ethyl acetate. Column cleaning with ethyl acetate on silica gel gave 33.5 g (= 98% of theory) of product.
1 H-NMR (100 MHz, CDCl₃)
8.1 (d, 2H), 7.4 (dd, 1H), 3.9-4.1 (m, 2H), 4.1-4.2 (m, 2H), 3.9 (s, 3H), 3.7-3.8 (m, 1H), 1.5-1.6 (d, d, 3H), 1.2 (t, 3H), 1.3 (t, 3H) ppm.

Example 19 2,3-dichloro-4- (4-phenylcyclohex-1-enylmethyl) pyridine

1.0 g of 2,3-dichloro-4- (4-phenyl-1-hydroxy-cyclohexylmethyl) pyridine (Example 17) and 1.2 g of para-toluenesulfonic acid hydrate were boiled with 30 ml of xylene. The xylene was allowed to distill off to a small residue. After cooling, the residue was shaken with sodium bicarbonate solution and ethyl acetate. The ethyl acetate phase was dried over sodium sulfate and concentrated. This left 0.8 g (= 80% of theory) of olefin. It contained 1% 2,3-dichloro-4 (4-phenyl-cyclohexylidenemethyl) pyridine.
1 H-NMR (100 MHz, CDCl₃)
8.2 (d, 1H), 7.1-7.3 (m, 6H), 6.3 (s, 0.13H, olefin 2), 5.5 (m, 0.87H, olefin 1), 3.4 (s, 0.9H), 3.8 (m, 1H), 1.7-2.6 (m, 6H) ppm.

The HPLC shows 4 peaks which can be assigned to the two racemates.  

Example 20 1- [1- (2,3-dichloropyridin-4-yl) ethyl] -4-phenylcyclohexanol

A solution of 64 mmol of lithium diisopropylamide in 64 ml of THF was added dropwise to 7.1 g of 2,3-dichloro-4-ethyl-pyridine in 40 ml of dry THF at -70 ° C. under nitrogen. After 2 hours at -70 ° C., 22 g of 4-phenyicyclohexanone in 60 ml of THF were added dropwise, and after a further 2 hours, 16.2 ml of chlorotrimethylsilane. The mixture was then allowed to come to room temperature, then poured onto sodium bicarbonate solution and extracted with methylene chloride. After concentration, the residue partially crystallized. The crystals were sucked off and washed with hexane.
Yield: 10.3 g = 75.3%
A further 1.6 g = 11.4% of the above product could be obtained from the mother liquor by column chromatography on silica gel with ethyl acetate / hexane 3/7 (R _f = 0.52). The second isomer (R _f = 0.41) was then eluted.
Yield: 0.6 g = 4.3%

Isomer 1

1 H-NMR (100 MHz, CDCl₃)
8.2 (d, 1H), 7.5 (d, 1H), 7.1-7.3 (m, 5H), 3.5 (q, 1H), 2.5 (m, 1H), 1 , 3-2.1 (m, 8H), 1.3 (d, 3H) ppm.

Isomer 2

1 H-NMR (100 MHz, CDCl₃)
8.2 (d, 1H), 7.8 (d, 1H), 7.1-7.3 (m, 5H), 3.9 (q, 1H), 2.6 (m, 1H), 1 , 3-2.3 (m, 8H), 1.3 (d, 3H) ppm.

Example 21 2,3-dichloro-4- [1- (4-phenylcyclohex-1-enyl) methyl)] pyridine

10.5 g of 1- [1- (2,3-dichloropyridin-4-yl) ethyl] -4-phenylcyclohexanol (Example 20) were treated with 12 ml of methylene chloride, 6 ml of trifluoroacetic acid, 12 ml Trifluoroacetic anhydride and 6 ml of boron trifluoride etherate boiled for 60 hours.  

Then all volatiles were distilled off in vacuo and the residue was shaken with sodium bicarbonate solution and methylene chloride. The methylene chloride phase was chromatographed on silica gel using ethyl acetate / hexane 1/6 as eluent.
Yield: 9.8 g (= 98% of theory); Mixture of diastereomers
1 H-NMR (100 MHz, CDCl₃) (mixture of diastereomers):
8.2 (2d, 1H), 7.1-7.3 (m, 2d, 6H), 5.7 (m, 1H), 3.9 (m, 1H), 1.5-2.9 ( m, 7H), 1.4 (d, 6H) ppm.

Example 22 3-chloro-2-ethyl-4- (4-phenyl-cyclohex-1-enylmethyl) pyridine

88 ml of 2-molar ethyl magnesium chloride solution in THF were mixed with 100 ml of toluene. Then 100 ml of solvent were distilled off at 20 ° C. and 1 mbar. The resulting solution was at 20 to 30 ° C to the solution of 27.7 g of 2,3-dichloro-4- [1- (4-phenyl-cyclohex-1-enyl)] - methyl-pyridine (Example 19) and 0 , 3 g [1,3-bis- (diphenylphosphino) propanium-nickel (II) chloride was added dropwise in 100 ml of toluene. After 17 hours, 6 ml of glacial acetic acid were added dropwise to the solution. After 30 minutes, the mixture was deacidified with sodium bicarbonate solution and the solution was concentrated. The residue was purified by column chromatography (silica gel / diisopropyl ether). The first product was the title connection with the R _f . 0.80 eluted from the column. Then the second fraction with the R _f = 0.55 was 2-ethyl-4- (4-phenyl-cyclohex-1-enylmethyl) pyridine as a mixture with 2-ethyl-4- (4-phenyl-cyclohexylidenemethyl) - Isolate pyridine.

Title link:
Yield: 59% (syrup)
1 H-NMR (100 MHz, CDCl₃)
8.3 (d, 2H), 7.1-7.4 (m, 5H), 7.0 (d, 2H), 5.5 (m, 1H), 3.4 (s, 2H), 3 , 0 (q, 2H), 2.8 (m, 1H), 1.7-2.4 (m, 6H), 1.3 (t, 3H) ppm.

Fraction 2:
Yield: 18% (syrup)
1 H-NMR (100 MHz, CDCl₃)
8.4 (2d, 1H), 7.1-7.4 (m, 5H), 7.0 (s, 1H), 7.0 (2d, 1H), 5.6 (m, 1H), 3rd , 3 (s, 2H), 2.8 (q, 2H), 2.8 (m, 1H), 1.6-2.4 (m, 6H), 1.3 (t, 3H) ppm.

Example 23 3-chloro-2-ethyl-4- (4-cis-phenyl-cyclohexylmethyl) pyridine

9.2 g of 3-chloro-2-ethyl-4- (4-phenyl-cyclohex-1-enylmethyl) pyridine (Example 22, fraction 1) was dissolved in 40 ml of glacial acetic acid and 20 ml of 2N HCl with 0.6 g of platinum dioxide hydrated. The hydrogenation was monitored by HPLC (column: Chiracel OD, 125 × 4.6 mm; eluent: n-hexane / 2-propanol 99.5: 0.5; flow rate: 1.0 ml / min. Detector: UV) . It was canceled as soon as the starting material had been converted. It was filtered, concentrated and the residue shaken with sodium bicarbonate solution and ethyl acetate. The ethyl acetate extract was concentrated and the product was purified by column chromatography on silica gel with diisopropyl ether.
Yield. 92% (syrup)

The product was dissolved in ether and converted into the hydrochloride with ethereal HCl. The ether was decanted from the precipitated hydrochloride and the hydrochloride was recrystallized from acetone.
Yield: 30%
1 H-NMR (100 MHz, CDCl₃)
8.5 (d, 2H), 7.6 (d, 2H), 7.1-7.4 (m, 5H), 3.4 (q, 2H), 3.1 (d, 2H), 2nd , 7 (m, 1H), 2.2 (m, 1H), 1.5-2.0 (m, 8H), 1.5 (t, 3H) ppm.

The hydrochloride can be extracted by shaking with sodium bicarbonate solution and ethyl acetate and evaporation of the ethyl acetate solution are the free base, which is a syrup.

Example 24 3-chloro-4- (4-phenyl-cyclohexylmethyl) -1H-pyrid-2-one

36 g of 2,3-dichloro-4- (4-phenyl-cyclohex-1-enylmethyl) pyridine (Example 19) dissolved in 200 ml of THF were mixed with 145 ml of a 1 molar BH₃ · THF solution. After 64 hours, 200 ml of octanoic acid were carefully added to the solution and the THF was distilled off. After 15 hours at 200 to 210 ° C, the acid was largely distilled off in vacuo. The residue was shaken with sodium bicarbonate solution and ethyl acetate. The aqueous phase was extracted several times with ethyl acetate. After concentrating the extracts, they were purified on silica gel using ethyl acetate as the eluent.
Yield: 50% (mixture of the cis and trans isomers)
1 H-NMR (100 MHz, DMSO)
12.0 (s, 1H), 7.1-7.4 (m, 6H), 6.1-6.3 (2d, 1H), 3.3 (s, 2H), 2.6 u. 2.6 (2d, 2H), 1.1-2.1 (m, 9H) ppm.

Example 25 2,3-dichloro-4- (4-cis-phenyl-cyclohexylmethyl) pyridine and 2,3-dichloro-4- (4-trans-phenyl-cyclohexylmethyl) pyridine

17.2 g of 3-chloro-4- (4-phenyl-cyclohexylmethyl) -1H-pyridin-2-one (Example 24) were boiled for 12 hours with 50 ml of phosphorus oxychloride and 0.5 ml of DMF. Then the excess of phosphorus oxychloride was largely distilled off and the residue was added to a mixture of ice and ethyl acetate. The mixture was stirred for 1 hour. It was then deacidified with sodium bicarbonate and the product extracted with ethyl acetate. Column cleaning on silica gel with ethyl acetate gave 6 g (= 33% of theory) of cis / trans mixture and 4.2 g (= 24% of theory) of starting material. The mixture of isomers was dissolved in hexane. The trans isomer crystallized in 14% yield (mp: 80 ° C.). The cis isomer was isolated by chromatography on silica gel with THF / hexane 1/10.
Yield: 10% cis isomer and 12% trans isomer
cis isomer:
1 H-NMR (100 MHz, CDCl₃)
8.1 (d, 1H), 7.1-7.4 (m, 5H), 7.0 (d, 1H), 2.9 (d, 2H), 2.6 (m, 1H), 2 , 1 (m, 1H), 1.5-1.9 (m, 8H) ppm.
trans isomer:
1 H-NMR (100 MHz, CDCl₃)
8.2 (d, 1H), 7.1-7.3 (m, 5H), 7.1 (d, 1H), 2.7 (d, 2H), 2.5 (m, 1H), 1 , 1-2.0 (m, 1H) ppm.

Example 26 3-chloro-2-ethyl-4- [1- (4-phenylcyclohex-1-enyl) ethyl] pyridine

10 g of 2,3-dichloro-4- [1- (4-phenyl-cyclohex-1-enyl)] ethyl pyridine (Example 21) and 0.3 g of [1,3-bi- (diphenyl-phosphino) -propanj-nickel (II) chloride were presented in toluene. 30 ml of a 2 molar solution of ethylmagnesium chloride in THF were added dropwise with stirring. After 17 hours, the THF was distilled off in vacuo and sodium bicarbonate solution was added. The organic phase was separated and the aqueous phase extracted twice more with ethyl acetate. The combined organic phases were concentrated after drying over sodium sulfate and the residue was purified by chromatography on silica gel. Hexane / ethyl acetate 9/1 was used as eluent.
Yield: 72% (syrup)
1 H-NMR (100 MHz, CDCl₃)
8.3-8.4 (2d, 1H), 7.1-7.4 (m, 5H), 7.0-7.1 (2d, 1H), 5.6-5.7 (m, 1H) ), 3.8-4.0 (m, 1H), 3.0 (q, 2H), 2.7-2.9 (m, 1H), 1.6-2.5 (m, 6H), 1.3 (t, 3H) ppm.

B. Examples of formulation

a) A dust is obtained by adding 10 parts by weight of active ingredient and Mixes 90 parts by weight of talc as an inert substance and in a hammer mill crushed.

• b) a wettable powder which is readily dispersible in water is obtained, by adding 25 parts by weight of active ingredient, 65 parts by weight of kaolin-containing quartz as an inert substance, 10 parts by weight of potassium lignosulfonate and 1 part by weight oleoylmethyltauric acid sodium as a wetting and dispersing agent and grind in a pin mill.
• c) A dispersion concentrate which is easily dispersible in water is prepared by mixing 40 parts by weight of active ingredient with 7 parts by weight of one Sulfosuccinic acid half ester, 2 parts by weight of a lignosulfonic acid Sodium salt and 51 parts by weight of water and mixed in one Grinding ball mill ground to a fineness of less than 5 microns.
• d) An emulsifiable concentrate can be prepared from 15 parts by weight Active ingredient, 75 parts by weight of cyclohexane as a solvent and 10 parts by weight Share oxyethylated nonylphenol (10 EO) as an emulsifier.
• e) Granules can be produced from 2 to 15 parts by weight of active ingredient and an inert granulate carrier material such as attapulgite, pumice granulate and / or quartz sand. It is advisable to use one Suspension of the wettable powder from Example b) with a solids content  of 30% and sprayed this onto the surface of an attapulgite granulate, dries and mixes intimately. The weight percentage is Spray powder about 5% and that of the inert carrier material about 95% of the finished granules.

C. Biological examples Use as an insecticide example 1 Musca domestica (housefly)

On the inside of the lid and the bottom of a petri dish were each 1 ml of the formulation to be tested emulsified in water, evenly applied and after drying the covering 10 adults each House fly (Musca domestica) entered. After closing the bowl these were kept at room temperature and after 3 hours the Mortality of the test animals determined. At 250 ppm (based on the content of Active ingredient) shows the preparations from Examples 11 and 16 a 100% mortality in the experimental animals used.

Example 2 Nilaparvata lugens

Rice seed was germinated on cotton wool in cultivated glasses and moist after growing to about 8 cm stem length with the leaves in the testing test solution given. After the drains were treated, they were treated in this way Rice plants placed separately in the breeding container according to the test concentration and with 10 larvae (L3) each of the species Nilaparvata lugens populated. After storing the sealed breeding container at 21 ° C after 4 days the mortality of the Cicada larvae can be determined. Under these test conditions, the Compounds from Examples 8, 7, 11 and 16 a 100% mortality in the used experimental animals.  

Example 3 Diabrotica undecimpunctata larvae

Wheat seeds were pre-germinated under water for 6 hours, then in 10 ml Glass test tubes were given and covered with 2 ml soil each. After adding The plants remained in the growing jars for 1 ml of water until they reached one Stand at a height of approx. 3 cm below room temperature (21 ° C). Subsequently were medium diabrotica undecimpunctata larval stages (10 each) in the Put the glass on the ground and after 2 hours 1 ml of the to be checked Concentration of test liquid on the surface of the earth in the glass pipetted. After standing for 5 days under laboratory conditions (21 ° C) Earth or the root parts are searched for living Diabrotica larvae and the Mortality found. The compound from Example 16 showed among the selected test conditions an effect that is 100% mortality in the Leads laboratory animals.

Example 4 Aphis fabae

Field beans heavily infested with black bean aphid (Aphis fabae) (Vicia faba) were with aqueous dilutions of wettable powder concentrates 250 ppm of active ingredient up to the stage of dripping sprayed. The aphid mortality was determined after 3 days. A 100% destruction could be achieved with the compounds according to Examples 7, 8, 11, 10, 13 and 16 can be achieved.

Example 5 Tetranychus urticae

Those heavily infested with bean spider mites (Tetranychus urticae, full population) Bean plants (Phaseolus v.) Were diluted with an aqueous Wettable powder concentrate, which contained 250 ppm of the respective active ingredient, sprayed. The mite's mortality was checked after 7 days. 100% Killing was carried out with the compounds according to Examples 7, 8, 11, 10, 13, 12 and 16 scored.  

Example 6 Trialeurodes vaporariorum

Leaves of the Phaseolus vulgaris bean were evenly coated with white eggs Fly (Trialeurodes vaporariorum) and after a development period of the White fly population at the L2-L3 stage even with the watery Sprayed test emulsions of the formulation. After 4 days the microscopic control of the larvae on the leaves that with the Compounds according to Examples 11, 13, 12 and 16 a 100% kill could be achieved.

Use as a fungicide Example 7 Plasmopara viticola

Wine seedlings of the "Grüner Veltliner" variety are grown about 6 weeks after the Sowing with 40% acetone / 60% water solutions of the claimed Connections treated to runoff. 24 hours after being discussed the plants by spraying with a zoosporangia suspension of Plasmopara viticola inoculated and placed in a climatic chamber at approx. 20 ° C and approx. 99% rel. Humidity. The experiments were started about 14 days after the Treatment evaluated. The degree of infection of the plants was assessed on a Scale from 0 to 4, in which 0 = 0-24% infection suppression, 1 = 25-49% Infestation suppression, 2 = 50-74% infestation suppression, 3 = 75-100% Infestation suppression and 4 = 98-100% infestation suppression. The Compound from Example 11 showed a 2 or 3 if spray solutions with a Content of 50 mg active substance / liter were used.

Example 8 Erysiphe graminis f. sp. hordei

Barley plants "Maris Otter" were in the 2-leaf stage with a 40% acetone / 60% water solution of the claimed compounds dripping wet treated. The plants were inoculated 24 hours after spraying by transferring coridia from previously infected plants. This  Plants were placed in a greenhouse at about 20 ° C and one relative humidity of 75 to 80%. The experiments were rough Evaluated 14 days after the inoculation. The degree of infection of the plants was rated on a scale from 0 to 4, in which 0 = 0-24% infection suppression, 1 = 25-49% infestation suppression, 2 = 50-74% infestation suppression, 3 = 75-100% infestation suppression and 4 = 98-100% infestation suppression mean. The compounds from Examples 11 and 8 were 2 or 3 evaluated when spray solutions with 50 mg active substance / liter are used were.

Example 9 Phytophtora infestans

Tomato plants "First in the field" were in the 3 to 4 leaf stage 40% acetone / 60% water solutions of the claimed compounds sprayed soaking wet. 24 hours later, the plants were inoculated with a Spore suspension (20,000 spores / ml) from Phytophtora infestans and for 2 Days in a climate chamber of approx. 15 ° C and a relative humidity of approx. 99% posed followed by 3 to 4 days at a relative humidity of 75 to 80 ° C. The experiments were started about 6 days after treatment evaluated. The degree of infection of the plants was rated on a scale of 0 to 4, in which 0 = 0-24% infection suppression, 1 = 25-49% Infestation suppression, 2 = 50-74% infestation suppression, 3 = 75-100% Infestation suppression and 4 = 98-100% infestation suppression. The Compound from Example 1 6 was rated 3 if spray solutions with a content of 50 mg active substance / liter were used.  

Use as an anti-parasitic Example 10 In vitro test on tropical cattle ticks (Boophilus microplus)

The effectiveness of the compounds according to the invention against ticks was demonstrated in the following experimental setup:
To prepare a suitable preparation of active compound, the active compounds were dissolved 10% (w / v) in a mixture consisting of dimethylformamide (85 g), nonylphenol polyglycol ether (3 g) and ethoxylated castor oil (7 g), and the emulsion concentrates thus obtained were dissolved in water diluted a test concentration of 500 ppm.

Ten fully-sucked females were added to each of these active ingredient dilutions the tropical tick, Boophilus microplus, dipped for five minutes. The Ticks were then dried on filter paper and then for the purpose the egg laying with the back attached to an adhesive film. The storage the ticks took place in an oven at 28 ° C and a humidity of 90%.

As a control, female ticks were only immersed in water. For Efficacy was assessed two weeks after treatment Inhibition of egg laying used. 100% say that none, 0 that all cells have laid eggs.

In this test, the compound according to Example 16 produces a 100% Inhibition of egg laying.

Claims (21)

1. compound of formula (I) and its N-oxides, in which
R represents the same or different radicals selected from the series
(C₁-C₄) alkyl,
(C₂-C₄) alkenyl,
(C₂-C₄) alkynyl,
(C₂-C₄) alkoxy,
(C₂-C₄) alkenyloxy,
Halogen (C₁-C₄) alkyl,
Halogen (C₂-C₄) alkenyl,
Halogen (C₂-C₄) alkynyl,
Halogen (C₁-C₄) alkoxy,
Halogen (C₁-C₄) alkenyloxy,
R⁵-O-CH₂-,
R⁵-O- CO-,
R⁶-CO-,
Halogen (C₁-C₄) alkoxymethyl,
Halogen (C₁-C₄) alkoxycarbonyl,
Halogen (C₂-C₄) alkenyloxymethyl,
Halogen (C₂-C₄) alkenyloxycarbonyl,
(C₁-C₄) alkylthio,
(C₂-C₄) alkenylthio,
(C₁-C₄) alkylsulfinyl,
(C₂-C₄) alkenylsulfinyl,
(C₁-C₄) alkylsulfonyl,
(C₂-C₄) alkenylsulfonyl,
Aryl,
Aralkenyl,
substituted amino,
Cyano and
Halogen;
m represents 0, 1, 2, 3 or 4;
R¹ and R² are the same or different and are selected from the series hydrogen,
(C₁-C₄) alkyl,
(C₂-C₄) alkenyl,
Halogen (C₁-C₄) alkyl,
Halogen (C₂-C₄) alkenyl,
Aryl and
Aralkyl; and
R³ represents hydrogen; or
R¹ and R³ together represent a bond and
R² is as defined above;
p represents an integer from 2 to 7;
R⁴ stands for the same or different radicals which are selected from the series
(C₅-C₁₀) alkyl,
(C₂-C₁₀) alkenyl,
(C₂-C₁₀) alkynyl,
(C₅-C₁₀) alkoxy,
(C₁-C₁₀) alkanoyloxy,
(C₂-C₁₀) alkenyloxy,
(C₅-C₁₀) acyl,
(C₁-C₁₀) alkoxy-carbonyl,
(C₂-C₁₀) alkenyloxycarbonyl,
Halogen (C₅-C₁₀) alkyl,
Halogen (C₅-C₁₀) alkenyl,
Halogen (C₅-C₁₀) alkoxy,
Halogen (C₂-C₁₀) alkenyloxy,
Halogen (C₂-C₁₀) acyl,
Halogen (C₂-C₁₀) alkoxy-carbonyl,
Halogen- (C₂-C₁₀) -al kenyloxy-carbonyl,
Aryl,
Aralkyl,
Heteroaryl and
Heteroarylalkyl;
n represents 1, 2 or 3;
R⁵ (C₁-C₁₀) alkyl,
(C₂-C₁₀) alkenyl,
(C₂-C₁₀) alkynyl,
(C₃-C₈) cycloalkyl or
Aralkyl;
R⁶ is defined as R⁵ or
Halogen (C₁-C₁₀) alkyl,
Halogen (C₂-C₂₀) alkenyl or
Means aryl;
Aryl means phenyl, naphthyl or biphenyl, each of which is optionally substituted;
Aralkyl is aryl (C₁-C₄) alkyl;
Heteroaryl is aryl in which at least 1 CH is replaced by N and / or at least 1 -CH = CH unit is replaced by NH, S or O, which is optionally substituted like aryl; and
Heteroarylalkyl means heteroaryl- (C₁-C₄) alkyl;
or their salts. 2. Compound of formula I according to claim 1 or its N-oxide, in which
R represents the same or different radicals selected from the series
(C₁-C₄) alkyl,
(C₂-C₄) alkenyl,
(C₂-C₄) alkynyl,
(C₁-C₄) alkoxy,
(C₂-C₄) alkenyloxy,
Halogen (C₁-C₄) alkyl,
Halogen (C₂-C₄) alkenyl,
Halogen (C₁-C₄) alkoxy,
Halogen (C₁-C₄) alkenyloxy,
R⁵-O-CH₂-,
R⁵-O-CO-,
Halogen- (C₁-C₄) -alko xymethyl,
Halogen (C₁-C₄) alkoxycarbonyl,
Halogen (C₂-C₄) alkenyloxymethyl,
Halogen (C₂-C₄) alkenyloxycarbonyl,
Cyano and
Halogen;
and the remaining residues and variables are as defined above; or their salts. 3. A compound of formula I according to claim 1 or 2 or its N-oxide, in which
R¹ and R² are the same or different and are selected from the series hydrogen and (C₁-C₄) alkyl
or
R¹ and R³ together represent a bond and
R² is as defined above;
and the remaining radicals and variables are as defined in any one of the preceding claims;
or their salts. 4. A compound of formula I according to any one of claims 1 to 3 or its N-oxide, in which p = 5;
or their salts. 5. A compound of formula I according to any one of claims 1 to 4 or its N-oxide, in which
R⁴ stands for the same or different radicals which are selected from the series
(C₅-C₁₀) alkyl,
(C₂-C₁₀) alkenyl,
(C₅-C₁₀) alkoxy,
(C₁-C₁₀) alkanoyloxy,
(C₂-C₁₀) alkenyloxy,
(C₅-C₁₀) acyl,
(C₁-C₁₀) alkoxy-carbonyl,
(C₂-C₁₀) alkenyloxycarbonyl,
Halogen (C₅-C₁₀) alkyl,
Halogen (C₅-C₁₀) alkenyl,
Halogen (C₅- C₁₀) alkoxy,
Halogen (C₂-C₁₀) alkenyloxy,
Halogen (C₂-C₁₀) acyl,
Halogen (C₂-C₁₀) alkoxy-carbonyl,
Halogen (C₂-C₁₀) alkenyloxycarbonyl,
Aryl,
Aralkyl,
Heteroaryl and
Heteroarylalkyl;
and the remaining radicals and variables are as defined in any one of the preceding claims;
or their salts. 6. Compounds of formula I according to one of claims 1 to 5 or their N-oxide, in which n = 1;
or their salts. 7. A compound of formula I according to claim 6 or its N-oxide, in which p = 5 and R⁴ is in the 4-position of cyclohexyl or cyclohexylidene;
or their salts. 8. A process for the preparation of a compound of formula I according to any one of claims 1 to 7 or its N-oxide, characterized₁ that one

• a) for the preparation of a compound of formula I in which R¹ and R³ together represent a bond,
• a₁) a compound of formula II, in which R⁴, n and p are as defined above,
  reacted in the presence of a base with a compound of formula III or formula IV in which R, R² and m are as defined above, R⁷ is aryl or (C₁-C₄) - alkoxy, R⁸ is aryl, aryl is as defined above and X⊖ is halide; or
• a₂) from a compound of formula V, in which R, R¹, R², R⁴, m, n and p are as defined above, in contrast to a basic or an acid catalyst, water is split off, or the hydroxyl group is split off after conversion to a leaving group to form the double bond, a compound of which Formula VI can arise in which R, R¹, R², R⁴, m, n and p are as defined above;
• b) for the preparation of a compound of the formula I in which R¹ and R³ are not together a bond,
  a compound of formula I in which R¹ and R³ together represent a bond and the remaining radicals and variables are as defined above, or a compound of formula VI as defined above under a₂) is hydrogenated; and optionally performing one or more of the following steps:
  - Introduction of substituents on pyridine;
  - Exchange or modification of reactive residues on the pyridine;
  - Conversion into the N-oxides with suitable oxidizing agents;
  - Transfer to their salts.

9. Means containing at least one compound according to one of the Claims 1 to 7 and at least one formulation agent. 10. Fungicidal composition according to claim 9, containing a fungicidally active Amount of at least one compound according to one of Claims 1 to 7 together with the usual additives for this application. 11. insecticidal, acaricidal or nematicidal agent according to claim 9, containing an effective amount of at least one compound according to one of the Claims 1 to 7 together with the usual additional for these applications or auxiliary substances. 12. Plant protection products containing a fungicidal, insecticidal, acaricidal or nematicidal amount of at least one compound according to one of the Claims 1 to 7 and at least one further active ingredient, preferably from the range of fungicides, insecticides, attractants, sterilants, acaricides, Nematicides and herbicides together with those customary for this application Auxiliaries and additives.   13. Agents for use in wood preservatives or as preservatives in sealants, in paints, in cooling lubricants for the Metalworking or in drilling and cutting oils containing an effective one Amount of at least one compound according to one of Claims 1 to 7 together with the auxiliaries and additives customary for this application. 14. A compound according to any one of claims 1 to 7 or means according to Claim 9, for use as a veterinary medicinal product, preferably in the Control of endo- or ectoparasites. 15. A method for producing an agent according to any one of claims 9 to 14, characterized in that the active ingredient and the other additives together and brings it into a suitable form of application. 16. Use of a compound according to any one of claims 1 to 7 or an agent according to any one of claims 9, 10, 12 and 13 as a fungicide. 17. Use of a compound according to any one of claims 1 to 7 or an agent according to any one of claims 9, 10 and 13 as a wood preservative or as a preservative in sealants, in paints, in Cooling lubricants for metalworking or in drilling and cutting oils. 18. Process for combating phytopathogenic fungi, thereby characterized in that one looks at this or the plants infested by them, Surfaces or substrates or on seed a fungicidally effective amount of A compound according to any one of claims 1 to 7 or an agent according to applied one of claims 9, 10, 12 and 13.   19. Procedures for controlling insect pests, acarina and nematodes, in which one looks at these or the plants, areas infested by them or substrates an effective amount of a compound according to any of the Claims 1 to 7 or an agent according to any one of claims 9, 10 and 12 applied. 20. Use of compounds according to one of claims 1 to 7 or an agent according to any one of claims 9, 10 and 12 for combating Insect pests, acarina and nematodes. 21. Seeds treated or coated with an effective amount of one A compound according to any one of claims 1 to 7 or an agent according to one of claims 9, 10, 12 and 13.