WO2001015532A1

WO2001015532A1 - Azabicyclo and azacyclo oxime and amine compounds as pesticides

Info

Publication number: WO2001015532A1
Application number: PCT/EP2000/008310
Authority: WO
Inventors: Stephen Lindell; Ulrich Sanft; Maria-Theresia Thönessen
Original assignee: Aventis Cropscience Gmbh
Priority date: 1999-08-27
Filing date: 2000-08-25
Publication date: 2001-03-08
Also published as: KR20020029115A; AU7413500A; EP1211940A1; CN1370048A; JP2003508412A; BR0013541A

Abstract

The use of azabicyclo and azacyclo oxime and amine compounds of the formula (I) to (IV) wherein the symbols and indices have the meanings given in the specification for controlling animal pests.

Description

Azabicyclo and azacyclo oxime and amine compounds as pesticides

Description

The invention relates to the field of pest control, especially the control of animal pests like arthropods, e.g. insects and arachnids, ecto- and endoparasites, helminths, nematodes and mollusks.

Carbamates of quinuclidinone 3-oximes are known as pesticides from FR-A 2 086 292 and carbamates of piperidine 4-oximes are known as pesticides from GB 1 ,244,483.

However, since modern pesticides must meet a wide range of demands, for example regarding level, duration and spectrum of action, use spectrum, toxicity, combination with other active substances, combination with formulation auxiliaries or synthesis, and since the occurrence of resistances is possible, the development of such substances can never be regarded as concluded, and there is constantly a high demand for novel pesticides which are advantageous over the known ones, at least as far as some aspects are concerned.

It was an object of the present invention to provide compounds which widen the spectrum of existing pesticides in various aspects.

It has now surprisingly been found that certain azabicyclo and azacyclo oxime and amine compounds are useful for controlling animal pests. Such compounds are disclosed in EP-A 0 445 731 as pharmaceuticals, in particular for the treatment of neurological disorders. There is no hint to a possible use in pest control.

Therefore, in one aspect of the invention there is provided the use of azabicyclo and azacyclo oxime and amine compounds of the formulae (I) to (IV) or agrochemically acceptable salts thereof for controlling animal pests,

(I) (ii)

Z

(III) (IV)

wherein n is one or two; p is zero, one, two, three or four;

R¹ and R² are independently hydrogen or a straight or branched lower alkyl group having from 1 to 4 carbon atoms, which is optionally substituted by one or more fluorine atoms; R³ is hydrogen, a straight or branched lower alkyl group having from 1 to 6 carbon atoms, (C₃-C₆)-cycloalkyl, hydroxy, a straight or branched lower alkoxy group having from 1 to 4 carbon atoms, an acyloxy group, wherein the acyl moiety has from 2 to 5 carbon atoms, or -(CH₂)_qNR⁴R⁵; q is zero, one, two, three or four; R⁴ and R⁵ are independently hydrogen or a straight or branched lower alkyl group having from 1 to 4 carbon atoms; Y is a bond or a straight or branched hydrocarbon chain having from 1 to 20 carbon atoms and optionally containing one to three double and/or triple bonds; Z is a cycloalkyl group having from 3 to 6 carbon atoms; an aromatic group selected from phenyl, 2- or 3-thienyl, 2- or 3-furanyl, 2- or 3-pyrrolyl, 3-, 4- or 5-isoxazolyl and 4- or 5-dithiazolyl, wherein the aromatic group is unsubstituted or is substituted with 1 or 2 substituents selected from chlorine, bromine, fluorine, trifluoromethyl, nitro, CO₂R⁹, amino, amino substituted with 1 or 2 straight or branched lower alkyl groups having froml to 4 carbon atoms and straight or branched alkoxy groups having from 1 to 4 carbon atoms; -NR⁶R⁷ , -C(O)NR⁶R⁷, -C(O)R⁸, CN, CO₂R⁹,OR¹⁰, SR¹⁰ or if Y is not a bond, hydrogen;

R⁶, R⁷ are independently hydrogen or a straight or branched alkyl group having from 1 to 4 carbon atoms;

R⁸ is a straight or branched alkyl group having from 1 to 6 carbon atoms;

R⁹ is hydrogen, a straight or branched lower alkyl group having from 1 to 6 carbon atoms or benzyl;

R¹⁰ is a straight or branched hydrocarbon having from 1 to 6 carbon atoms and optionally containing 1 or 2 double and/or triple bonds; with the proviso that compounds of formula (I) and (IV) wherein n or p is 2;

Y is a bond and

Z is C(O)NR⁶R⁷ are excluded.

In the compounds depicted by general Formulae (I), (II), (III) and (IV) the various substituents are further described as follows. Illustrative examples of straight or branched lower alkyl having from 1 to 4 carbon atoms or from 1 to 6 carbon atoms include methyl, trifluoromethyl, ethyl, 2,2,2-trifluoroethyl, n-propyl, isopropyl, n-butyl, tert.-butyl, n-pentyl and n-hexyl.

Illustrative examples of lower alkoxy groups having from 1 to 4 carbon atoms are methoxy, trifluoromethoxy, ethoxy and n-propoxy. Illustrative examples of a saturated straight or branched hydrocarbon chain having from 1 to 8 carbon atoms include n-octyl, n-heptyl, and all the illustrative examples of straight or branched lower alkyl groups having from 1 to 6 carbon atoms set forth above.

Illustrative examples of straight or branched unsaturated hydrocarbon chains which contain from 1 to 3 unsaturations which are double or triple bonds are ethenyl, 2,4-pentadienyl, 1 ,4-pentadienyl, 2,4-pentadiynyl, 1 ,4-pentadiynyl, (E&Z)-2-penten- 4-ynyl, 2-pentyn-4-enyl, 2-propenyl, 3-butenyl, 1-methyl-2-propenyl, 2-pentenyl, 2-ethyl-3-butenyl, 4-hexenyl, ethynyl, 2-propynyI, l-methyl-2-propynyl, 1 -ethyl-2- propynyl, 1-methyl-3-butynyl, 3-butynyl, or 4-pentynyl. Illustrative examples of cycloalkyl groups having from 3 to 6 carbon atoms are cyclopropyl, cyclobutyl and cyclohexyl.

Agrochemically acceptable acid addition salts of the compounds of Formulae (I), (II), (III) and (IV) are illustratively hydrochloric, hydrobromic, sulfuric, phosphoric, acetic, benzoic, citric, malonic, salicylic, malic, fumaric, oxalic, succinic, tartaric, lactic, gluconic, ascorbic, maleic, asparatic, benzenesulfonic, methane- and ethanesulfonic, hydroxymethane- und hydroxyethanesulfonic.

Preferred compounds of the present invention are those of Formulae (I) and (III) with the compounds of Formula (I) being more preferred. The most preferred compounds of this invention are those of Formula (I) wherein n is one, i.e., compounds of the following Formula (V):

(V)

where Y, Z and R³ have the same meanings as set forth above for Formula (I), (II), (III), and (IV). Compounds of Formula V wherein R³ is hydrogen are more preferred Compounds of Formula (I) wherein n is two may be depicted as set forth below in Formula (VI):

(VI)

wherein Y, Z and R³ have the meanings defined above.

In the compounds of Formulae (III) and (IV) the =NO-Y-Z group is attached to either the 2-, 3- or 4-position (Formula III) or the 3- or 4-position (Formula IV) of the ring.

Compounds of the present invention may exist in either of two Z and E isomeric forms. The present invention includes both forms of the compounds as well as mixtures of the Z and E forms. Illustratively Formulae (VII) and (VIII) depict the Z and E forms of the compounds of Formula (I). Moreover, in those compounds in which there is a double bond in a carbon chain, both the Z and E forms of the olefins are included in the present invention.

The compounds of formulae (I) to (IV) are partly known and partly new. Accordingly, in a further aspect of the invention there is provided a compound of formula (I), (II), (III) or (IV), wherein the symbols and indices have the meanings given above; with the proviso that at least one of R¹ and R² is a straight or branched lower alkyl group having from 1 to 4 carbon atoms, which is substituted by one or more fluorine atoms, and/or Z is 3-, 4- or 5-isoxazolyl or 4- or 5- dithiazolyl.

Z form E form (VII) (VIII)

The compounds of Formulae (I), (III), and (IV) can be prepared by reacting a ketone of the following Formulae (IX), (X) and (XI) with an amine of the formula NH₂OR*HCI wherein Y, Z and R³ have the meanings defined in Formulas (I), (II), (III) and (IV) as depicted below:

Formula (I)

Formula (III)

(X) Formula (IV)

(XI) In each of the above depicted reactions, typically methanol is used as the solvent and the reaction is carried out at room temperature or at elevated temperature, such as reflux.

The compounds of Formula (II) are prepared by reducing Formula (I) compounds by procedures well known in the art, for example by treatment with sodium cyanoborohydride under controlled pH conditions. Therefore, not only are the compounds of Formula (I) useful for controlling animal pests, they are also useful as starting material to make further useful pesticides. Similarly, compounds wherein -Y-Z is hydrogen may be used to prepare compounds of Formula (I) wherein -Y-Z is the group -C(=O)R⁸ or -C(=O)NR⁶R⁷.

The salts can be prepared by contacting the free base form of the compounds of the invention with a sufficient amount of the desired acid to produce the salt in the conventional manner. The free base forms may be regenerated, if desired, by treating the salt form with a base. For example, dilute aqueous solutions of such bases as sodium hydroxide, potassium carbonate, ammonia, and sodium bicarbonate may be utilized for this purpose.

The free base forms of the compounds of this invention differ somewhat from their respective salt forms in such physical properties as melting point and solubility in polar solvents, but the salts are otherwise equivalent to their respective free acid or base forms for the use according to the invention. The starting materials represented by Formulae (IX), (X) and (XI) are known in the art or can be prepared by procedures generally known in the art. See, for example, K. Nador et al., Arzneim. Forsch., 1962, 12, 305 and J.Sauders et al., J. Chem. Soc, Chem. Comm. 1988, 1618 and R.J. Snow and L.J. Street, Tet. Lett. 1989, 30, 5795 and L. J. Street et al., J. M. ed. Chem., 1990, 33, 2690. Also, the amines represented by NH₂O-Y-Z are commercially available or may be prepared by procedures generally known in the art. See for example H. Tecle et al., J. Med. Chem., 1998, 41 , 2524.

Compounds of formulae (I) to (IV) having hydrolyzable groups mentioned above may be prepared from the corresponding secondary amines by methods well known in the art, for example, alkanoyl derivatives may be prepared by reaction with an alkanoyl halide.

Collections of compounds of the formulae (I) to (IV) which can be synthesized by the abovementioned schemes may also be prepared in a parallel manner, and this may be effected manually or in a semiautomated or fully automated manner. In this case, it is possible, for example, to automate the procedure of the reaction, work-up or purification of the products or of the intermediates. In total, this is to be understood as meaning a procedure as it is described, for example, by S.H. DeWitt in "Annual Reports in Combinatorial Chemistry and Molecular Diversity: Automated synthesis", Volume 1 , Verlag Escom 1997, pages 69 to 77.

Commercially available apparatus as offered by, for example, Stem Corporation, Woodrolfe Road, Tollesbury, Essex, CM9 8SE, England or H+P Labortechnik GmbH, Bruckmannring 28, 85764 Oberschleiβheim, Germany, may be used for the parallel procedure of the reaction and work-up. For the parallel purification of compounds of the formulae (I) to (IV), or of intermediates obtained during the preparation, use may be made, inter alia, of chromatography apparatus, for example from ISCO, Inc., 4700 Superior Street, Lincoln, NE 68504, USA. The apparatus mentioned leads to a modular procedure in which the individual process steps are automated, but manual operations must be performed between the process steps. This can be prevented by employing semi-integrated or fully integrated automation systems where the automation modules in question are operated by, for example, robots. Such automation systems can be obtained, for example, from Zymark Corporation, Zymark Center, Hopkinton, MA 01748, USA.

In addition to what has been described here, compounds of the formulae (I) to (IV) may be prepared in part or fully by solid-phase-supported methods. For this purpose, individual intermediate steps or all intermediate steps of the synthesis or of a synthesis adapted to suit the procedure in question are bound to a synthetic resin. Solid-phase-supported synthesis methods are described extensively in the specialist literature, for example Barry A. Bunin in "The Combinatorial Index", Academic Press, 1998.

The use of solid-phase-supported synthesis methods permits a series of protocols which are known from the literature and which, in turn, can be performed manually or in an automated manner. For example, the "tea-bag method" (Houghten, US 4,631 ,211 ; Houghten et al., Proc. Natl. Acad. Sci, 1985, 82, 5131-5135), in which products by IRORI, 11149 North Torrey Pines Road, La Jolla, CA 92037, USA, are employed, may be semiautomated. The automation of solid-phase-supported parallel syntheses is performed successfully, for example, by apparatuses by Argonaut Technologies, Inc., 887 Industrial Road, San Carlos, CA 94070, USA or MultiSynTech GmbH, Wullener Feld 4, 58454 Witten, Germany.

The preparation of the processes described herein yields compounds of the formulae (I) to (IV) in the form of substance collections which are termed libraries.

The compounds of the Formulae (I) to (IV) are suitable for controlling animal pests, in particular arthropods, e.g. insects and arachnids, helminths, nematodes, ecto- and endoparasites and mollusks, especially for controlling insects and arachnids which are encountered in agriculture, in livestock breeding, in forests, in the protection of stored goods and materials, and in the hygiene sector. They are active against normally sensitive and resistant species and against all or individual developmental stages. The abovementioned pests include: from the order of the Acarina, for example, Acarus siro, Argas spp., Ornithodoros spp., Dermanyssus gallinae, Eriophyes ribis, Phyllocoptruta oleivora, Boophilus spp.,

Rhipicephalus spp., Amblyomma spp., Hyalomma spp., Ixodes spp., Psoroptes spp.,

Chorioptes spp., Sarcoptes spp., Tarsonemus spp., Bryobia praetiosa, Panonychus spp., Tetranychus spp., Eotetranychus spp., Oligonychus spp., Eutetranychus spp.

From the order of the Isopoda, for example, Oniscus aselus, Armadium vulgare,

Porcellio scaber.

From the order of the Diplopoda, for example, Blaniulus guttulatus.

From the order of the Chilopoda, for example, Geophilus carpophagus, Scutigera spp.

From the order of the Symphyla, for example, Scutigerella immaculata.

From the order of the Thysanura, for example, Lepisma saccharina.

From the order of the Collembola, for example, Onychiurus armatus.

From the order of the Orthoptera, for example, Blatta orientalis, Periplanata americana, Leucophaea maderae, Blattella germanica, Acheta domesticus,

Gryllotalpa spp., Locusta migratoria migratorioides, Melanoplus differentialis,

Schistocerca gregaria.

From the order of the Isoptera, for example, Reticulitermes spp.

From the order of the Anoplura, for example, Phylloera vastatrix, Pemphigus spp.,

Pediculus humanus corporis, Haematopinus spp., Linognathus spp.

From the order of the Mallophaga, for example, Trichodectes pp., Damalinea spp.

From the order of the Thysanoptera, for example, Hercinothrips femoralis, Thrips tabaci.

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

From the order of the Homoptera, for example, 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, for example, 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, for example, 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, Anthonomus 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, for example, Diprion spp., Hoplocampa spp., Lasius spp., Monomorium pharaonis, Vespa spp.

From the order of the Diptera, for example, 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, Tipuia paludosa. From the order of the Siphonaptera, for example, Xenopsylla cheopsis,

Ceratophyllus spp.

From the order of the Arachnida, for example, Scorpio maurus, Latrodectus mactans.

From the class of the helminths, for example, Haemonchus, Trichostrongulus,

Ostertagia, Cooperia, Chabertia, Strongyloides, Oesophagostomum, Hyostrongulus,

Ancylostoma, Ascaris and Heterakis and also Fasciola.

From the class of the Gastropoda, for example, Deroceras spp., Arion spp., Lymnaea spp., Galba spp., Succinea spp., Biomphalaria spp., Bulinus spp., Oncomelania spp. From the class of the Bivalva, for example, Dreissena spp.

The plant-parasitic nematodes which can be controlled in accordance with the invention include, for example, the root-parasitic soil-dwelling nematodes such as, 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 Pratylenchus 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 longicaudatus, Longidorus such as Longidorus elongatus, Trichodorus such Trichodorus primitivus and Xiphinema such as Xiphinema index.

Other nematode genera which can be controlled using the compounds according to the invention are Ditylenchus (stem parasites, such as Ditylenchus dipsaci and Ditylenchus destructor), Aphelenchoides (foliar nematodes, such as Aphelenchoides ritzemabosi) and Anguina (seed nematodes, such as Anguina tritici). The invention also relates to compositions, for example crop protection compositions, preferably insecticidal, acaricidal, ixodicidal, nematicidal, molluskicidal or helminthicidal, especially preferably insecticidal and acaricidal, compositions which comprise one or more compounds of the formula (I) in addition to suitable formulation auxiliaries.

In general, the compositions according to the invention comprise 1 to 95% by weight of one or more active substances of the Formulae (I) to (IV).

To prepare the compositions according to the invention, the active substance and the other additives are combined and brought into suitable use form.

They can be formulated in various ways, depending on the biological and/or chemical-physical parameters which prevail. The following are examples of possible formulations:

Wettable powders (WP), emulsifiable concentrates (EC), aqueous solutions (SL), emulsions, sprayable solutions, oil- or water-based dispersions (SC), suspoemulsions (SE), dusts (DP), seed-dressing products, granules in the form of microgranules, spray granules, coated granules and absorption granules, water- dispersible granules (WG), ULV formulations, microcapsules, waxes or baits.

These individual types of formulations are known in principle and are described, for example, in:

Winnacker-Kϋchler, "Chemical Technology", Volume 7, C. Hauser Verlag Munich, 4th Edition 1986; van Falkenberg, "Pesticides Formulations", Marcel Dekker N.Y., 2nd Ed. 1972-73; K. Martens, "Spray Drying Handbook", 3rd Ed. 1979, G. Goodwin Ltd. London.

The necessary formulation auxiliaries such as inert materials, surfactants, solvents and other additives, are also known and described, for example, in Watkins, "Handbook of Insecticide Dust Diluents and Carriers", 2nd Ed., Darland Books, Caldwell N.J.; H. v. Olphen, "Introduction to Clay Colloid Chemistry", 2nd Ed., J. Wiley & Sons, N.Y.; Marsden, "Solvents Guide", 2nd Ed., Interscience, N.Y. 1950; McCutcheon's, "Detergents and Emulsifiers Annual", MC Publ. Corp., Ridgewood N.J.; Sisley and Wood, "Encyclopedia of Surface Active Agents", Chem. Publ. Co. Inc., N.Y. 1964; Schδnfeldt, "Grenzflachenaktive Athylenoxidaddukte", [Surface- active ethylene oxide adducts] Wiss. Verlagsgesell., Stuttgart 1967; Winnacker- Kϋchler, "Chemische Technologie", Volume 7, C. Hanser Veriag Munich, 4th Edition 1986.

Based on these formulations, it is also possible to prepare combinations with other pesticidally active materials, fertilizers and/or growth regulators, for example in the form of a ready-mix formulation or a tank mix. Wettable powders are preparations which are uniformly dispersible in water which, besides the active substance, also comprise wetters, for example polyoxyethylated alkylphenols, polyoxyethylated fatty alcohols, alkylsulfonates or alkylphenolsulfonates and dispersants, for example sodium lignosulfonate or sodium 2,2'- dinaphthylmethane-6,6'-disulfonate, in addition to a diluent or inert material.

Emulsifiable concentrates are prepared by dissolving the active substance in an organic solvent, for example butanol, cyclohexanone, dimethylformamide, xylene or else higher-boiling aromatics or hydrocarbons, with addition of one or more emulsifiers. As emulsifiers, the following can be used, for example: calcium alkylarylsulfonates such as calcium dodecylbenzenesulfonate, or nonionic emulsifiers such as fatty acid polyglycol esters, alkylaryl polyglycol ethers, fatty alcohol polyglycol ethers, propylene oxide/ethylene oxide condensates, alkyl polyethers, sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters or polyoxyethylene sorbitol esters.

Dusts can be obtained, for example, by grinding the active substance with finely divided solid materials, for example talc or natural clays, such as kaolin, bentonite, pyrophyllite or diatomaceous earth. Granules can be prepared either by atomizing the active substance onto adsorptive, granulated inert material or by applying active substance concentrates onto the surface of carrier materials such as sand or kaolinites, or of granulated inert material, by means of adhesives, for example polyvinyl alcohol or sodium polyacrylate, or else mineral oils. Suitable active substances can also be granulated in the manner which is customary for the preparation of fertilizer granules, if desired as a mixture with fertilizers.

The active substance concentration in wettable powders is, for example, approximately 10 to 90% by weight, the remainder to 100% by weight is composed of customary formulation auxiliaries. In the case of emulsifiable concentrates, the active substance concentration may be approximately 5 to 80% by weight. Formulations in the form of dusts usually comprise 5 to 20% by weight of active substance, sprayable solutions approximately 2 to 20% by weight. In the case of granules, the active substance content depends partly on whether the active compound is in liquid or solid form and on which granulation auxiliaries, fillers and the like are being used.

Besides, the abovementioned active substance formulations comprise, if appropriate, the tackifiers, wetters, dispersants, emulsifiers, penetrants, solvents, fillers or carriers which are conventional in each case.

For use, the concentrates, which are present in commercially available form, are, if desired, diluted in the customary manner, for example in the case of wettable powders, emulsifiable concentrates, dispersions and in some cases also microgranules using water. Preparations in the form of dusts and granules and sprayable solutions are usually not diluted any further with other inert substances prior to use.

The application rate required varies with the external conditions such as, inter alia, temperature and humidity. It may vary within wide limits, for example between 0.0005 and 10.0 kg/ha or more of active substance, but it is preferably between 0.001 and 5 kg/ha. The active substances according to the invention, in their commercially available formulations and in the use forms prepared from these formulations (see the abovementioned compositions) may be present in mixtures with other active substances such as insecticides, attractants, sterilants, acaricides, nematicides, fungicides, molluskicides, growth regulatory substances or herbicides.

The pesticides include, for example, phosphoric esters, carbamates, carboxylic esters, formamidines, tin compounds and materials produced by microorganisms.

Preferred components in mixtures are:

1. from the group of the phosphorus compounds acephate, azamethiphos, azinphos-ethyl, azinphos-methyl, bromophos, bromophos- ethyl, cadusafos (F-67825), chlorethoxyphos, chlorfenvinphos, chlormephos, chlorpyrifos, chlorpyrifos-methyl, demeton, demeton-S-methyl, demeton-S-methyl sulfone, dialifos, diazinon, dichlorvos, dicrotophos, dimethoate, disulfoton, EPN, ethion, ethoprophos, etrimfos, famphur, fenamiphos, fenitriothion, fensulfothion, fenthion, fonofos, formothion, fosthiazate (ASC-66824), heptenophos, isazophos, isothioate, isoxathion, malathion, methacrifos, methamidophos, methidathion, salithion, mevinphos, monocrotophos, naled, omethoate, oxydemeton-methyl, parathion, parathion-methyl, phenthoate, phorate, phosalone, phosfolan, phosphocarb (BAS-301), phosmet, phosphamidon, phoxim, pirimiphos, pirimiphos- ethyl, pirimiphos-methyl, profenofos, propaphos, proetamphos, prothiofos, pyraclofos, pyridapenthion, quinalphos, sulprofos, temephos, terbufos, tebupirimfos, tetrachlorvinphos, thiometon, triazophos, trichlorphon, vamidothion;

2. from the group of the carbamates alanycarb (OK-135), aldicarb, 2-sec-butylphenyl methylcarbamate (BPMC), carbaryl, carbofuran, carbosulfan, cloethocarb, benfuracarb, ethiofencarb, furathiocarb, HCN- 801 , isoprocarb, methomyl, 5-methyl-m-cumenylbutyryl (methyl)carbamate, oxamyl, pirimicarb, propoxur, thiodicarb, thiofanox, 1-methylthio(ethylideneamino)-N-methyl- N-(morpholinothio)carbamate (UC 51717), triazamate;

3. from the group of the carboxylic esters acrinathrin, allethrin, alphametrin, 5-benzyl-3-furylmethyl (E)- (1R)-cis-2,2-dimethyl- 3-(2-oxothiolan-3-ylidenemethyl)cyclopropanecarboxylate, beta-cyfluthrin, beta-cypermethrin, bioallethrin, bioallethrin ((S)-cyclopentylisomer), bioresmethrin, bifenthrin, (RS)-1-cyano-1-(6-phenoxy-2-pyridyl)methyl (1 RS)-trans-3-(4-tert- butylphenyl)-2,2-dimethylcyclopropanecarboxylate (NCI 85193), cycloprothrin, cyfluthrin, cyhalothrin, cythithrin, cypermethrin, cyphenothrin, deltamethrin, empenthrin, esfenvalerate, fenfluthrin, fenpropathrin, fenvalerate, flucythrinate, flumethrin, fluvalinate (D isomer), imiprothrin (S-41311), lambda-cyhalothrin, permethrin, phenothrin ((R) isomer), prallethrin, pyrethrins (natural products), resmethrin, tefluthrin, tetramethrin, theta-cypermethrin (TD-2344), tralomethrin, transfluthrin, zeta-cypermethrin (F-56701);

4. from the group of the amidines amitraz, chlordimeform;

5. from the group of the tin compounds cyhexatin, fenbutatin oxide;

6. others abamectin, ABG-9008, acetamiprid, anagrapha falcitera, AKD-1022, AKD-3059, ANS-118, bacillus thuringiensis, beauveria bassianea, bensultap, bifenazate (D- 2341), binapacryl, BJL-932, bromopropylate, BTG-504, BTG-505, buprofezin, camphechlor, cartap, chlorobenzilate, chlorfenapyr, chlorfluazuron, 2- (4-chlorophenyl)-4,5-diphenylthiophene (UBI-T 930), chlorfentezine, chromafenozide (ANS-118), CG-216, CG-217, CG-234, A-184699, 2-naphthylmethyl cyclopropanecarboxylate (Ro12-0470), cyromazin, diacloden (thiamethoxam), diafenthiuron, ethyl 2-chloro-N-(3,5-dichloro-4-(1 ,1 ,2,3,3,3-hexafluoro-1- propyloxy)phenyl)carbamoyl)-2-carboximidate, dicofol, diflubenzuron, N-(2,3-dihydro- 3-methyl-1 ,3-thiazol-2-ylidene)-2,4-xylidine, dinobuton, dinocap, diofenolan, DPX- 062, emamectin benzoate (MK-244), endosulfan, ethiprole (sulfethiprole), ethofenprox, etoxazole (YI-5301), fenazaquin, fenoxycarb, fipronil, fluazuron, flumite (flufenzine, SZI-121), 2-fluoro-5-(4-(4-ethoxyphenyl)-4-methyl-1-pentyl)diphenyl ether (MTI 800), granulosis and nuclear polyhedrosis viruses, fenpyroximate, fenthiocarb, flubenzimine, flucycloxuron, flufenoxuron, flufenprox (ICI-A5683), fluproxyfen, gamma-HCH, halofenozide (RH-0345), halofenprox (MTI-732), hexaflumuron (DE_473), hexythiazox, HOI-9004, hydramethylnon (AC 217300), lufenuron, imidacloprid, indoxacarb (DPX-MP062), kanemite (AKD-2023), M-020, MTI-446, ivermectin, M-020, methoxyfenozide (intrepid, RH-2485), milbemectin, NC-196, neemgard, nitenpyram (TI-304), 2-nitromethyl-4,5-dihydro-6H-thiazine (DS 52618), 2-nitromethyl-3,4-dihydrothiazole (SD 35651 ), 2-nitromethylene-1 ,2-thiazinan-3- ylcarbamaldehyde (WL 108477), pyriproxyfen (S-71639), NC-196, NC-1111 , NNI- 9768, Novaluron (MCW-275), OK-9701 , OK-9601 , OK-9602, propargite, pymethrozine, pyridaben, pyrimidifen (SU-8801), RH-0345, RH-2485, RYI-210, S- 1283, S-1833, SB7242, SI-8601 , silafluofen, silomadine (CG-177), spinosad, SU- 9118, tebufenozide, tebufenpyrad (MK-239), teflubenzuron, tetradifon, tetrasul, thiacloprid, thiocyclam, TI-435, tolfenpyrad (OMI-88), triazamate (RH-7988), triflumuron, verbutin, vertalec (mykotal), YI-5301.

The active substance content of the use forms prepared from the commercially available formulations may range from 0.00000001 up to 95% by weight of active substance, preferably between 0.00001 and 1% by weight. Application is effected in a customary manner adapted to suit the use forms.

The invention also relates to a method of controlling animal pests, preferably harmful insects, Acarina, helminths, mollusks and/or nematodes in which an effective amount of one or more compounds of formulae (I) to (IV) or of a composition comprising of one or more compounds of formulae (I) to (IV) is applied to the animal pests or to the plants, areas or substrates infested with them. The compounds of formulae (I) to (IV) are also suitable for use in the veterinary medicine sector, preferably for controlling endoparasites and ectoparasites, and in the field of animal keeping. In a further aspect of the invention there is provided the use of a compound of the formula (I) to (IV) in the preparation of a veterinary medicine, preferably for treating ecto- and endoparasites.

The active substances according to the invention may be applied in the known manner, such as by oral administration in the form of, for example, tablets, capsules, drinks or granules, by dermal application in the form of, for example, dipping, spraying, pouring on and spotting on, and dusting, and by parenteral administration in the form of, for example, an injection.

In addition, the compounds of formula (I) to (IV) are also suitable for use in technology, for example as wood preservative, as preservative in paints, in cooling lubricants for metalworking, or as preservative in drilling and cutting oils.

Accordingly, the compounds of formulae (I) to (IV) can also be employed particularly advantageously in livestock keeping (for example cattle, sheep, pigs and poultry such as chickens, geese and the like). In a preferred embodiment of the invention, the compounds, if appropriate in suitable formulations (cf. above), are administered orally to the animals, if appropriate together with the drinking water or feed. Since excretion in the feces is highly efficient, the development of insects in the animals' feces can be prevented very easily in this manner. The dosages and formulations which are suitable in each case depend, in particular, on the species and the developmental stage of the productive livestock and also on the risk of infestation and can be determined readily and established by customary methods. For example, the compounds can be employed in cattle at dosages of 0.01 to 1 mg/kg bodyweight.

In addition the compounds or compositions according to the invention can be applied in combination with fungicides known from the literature. Such fungicides are described e.g. in C.D.S. Tomlin, S.B. Walker, The Pesticide Manual, 11^th ed., British Crop Protection Council, Farnham 1997.

The invention also relates to seed, treated or coated with an effective amount of one or more compounds of formulae (I) to (IV) or of a composition according to the invention.

The compounds of the formulae (I) to (IV) can also be employed for controlling harmful organisms in crops of known genetically engineered plants or genetically engineered plants yet to be developed. As a rule, the transgenic plants are distinguished by especially advantageous properties, for example by resistances to particular crop protection agents, resistances to plant diseases or pathogens of plant diseases, such as particular insects or microorganisms such as fungi, bacteria or viruses. Other particular properties concern, for example, the harvested material with regard to quantity, quality, storage properties, composition and specific constituents.

The use in economically important transgenic crops of useful plants and ornamentals is preferred, for example of cereals such as wheat, barley, rye, oats, millet, rice, cassava and maize or else crops of sugar beet, cotton, soya, oilseed rape, potatoes, tomatoes, peas and other types of vegetables.

When used in transgenic crops, in particular those which have resistances to insects, effects are frequently observed, in addition to the effects against harmful organisms to be observed in other crops, which are specific for application in the transgenic crop in question, for example an altered or specifically widened spectrum of pests which can be controlled, or altered application rates which may be employed for application.

The invention therefore also relates to the use of compounds of the formulae (I) to (IV) for controlling harmful organisms in transgenic crop plants. The use according to the invention of compounds of the formula (I) or of compositions comprising them, for example as insecticide, acaricide, molluskicide, nematicide or helminthicide, also includes the case where the compound of the formula (I) or its salt is formed from a precursor only after application, for example in the insect, in a plant or in the soil.

The disclosures in European patent application no. 99116945.9 from which this application claims priority, and in the abstract accompanying this application are incorporated herein by reference.

The invention will now be illustrated, but in no way limited, by the following Examples.

The compounds listed in the following Tables can be prepared using experimantal procedures analoguous to those described above or in examples 1 to 67 of EP-A 0 455731 which are hereby incorporated by reference:

Example 1

1 -Azabicyclo [2.2.1]hept-3-one, O-ethyloxime hydrochloride

1-Azabicyclo [2.2.1]hept-3-one (prepared as described in J. Med. Chem., 1990, 33, 2690) (0.1 g, 0.9 mmol) was dissolved in methanol (8 ml), O-ethylhydroxyiamine hydrochloride (0.09 g, 0.9 mmol) was added and the mixture was heated at reflux for 3 hrs. The reaction mixture was concentrated in vacuo to give the title compound as a mixture of isomers (0.2 g); m/z (positive ion electrospray) 155 (M+l)

Example 2

1 -Azabicyclo [2.2.1]hept-3-one, O-(2-propynyl)-oxime hydrochloride 1 -Azabicyclo [2.2.1]hept-3-one (0.15 g, 1.35 mmol) was dissolved in methanol (12 ml), O-propargylhydroxylamine hydrochloride (prepared as described in J. Med. Chem., 1998, 41 , 2524) (0.15 g, 1.35 mmol) was added and the mixture was heated at reflux for 3 hrs. The reaction mixture was concentrated in vacuo, triturated with dichloromethane and filtered to give the title compound as a mixture of isomers (0.19 g); m/z (positive ion electrospray) 165 (M+l).

Example 3

1-Azabicyclo[2.2.1]octan-3-one, O-acetyloxime

Hydroxylammonium chloride (0.86 g, 12.3 mmol) was added to a solution of 3- quinuclidinone (2.0 g, 12.3 mmol) in methanol (200 ml) and the mixture was heated at reflux for 4 hrs. The solvent was evaporated in vacuo and the residue crystallized from acetone to give 1 -azabicyclo[2.2.2]octane-3-one oxime hydrochloride (2.1 g). This material (0.1 g, 0.57 mmol), acetic anhydride (0.06 g, 0.62 mmol), triethylamine (0.18 ml, 12.5 mmol) and 4-dimethylaminopyridine (0.005 g, 0.03 mmol) were dissolved together in CH₂CI₂ (10 ml). After 28 hrs at ambient temperature, the mixture was washed twice with saturated NaHCO₃ solution. The combined aqueous washes were extracted with CH₂CI₂ and the organic extracts were combined, dried (MgSO ) and evaporated to give the title compound as a mixture of isomers (0.13 g); m/z (positive ion electrospray) 183 (M+l).

Table 1

^a Data from EP-A 0455731 ^b Positive ion electrospray MS (ES M+1 data)

Ph means phenyl

Table 2

^a Data from EP-A 0 455 731 ^b Positive ion electrospray MS (ES M+1 data)

N-Methyl-8-azabicyclo[3.2.1]octan-3-one methyloxime hydrochloride ^d N-Methyl-8-azabicyclo[3.2.1]octan-2-one methyloxime

Table 3

^a Data from EP-A 0455 731 ^b Positive ion electrospray MS (ES M+1 data) ^c 4-Piperidinone O-methyloxime hydrochloride ^d 1-Ethyl-3-piperidinone O-methyloxime

B. Formulation examples

a) A dust is obtained by mixing 10 parts by weight of active substance and 90 parts by weight of talc as inert material and comminuting the mixture in a hammer mill.

b) A wettable powder which is readily dispersible in water is obtained by mixing 25 parts by weight of active substance, 65 parts by weight of kaolin-containing quartz as inert material, 10 parts by weight of potassium lignosulfonate and

1 part by weight of sodium oleoylmethyltaurinate as wetter and dispersant and grinding the mixture in a pinned-disk mill.

c) A dispersion concentrate which is readily dispersible in water is prepared by mixing 40 parts by weight of active substance with 7 parts by weight of a sulfosuccinic monoester, 2 parts by weight of a sodium lignosulfonate and

51 parts by weight of water and grinding the mixture in a ball mill to a fineness of below 5 microns.

d) An emulsifiable concentrate can be prepared from 15 parts by weight of active substance, 75 parts by weight of cyclohexanone as solvent and 10 parts by weight of oxyethylated nonylphenol (10 EO) as emulsifier.

e) Granules can be prepared from 2 to 15 parts by weight of active substance and an inert granule carrier material such as attapulgite, pumice granules and/or quartz sand. It is expedient to use a suspension of the wettable powder of Example b) with a solids content of 30%, which is sprayed onto the surface of attapulgite granules, and these are dried and mixed intimately. The wettable powder amounts to approx. 5% by weight and the inert carrier material to approx. 95% by weight of the finished granules. C. Biological examples

Example 1 Effect on the spider mite Tetranychus urticae

Bean plants (Phaseolus vulgaris) which were severely infested with a complete population of spider mites (Tetranychus urticae) were dipped into an aqueous solution of the formulated preparation to be tested. After 6 days storage in a controlled-environment cabinet at approx. 25^CC, the mortality of all mite stages was determined. At a concentration of 300 ppm (based on the active substance content) a 50 - 100 % mortality was caused by the preparations of examples 1 , 2, 4, 20, 28, 81 , 92, 117, 120, 141 and 142.

Example 2 Effect on the egg-larval stage of Heliothis virescens

A Petri dish whose bottom was covered with filter paper and which contained approx. 5 ml of nutrient medium was prepared. Filter paper sections containing approx. 30 24-hour-old eggs of the tobacco budworm (Heliothis virescens) were immersed for 5 seconds into an aqueous solution of the formulated preparation to be tested and subsequently placed in the Petri dish. A further 200 μl of the aqueous solution were distributed over the nutrient medium. After 6 days' storage at approx. 25°C, the mortality of the preparation on the eggs and any larvae hatched from them was determined. At a concentration of 300 ppm a 50 - 100 % mortality was shown by the preparations of example 2.

Example 3 Effect on larvae of Nilaparvata lugens

The leaves of 12 rice plants having a stem length of 8 cm are dipped for 5 seconds into an aqueous solution of the formulated preparation to be examined. After the solution has dripped off, the rice plants are placed in a Petri dish and populated with approximately 20 larvae (L3 stage) of the rice leaf hopper species Nilaparvata lugens. After 6 days' storage at approx. 25°C, the mortality among the leaf hopper larvae is determined. At a concentration of 300 ppm a 50 - 100 % mortality was shown by the preparations of examples 2 and 28.

Example 4 Systemic Effect on Aphis fabae

Germinated broad bean seeds (Vicia faba) with radicles are transferred into brown glass bottles filled with tap water. Four milliliters of an aqueous solution of the formulated preparation to be examined are pipetted into the brown glass bottle. The broad bean is subsequently heavily populated with approximately 100 black bean aphids (Aphis fabae). After 6 days' storage at approx. 25°C, the root-systemic activity of the preparation on the aphids is determined. At a concentration of of 30 ppm a mortality of 50-100% among the aphids by root-systemic action was shown by the preparation of examples 2, 81 and 144.

Example 5 Effect on the cattle tick Boophilus miroplus

Five recently fed adult female cattle ticks (Boophilus miroplus) were dipped for 5 minutes into an aqueous solution of the formulated preparation to be tested. The ticks were stored in a Petri dish at approx. 30°C for 6 days and then (as an indirect measure of tick mortality) the inhibition of oviposition was determined. At a concentration of 300 ppm a 50 - 100 % inhibition of oviposition was shown by the preparations of examples 2 and 4.

Claims

Patent claims:

1. The use of an azabicyclo and azacyclo oxime and amine compound of the formula (I) to (IV) or an agrochemically acceptable salt thereof for controlling animal pests,

(I) (N)

-Z

(III) (IV)

wherein n is one or two; p is zero, one, two, three or four;

R¹ and R² are independently hydrogen or a straight or branched lower alkyl group having from 1 to 4 carbon atoms, which is optionally substituted by one or more fluorine atoms; R³ is hydrogen, a straight or branched lower alkyl group having from 1 to 6 carbon atoms, (C₃-C₆)-cycloalkyl, hydroxy, a straight or branched lower alkoxy group having from 1 to 4 carbon atoms, an acyloxy group, wherein the acyl moiety has from 2 to 5 carbon atoms, or -(CH₂)_qNR⁴R⁵; q is zero, one, two, three or four; R⁴ and R⁵ are independently hydrogen or a straight or branched lower alkyl group having from 1 to 4 carbon atoms;

Y is a bond or a straight or branched hydrocarbon chain having from 1 to 20 carbon atoms and optionally containing one to three double and/or triple bonds;

Z is a cycloalkyl group having from 3 to 6 carbon atoms; an aromatic group selected from phenyl, 2- or 3-thienyl, 2- or 3-furanyl, 2- or 3-pyrrolyl, 3-, 4- or 5-isoxazolyl and 4- or 5-dithiazolyl, wherein the aromatic group is unsubstituted or is substituted with 1 or 2 substituents selected from chlorine, bromine, fluorine, trifluoromethyl, nitro, amino, amino substituted with 1 or 2 straight or branched lower alkyl groups having froml to 4 carbon atoms and straight or branched alkoxy groups having from 1 to 4 carbon atoms; -NR⁶R⁷ , -C(O)NR⁶R⁷, -C(O)R⁸, CN, CO₂R⁹,OR¹⁰, SR¹⁰ or if Y is not a bond, hydrogen;

R⁸ is a straight or branched alkyl group having from 1 to 6 carbon atoms;

Y is a bond and Z is C(O)NR⁶R⁷ are excluded.

2. The use as claimed in claim 1 , wherein Y is a straight or branched hydrocarbon chain having from 1 to 20 carbon atoms and optionally contains from 1 to 3 double and/or triple bonds, and Z is hydrogen.

3. The use as claimed in claim 1 , wherein Z is a cycloalkyl group having from 3 to 6 carbon atoms; an aromatic group selected from phenyl, 2- or 2-thienyl, 2- or 3-furanyl, 2- or 3-pyrrolyl, 3-, 4- or 5-isoxazolyl and 4- or 5-dithiazolyl wherein the aromatic group is unsubstituted or is substituted with 1 or 2 substituents selected from chlorine, bromine, fluorine, trifluoromethyl, nitro, amino, amino substituted with 1 or 2 straight or branched lower alkyl groups having froml to 4 carbon atoms, or straight or branched alkoxy having from 1 to 4 carbon atoms;

4. The use as claimed in one or more of claims 1 to 3 in which the compound of formulae (I) to (IV) is in the form of an agrochemically acceptable acid addition salt or quarternary ammonium salt.

5. A crop protection composition which comprises at least one compound according to formulae (I) to (IV) in any of claims 1 to 4 and at least one formulation auxiliary.

6. An insecticidal, acaricidal, molluskicidal or nematicidal composition as claimed in claim 5 which comprises an effective amount of at least one compound of formulae (I) to (IV) according to any of claims 1 to 4 together with additives or auxiliaries conventionally used for this application.

7. A crop protection composition which comprises a insecticidally, acaricidally, molluskicidally or nematicidally effective amount of at least one compound of formulae (I) to (IV) according to any of claims 1 to 4 and at least one further active substance together with auxiliaries and additives conventionally used for this application.

8. A composition for use in the protection of timber or as preservative in sealants, in paints, in cooling lubricants for metalworking or in drilling and cutting oils, comprising an effective amount of at least one compound of formulae (I) to (IV) according to any of claims 1 to 4 together with auxiliaries and additives conventionally used for these applications.

9. A compound according to formula (I) to (IV) in any of claims 1 to 4 or a composition as claimed in claim 6 for use in the preparation of a veterinary medicament for treating ecto- and/or endoparasites.

10. A process for the preparation of a composition as claimed in any of claims 5 to 8, which comprises combining the active substance and the other additives and bringing the mixture into a suitable use form.

11. The use of a compound according to any of claims 1 to 4 or of a composition as claimed in any of claims 5, 6 and 9 as timber preservative or as preservative in sealants, in paints, in cooling lubricants for metalworking or in drilling and cutting oils.

12. A method of controlling harmful insects, acarina, mollusks and nematodes, in which an effective amount of a compound according to formulae (I) to (IV) in any of claims 1 to 4 or of a composition as claimed in any of claims 5, 6 or 7 is applied to these or to the plants, areas or substrates infested with them.

13. Seed, treated or coated with an effective amount of a compound according to any of claims 1 to 4 or of a composition as claimed in any of claims 5, 6 or 7.

14. A compound of formula (I), (II), (III) or (IV), according to any of claims 1 to 3, wherein the symbols and indices have the meanings given in any of claims 1 to 3 with the proviso that at least one of R¹ and R² is a straight or branched lower alkyl group having from 1 to 4 carbon atoms, which is substituted by one or more fluorine atoms, and/or Z is 3-, 4- or 5-isoxazolyi or 4- or 5- dithiazolyl.