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WO1999055703A1 - 2-alkyl-3-(hetero)aryl-8-azabicyclo[3.2.1]alcanes utilises comme pesticides - Google Patents

2-alkyl-3-(hetero)aryl-8-azabicyclo[3.2.1]alcanes utilises comme pesticides Download PDF

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Publication number
WO1999055703A1
WO1999055703A1 PCT/GB1999/001192 GB9901192W WO9955703A1 WO 1999055703 A1 WO1999055703 A1 WO 1999055703A1 GB 9901192 W GB9901192 W GB 9901192W WO 9955703 A1 WO9955703 A1 WO 9955703A1
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WIPO (PCT)
Prior art keywords
optionally substituted
hydrogen
alkyl
formula
compound
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Application number
PCT/GB1999/001192
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English (en)
Inventor
David Philip John Pearson
Mary Bernadette Aspinall
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Zeneca Limited
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Publication date
Application filed by Zeneca Limited filed Critical Zeneca Limited
Priority to AU36152/99A priority Critical patent/AU3615299A/en
Publication of WO1999055703A1 publication Critical patent/WO1999055703A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
    • C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system

Definitions

  • This invention relates to novel bicyclic amine derivatives, to processes for preparing them, to insecticidal compositions comprising them and to methods of using them to combat and control insect pests.
  • Insecticidal bicyclic amines are disclosed in WO 96/37494.
  • the present invention provides a compound of formula (I):
  • Ar is optionally substituted aryl or optionally substituted heteroaryl;
  • R is hydrogen, cyano, optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted alkenyl, optionally substituted alkynyl, R 3 CO, sulphonyl, CS 2 R 9 or R 7 X" (where X" represents oxygen or a group NR 8 ), provided that when R is optionally substituted alkeny
  • R 9 is hydrogen, optionally substituted alkyl or optionally substituted alkenyl
  • R'° is hydrogen, optionally substituted alkyl, optionally substituted aryl, optionally substituted alkoxy, optionally substituted alkenyloxy, optionally substituted aryloxy or NH 2 ; provided that when A is -CH 2 CH 2 -, Ar is 4-chloro-phenyl and R is CH 3 then R 1 is not hydrogen; or an acid addition salt, quaternary ammonium salt or N-oxide derived therefrom.
  • bicyclic amine compounds of formula (I) are capable of existing in more than one isomeric form and the present invention embraces within its scope all forms and mixtures thereof in all proportions.
  • Alkyl groups and moieties of alkoxy can contain up to 15 carbon atoms, preferably 1 to 6, especially 1 to 4 carbon atoms. They can be in the form of straight or branched chains, for example methyl, ethyl, - or iso-propyl, or n-, sec-, iso- or tert-butyl. Alkyl groups and moieties can be optionally substituted by halogen, hydroxy, alkoxy, haloalkoxy, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aryloxy or optionally substituted heteroaryloxy.
  • Alkenyl and alkynyl groups and moieties of alkenyloxy can contain up to 15 carbon atoms, preferably 2 to 6, especially 2 to 4 carbon atoms. They can be in the form of straight or branched chains, and the alkenyl moieties, where appropriate, can be of either the cis or trans configuration. Examples are vinyl, allyl and propargyl. Alkenyl and alkynyl groups and moieties can be optionally substituted by halogen, optionally substituted aryl or optionally substituted heteroaryl.
  • Aryl groups and moieties of aryloxy include naphthyl but are preferably phenyl.
  • Heteroaryl groups and moieties of heteroaryloxy include 5- and 6-membered aromatic rings containing one, two, three or four heteroatoms selected from the list comprising oxygen, sulphur and nitrogen and can be fused to benzenoid ring systems.
  • Examples are pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl (1,2,3-, 1,2,4- and 1,3,5-), furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl (1,2,3- and 1,2,4-), tetrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, quinolinyl, isoquinolinyl, cinnolinyl, quinazolinyl, quinoxalinyl, indolinyl, isoindolinyl, benzofuranyl, benzothienyl and benzimidazolinyl. - 3 -
  • Sulphonyl includes alkylS(O) 2 (for example methylS(O) 2 ) and phenylS(O) : optionally substituted by alkyl (for example 4-CH 3 C 6 H 4 S(O) 2 ).
  • Amino includes H 2 N, mono- or di-(optionally substituted alkyl)amino or phenyl(optionally substituted alkyl)amino, wherein alkyl is optionally substituted by halogen, alkoxy or haloalkoxy, or di-phenylamino.
  • Halogen includes fluorine, chlorine, bromine and iodine.
  • Aryl and heteroaryl rings can be optionally substituted by halogen, hydroxy, mercapto, C alkyl (especially methyl and ethyl), C 2 . 4 alkenyl (especially allyl), C 2 ⁇ alkynyl (especially propargyl), C M alkoxy (especially methoxy), C 2-4 alkenyloxy (especially allyloxy), C 2 .
  • alkynyloxy especially propargyloxy
  • halo(C M )alkyl especially trifluoromethyl
  • halo(C )alkoxy especially trifluoromethoxy
  • C M alkylthio especially methylthio
  • hydroxy(C M )alkyl especially C M alkoxy(C )alkyl, C 3 . 6 cycloalkyl, C 3 .
  • Optionally substituted methylenedioxy includes -OCH 2 O-, -OCHFO-, -OCF 2 O-, -OCH(CH 3 )O- and -OC(CH 3 ) 2 O-.
  • Substituents which may be present in the aryl or heteroaryl rings of any of the foregoing substituents include one or more of the following: halogen, hydroxy, mercapto, C M alkyl, C 2 _ 4 alkenyl, C 2 ⁇ alkynyl, C M alkoxy, C ⁇ alkenyloxy, C 2J , alkynyloxy, halo(C M )alkyl, halo(C,.
  • Suitable acid addition salts include salts of a compound of formula (I) with an inorganic acid such as hydrochloric, hydrobromic, sulphuric, nitric or phosphoric acid, or an organic carboxylic acid such as oxalic, tartaric, lactic, butyric, toluic, hexanoic or phthalic acid, or a sulphonic acid such as methane, benzene or toluene sulphonic acid.
  • organic carboxylic acids include haloacids such as trifluoroacetic acid. It is preferred that A is -CH 2 CH 2 -.
  • Ar is pyridyl optionally substituted with halogen, C M alkyl, C M alkoxy, cyano, C 2 alkenyl or C 2 ⁇ alkynyl. It is further preferred that Ar is pyridyl optionally substituted with halogen.
  • R is C alkyl, CH 2 (C,. 3 haloalkyl), benzyl, CH 2 (C 2 . 5 alkenyl) or CH 2 (C 2 . 5 alkynyl).
  • R is C M alkyl, CH 2 (C,. 3 haloalkyl), CH 2 (C 2 . 5 alkenyl) or CH 2 (C 2 . 5 alkynyl). It is even more preferred that R is C M alkyl or CH 2 (C,. 3 haloalkyl).
  • R 1 is cyano. - 5 -
  • the present invention provides a compound of formula (I) where A is -CH 2 CH 2 -; Ar is pyridine optionally substituted by halogen (especially chlorine or bromine); R is C M alkyl or C haloalkyl; R 1 is cyano and R 2 is C, profession 2 alkyl.
  • the present invention provides a compound of formula (I) where A is -CH 2 CH 2 -; Ar is heteroaryl optionally substituted by halogen; R is hydrogen or optionally substituted alkyl; R' is cyano; and R 2 is methyl.
  • the present invention provides a compound of formula (I) where A is -CH 2 CH 2 -; Ar is pyridine optionally substituted by halogen (especially chlorine or bromine); R is hydrogen, optionally substituted alkyl, alkenyl, optionally substituted benzyl or R 3 CO; R 3 is hydrogen, optionally substituted alkoxy or optionally substituted alkenyloxy; R 1 is cyano; and R 2 is methyl.
  • Ra is alkyl or phenylalkyl.
  • a compound of formula (I) can be prepared from a compound of formula (II) by treating it with a suitable base, for example potassium carbonate, in the presence of a compound of formula RL where L is a suitable leaving group (for example halogen or triflate).
  • a suitable base for example potassium carbonate
  • L is a suitable leaving group (for example halogen or triflate).
  • a compound of formula (I) can be prepared from a compound of formula (II) by reductive amination with an aldehyde (R 3 CHO; where R 3 CH 2 is R 2 ) in the presence of a suitable reducing agent (for example formic acid).
  • R 3 CHO aldehyde
  • R 3 CH 2 is R 2
  • a suitable reducing agent for example formic acid
  • a compound of formula (II) can be prepared by demethylating a compound of formula (III) by, for instance, treating it first with a chloroformate ester (for example vinyl chloroformate) to produce a carbamate, followed by acid hydrolysis.
  • a chloroformate ester for example vinyl chloroformate
  • a compound of formula (III), wherein R 1 is cyano can be prepared by treating a compound of formula (IV) first with a suitable base, for example lithium diisopropylamide (LDA), followed by reaction with an aryl or heteroaryl halide (ArHal).
  • a compound of formula (IV) can be prepared by treating a compound of formula (V) with tosylmethyl isocyanide in the presence of a suitable base (for example potassium ethoxide).
  • a compound of formula (IV) can be prepared from a compound of formula (XII) by treatment with thionyl chloride, to give a compound of formula (XI) followed by treatment with cyanide as described in J. Am. Chem.
  • a compound of formula (I), wherein R 1 is cyano can be prepared from a compound of formula (VI) by treatment with a suitable base, for example LDA, followed by reaction with an aryl or heteroaryl halide (ArHal).
  • a suitable base for example LDA
  • ArHal aryl or heteroaryl halide
  • a compound of formula (VI) may be prepared from a compound of formula (VII) by treatment with a suitable base, for example potassium carbonate, in the presence of a compound of formula RL where L is a suitable leaving group (for example halogen or triflate).
  • a suitable base for example potassium carbonate
  • L is a suitable leaving group (for example halogen or triflate).
  • a compound of formula (VII) can be prepared by demethylating a compound of formula (IV) by, for instance, treatment first with a chloroformate ester (for example vinyl chloroformate) to produce a carbamate, followed by acid hydrolysis.
  • a compound of formula (VI) may be prepared by treating a compound of formula (VIII) with tosylmethyl isocyanide in the presence of a suitable base (for example potassium ethoxide).
  • a compound of formula (VIII) may be prepared by the Robinson tropinone synthesis, see, for instance, J. Chem. Soc, 1917, 111, 762.
  • a compound of formula (VIII) may be prepared from a compound of formula (X) by reaction with an amine (RaNH 2 ) - 8 -
  • a compound of formula (VIII) may be prepared by reaction of a compound of formula (IX) with a compound of formula R 2 L where L is a suitable leaving group, for example halogen or triflate, in the presence of a suitable base (for example LDA).
  • L is a suitable leaving group, for example halogen or triflate
  • a compound of formula (I), in which R 1 is other than cyano can be prepared from a compound of formula (I), in which R 1 is cyano, by using or adapting methods described in the literature which either convert a cyano group to, or replace a cyano group with, an R 1 group.
  • a compound of formula (I), in which A is other than -CH 2 -CH 2 - can be prepared using processes as described in PCT/GB97/03054, pages 17 and 18.
  • the invention provides compounds of formulae (IV), (V), (VI), (VII), (VIII), (XI) and (XII) which are useful as intermediates in the preparation of the compounds of formula (I).
  • the present invention provides processes for preparing the compounds of formula (I).
  • the compounds of formula (I) or acid addition salts, quaternary ammonium salts or N-oxides derived therefrom can be used to combat and control infestations of insect pests such as Lepidoptera, Diptera, Homoptera and Coleoptera and also other invertebrate pests, for example, acarine, nematode and mollusc pests. Insects, acarines, nematodes and molluscs are hereinafter collectively referred to as pests.
  • the pests which may be combated and controlled by the use of the invention compounds include those pests associated with agriculture (which term includes the growing of crops for food and fibre products), horticulture and animal husbandry, companion animals, forestry and the storage of products of vegetable origin (such as fruit, grain and timber) and also those pests associated with the transmission of diseases of man and animals.
  • pest species which may be controlled by the compounds of formula (I) include: Myzus persicae (aphid), Aphis gossypii (aphid), Aphis fabae (aphid), Lygus spp. (capsids), Dvsdercus spp.
  • capsids Nilaparvata lugens (planthopper), Nephotettix cincticeps (leafhopper), Nezara spp. (stinkbug), Euschistus spp. (stinkbugs), Leptocorisa spp. (stinkbugs), Frankliniella occidentalis (thrip), Thrips spp. (thrips), Leptinotarsa decemlineata (Colorado potato beetle), Anthonomus grandis (boll weevil), Aonidiella spp. (scale insects), Trialeurodes spp.
  • Diabrotica spp. rootworms
  • Panonychus ulmi European red mite
  • Panonychus citri citrus red mite
  • Tetranychus urticae two-spotted spider mite
  • Tetranychus cinnabarinus carmine spider mite
  • Phyllocoptruta oleivora citrus rust mite
  • Polyphagotarsonemus latus broad mite
  • Brevipalpus spp. flat mites
  • Liriomyza spp. leafrniners
  • Musca domestica housefly
  • Aedes aegypti mosquito
  • Anopheles spp. mosquitoes
  • insects which adversely affect the health of the public or of animals.
  • the compound In order to apply a compound of formula (I) to a pest, a locus of pest, or to a plant susceptible to attack by a pest, the compound is usually formulated into a composition which includes, in addition to the compound of formula (I), a suitable inert diluent or carrier and, optionally, a surface active agent. It is preferred that all compositions (both solid and liquid formulations) comprise, by weight, 0.0001 to 95%, more preferably 1 to 85%, for example 5 to 60%, of a compound of formula (I).
  • the composition is generally used for the control of pests such that a compound of formula (I) is applied at a rate of from O.lg to 10kg per hectare, preferably from lg to 6kg per hectare.
  • the present invention provides an insecticidal, acaricidal, nematicidal or molluscicidal composition
  • an insecticidally, acaricidally, nematicidally or molluscicidal composition comprising an insecticidally, acaricidally, nematicidally or molluscicidally effective amount of a compound of formula (I) and a - 10 -
  • compositions are preferably an insecticidal, acaricidal or nematicidal composition.
  • the invention provides a method of combating and controlling pests at a locus which comprises treating the pests or the locus of the pests with an insecticidally, acaricidally, nematicidally or molluscicidally effective amount of a composition comprising a compound of formula (I).
  • the compounds of formula (I) are preferably used against insects, acarines or nematodes.
  • compositions can be chosen from a number of formulation types, including dustable powders (DP), soluble powders (SP), water soluble granules (SG), water dispersible granules (WG), wettable powders (WP), granules (GR) (slow or fast release), soluble concentrates (SL), oil miscible liquids (OL), ultra low volume liquids (UL), emulsifiable concentrates (EC), emulsions (both oil in water (EW) and water in oil (EO)), suspension concentrates (SC), aerosols, fogging/smoke formulations, capsule suspensions (CS) and seed dressings.
  • the formulation type chosen in any instance will depend upon the particular purpose envisaged and the physical, chemical and biological properties of the compound of formula (I).
  • Dustable powders may be prepared by mixing a compound of formula (I) with one or more solid diluents (for example natural clays, kaolin, pyrophyllite, bentonite, alumina, montmorillonite, kieselguhr, chalk, diatomaceous earths, calcium phosphates, calcium and magnesium carbonates, sulphur, lime, flours, talc and other organic and inorganic solid carriers) and mechanically grinding the mixture to a fine powder.
  • solid diluents for example natural clays, kaolin, pyrophyllite, bentonite, alumina, montmorillonite, kieselguhr, chalk, diatomaceous earths, calcium phosphates, calcium and magnesium carbonates, sulphur, lime, flours, talc and other organic and inorganic solid carriers
  • Soluble powders can be prepared by mixing a compound of formula (I) with one or more water-soluble inorganic salts (such as sodium bicarbonate, sodium carbonate or magnesium sulphate) or one or more water-soluble organic solids (such as a polysaccharide) and, optionally, one or more wetting agents, one or more dispersing agents or a mixture of said agents to improve water dispersibility/solubility. The mixture is then ground to a fine powder. Similar compositions may also be granulated to form water soluble granules (SG).
  • water-soluble inorganic salts such as sodium bicarbonate, sodium carbonate or magnesium sulphate
  • water-soluble organic solids such as a polysaccharide
  • WP Wettable powders
  • WG Water dispersible granules
  • Granules may be formed either by granulating a mixture of a compound of formula (I) and one or more powdered solid diluents or carriers, or from pre-formed blank granules by absorbing a compound of formula (I) (or a solution thereof, in a suitable agent) in a porous granular material (such as pumice, attapulgite clays, fuller's earth, kieselguhr, diatomaceous earths or ground corn cobs) or by adsorbing a compound of formula (I) (or a solution thereof, in a suitable agent) on to a hard core material (such as sands, silicates, mineral carbonates, sulphates or phosphates) and drying if necessary.
  • a hard core material such as sands, silicates, mineral carbonates, sulphates or phosphates
  • Agents which are commonly used to aid absorption or adsorption include aliphatic and aromatic petroleum solvents, alcohols, polyvinyl acetates, polyvinyl alcohols, ethers, ketones, esters, dextrins, sugars and vegetable oils.
  • One or more other additives may also be included in granules (for example an emulsifying agent, wetting agent or dispersing agent).
  • Soluble concentrates can be prepared by dissolving a compound of formula (I) in water or an organic solvent, such as a ketone, alcohol or glycol ether. These solutions may contain a surface active agent (for example to improve water dilution or prevent crystallisation in a spray tank).
  • Emulsifiable concentrates (EC) or oil in water emulsions (EW) may be prepared by dissolving a compound of formula (I) in an organic solvent (optionally containing one or more wetting agents, one or more emulsifying agents or a mixture of said agents) and, for an emulsion, subsequently adding, under high shear agitation, the mixture to water (which may contain one or more wetting agents, one or more emulsifying agents or a mixture of said agents).
  • Suitable organic solvents for use in ECs include ketones (such as cyclohexanone or methylcyclohexanone) and alcohols (such as benzyl alcohol, furfuryl alcohol or butanol).
  • Suitable organic solvents for use in ECs or EWs include vegetable oils, N-substituted pyrrolidones, glycol ethers, chlorinated hydrocarbons (such as chlorobenzenes) and aromatic solvents (such as alkylbenzenes or alkylnaphthalenes).
  • SC Suspension concentrates
  • SCs may comprise aqueous or non-aqueous suspensions of finely divided insoluble solid particles of a compound of formula (I).
  • SCs may be prepared by ball or bead milling the solid compound of formula (I) in a suitable medium with one or more dispersing agents, to produce a fine particle suspension of the compound.
  • wetting agents may be included in the composition and a suspending agent may be included to reduce the rate at which the particles settle.
  • Aerosol formulations comprise a compound of formula (I) and a suitable propellant (for example n-butane).
  • a compound of formula (I) may also be dissolved or dispersed in a suitable medium (for example water or a water miscible liquid, such as n-propanol) to provide compositions for use in non-pressurised, hand-actuated spray pumps.
  • a compound of formula (I) can be mixed in the dry state with a pyrotechnic mixture to form a composition suitable for generating, in an enclosed space, a smoke containing the compound.
  • Capsule suspensions (CS) can be prepared in a manner similar to the preparation of
  • compositions may provide for controlled release of the compound of formula (I) and they can be used for seed treatment.
  • a compound of formula (I) may also be formulated in a biodegradable polymeric matrix to provide a slow, controlled release of the compound.
  • a composition may include one or more additives to improve the biological performance of the composition (for example by improving wetting, retention or distribution on surfaces; resistance to rain on treated surfaces; or uptake or mobility of a compound of formula (I)).
  • additives include surface active agents, spray additives based on oils, for example certain mineral oils or natural plant oils (such as soya bean and rape seed oil), and blends of these with other bio-enhancing adjuvants.
  • a compound of formula (I) may also be formulated for use as a seed treatment, for example as a powder composition, including a powder for dry seed treatment (DS), a water soluble powder (SS) or a water dispersible powder for slurry treatment (WS), or as a liquid composition, including a fiowable concentrate (FS), a solution (LS) or a capsule suspension (CS).
  • DS powder for dry seed treatment
  • SS water soluble powder
  • WS water dispersible powder for slurry treatment
  • CS capsule suspension
  • the preparations of DS, SS, WS, FS and LS compositions are very similar to those of, respectively, DP, SP, WP, SC and SL compositions described above.
  • Compositions for treating seed may include an agent for assisting the adhesion of the composition to the seed (for example a mineral oil).
  • Wetting agents, dispersing agents and emulsifying agents may be of the cationic, anionic, amphoteric or non-ionic type.
  • Suitable agents of the cationic type include quaternary ammonium compounds (for example cetyltrimethyl ammonium bromide), imidazolines and amine salts.
  • Suitable anionic agents include alkali metals salts of fatty acids, salts of aliphatic monoesters of sulphuric acid (for example sodium lauryl sulphate), salts of sulphonated aromatic compounds (for example sodium dodecylbenzenesulphonate, butylnaphthalene sulphonate and mixtures of sodium diisopropyl- and triisopropyl-naphthalene sulphonates), ether sulphates, alcohol ether sulphates (for example sodium laureth-3 -sulphate), ether carboxylates (for example sodium laureth-3-carboxylate), phosphate esters (products from the reaction between one or more fatty alcohols and phosphoric acid (predominately monoesters) or phosphorus pentoxide (pre
  • Suitable agents of the non-ionic type include condensation products of ethylene oxide with fatty alcohols (such as oleyl alcohol or cetyl alcohol) or with alkylphenols (such as octylphenol, nonylphenol or octylcresol); partial esters derived from long chain fatty acids or hexitol anhydrides; condensation products of said partial esters with ethylene oxide; block polymers (comprising ethylene oxide and propylene oxide); alkanolamides; simple esters (for example fatty acid polyethylene glycol esters) or their ethoxylated derivatives; amine oxides (for example lauryl dimethyl amine oxide); and lecithins.
  • fatty alcohols such as oleyl alcohol or cetyl alcohol
  • alkylphenols such as octylphenol, nonylphenol or octylcresol
  • partial esters derived from long chain fatty acids or hexitol anhydrides condensation products of said partial esters
  • Suitable suspending agents include hydrophilic colloids (such as polysaccharides, polyvinylpyrrolidone or sodium carboxymethylcellulose) and swelling clays (such as bentonite or attapulgite).
  • hydrophilic colloids such as polysaccharides, polyvinylpyrrolidone or sodium carboxymethylcellulose
  • swelling clays such as bentonite or attapulgite
  • compositions for use as aqueous preparations are generally supplied in the form of a concentrate containing a high proportion of the active ingredient, the concentrate being added to water before use.
  • These concentrates which may include SLs, SCs, ECs, EWs, SGs, SPs, WPs, WGs and CSs, are often required to withstand storage for prolonged periods and, after such storage, to be capable of addition to water to form aqueous preparations which remain homogeneous for a sufficient time to enable them - 14 -
  • aqueous preparations may contain varying amounts of a compound of formula (I) (for example 0.0001 to 10%, by weight) depending upon the purpose for which they are to be used.
  • a compound of formula (I) can be used in mixtures with fertilisers (for example nitrogen-, potassium- or phosphorus-containing fertilisers).
  • fertilisers for example nitrogen-, potassium- or phosphorus-containing fertilisers.
  • Suitable formulation types include granules of fertiliser.
  • the mixtures suitably contain up to 25% by weight of the compound of formula (I).
  • the invention therefore also provides a fertiliser composition
  • a fertiliser composition comprising a fertiliser and a compound of formula (I).
  • the compositions are applied to the pests, to a locus of the pests (such as a habitat of the pests, or a growing plant liable to infestation by the pests) by any of the known means of applying pesticidal compositions, for example by dusting, dipping, spraying or injecting or by irrigation, distribution or incorporation of a composition (such as a granular composition or a composition packed in a water-soluble bag) in soil or an aqueous environment.
  • a composition such as a granular composition or a composition packed in a water-soluble bag
  • the compound of formula (I) may be the sole active ingredient of the composition or it may be admixed with one or more additional active ingredients such as an insecticide, synergist, herbicide, fungicide or plant growth regulator where appropriate.
  • An additional active ingredient may: provide a composition having a broader spectrum of activity or increased persistence at a locus; synergise the activity or complement the activity (for example by increasing the speed of effect or overcoming repellency) of the compound of formula (I); or help to overcome or prevent the development of resistance to individual components.
  • the particular additional active ingredient will depend upon the intended utility of the composition.
  • Suitable pesticides include the following: a) Pyrethroids, such as permethrin, cypermethrin, fenvalerate, esfenvalerate, deltamethrin, cyhalothrin (in particular lambda-cyhalothrin), bifenthrin, fenpropathrin, cyfluthrin, tefluthrin, fish safe pyrethroids (for example ethofenprox), natural pyrethrin, tetramethrin, s-bioallethrin, fenfluthrin, prallethrin or 5-benzyl-3-furylmethyl-(E)-(lR,3S)-2,2-dimethyl- 3-(2-oxothiolan-3-ylidenemethyl)cyclopropane carboxylate; b) Organophosphates, such as profenofos, sulprofos, acephate
  • Chloronicotinyl compounds such as imidacloprid, acetamiprid, nitenpyram or thiomethoxam; m) Diacylhydrazines, such as tebufenozide; n) Diphenyl ethers, such as diofenolan or pyriproxifen; o) Indoxacarb; p) Chlorfenapyr; or q) Pymetrozine.
  • other pesticides having particular targets may be employed in the composition, if appropriate for the intended utility of the composition.
  • selective insecticides for particular crops for example stemborer specific insecticides for use in rice (such as cartap or buprofezin) can be employed.
  • insecticides or acaricides specific for particular insect species/stages may also be included in the compositions (for example acaricidal ovo-larvicides, such as clofentezine, flubenzimine, hexythiazox or tetradifon; acaricidal - 16 -
  • motilicides such as dicofol or propargite
  • acaricides such as bromopropylate or chlorobenzilate
  • growth regulators such as hydramethylnon, cyromazine, methoprene, chlorfluazuron or diflubenzuron
  • synergists for use in the compositions include piperonyl butoxide, sesamex, safroxan and dodecyl imidazole.
  • Suitable herbicides, fungicides and plant-growth regulators for inclusion in the compositions will depend upon the intended target and the effect required.
  • a rice selective herbicide which can be included is propanil.
  • An example of a plant growth regulator for use in cotton is PIXTM.
  • Examples of fungicides for use in rice include blasticides, such as blasticidin-S.
  • Some mixtures may comprise active ingredients which have significantly different physical, chemical or biological properties such that they do not easily lend themselves to the same conventional formulation type.
  • other formulation types may be prepared.
  • one active ingredient is a water insoluble solid and the other a water insoluble liquid
  • SE suspoemulsion
  • the invention is illustrated by the following Examples, in which the ingredients below are referred to by their Registered Trade Marks and have the following compositions.
  • EXAMPLE 1 This Example illustrates the preparation of endo-2-mefhyl-endo-cyano-3-(5- chloropyrid-3-yl)-8-(2,2,2-trifluoroethyl)-8-azabicyclol[3.2.1]octane (Compound No. 1 of Table I).
  • Step 1 n-Butyllithium (10.63ml of a 2.5M solution in hexane) was added to a solution of diisopropylamine in tetrahydrofuran (40ml) at -70°C.
  • the resulting mixture was allowed to warm to room temperature, kept at room temperature for 30minutes and cooled to -70°C after which a solution of 8-(2,2,2-trifluoroethyl)-8-azabicyclo[3.2.1]octan-3-one (5.00g) in tetrahydrofuran (60ml) was added over 30minutes at -50°C. After 2hours at below -50°C the mixture was warmed to about -5°C and methyl iodide (17.15g) added rapidly in one portion. The resulting mixture was allowed to stand at room temperature for 2'/ lays.
  • reaction mixture was poured into water (500ml) and the aqueous extracted with chloroform (8x100ml). The organic extracts were combined, washed with brine (4x100ml), dried (MgSO 4 ), filtered and evaporated in vacuo to leave a brown oil.
  • the reaction mixture was diluted with hexane and filtered.
  • the filtrate was dried (MgSO 4 ), filtered, dried again (MgSO 4 ), filtered again and the resulting filtrate concentrated in vacuo to leave an orange oil.
  • the oil was washed with hexane, the hexane washings were filtered through HIFLOTM and concentrated in vacuo to leave a mix of a yellow oil and a - 18 -
  • reaction mixture was poured into brine and extracted (twice) with ethyl acetate.
  • organic extracts were combined, dried (MgSO 4 ), filtered and evaporated in vacuo to leave a brown gum which was purified by column chromatography (silica; hexane:ethyl acetate 90:10) to give the title compound (as a racemate) as a clear oil which solidified on scratching (0.369g, mp 73-76°C).
  • the two enantiomers of the title compound could by separated using a ChiracelTM 00 column (25cm x 4.6mm) eluting with hexane:ethyl acetate 98:2.
  • EXAMPLE 2 This Example illustrates the preparation of endo-2-methyl-endo-3-cyano-3-(5- chloropyrid-3-yl)-8-methyl-8-azabicyclo[3.2.1]octane (Compound No. 2 of Table I).
  • Step l Sodium hydride (8.8g of a 60% suspension in oil) was washed with hexane, suspended in tetrahydrofuran (400ml) and cooled to about -5°C. To this was added a solution of ethyl 2-methylacetoacetate (31.3g) in tetrahydrofuran (200ml) over 45minutes keeping the temperature below 0°C.
  • Step 2 Succinic dialdehyde (14.78ml of a 40% by weight solution in water) was added to a mixture of diethyl l-methyl-acetone-l,3-dicarboxylate (12.252g) and water (6ml). The resulting mixture was cooled in an ice bath and a solution of methylamine hydrochloride (0.9equivalents) was added. The reaction mixture was allowed to warm to room temperature and stand overnight.
  • the reaction mixture was diluted with water (50ml), made basic by the addition of potassium carbonate and extracted with dichloromethane (6x100ml). The organic extracts were combined, washed with brine (2x100ml), dried (MgSO 4 ), filtered and evaporated in vacuo to leave an oil.
  • the oil was heated in hydrochloric acid (6N, 50ml) for 3hours. Water was added and the mixture made basic by the addition of potassium carbonate. The resulting mixture was extracted with dichloromethane (8x100ml). The extracts were combined, washed with brine (400ml), dried (MgSO 4 ), filtered and evaporated in vacuo to leave a brown oil.
  • the aqueous layer was made basic by the addition of potassium carbonate and extracted with ethyl acetate.
  • the organic extracts were dried (MgSO 4 ), filtered and evaporated in vacuo to leave a brown oil which was purified by column chromatography (silica; dichloromethane, dichloromethane: methanol 98:2, finally dichloromethane :mefhanol 95:5) to give the title compound as an orange solid (0.138g).
  • EXAMPLE 3 This Example illustrates the preparation of endo-2-methyl-endo-cyano-3-(5- bromopyrid-3-yl)-8-(2,2,2-trifluoroethyl)-8-azabicyclol[3.2. IJoctane (Compound No. 3 of Table I).
  • n-Butyllithium (1.36ml of a 2.5M solution in hexane) was added dropwise to a solution of diisopropylamine (0.347g) in tetrahydrofuran (2.5ml) at -65°C under nitrogen. The resulting mixture was allowed to warm to 0°C for 15minutes and was then cooled to -65°C.
  • reaction mixture was partitioned between hydrochloric acid (2M) and ethyl acetate.
  • the aqueous layer was made basic by the addition of potassium carbonate and extracted with ethyl acetate.
  • the organic extracts were dried (MgSO 4 ), filtered and evaporated in vacuo to leave a brown oil which was purified by column chromatography (silica; hexane:ethyl acetate 1:9) to give the title compound as a white solid (0.072g, mp 67-69°C).
  • EXAMPLE 4 This Example illustrates an emulsifiable concentrate composition which is readily convertible, by addition to water, into a preparation suitable for spraying purposes.
  • the emulsifiable concentrate has the following composition:
  • EXAMPLE 5 This Example illustrates a wettable powder composition which is readily convertible, by addition to water, into a preparation suitable for spraying purposes.
  • the wettable powder has the following composition:
  • EXAMPLE 6 This Example illustrates a dustable powder which may be applied directly to plants or other surfaces.
  • the dustable powder has the following composition:
  • This Example illustrates an oil miscible liquid formulation suitable for application by ultra low volume techniques after mixing with an organic diluent.
  • the formulation has the following composition:
  • This Example illustrates a capsule suspension concentrate which is readily convertible, by addition to water, into a preparation suitable for application as an aqueous spray.
  • the capsule suspension concentrate has the following composition:
  • EXAMPLE 9 This Example illustrates a ready for use granular formulation that is prepared from a pre-formed granular carrier.
  • the granular formulation has the following composition:
  • This Example illustrates a ready for use granular formulation that is prepared by granulation of the powdered components.
  • the granular formulation has the following composition:
  • This Example illustrates an aqueous suspension concentrate composition which is readily convertible, by addition to water, into a preparation suitable for spraying purposes.
  • the suspension concentrate has the following composition:
  • EXAMPLE 12 This Example illustrates a water dispersible granule formulation which is readily convertible, by addition to water, into a preparation suitable for spraying purposes.
  • the water dispersible granule has the following composition:
  • EXAMPLE 13 This Example illustrates the insecticidal properties of compounds of formula (I).
  • the activities of individual compounds of formula (I) were determined using a variety of pests. With the exception of nematodes, the pests were treated with a liquid composition containing 500 parts per million (ppm) by weight of a compound unless otherwise stated. Each composition was made by dissolving the compound in an acetone and ethanol (50:50 by volume) mixture and diluting the solution with water containing 0.05% by volume of a wetting agent, SYNPERONIC NP8, until the liquid composition contained the required concentration of the compound.
  • a wetting agent SYNPERONIC NP8
  • test procedure adopted with regard to each pest was essentially the same and comprised supporting a number of the pests on a medium which was usually a substrate, a host plant or a foodstuff on which the pests feed, and treating either or both the medium and the pests with a composition.
  • Pest mortality was assessed usually between two and five days after treatment.
  • Knockdown of housefly was assessed 15 minutes after treatment.
  • test procedure for nematodes involved dissolving the compound in an acetone and ethanol (50:50 by volume) mixture and diluting the solution with water to obtain a final concentration of the compound of 12.5ppm.
  • results of the tests against peach aphid are presented below.
  • the results indicate a grading of mortality (score) designated as A, B or C wherein C indicates less than 40% mortality, B indicates 40-79% mortality and A indicates 80-100%) mortality.
  • Score grading of mortality
  • Chinese cabbage leaves were infested with aphids, the infested leaves were sprayed with the test composition, and the mortality assessed after 3 days.

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  • Health & Medical Sciences (AREA)
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  • General Health & Medical Sciences (AREA)
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Abstract

L'invention concerne un composé de formule (I) dans laquelle A représente un groupe bidenté de formule -CH2-X-CH2 (où X représente méthylène, soufre ou oxygène ), X'C=CY ou X'WC-CYZ (où X', W et Z représentent, indépendamment, hydrogène, hydroxy, R6C(O)O, alcoxy, trialkylsilyloxy, cyano ou halogène, ou X' et W ou Y et Z forment un groupe carbonyle conjointement avec le carbone auquel ils sont fixés); AR représente un aryle ou un hétéroaryle éventuellement substitués; R représente hydrogène, cyano, un alkyle éventuellement substitué, un aryle éventuellement substitué, un hétéroaryle éventuellement substitué, un alcényle éventuellement substitué, un alcynyle éventuellement substitué, R3CO, sulphonyle, CS¿2?R?9 ou R7¿X'' (où X'' représente oxygène ou un groupe NR8), étant entendu que lorsque R représente un alcényle éventuellement substitué ou un alcynyle éventuellement substitué, ledit groupe n'a pas d'atome de carbone insaturé lié directement à l'azote du cycle de formule (I); R1 représente hydrogène, cyano, hydroxy, un alkyle éventuellement substitué, un alcoxy éventuellement substitué, amino, nitro, isocyanato, un hétéroaryle éventuellement substitué, amidoximido, HN=C(R?4), R4R5C=N, R10CO, R10¿CONH, un alcényle éventuellement substitué ou un alcynyle éventuellement substitué; R2 représente C¿1-2?alkyle; R?3¿ représente hydrogène, un alkyle éventuellement substitué, un aryle éventuellement substitué, un alcoxy éventuellement substitué, un alcényloxy éventuellement substitué, un aryloxy éventuellement substitué ou NH¿2 ?; R?4, R5, R7 et R8¿ représentent, indépendamment, hydrogène, un alkyle éventuellement substitué, un aryle éventuellement substitué, un alcynyle, un alcoxycarbonyle ou CO¿2H; R?6 représente hydrogène, un alkyle éventuellement substitué, un aryle éventuellement substitué, un alcoxy éventuellement substitué, un alcoxy éventuellement substitué, un alcényloxy éventuellement substitué ou un aryloxy éventuellement substitué; R9 représente hydrogène, un alkyle éventuellement substitué ou un alcényle éventuellement substitué; R10 représente hydrogène, un alkyle éventuellement substitué, un aryle éventuellement substitué, un alcoxy éventuellement substitué, un alcényloxy éventuellement substitué, un aryloxy éventuellement substitué ou NH¿2?. L'invention concerne également un sel d'addition acide, un sel d'ammonium quaternaire ou un N-oxyde dérivé du composé précité, des procédés de préparation de ces composés, les compositions les renfermant et des procédés d'utilisation de ces composés pour lutter contre les insectes, les acariens, les nématodes ou les mollusques.
PCT/GB1999/001192 1998-04-29 1999-04-19 2-alkyl-3-(hetero)aryl-8-azabicyclo[3.2.1]alcanes utilises comme pesticides WO1999055703A1 (fr)

Priority Applications (1)

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GBGB9809161.4A GB9809161D0 (en) 1998-04-29 1998-04-29 Chemical compounds
GB9809161.4 1998-04-29

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002057263A1 (fr) * 2001-01-17 2002-07-25 Syngenta Limited Octanes 8-azabicyclo "3.2.1.! utilises comme insecticides

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5366975A (en) * 1991-07-01 1994-11-22 The General Hospital Corporation Invertebrate phenylethanolamine transporter and the use thereof
WO1996037494A1 (fr) * 1995-05-24 1996-11-28 Zeneca Limited Amines biclycliques utilisees comme insecticide
WO1997043286A1 (fr) * 1996-05-13 1997-11-20 Zeneca Limited Amines bicycliques utilisees comme insecticides
WO1998007427A1 (fr) * 1996-08-22 1998-02-26 Research Triangle Institute Ligands liant des recepteurs de cocaine

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5366975A (en) * 1991-07-01 1994-11-22 The General Hospital Corporation Invertebrate phenylethanolamine transporter and the use thereof
WO1996037494A1 (fr) * 1995-05-24 1996-11-28 Zeneca Limited Amines biclycliques utilisees comme insecticide
GB2301819A (en) * 1995-05-24 1996-12-18 Zeneca Ltd Insecticidal bicyclic amines
WO1997043286A1 (fr) * 1996-05-13 1997-11-20 Zeneca Limited Amines bicycliques utilisees comme insecticides
WO1998007427A1 (fr) * 1996-08-22 1998-02-26 Research Triangle Institute Ligands liant des recepteurs de cocaine

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
A. P. KOZIKOWSKI ET AL.: "Chemistry and Biology of the 2-beta-Alkyl-3-beta-phenyl Analogues of Cocaine: Subnanomolar Affinity Ligands That Suggest a New Pharmacophore Model at the C-2 Position", J. MED. CHEM., vol. 36, no. 16, 1995, pages 3086 - 3093, XP002109337 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002057263A1 (fr) * 2001-01-17 2002-07-25 Syngenta Limited Octanes 8-azabicyclo "3.2.1.! utilises comme insecticides

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AU3615299A (en) 1999-11-16

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