WO2005082917A1 - 4-phosphorylpyrazole derivatives for pesticidal use - Google Patents

4-phosphorylpyrazole derivatives for pesticidal use Download PDF

Info

Publication number
WO2005082917A1
WO2005082917A1 PCT/EP2005/000581 EP2005000581W WO2005082917A1 WO 2005082917 A1 WO2005082917 A1 WO 2005082917A1 EP 2005000581 W EP2005000581 W EP 2005000581W WO 2005082917 A1 WO2005082917 A1 WO 2005082917A1
Authority
WO
WIPO (PCT)
Prior art keywords
alkyl
formula
compound
cycloalkyl
substituted
Prior art date
Application number
PCT/EP2005/000581
Other languages
French (fr)
Inventor
Uwe Döller
Michael Maier
Anke Kuhlmann
Daniela Jans
Pinchuk Alexander Michailovich
Marchenko Anatoliy Pavlovich
Koydan Georgiy Nikolaevich
Original Assignee
Bayer Cropscience S.A.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Bayer Cropscience S.A. filed Critical Bayer Cropscience S.A.
Publication of WO2005082917A1 publication Critical patent/WO2005082917A1/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
    • C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom
    • 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
    • A01N57/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds
    • A01N57/26—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds having phosphorus-to-nitrogen bonds
    • A01N57/32—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds having phosphorus-to-nitrogen bonds containing heterocyclic radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
    • C07F9/6503—Five-membered rings
    • C07F9/65031—Five-membered rings having the nitrogen atoms in the positions 1 and 2

Definitions

  • the invention relates to 4-phosphorylpyrazole derivatives, processes for their preparation, to compositions thereof, and to their use for the control of pests, specifically arthropods (including insects and arachnids) and helminths (including nematodes).
  • Another object of the invention is to provide new pesticides which may be used in lower dose than existing pesticides.
  • Another object of the invention is to provide new pesticides which are substantially non-emetic.
  • Another object of the invention is to provide new pesticides which are safer to the user and the environment.
  • the present invention provides a compound which is a 4-phosphorylpyrazole derivative of formula (I):
  • W is C-halogen, C-CH 3 or N;
  • R 2 is hydrogen, halogen, CH 3> NH-(C C 6 )-alkyl or N[(C C 6 )-alkyl] 2 ;
  • R 3 is (C C 3 )-haloalkyl, (C C 3 )-haloalkoxy or SF 5 ;
  • X is O or S
  • Y and Z are each independently O, S, NR a or a covalent bond
  • R a is H or (C ⁇ -C 6 )-alkyl
  • R 4 is NR 7 R 8 , OH, H, halogen, (C C 6 )-alkoxy, (d-C ⁇ J-alk l, OCO-(CrC 6 )-alkyl,
  • R 5 and R 6 are each independently H, (C 2 -C 6 )-alkenyl, (C 2 -C 6 )-haloalkenyl, (C 2 -C 6 )- alkynyl, (C 2 -C 6 )-haloalkynyl, (C 3 -C 7 )-cycloalkyl, (CH 2 ) q R 9 or (CH 2 ) q R 10 ; or are (C 2 -C 6 )-alkenyl, (C 2 -C 6 )-haloalkenyl, (C 2 -C 6 )- alkynyl, (C 2 -C 6 )-haloalkynyl, (C 3 -C 7 )-cycloalkyl, (CH 2 ) q R 9 or (CH 2 ) q R 10 ; or are (C 2 -C 6 )-alkenyl, (C 2 -C 6 )-haloalkenyl, (C
  • C 6 )-alkyl unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, (C ⁇ -C 6 )-alkoxy, (C ⁇ -C 6 )-haloalkoxy, (C 3 -C 6 )-alkenyloxy,
  • R 7 is H, (C 2 -C 6 )-alkenyl, (C 2 -C 6 )-haloalkenyl, (C 2 -C 6 )-alkynyl, (C 2 -C 6 )-haloalkynyl,
  • R 8 is H, (C 2 -C 6 )-alkynyl, CO 2 -(C ⁇ -C 6 )-alkyl, (C 3 -C 7 )-cycloalkyl, (CH 2 ) q R 9 , (CH 2 ) q R 10 , or SO 2 R 15 ; or (C ⁇ -C 6 )-alkyl, (C 2 -C 6 )-alkenyl or CO-(C ⁇ -C 6 )-alkyl which last three mentioned groups are unsubstituted or substituted by one or more R 14 radicals;
  • R 9 is phenyl unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, (C ⁇ -C 6 )-alkyl, (C ⁇ -C 6 )-haloalkyl, (C ⁇ -C 6 )-alkoxy, (d-C 6 )- haloalkoxy, CN, NO 2) S(O) p R 11 and NR 13 R 16 ;
  • R 10 is heterocyclyl unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, (C ⁇ -C 4 )-alkyl, (C ⁇ -C )-haloalkyl, (d-C )-alkoxy,
  • R 11 is (d-C 6 )-alkyl, (d-C 6 )-haloalkyl, (C 2 -C 6 )-alkenyl, (C 2 -C 6 )-haloalkenyl, (C 2 -
  • R 12 is H, (CrC 6 )-alkyl, (d-C 6 )-haloalkyl, (C 3 -C 7 )-cycloalkyl, (C C 6 )-alkyl-(C 3 -C 7 )- cycloalkyl, (CH 2 ) q R 9 or (CH 2 ) q R 10 ;
  • R 13 and R 16 are each independently H, (d-C 6 )-alkyl, (d-C 6 )-haloalkyl, (C 3 -
  • R 12 and R 13 together with the attached N atom form a five- or six-membered saturated ring which optionally contains an additional hetero atom in the ring which is selected from O, S and N, the ring being unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, (C ⁇ -C 6 )-alkyl, (d-C ⁇ )- haloalkyl and halogen;
  • R 14 is halogen, (d-C 6 )-alkoxy, (d-C 6 )-haloalkoxy, (C 3 -C 7 )-cycloalkyl, S(O) p R 11 ,
  • R 15 is (C 3 -C 7 )-cycloalkyl, (C 2 -C 6 )-alkenyl, (C 2 -C 6 )-haloalkenyl or R 10 ; or phenyl unsubstituted or substituted by one or more radicals selected from R 17 ; or is (C ⁇ -
  • C 6 )-alkyl unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, (d-C 6 )-alkoxy, (d-C 6 )-haloalkoxy, (C 2 -C 6 )-alkenyloxy,
  • R 17 is halogen, (d-C 6 )-alkyl, (d-C 6 )-haloalkyl, (C C 6 )-alkoxy, (C ⁇ -C 6 )-haloalkoxy,
  • R 18 is phenyl unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, (C ⁇ -C 6 )-alkyl, (d-C 6 )-haloalkyl, (C ⁇ -C 6 )-alkoxy, (Ci-C ⁇ )- haloalkoxy, CN, NO 2 , S(O) p R 11 , NR 12 R 13 , COR 11 , COR 9 , CONR 12 R 13 , SO 2 NR 12 R 13 ,
  • R 19 is a heteroaromatic radical selected from the group consisting of pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, thienyl, thiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, furyl, pyrrolyl, pyrazolyl, imidazolyl and triazolyl, which groups are unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, (C ⁇ -C6)-alkyl, (C C 6 )-haloalkyl and (d-C 6 )-alkoxy;
  • V is H, (CrC ⁇ )-alkyl, (C C 6 )-haloalkyl, (C 2 -C 6 )-alkenyl, (C 2 -C 6 )-alkynyl, (CH 2 ) q R 9 ,
  • Q is (C C 6 )-alkyl or CH 2 R 9 ;
  • R 20 is (C ⁇ -C 6 )-alkyl or (d-C 6 )-haloalkyl; m, n, p and r are each independently zero, one or two; q is 0 or 1 to 4; and each heterocyclyl in the above-mentioned radicals is independently a heterocyclic radical having 3 to 6 ring atoms and 1 , 2 or 3 hetero atoms in the ring selected from the group consisting of N, O and S; or a pesticidally acceptable salt thereof.
  • the invention also encompasses any stereoisomer, enantiomer or geometric isomer, and mixtures thereof.
  • Suitable salts with bases include alkali metal (e.g. sodium and potassium), alkaline earth metal (e.g. calcium and magnesium), ammonium and amine (e.g. diethanolamine, triethanolamine, octylamine, morpholine and dioctylmethylamine) salts.
  • Suitable acid addition salts e.g. formed by compounds of formula (I) containing an amino group, include salts with inorganic acids, for example hydrochlorides, sulphates, phosphates and nitrates and salts with organic acids for example acetic acid.
  • Halogen atom means fluorine, chlorine, bromine or iodine.
  • halo before the name of a radical means that this radical is partially or completely halogenated, that is to say, substituted by F, CI, Br, or I, in any combination, preferably by F or CI.
  • Alkyl groups and portions thereof may be straight- or branched-chain.
  • (C ⁇ -C 6 )-alkyl is to be understood as meaning an unbranched or branched hydrocarbon radical having 1 , 2, 3, 4, 5 or 6 carbon atoms, such as, for example a methyl, ethyl, propyl, isopropyl, 1 -butyl, 2-butyl, 2-methylpropyl or tert- butyl radical.
  • (CrC 6 )Haloalkyl means an alkyl group mentioned under the expression
  • (C ⁇ -C 6 )alkyl in which one or more hydrogen atoms are replaced by the same number of identical or different halogen atoms, such as monohaloalkyl, perhaloalkyl,
  • (d-C 6 )Alkoxy means an alkoxy group whose carbon chain has the meaning given under the expression "(CrC ⁇ Jalkyl”.
  • “Haloalkoxy” is, for example, OCF 3 , OCHF 2 ,
  • (C 2 -C 6 )Alkenyl means an unbranched or branched non-cyclic carbon chain having a number of carbon atoms which corresponds to this stated range and which contains at least one double bond which can be located in any position of the respective unsaturated radical.
  • (C 2 -C 6 )Alkenyl accordingly denotes, for example, the vinyl, allyl, 2-methyl-2-propenyl, 2-butenyl, pentenyl, 2-methylpentenyl or the hexenyl group.
  • (C 2 -C 6 )Alkynyl means an unbranched or branched non-cyclic carbon chain having a number of carbon atoms which corresponds to this stated range and which contains one triple bond which can be located in any position of the respective unsaturated radical.
  • “(C 2 -C 6 )Alkynyl” accordingly denotes, for example, the propargyl, 1-methyl-2-propynyl, 2-butynyl or 3-butynyl group.
  • Cycloalkyl groups preferably have from three to seven carbon atoms in the ring and are optionally substituted by halogen or alkyl.
  • (C ⁇ -C 6 )-alkyl-(C 3 -C 7 )-cycloalkyr means a (d-C 6 )alkyl group which is substituted by a (C 3 -C 7 )cycloalkyl ring.
  • COCH 2 -(C ⁇ -C )-alkoxy means for example methoxyacetyi.
  • alkyl substituted by cycloalkyl is cyclopropylmethyl; an example of alkyl substituted by alkoxy is methoxymethyl (CH 2 OCH 3 ); and an example of alkyl substituted by alkylthio is methylthiomethyl (CH 2 SCH 3 ).
  • CO 2 -(C ⁇ -C 6 )-Alkyl means a (C ⁇ -C 6 )-alkoxycarbonyl radical.
  • CO 2 -(C ⁇ -C 4 )-Alkyl-(C 3 -C 7 )-cycloalkyl means a (C ⁇ -C )-alkoxycarbonyl radical which alkoxy moiety is substituted by a (C 3 -C 7 )-cycloalkyl radical.
  • (C ⁇ -C )-Alkyl-(C 3 -C )-cycloalkyl means a (C ⁇ -C 4 )-alkyl group which is substituted by a (C 3 -C 7 )-cycloalkyl ring.
  • heterocyclyl group can be saturated, unsaturated or heteroaromatic; it preferably contains one or more, in particular 1, 2 or 3, hetero atoms in the heterocyclic ring, preferably selected from the group consisting of N, O and S; it is preferably an aliphatic heterocyclyl radical having 3 to 7 ring atoms or a heteroaromatic radical having 5 to 7 ring atoms.
  • the "heterocyclyl” group may be unsubstituted or substituted, preferably by one or more radicals (preferably 1, 2 or 3 radicals) selected from the group consisting of halogen, alkoxy, haloalkoxy, alkylthio, hydroxyl, amino, nitro, carboxyl, cyano, alkoxycarbonyl, alkylcarbonyl, formyl, carbamoyl, mono- and dialkylaminocarbonyl, substituted amino such as acylamino, mono- and dialkylamino, and alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkyl and haloalkyl, and additionally also oxo.
  • the oxo group can also be present at those hetero ring atoms where various oxidation numbers are possible, for example in the case of N and S.
  • pests means arthropod pests (including insects and arachnids), and helminths (including nematodes).
  • R 1 is CN or CSNH 2 (more preferably R 1 is CN).
  • W is C-CI or N (more preferably W is C-CI).
  • R 2 is CI.
  • R 3 is CF 3 or OCF 3 (more preferably R 3 is CF 3 ).
  • X is O.
  • Y is a covalent bond
  • R 4 is NR 7 R 8 .
  • R 5 and R 6 are each independently (C 3 -C 4 )-alkenyl, (C 3 -C )-haloalkenyl,
  • (C ⁇ -C 3 )-alkyl unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, (d-C 3 )-alkoxy, (d-C 3 )-haloalkoxy, (C 3 -C 4 )-alkenyloxy,
  • R 5 and R 6 are each independently (C ⁇ -C 3 )-alkyl or (CH 2 ) q R 9 , wherein q is 0 or 1.
  • R 7 is H, (C 3 -C )-alkenyl, (C 3 -C 4 )-haloalkenyl, (C 3 -C )-alkynyl, (C 3 -
  • CONR 12 R 13 CO 2 -(CH 2 ) q R 10 , (CH 2 ) q R 9 , (CH 2 ) q R 10 , COR 12 or COCH 2 -(d-C 3 )-alkoxy; or (CrC 6 )-alkyl unsubstituted or substituted by one or more R 14 radicals.
  • R 7 is H, (C 1 -C 3 )-alkyl unsubstituted or substituted by S(O) p (C ⁇ -C 3 )- alkyl.
  • R 8 is H, (C 3 -C 4 )-alkynyl, CO 2 -(d-C 3 )-alkyl r (C 3 -C 6 )-cycloalkyl or SO 2 R 15 ; or (C ⁇ -C 3 )-alkyl, (C 3 -C 4 )-alkenyl or CO-(C C 3 )-alkyl which last three mentioned groups are unsubstituted or substituted by one or more R 14 radicals.
  • R ⁇ is H or (C C 3 )-alkyl.
  • a preferred class of compounds of formula (I) are those in which:
  • R 1 is CN or CSNH 2 (more preferably R 1 is CN);
  • W is C-CI or N
  • R 2 is CI
  • R 3 is CF 3 or OCF 3 (more preferably R 3 is CF 3 );
  • R 4 is NR 7 R 8 ;
  • R 5 and R 6 are each independently H, (C 3 -C 4 )-alkenyl, (C 3 -C 4 )-haloalkenyl, (C 3 -C )- alkynyl, (C 3 -C 4 )-haloalkynyl, (C 3 -C 6 )-cycloalkyl, (CH 2 ) q R 9 or (CH 2 ) q R 10 ; or are (d-
  • C 3 )-alkyl unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, (CrC 3 )-alkoxy, (CrC 3 )-haloalkoxy, (C 3 -C )-alkenyloxy,
  • R 7 is H, (C 3 -C 4 )-alkenyl, (C 3 -C 4 )-haloalkenyl, (C 3 -C 4 )-alkynyl, (C 3 -C 4 )-haloalkynyl,
  • R 8 is H, (C 3 -C 4 )-alkynyl, CO 2 -(d-C 3 )-alkyl, (C 3 -C 6 )-cycloalkyl or SO 2 R 15 ; or (C 1 -C 3 )- alkyl, (C 3 -C )-alkenyl or CO-(d-C 3 )-alkyl which last three mentioned groups are unsubstituted or substituted by one or more R 14 radicals.
  • a further preferred class of compounds of formula (I) are those wherein:
  • R 1 is CN or CSNH 2 (more preferably R 1 is CN);
  • W is C-CI
  • R 2 is CI
  • R 3 is CF 3 ;
  • R 4 is NH 2 or NHCH 3 (more preferably R 4 is NHCH 3 );
  • X is O or S
  • Y and Z are each O, S or a covalent bond
  • R 5 and R 6 are each independently H, (C 3 -C 4 )-alkenyl, (C 3 -C 4 )-haloalkenyl, (C 3 -C 4 )- alkynyl, (C 3 -C 4 )-haloalkynyl, (C 3 -C 6 )-cycloalkyl, (CH 2 ) q R 9 or (CH 2 ) q R 10 ; or are (d-
  • C 3 )-alkyl unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, (d-C 3 )-alkoxy, (d-C 3 )-haloa!koxy, (C 3 -C 4 )-alkenyioxy,
  • R 7 is H, (C 3 -C 4 )-alkenyl, (C 3 -C 4 )-haloalkenyl, (C 3 -C 4 )-alkynyl, (C 3 -C 4 )-haloalkynyl,
  • R 8 is H, (C 3 -C 4 )-alkynyl, CO 2 -(d-C 3 )-alkyl, (C 3 -C 6 )-cycloalkyl or SO 2 R 15 ; or (d-C 3 )- alkyl, (C 3 -C 4 )-alkenyl or CO-(C ⁇ -C 3 )-alkyl which last three mentioned groups are unsubstituted or substituted by one or more R 4 radicals.
  • Y and Z are each O, S or a covalent bond
  • R 5 and R 6 are each independently H, (d-C 6 )-alkyl, (C 2 -C 6 )-alkenyl, (C 2 -C 6 )-alkynyl, (C 3 -C 7 )-cycloalkyl, (d-C 6 )-alkyl-(C 3 -C 7 )-cycloalkyl, (CH 2 ) q R 9 or (CH 2 ) q pyridyl.
  • a further preferred class of compounds of formula (I) are those wherein:
  • R 1 is CN
  • W is C-CI
  • R 2 is CI
  • R 3 is CF 3 ;
  • R 4 is NR 7 R 8 ;
  • X is O
  • Y and Z are each a covalent bond
  • R 5 and R 6 are each the same or different (d-C 6 )-alkyl
  • R 7 is H, (C 2 -C 6 )-aIkenyl, (C 2 -C 6 )-alkynyl, (C 3 -C 7 )-cycloalkyl, (CH 2 ) q R 9 or
  • R 8 is H, (C 2 -C 6 )-alkenyl, (C 2 -C 6 )-alkynyl, CO 2 -(C C 6 )-alkyl, (C 3 -C 7 )-cycloalkyl,
  • R 15 is (C C 6 )-alkyl unsubstituted or substituted by R 18 .
  • the compounds of general formula (I) can be prepared by the application or adaptation of known methods (i.e. methods heretofore used or described in the chemical literature.
  • R 5 and R 6 are as defined above with the exclusion of H, and X , Y and Zare as defined above.
  • a base is optionally present in the reaction which is generally performed in an inert solvent such as tetrahydrofuran, dioxan, acetonitrile, toluene, diethyl ether, dichloromethane, dimethylsulfoxide or N.N-dimethylformamide, at a temperature of from 0°C to 150°C, preferably from 20°C to 100°C.
  • the base is generally an alkali metal hydroxide such as potassium hydroxide, an alkali metal hydride such as sodium hydride, an alkali metal carbonate such as potassium carbonate or sodium carbonate, an alkali metal alkoxide such as sodium methoxide, an alkaline earth metal carbonate such as calcium carbonate, or an organic base such as a tertiary amine, for example triethylamine or ethyldiisopropylamine, or pyridine, or 1 ,8-diazabicyclo[5.4.0]undec-7-en (DBU).
  • alkali metal hydroxide such as potassium hydroxide
  • an alkali metal hydride such as sodium hydride
  • an alkali metal carbonate such as potassium carbonate or sodium carbonate
  • an alkali metal alkoxide such as sodium methoxide
  • an alkaline earth metal carbonate such as calcium carbonate
  • organic base such as a tertiary amine, for example trie
  • the hydrolysis is generally performed using an acid such as hydrochloric acid or 4-toluenesulfonic acid, optionally in a solvent such as dioxan, at a temperature of from 0°C to 100°C.
  • compounds of formula (I) wherein R 5 and/or R 6 is H, Y and Z are each O, S or NR a , R 1 is CN, and the other values are as defined above, may be prepared by the hydrolysis of the corresponding compound of formula (I) in which R 5 and/or R ⁇ is (d-C 6 )-alkyl, benzyl or trialkylsilyl such as trimethylsilyl.
  • the hydrolysis reaction is generally performed using an acid such as trifluoroacetic acid or hydrochloric acid optionally in a solvent such as dioxan.
  • an oxidant preferably hydrogen peroxide, in an inert solvent for example dichloromethane or dioxan, at a temperature of from 0°C to 50°C.
  • compounds of formula (I) wherein R 1 is CSNH 2 may be prepared by the reaction of the corresponding compound of formula (I) wherein R 1 is CN, with an alkali or alkaline earth metal hydrosulfide, such as lithium, potassium, calcium or preferably sodium hydrosulfide, in an inert solvent for example N,N-dimethylformamide, pyridine, dioxan, tetrahydrofuran, sulfolane, dimethyl sulfoxide, methanol or ethanol at a temperature of from -35°C to 50°C preferably 0°C to 30°C.
  • an alkali or alkaline earth metal hydrosulfide such as lithium, potassium, calcium or preferably sodium hydrosulfide
  • the hydrosulfide may be generated in situ by treatment with H 2 S in the presence of an organic base, such as a metal alkoxide or trialkylamine or an inorganic base, such as an alkaline or alkaline earth metal hydroxide or a carbonate, such as sodium, potassium or ammonium carbonate.
  • an organic base such as a metal alkoxide or trialkylamine or an inorganic base, such as an alkaline or alkaline earth metal hydroxide or a carbonate, such as sodium, potassium or ammonium carbonate.
  • a metal complexing agent such as a crown ether, can be of benefit in accelerating the reaction.
  • the reaction of hydrosulfide salt with the compound of formula (I) wherein R 1 is CN, can also be conducted in a two-phase water/organic solvent system using a phase transfer catalyst such as a crown ether or a tetraalkylammonium salt such as tetra-n- butylammonium bromide or benzyltrimethylammonium chloride.
  • a phase transfer catalyst such as a crown ether
  • a tetraalkylammonium salt such as tetra-n- butylammonium bromide or benzyltrimethylammonium chloride.
  • Organic solvents suitable for use in a two-phase system with water include benzene, toluene, dichloromethane, 1-chlorobutane and methyl tertiary-butyl ether.
  • compounds of formula (I) wherein R 1 is CSNH 2 may be prepared by the reaction of the corresponding compound of formula (I) wherein R 1 is CN, with a bis(trialkylsilyl)sulfide, preferably bis(trimethylsilyl)sulfide, in the presence of a base generally an alkali metal alkoxide such as sodium methoxide, in a solvent such as N,N-dimethylformamide, at a temperature of from 0°C to 60°C.
  • a base generally an alkali metal alkoxide such as sodium methoxide
  • solvent such as N,N-dimethylformamide
  • reaction is generally performed in the presence of a base, for example an alkali metal hydride such as sodium hydride, or an alkali metal alkoxide such as potassium tert-butoxide, in an inert solvent such as tetrahydrofuran at a temperature from 0 to 60°C.
  • a base for example an alkali metal hydride such as sodium hydride, or an alkali metal alkoxide such as potassium tert-butoxide, in an inert solvent such as tetrahydrofuran at a temperature from 0 to 60°C.
  • an alkali metal carbonate such as potassium carbonate
  • an organic base such as a trialkylamine, for example triethylamine or N,N-diisopropylethylamine
  • an inert solvent such as acetone
  • the base is preferably an alkali metal bicarbonate such as sodium bicarbonate
  • the solvent is for example dichloromethane
  • the temperature is from 0°C to the reflux temperature of the solvent.
  • V is as defined above with the exclusion of H, and L 1 is a leaving group.
  • L 1 is preferably halogen, alkylsulfonyloxy or arylsulfonyloxy (more preferably chlorine, bromine, iodine, methylsulfonyloxy or p- toluenesulfonyloxy).
  • the reaction is generally performed in an inert solvent such as tetrahydrofuran, dioxan, acetonitrile, toluene, diethyl ether, dichloromethane, dimethylsulfoxide or N,N-dimethylformamide, at a temperature of from -30°C to 200°C, preferably at 20°C to 100°C.
  • an inert solvent such as tetrahydrofuran, dioxan, acetonitrile, toluene, diethyl ether, dichloromethane, dimethylsulfoxide or N,N-dimethylformamide
  • a base is optionally present in the reaction, and when present is preferably an alkali metal hydroxide such as potassium hydroxide, an alkali metal hydride such as sodium hydride, an alkali metal carbonate such as potassium carbonate or sodium carbonate, an alkali metal alkoxide such as sodium methoxide, an alkaline earth metal carbonate such as calcium carbonate, or an organic base such as a tertiary amine, for example triethylamine or ethyldiisopropylamine, or pyridine, or 1 ,8-diazabicyclo[5.4.0]undec-7-en (DBU).
  • an alkali metal hydroxide such as potassium hydroxide
  • an alkali metal hydride such as sodium hydride
  • an alkali metal carbonate such as potassium carbonate or sodium carbonate
  • an alkali metal alkoxide such as sodium methoxide
  • an alkaline earth metal carbonate such as calcium carbonate
  • organic base such as
  • VIII is preferably an acid halide
  • L 1 is preferably chlorine or bromine (more preferably chlorine).
  • the reaction is generally performed using similar bases, solvents and temperatures as are employed for the alkylations.
  • VIII is preferably a sulfonyl halide and L 1 is preferably chlorine or bromine (more preferably chlorine).
  • the reaction is generally performed using similar bases, solvents and temperatures as are employed for the alkylations.
  • compounds of formula (I) wherein R 4 is NR 7 R 8 , one of R 7 or R 8 is as defined above with the exclusion of H, R 1 is CN and the other values are as defined above, may be prepared by the alkylation, acylation or sulfonylation of the corresponding compound of formula (I) in which R 4 is NHR 7 or NHR 8 , wherein R 7 or R 8 are as defined above, with a compound of formula (IX) or (X) respectively:
  • R 7 and R 8 are as defined above with the exclusion of H, and L 2 and L 3 are each a leaving group.
  • R 7 is (C 2 -C 6 )-alkenyl, (C 2 -C 6 )-haloalkenyl, (C 2 -C 6 )-alkynyl, (C 2 - C 6 )-haloalkynyl, (C 3 -C 7 )-cycloalkyl, (CH 2 ) q R 9 , (CH 2 ) q R 10 or (d-C 6 )-alkyl which last mentioned group is unsubstituted or substituted by one or more R 14 radicals; or where R 8 is (C 2 -C 6 )-alkynyl, (C 3 -C 7 )-cycloalkyl, (CH 2 ) q R 9 , (CH 2 ) q R 10 , (d-C 6 )-alkyl or (C 2 -C 6 )-alkenyl which last two mentioned groups are unsubstituted or substituted by one or more R 14 radicals
  • compounds of formula (I) wherein n is 1 or 2 and the other values are as defined above may be prepared by the oxidation of the corresponding compound in which n is 0 or 1.
  • the oxidation is generally performed using a peracid such as 3-chloroperbenzoic acid in a solvent such as dichloromethane or 1 ,2-dichloroethane, at a temperature of from 0°C to the reflux temperature of the solvent.
  • compounds of formula (I) wherein R 4 is OH, H, halogen, (C C 6 )-alkoxy, (d-C 6 )-alkyl, OCO-(d-C 6 )-alkyl or S(O) m -(d- C 6 )-alkyl may be prepared by the adaptation of known methods, for example as described in WO 8703781, WO 0140195 or EP 295117, or references cited therein.
  • reaction is generally performed in the presence of a base such as a trialkylamine for example triethylamine, in a solvent for example ether, at a temperature of from 0°C to 50°C.
  • a base such as a trialkylamine for example triethylamine
  • R 5 and R 6 are as defined above, and L is a leaving group for example halogen, preferably Br or I, in a solvent for example ether, at a temperature of from -70°C to +30°C.
  • the apparatuses mentioned lead 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.
  • compounds of the formula (I) may be prepared in part or fully by solid-phase-supported methods.
  • 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 preparation of the processes described herein yields compounds of the formula (I) in the form of substance collections which are termed libraries.
  • the present invention also relates to libraries which comprise at least two compounds of the formula (I).
  • Lithium azide (0.46 g, 0.094 mol) was added to a solution of diethyl 1-(2,6-dichIoro-4- trifluoromethylphenyI)-3-cyano-5-[(E)-dimethylaminomethylideneamino]pyrazol-4- ylphosphonate (0.78 g, 0.0016 mol) in N,N-dimethylformamide (8 ml) and the mixture heated at 95-100°C for 1 hour. After evaporation in vacuo at 90°C, water (5 ml) was added, and the residue extracted with benzene (3x5 ml). The aqueous layer was separated and the pH adjusted to 1 with hydrochloric acid.
  • Trimethylsilyl iodide (1.02 g, 0.0151 mol) was added to a solution of diethyl 1-(2,6- dichloro-4-trifluoromethylphenyl)-3-cyano-5-[(E)- dimethylaminomethylideneamino]pyrazol-4-ylphosphonate (0.76 g, 0.0015 mol) in acetonitrile (3 ml) and the mixture left for 24 hours at 20°C. The solvent was evaporated in vacuo, the residue extracted with water (4x10 ml) at 50°C and the pH adjusted to 9 with sodium bicarbonate. After 3 days the mixture was filtered, the filtrate was treated with activated carbon, filtrered and evaporated in vacuo.
  • R 1 is CN; R 2 is CI; W is C-CI; R 3 is CF 3 ; R 4 is NH 2 ; X is O; and Z and Y are covalent bonds.
  • Table 8 Compounds of formula (I) in which R 1 is CN; R 2 is CI; W is C-CI; R 3 is CF 3 ; R 4 is NHCH 3 ; and X, Y and Z are O.
  • Table 11 Compounds of formula (I) in which R 2 is CI; W is C-CI; X is O; and R 3 is CF 3 .
  • a method for the control of pests at a locus which comprises applying thereto an effective amount of a compound of formula (I) or a salt thereof.
  • the said compound is normally used in the form of a pesticidal composition (i.e. in association with compatible diluents or carriers and/or surface active agents suitable for use in pesticidal compositions), for example as hereinafter described.
  • compound of the invention as used hereinafter embraces a 4- phosphorylpyrazole derivatives of formula (I) as defined above and a pesticidally acceptable salt thereof.
  • One aspect of the present invention as defined above is a method for the control of pests at a locus.
  • the locus includes, for example, the pest itself, the place (plant, field, forest, orchard, waterway, soil, plant product, or the like) where the pest resides or feeds, or a place susceptible to future infestation by the pest.
  • the compound of the invention may therefore be applied directly to the pest, to the place where the pest resides or feeds, or to the place susceptible to future infestation by the pest.
  • the present invention provides pesticidally active compounds and methods of use of said compounds for the control of a number of pest species which includes: arthropods, especially insects or mites, or plant nematodes.
  • the compound of the invention may thus be advantageously employed in practical uses, for example, in agricultural or horticultural crops, in forestry, in veterinary medicine or livestock husbandry, or in public health.
  • the compounds ofthe invention may be used for example in the following applications and on the following pests:
  • soil insects such as corn rootworm, termites (especially for protection of structures), root maggots, wireworms, root weevils, stalkborers, cutworms, root aphids, or grubs. They may also be used to provide activity against plant pathogenic nematodes, such as root-knot, cyst, dagger, lesion, or stem or bulb nematodes, or against mites.
  • plant pathogenic nematodes such as root-knot, cyst, dagger, lesion, or stem or bulb nematodes, or against mites.
  • the compounds are advantageously applied to or incorporated at an effective rate into the soil in which crops are planted or to be planted or to the seeds or growing plant roots.
  • the compounds are especially useful in the control of many insects, especially filth flies or other Dipteran pests, such as houseflies, stableflies, soldierflies, hornflies, deerflies, horseflies, midges, punkies, blackflies, or mosquitoes.
  • filth flies or other Dipteran pests such as houseflies, stableflies, soldierflies, hornflies, deerflies, horseflies, midges, punkies, blackflies, or mosquitoes.
  • compounds of the invention are useful against attack by arthropods, more especially beetles, including weevils, moths or mites, for example Ephestia spp. (flour moths),
  • Anthrenus spp. (carpet beetles), Tribolium spp. (flour beetles), Sitophilus spp. (grain weevils) or Acarus spp. (mites).
  • Hemiptera and Homoptera e.g. Psylla spp., Bemisia spp., Trialeurodes spp., Aphis spp., Myzus spp., Megoura viciae, Phylloxera spp., Nephotettix spp. (rice leaf hoppers), Nilaparvata spp..
  • Thysanoptera such as Thrips tabaci.
  • Orthoptera such as Locusta and Schistocerca spp., (locusts and crickets) e.g. Gryllus spp., and Acheta spp. for example, Blatta orientalis, Periplaneta americana, Blatella germanica, Locusta migratoria migratorioides, and Schistocerca gregaria.
  • Botembola e.g. Periplaneta spp. and Blatella spp. (roaches).
  • arthropods of agricultural significance such as Acari (mites) e.g. Tetranychus spp., and Panonychus spp..
  • root-knot nematodes such as Meloidogyne spp. (e.g. M. incognita).
  • arthropods which are parasitic internally or externally upon vertebrates, particularly warm-blooded vertebrates, for example domestic animals, e.g. cattle, sheep, goats, equines, swine, poultry, dogs or cats, for example Acarina, including ticks (e.g. soft-bodied ticks including Argasidae spp. e.g. Argas spp. and Ornithodorus spp. (e.g. Ornithodorus moubata); hard-bodied ticks including Ixodidae spp., e.g. Boophilus spp. e.g.
  • ticks e.g. soft-bodied ticks including Argasidae spp. e.g. Argas spp. and Ornithodorus spp. (e.g. Ornithodorus moubata
  • hard-bodied ticks including Ixodidae spp., e.g. Boophilus spp.
  • mites e.g. Damalini
  • the compounds of formula (I) are used for the control of parasites of animals.
  • the animal to be treated is a domestic companion animal such as a dog or a cat.
  • the compounds of formula (I) or salts or compositions thereof are used for the preparation of a veterinary medicament.
  • a further feature of the invention thus relates to the use of a compound of formula (I) or a salt thereof, or of a composition thereof, for the control of pests.
  • a method for example, comprises applying to the plants or to the medium in which they grow an effective amount of a compound of the invention.
  • the compound of the invention is generally applied to the locus in which the arthropod or nematode infestation is to be controlled at an effective rate in the range of about 2g to about 1 kg of the active compound per hectare of locus treated.
  • a lower rate may offer adequate protection.
  • adverse weather conditions, resistance of the pest or other factors may require that the active ingredient be used at higher rates.
  • an effective rate range of the active compound is from about 10g/ha to about 400g/ha, more preferably from about 50g/ha to about 200 g/ha.
  • the active compound When a pest is soil-borne, the active compound generally in a formulated composition, is distributed evenly over the area to be treated (ie, for example broadcast or band treatment) in any convenient manner and is applied at rates from about 10g/ha to about 400g ai/ha, preferably from about 50g/ha to about 200 g ai/ha.
  • the liquid solution or suspension When applied as a root dip to seedlings or drip irrigation to plants the liquid solution or suspension contains from about 0.075 to about 1000 mg ai/l, preferably from about 25 to about 200 mg ai/l.
  • Application may be made, if desired, to the field or crop-growing area generally or in close proximity to the seed or plant to be protected from attack.
  • the compound of the invention can be washed into the soil by spraying with water over the area or can be left to the natural action of rainfall.
  • the formulated compound can, if desired, be distributed mechanically in the soil, for example by ploughing, disking, or use of drag chains.
  • Application can be prior to planting, at planting, after planting but before sprouting has taken place, or after sprouting.
  • the compound of the invention and methods of control of pests therewith are of particular value in the protection of field, forage, plantation, glasshouse, orchard or vineyard crops, of ornamentals, or of plantation or forest trees, for example: cereals (such as wheat or rice), cotton, vegetables (such as peppers), field crops (such as sugar beets, soybeans or oil seed rape), grassland or forage crops (such as maize or sorghum), orchards or groves (such as of stone or pit fruit or citrus), ornamental plants, flowers or vegetables or shrubs under glass or in gardens or parks, or forest trees (both deciduous and evergreen) in forests, plantations or nurseries.
  • cereals such as wheat or rice
  • cotton such as peppers
  • field crops such as sugar beets, soybeans or oil seed rape
  • grassland or forage crops such as maize or sorghum
  • orchards or groves such as of stone or pit fruit or citrus
  • the compound of the invention and methods of use thereof are of particular value in the control of arthropods or helminths which are injurious to, or spread or act as vectors of diseases of domestic animals, for example those hereinbefore mentioned, and more especially in the control of ticks, mites, lice, fleas, midges, or biting, nuisance or myiasis flies.
  • the compounds of the invention are particularly useful in controlling arthropods or helminths which are present inside domestic host animals or which feed in or on the skin or suck the blood of the animal, for which purpose they may be administered orally, parenterally, percutaneously or topically.
  • compositions hereinafter described for application to growing crops or crop growing loci or as a seed dressing may, in general, alternatively be employed in the protection of stored products, household goods, property or areas of the general environment.
  • Suitable means of applying the compounds of the invention include: to growing crops as foliar sprays (for example as an in-furrow spray), dusts, granules, fogs or foams or also as suspensions of finely divided or encapsulated compositions as soil or root treatments by liquid drenches, dusts, granules, smokes or foams; to seeds of crops via application as seed dressings, e.g.
  • compositions in which the active ingredient exhibits an immediate and/or prolonged action over a period of time against the arthropods or helminths for example by incorporation in feed or suitable orally- ingestible pharmaceutical formulations, edible baits, salt licks, dietary supplements, pour-on formulations, sprays, baths, dips, showers, jets, dusts, greases, shampoos, creams, wax smears or livestock self-treatment systems; to the environment in general or to specific locations where pests may lurk, including stored products, timber, household goods, or domestic or industrial premises, as sprays, fogs, dusts, smokes, wax-smears, lacquers, granules or baits, or in tricklefeeds to waterways, wells, reservoirs or other running or standing water.
  • the compounds of formula (I) are particularly useful for the control of parasites of animals when applied orally, and in a further preferred aspect of the invention the compounds of formula (I) are used for the control of parasites of animals by oral application.
  • the compounds of the formula (I) or salts thereof may be administered before, during or after meals.
  • the compounds of the formula (I) or salts thereof may be mixed with a carrier and/or foodstuff.
  • the compound of the formula (I) or salt thereof is administered orally in a dose to the animal in a dose range generally from 0.1 to 500 mg/kg of the compound of the formula (I) or salt thereof per kilogram of animal body weight (mg/kg).
  • the frequency of treatment of the animal, preferably the domestic animal to be treated by the compound of the formula (I) or salt thereof is generally from about once per week to about once per year, preferably from about once every two weeks to once every three months.
  • the compounds of the invention may be administered most advantageously with another parasiticidally effective material, such as an endoparasiticide, and/or an ectoparasiticide, and/or an endectoparasiticide.
  • another parasiticidally effective material such as an endoparasiticide, and/or an ectoparasiticide, and/or an endectoparasiticide.
  • such compounds include macrocyclic lactones such as avermectins or milbemycins e.g., ivermectin, pyratel or an insect growth regulator such as lufenuron or methoprene.
  • the compounds of the formula (I) can also be employed for controlling harmful organisms in crops of known genetically engineered plants or genetically engineered plants yet to be developed.
  • 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.
  • transgenic plants are known where the starch content is increased, or the starch quality is altered, or where the harvested material has a different fatty acid composition.
  • 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.
  • the invention therefore also relates to the use of compounds of the formula (I) for controlling harmful organisms in transgenic crop plants.
  • a pesticidal composition comprising one or more compounds of the invention as defined above, in association with, and preferably homogeneously dispersed in one or more compatible pesticidally acceptable diluents or carriers and/or surface active agents [i.e. diluents or carriers and/or surface active agents of the type generally accepted in the art as being suitable for use in pesticidal compositions and which are compatible with compounds of the invention].
  • compositions In practice, the compounds of the invention most frequently form parts of compositions. These compositions can be employed to control arthropods, especially insects, or plant nematodes or mites.
  • the compositions may be of any type known in the art suitable for application to the desired pest in any premises or indoor or outdoor area.
  • These compositions contain at least one compound of the invention as the active ingredient in combination or association with one or more other compatible components which are for example, solid or liquid carriers or diluents, adjuvants, surface-active-agents, or the like appropriate for the intended use and which are agronomically or medicinally acceptable.
  • These compositions which may be prepared by any manner known in the art, likewise form a part of this invention.
  • the compounds of the invention in their commercially available formulations and in the use forms prepared from these formulations may be present in mixtures with other active substances such as insecticides, attractants, sterilants, acaricides, nematicides, fungicides, growth regulatory substances or herbicides.
  • the pesticides include, for example, phosphoric esters, carbamates, carboxylic esters, formamidines, tin compounds and materials produced by microorganisms.
  • compositions according to the invention usually contain about 0.05 to about 95% (by weight) of one or more active ingredients according to the invention, about 1 to about 95% of one or more solid or liquid carriers and, optionally, about 0.1 to about 50% of one or more other compatible components, such as surface-active agents or the like.
  • carrier denotes an organic or inorganic ingredient, natural or synthetic, with which the active ingredient is combined to facilitate its application, for example, to the plant, to seeds or to the soil. This carrier is therefore generally inert and it must be acceptable (for example, agronomically acceptable, particularly to the treated plant).
  • the carrier may be a solid, for example, clays, natural or synthetic silicates, silica, resins, waxes, solid fertilizers (for example ammonium salts), ground natural minerals, such as kaolins, clays, talc, chalk, quartz, attapulgite, montmorillonite, bentonite or diatomaceous earth, or ground synthetic minerals, such as silica, alumina, or silicates especially aluminium or magnesium silicates.
  • solid carriers for granules the following are suitable: crushed or fractionated natural rocks such as calcite, marble, pumice, sepiolite and dolomite; synthetic granules of inorganic or organic meals; granules of organic material such as sawdust, coconut shells, corn cobs, corn husks or tobacco stalks; kieselguhr, tricalcium phosphate, powdered cork, or absorbent carbon black; water soluble polymers, resins, waxes; or solid fertilizers.
  • Such solid compositions may, if desired, contain one or more compatible wetting, dispersing, emulsifying or colouring agents which, when solid, may also serve as a diluent.
  • the carrier may also be liquid, for example: water; alcohols, particularly butanol or glycol, as well as their ethers or esters, particularly methylglycol acetate; ketones, particularly acetone, cyclohexanone, methylethyl ketone, methylisobutylketone, or isophorone; petroleum fractions such as paraffinic or aromatic hydrocarbons, particularly xylenes or alkyl naphthalenes; mineral or vegetable oils; aliphatic chlorinated hydrocarbons, particularly trichloroethane or methylene chloride; aromatic chlorinated hydrocarbons, particularly chlorobenzenes; water-soluble or strongly polar solvents such as dimethylformamide, dimethyl sulphoxide, or N- methylpyrrolidone; liquefied gases; or the like or a mixture thereof.
  • the surface-active agent may be an emulsifying agent, dispersing agent or wetting agent of the ionic or non-ionic type or a mixture of such surface-active agents.
  • these are e.g., salts of polyacrylic acids, salts of lignosulphonic acids, salts of phenolsulphonic or naphthalenesulphonic acids, polycondensates of ethylene oxide with fatty alcohols or fatty acids or fatty esters or fatty amines, substituted phenols (particularly alkylphenols or arylphenols), salts of sulphosuccinic acid esters, taurine derivatives (particularly alkyltaurates), phosphoric esters of alcohols or of polycondensates of ethylene oxide with phenols, esters of fatty acids with polyols, or sulphate, sulphonate or phosphate functional derivatives of the above compounds.
  • compositions of the invention may further contain other additives such as adhesives or colorants.
  • Adhesives such as carboxymethylcellulose or natural or synthetic polymers in the form of powders, granules or lattices, such as arabic gum, polyvinyl alcohol or polyvinyl acetate, natural phospholipids, such as cephalins or lecithins, or synthetic phospholipids can be used in the formulations.
  • colorants such as inorganic pigments, for example: iron oxides, titanium oxides or Prussian Blue; organic dyestuffs, such as alizarin dyestuffs, azo dyestuffs or metal phthalocyanine dyestuffs; or trace nutrients such as salts of iron, manganese, boron, copper, cobalt, molybdenum or zinc.
  • inorganic pigments for example: iron oxides, titanium oxides or Prussian Blue
  • organic dyestuffs such as alizarin dyestuffs, azo dyestuffs or metal phthalocyanine dyestuffs
  • trace nutrients such as salts of iron, manganese, boron, copper, cobalt, molybdenum or zinc.
  • the compounds of the invention are therefore generally in the form of compositions, which are in various solid or liquid forms.
  • Solid forms of compositions which can be used are dusting powders (with a content of the compound of the invention, ranging up to 80%), wettable powders or granules (including water dispersible granules), particularly those obtained by extrusion, compacting, impregnation of a granular carrier, or granulation starting from a powder (the content of the compound of the invention, in these wettable powders or granules being between about 0.5 and about 80%).
  • Solid homogenous or heterogenous compositions containing one or more compounds of the invention may be used to treat standing or running water over a period of time. A similar effect may be achieved using trickle or intermittent feeds of water dispersible concentrates as described herein.
  • Liquid compositions for example, include aqueous or non-aqueous solutions or suspensions (such as emulsifiable concentrates, emulsions, flowables, dispersions, or solutions) or aerosols.
  • Liquid compositions also include, in particular, emulsifiable concentrates, dispersions, emulsions, flowables, aerosols, wettable powders (or powder for spraying), dry flowables or pastes as forms of compositions which are liquid or intended to form liquid compositions when applied, for example as aqueous sprays (including low and ultra-low volume) or as fogs or aerosols.
  • Liquid compositions for example, in the form of emulsifiable or soluble concentrates most frequently comprise about 5 to about 80% by weight of the active ingredient, while the emulsions or solutions which are ready for application contain, in their case, about 0.01 to about 20% of the active ingredient.
  • the emulsifiable or soluble concentrates may contain, when required, about 2 to about 50% of suitable additives, such as stabilizers, surface-active agents, penetrating agents, corrosion inhibitors, colorants or adhesives.
  • suitable additives such as stabilizers, surface-active agents, penetrating agents, corrosion inhibitors, colorants or adhesives.
  • Emulsions of any required concentration which are particularly suitable for application, for example, to plants, may be obtained from these concentrates by dilution with water.
  • the emulsions may be in the form of water-in-oil or oil-in-water type and they may have a thick consistency.
  • liquid compositions of this invention may, in addition to normal agricultural use applications be used for example to treat substrates or sites infested or liable to infestation by arthropods (or other pests controlled by compounds of this invention) including premises, outdoor or indoor storage or processing areas, containers or equipment or standing or running water.
  • aqueous dispersions or emulsions or spraying mixtures can be applied, for example, to crops by any suitable means, chiefly by spraying, at rates which are generally of the order of about 100 to about 1 ,200 liters of spraying mixture per hectare, but may be higher or lower (eg. low or ultra-low volume) depending upon the need or application technique.
  • the compound or compositions according to the invention are conveniently applied to vegetation and in particular to roots or leaves having pests to be eliminated.
  • Another method of application of the compounds or compositions according to the invention is by chemigation, that is to say, the addition of a formulation containing the active ingredient to irrigation water.
  • This irrigation may be sprinkler irrigation for foliar pesticides or it can be ground irrigation or underground irrigation for soil or for systemic pesticides.
  • the concentrated suspensions which can be applied by spraying, are prepared so as to produce a stable fluid product which does not settle (fine grinding) and usually contain from about 10 to about 75% by weight of active ingredient, from about 0.5 to about 30% of surface-active agents, from about 0.1 to about 10% of thixotropic agents, from about 0 to about 30% of suitable additives, such as anti-foaming agents, corrosion inhibitors, stabilizers, penetrating agents, adhesives and, as the carrier, water or an organic liquid in which the active ingredient is poorly soluble or insoluble Some organic solids or inorganic salts may be dissolved in the carrier to help prevent settling or as antifreezes for water.
  • the wettable powers are usually prepared so that they contain from about 10 to about 80% by weight of active ingredient, from about 20 to about 90% of a solid carrier, from about 0 to about 5% of a wetting agent, from about 3 to about 10% of a dispersing agent and, when necessary, from about 0 to about 80% of one or more stabilizers and/or other additives, such as penetrating agents, adhesives, anti-caking agents, colorants, or the like.
  • the active ingredient is thoroughly mixed in a suitable blender with additional substances which may be impregnated on the porous filler and is ground using a mill or other suitable grinder. This produces wettable powders, the wettability and the suspendability of which are advantageous.
  • the "water dispersible granules (WG)" (granules which are readily dispersible in water) have compositions which are substantially close to that of the wettable powders. They may be prepared by granulation of formulations described for the wettable powders, either by a wet route (contacting finely divided active ingredient with the inert filler and a little water, e.g. 1 to 20% by weight, or with an aqueous solution of a dispersing agent or binder, followed by drying and screening), or by a dry route (compacting followed by grinding and screening).
  • WG water dispersible granules
  • compositions for application to control arthropod or plant nematode pests usually contain from about 0.00001% to about 95%, more particularly from about 0.0005% to about 50% by weight of one or more compounds of the invention, or of total active ingredients (that is to say the compounds of the invention, together with other substances toxic to arthropods or plant nematodes, synergists, trace elements or stabilizers).
  • the actual compositions employed and their rate of application will be selected to achieve the desired effect(s) by the farmer, livestock producer, medical or veterinary practitioner, pest control operator or other person skilled in the art.
  • Solid or liquid compositions for application topically to animals, timber, stored products or household goods usually contain from about 0.00005% to about 90%, more particularly from about 0.001% to about 10%, by weight of one or more compounds of the invention.
  • these normally contain from about 0.1 % to about 90% by weight of one or more compounds of the invention.
  • Medicated feedstuffs normally contain from about 0.001% to about 3% by weight of one or more compounds of the invention.
  • Concentrates or supplements for mixing with feedstuffs normally contain from about 5% to about 90%, preferably from about 5% to about 50%, by weight of one or more compounds of the invention.
  • Mineral salt licks normally contain from about 0.1% to about 10% by weight of one or more compounds of formula (I) or pesticidally acceptable salts thereof.
  • Dusts or liquid compositions for application to livestock, goods, premises or outdoor areas may contain from about 0.0001% to about 15%, more especially from about 0.005% to about 2.0%, by weight, of one or more compounds of the invention.
  • Suitable concentrations in treated waters are between about 0.0001 ppm and about 20 ppm, more particularly about 0.001 ppm to about 5.0 ppm. of one or more compounds of the invention, and may be used therapeutically in fish farming with appropriate exposure times.
  • Edible baits may contain from about 0.01 % to about 5%, preferably from about 0.01% to about 1.0%, by weight, of one or more compounds of the invention.
  • the dosage of compounds of the invention will depend upon the species, age, or health of the vertebrate and upon the nature and degree of its actual or potential infestation by arthropod or helminth pests.
  • a single dose of about 0.1 to about 100 mg, preferably about 2.0 to about 20.0 mg, per kg body weight of the animal or doses of about 0.01 to about 20.0 mg, preferably about 0.1 to about 5.0 mg, per kg body weight of the animal per day, for sustained medication are generally suitable by oral or parenteral administration.
  • sustained release formulations or devices the daily doses required over a period of months may be combined and administered to animals on a single occasion.
  • composition EXAMPLES 2A - 2M illustrate compositions for use against arthropods, especially mites or insects, or plant nematodes, which comprise, as active ingredient, compounds of the invention, such as those described in preparative examples.
  • the compositions described in EXAMPLES 2A - 2M can each be diluted to give a sprayable compositon at concentrations suitable for use in the field.
  • Generic chemical descriptions of the ingredients (for which all of the following percentages are in weight percent), used in the composition EXAMPLES 2A - 2M exemplified below, are as follows: Trade Name Chemical Description
  • Soprophor BSU Tristyrylphenol ethylene oxide condensate
  • Arylan CA A 70% w/v solution of calcium dodecylbenzenesulfonate
  • Rhodigel 23 Polysaccharide xanthan gum
  • a water soluble concentrate is prepared with the composition as follows: Active ingredient 7% Ethylan BCP 10% N-methylpyrrolidone 83%
  • EC emulsifiable concentrate
  • the first three components are dissolved in N-methylpyrrolidone and to this is then added the Solvesso 150 to give the final volume.
  • a wettable powder is prepared with the composition as follows: Active ingredient 40% Arylan S 2% Darvan NO2 5% Celite PF 53%
  • the ingredients are mixed and ground in a hammer-mill to a powder with a particle size of less than 50 microns.
  • An aqueous-flowable formulation is prepared with the composition as follows: Active ingredient 40.00% Ethylan BCP 1.00% Sopropon T360. 0.20% Ethylene glycol 5.00% Rhodigel 230. 0.15% Water 53.65%
  • the ingredients are intimately mixed and are ground in a bead mill until a mean particle size of less than 3 microns is obtained.
  • An emulsifiable suspension concentrate is prepared with the composition as follows: Active ingredient 30.0% Ethylan BCP 10.0% Bentone 38 0.5% Solvesso 150 59.5%
  • the ingredients are intimately mixed and ground in a beadmill until a mean particle size of less than 3 microns is obtained.
  • a water dispersible granule is prepared with the composition as follows: Active ingredient 30% Darvan No 2 15% Arylan S 8% Celite PF 47%
  • the ingredients are mixed, micronized in a fluid-energy mill and then granulated in a rotating pelletizer by spraying with water (up to 10%).
  • the resulting granules are dried in a fluid-bed drier to remove excess water.
  • a dusting powder is prepared with the composition as follows: Active ingredient 1 to 10% Talc powder-superfine 99 to 90% The ingredients are intimately mixed and further ground as necessary to achieve a fine powder.
  • This powder may be appplied to a locus of arthropod infestation, for example refuse dumps, stored products or household goods or animals infested by, or at risk of infestation by, arthropods to control the arthropods by oral ingestion.
  • Suitable means for distributing the dusting powder to the locus of arthropod infestation include mechanical blowers, handshakers or livestock self treatment devices.
  • An edible bait is prepared with the composition as follows: Active ingredient 0.1 to 1.0% Wheat flour 80% Molasses 19.9 to 19%
  • the ingredients are intimately mixed and formed as required into a bait form.
  • This edible bait may be distributed at a locus, for example domestic or industrial premises, e.g. kitchens, hospitals or stores, or outdoor areas, infested by arthropods, for example ants, locusts, cockroaches or flies, to control the arthropods by oral ingestion.
  • a solution formulation is prepared with a composition as follows: Active ingredient 15% Dimethyl sulfoxide 85%
  • the active ingredient is dissolved in dimethyl sulfoxide with mixing and or heating as required.
  • This solution may be applied percutaneously as a pour-on application to domestic animals infested by arthropods or, after sterilization by filtration through a polytetrafluoroethylene membrane (0.22 micrometer pore size), by parenteral injection, at a rate of application of from 1.2 to 12 ml of solution per 100 kg of animal body weight.
  • a wettable powder is prepared with the composition as follows: Active ingredient 50% Ethylan BCP 5% Aerosil 5% Celite PF 40%
  • the Ethylan BCP is absorbed onto the Aerosil which is then mixed with the other ingredients and ground in a hammer-mill to give a wettable powder, which may be diluted with water to a concentration of from 0.001% to 2% by weight of the active compound and applied to a locus of infestation by arthropods, for example, dipterous larvae or plant nematodes, by spraying, or to domestic animals infested by, or at risk of infection by arthropods, by spraying or dipping, or by oral administration in drinking water, to control the arthropods.
  • arthropods for example, dipterous larvae or plant nematodes
  • a slow release bolus composition is formed from granules containing the following components in varying percentages(similar to those described for the previous compositions) depending upon need: Active ingredient Density agent Slow-release agent Binder The intimately mixed ingredients are formed into granules which are compressed into a bolus with a specific gravity of 2 or more. This can be administered orally to ruminant domestic animals for retention within the reticulo-rumen to give a continual slow release of active compound over an extended period of time to control infestation of the ruminant domestic animals by arthropods.
  • a slow release composition in the form of granules, pellets, brickettes or the like can be prepared with compositions as follows: Active ingredient 0.5 to 25% Polyvinyl chloride 75 to 99.5% Dioctyl phthalate (plasticizer) The components are blended and then formed into suitable shapes by melt-extrusion or molding. These composition are useful, for example, for addition to standing water or for fabrication into collars or eartags for attachment to domestic animals to control pests by slow release.
  • a water dispersible granule is prepared with the composition as follows: Active ingredient 85%(max) Polyvinylpyrrolidone 5% Attapulgite clay 6% Sodium lauryl sulfate 2% Glycerine 2%
  • the ingredients are mixed as a 45% slurry with water and wet milled to a particle size of 4 microns, then spray-dried to remove water.
  • METHOD A Screening method to test systemicity of compounds against Ctenocephalides felis (Cat flea)
  • a test container was filled with 10 adults of Ctenocephalides felis.
  • a glass cylinder was closed on one end with parafilm and placed on top of the test container.
  • the test compound solution was then pipetted into bovine blood and added to the glass cylinder.
  • the treated Ctenocephalides felis were held in this artificial dog test (blood 37 °C, 40-60 % relative humidity; Ctenocephalides felis 20-22°C, 40-60 % relative humidity) and assessment performed at 24 and 48 hours after application.
  • METHOD B Diabrotica undecimpunctata (southern corn rootworm) screen Two days before application, seeds of maize were soaked in water under warm conditions to elicit fast germination. One day before application, eggs of Diabrotica undecimpunctata were transferred to one half of a Japanese filter paper placed in a plastic petri dish. Afterwards, a sprouted maize seed was placed on a moistened pad beside the filter paper. Three drops of 200 microlitres of test compound solution were carefully pipetted onto the egg. The remainder of the solution was placed on the maize and then the Petri dish was closed. The treated eggs in the Petri dishes were held in a climate chamber for 6 days. The compound efficacy (percentage of dead eggs and/or larvae in comparison to untreated control) was assessed 6 days after application using a binocular microscope.
  • the leaves of 12 rice plants having a stem length of 8 cm were dipped for 5 seconds into an aqueous solution of the formulated test compound. After the solution had run off, the rice plants treated in this manner were placed in a Petri dish and populated with about 20 larvae (L3 stage) of Nephotettix cincticeps. The Petri dish was closed and then stored in a climate chamber (16 hours of light/day, 25°C, 40-60% relative humidity). After 6 days storage, the percentage mortality of leafhopper larvae was determined.
  • test compounds were dropped onto filter paper, dried and the filter paper placed into test tubes and infested with 10 adults of Ctenocephalides felis.
  • the treated Ctenocephalides felis were held in a climate chamber (26°C, 80% RH) and the percentage efficacy assessed 24 hours and 48 hours after application in comparison with the untreated control.
  • Compound number 1-2 was active in one or more of the above test methods.

Abstract

The invention relates to 4-phosphorylpyrazole derivatives of formula (I) or salts thereof: wherein the various symbols are as defined in the description, to processes for their preparation, to compositions thereof, and to their use for the control of pests (including arthropods and helminths).

Description

Description 4-PHOSPHORY PYRAZOLE DERIVATIVES FOR PESTICIDAL USE
The invention relates to 4-phosphorylpyrazole derivatives, processes for their preparation, to compositions thereof, and to their use for the control of pests, specifically arthropods (including insects and arachnids) and helminths (including nematodes).
The control of insects, arachnids and helminths with 1 -arylpyrazole compounds has been described in, for example, patent publication numbers WO 87/03781 , EP
0295117 and US 4695308.
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 compounds which are advantageous over the known compounds, at least as far as some aspects are concerned.
It is an object of the present invention to provide new pesticides which may be used in domestic companion animals.
It is advantageous to apply pesticides to animals in oral form so as to prevent the possible contamination of humans or the surrounding environment.
Another object of the invention is to provide new pesticides which may be used in lower dose than existing pesticides.
Another object of the invention is to provide new pesticides which are substantially non-emetic.
Another object of the invention is to provide new pesticides which are safer to the user and the environment.
These objects are met in whole or in part by the present invention. The present invention provides a compound which is a 4-phosphorylpyrazole derivative of formula (I):
Figure imgf000003_0001
wherein:
R1 is CN, CSNH2 or C(=N-V)-S(O)rQ;
W is C-halogen, C-CH3 or N;
R2 is hydrogen, halogen, CH3> NH-(C C6)-alkyl or N[(C C6)-alkyl]2;
R3 is (C C3)-haloalkyl, (C C3)-haloalkoxy or SF5;
X is O or S;
Y and Z are each independently O, S, NRa or a covalent bond;
Ra is H or (Cι-C6)-alkyl;
R4 is NR7R8, OH, H, halogen, (C C6)-alkoxy, (d-CβJ-alk l, OCO-(CrC6)-alkyl,
S(O)m-(Cι-Cβ)-al yl or N=CHN-[(Cι-C6)-alkyl]2;
R5 and R6 are each independently H, (C2-C6)-alkenyl, (C2-C6)-haloalkenyl, (C2-C6)- alkynyl, (C2-C6)-haloalkynyl, (C3-C7)-cycloalkyl, (CH2)qR9 or (CH2)qR10; or are (C
C6)-alkyl unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, (Cι-C6)-alkoxy, (Cι-C6)-haloalkoxy, (C3-C6)-alkenyloxy,
(C3-C6)-haloalkenyloxy, (C3-C6)-alkynyloxy, (C3-C6)-haloalkynyloxy, (C3-C7)- cycloalkyl, S(O)pR11, CN, NO2, OH, COR12, NR12R13, S(O)pR9, OR9 and CO2R12;
R7 is H, (C2-C6)-alkenyl, (C2-C6)-haloalkenyl, (C2-C6)-alkynyl, (C2-C6)-haloalkynyl,
(C3-C7)-cycloalkyl, CO2-(C1-C6)-alkyl, CO2-(C3-C7)-cycloalkyl, CO2-(Cι-C4)-alkyl-(C3-
C7)-cycloalkyl, CO2-(C2-C6)-alkenyl, CO2-(CH2)qR9, CONR12R13, CO2-(CH2)qR10,
(CH2)qR9, (CH2)qR10, COR12 or COCH2-(C C4)-alkoxy; or (d-Cej-alkyl unsubstituted or substituted by one or more R14 radicals; R8 is H, (C2-C6)-alkynyl, CO2-(Cι-C6)-alkyl, (C3-C7)-cycloalkyl, (CH2)qR9, (CH2)qR10, or SO2R15; or (Cι-C6)-alkyl, (C2-C6)-alkenyl or CO-(Cι-C6)-alkyl which last three mentioned groups are unsubstituted or substituted by one or more R14 radicals;
R9 is phenyl unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, (Cι-C6)-alkyl, (Cι-C6)-haloalkyl, (Cι-C6)-alkoxy, (d-C6)- haloalkoxy, CN, NO2) S(O)pR11 and NR13R16;
R10 is heterocyclyl unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, (Cι-C4)-alkyl, (Cι-C )-haloalkyl, (d-C )-alkoxy,
S(O)pR11, OH and oxo;
R11 is (d-C6)-alkyl, (d-C6)-haloalkyl, (C2-C6)-alkenyl, (C2-C6)-haloalkenyl, (C2-
C6)-alkynyl, (C2-C6)-haloalkynyl or (C3-C7)-cycloalkyl;
R12 is H, (CrC6)-alkyl, (d-C6)-haloalkyl, (C3-C7)-cycloalkyl, (C C6)-alkyl-(C3-C7)- cycloalkyl, (CH2)qR9 or (CH2)qR10;
R13 and R16are each independently H, (d-C6)-alkyl, (d-C6)-haloalkyl, (C3-
C7)-cycloalkyl or (Cι-C6)-alkyl-(C3-C7)-cycloalkyl; or
R12 and R13 together with the attached N atom form a five- or six-membered saturated ring which optionally contains an additional hetero atom in the ring which is selected from O, S and N, the ring being unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, (Cι-C6)-alkyl, (d-Cβ)- haloalkyl and halogen;
R14 is halogen, (d-C6)-alkoxy, (d-C6)-haloalkoxy, (C3-C7)-cycloalkyl, S(O)pR11,
CO2-(d-C6)-alkyl, O(C=O)-(d-C6)-alkyl, CO-(d-C6)-alkyl, CO-(Cι-C6)-haloalkyl,
NR12R13, CONR12R13, SO2NR12R13, OH, CN, NO2, OR9, NR12COR16, NR12SO2R11 or
OR10;
R15 is (C3-C7)-cycloalkyl, (C2-C6)-alkenyl, (C2-C6)-haloalkenyl or R10; or phenyl unsubstituted or substituted by one or more radicals selected from R17; or is (Cι-
C6)-alkyl unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, (d-C6)-alkoxy, (d-C6)-haloalkoxy, (C2-C6)-alkenyloxy,
(C2-C6)-haloalkenyloxy, (C2-C6)-alkynyloxy, (C2-C6)-haloalkynyloxy, (C3-C7)- cycloalkyl, S(O)pR9, S(O)pR10, S(O)pR11, CN, NO2, OH, COR12, NR12COR16,
NR12SO2R11, CONR12R13, NR12R13, OR9, OR10, R18, R10 and CO2R12; R17 is halogen, (d-C6)-alkyl, (d-C6)-haloalkyl, (C C6)-alkoxy, (Cι-C6)-haloalkoxy,
CN, NO2, S(O)pR11, NR12R13, COR11, COR9, CONR12R13, SO2NR12R13, R9, SF5, OH,
OR9, R19, OR19, SO3H or (Cι-C6)-a!kylideneimino;
R18 is phenyl unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, (Cι-C6)-alkyl, (d-C6)-haloalkyl, (Cι-C6)-alkoxy, (Ci-Cβ)- haloalkoxy, CN, NO2, S(O)pR11, NR12R13, COR11, COR9, CONR12R13, SO2NR12R13,
OH, SO3H and (d-C6)-alkylideneimino;
R19 is a heteroaromatic radical selected from the group consisting of pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, thienyl, thiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, furyl, pyrrolyl, pyrazolyl, imidazolyl and triazolyl, which groups are unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, (Cι-C6)-alkyl, (C C6)-haloalkyl and (d-C6)-alkoxy;
V is H, (CrCβ)-alkyl, (C C6)-haloalkyl, (C2-C6)-alkenyl, (C2-C6)-alkynyl, (CH2)qR9,
COR20, CO2-(C C6)-alkyl or S(O)pR20;
Q is (C C6)-alkyl or CH2R9;
R20 is (Cι-C6)-alkyl or (d-C6)-haloalkyl; m, n, p and r are each independently zero, one or two; q is 0 or 1 to 4; and each heterocyclyl in the above-mentioned radicals is independently a heterocyclic radical having 3 to 6 ring atoms and 1 , 2 or 3 hetero atoms in the ring selected from the group consisting of N, O and S; or a pesticidally acceptable salt thereof.
These compounds possess valuable pesticidal properties.
The invention also encompasses any stereoisomer, enantiomer or geometric isomer, and mixtures thereof.
By the term "pesticidally acceptable salts" is meant salts the anions or cations of which are known and accepted in the art for the formation of salts for pesticidal use. Suitable salts with bases, e.g. formed by compounds of formula (I) containing a carboxylic acid group, include alkali metal (e.g. sodium and potassium), alkaline earth metal (e.g. calcium and magnesium), ammonium and amine (e.g. diethanolamine, triethanolamine, octylamine, morpholine and dioctylmethylamine) salts. Suitable acid addition salts, e.g. formed by compounds of formula (I) containing an amino group, include salts with inorganic acids, for example hydrochlorides, sulphates, phosphates and nitrates and salts with organic acids for example acetic acid.
In the present specification, including the accompanying claims, the aforementioned substituents have the following meanings:
Halogen atom means fluorine, chlorine, bromine or iodine.
The term "halo" before the name of a radical means that this radical is partially or completely halogenated, that is to say, substituted by F, CI, Br, or I, in any combination, preferably by F or CI.
Alkyl groups and portions thereof (unless otherwise defined) may be straight- or branched-chain.
The expression "(Cι-C6)-alkyl" is to be understood as meaning an unbranched or branched hydrocarbon radical having 1 , 2, 3, 4, 5 or 6 carbon atoms, such as, for example a methyl, ethyl, propyl, isopropyl, 1 -butyl, 2-butyl, 2-methylpropyl or tert- butyl radical.
Alkyl radicals and also in composite groups, unless otherwise defined, preferably have 1 to 4 carbon atoms.
"(CrC6)Haloalkyl" means an alkyl group mentioned under the expression
"(Cι-C6)alkyl" in which one or more hydrogen atoms are replaced by the same number of identical or different halogen atoms, such as monohaloalkyl, perhaloalkyl,
CF3, CHF2, CH2F, CHFCHs, CF3CH2) CF3CF2, CHF2CF2, CH2FCHCI, CH2CI, CCI3,
CHCI2 or CH2CH2CI.
"(d-C6)Alkoxy" means an alkoxy group whose carbon chain has the meaning given under the expression "(CrCβJalkyl". "Haloalkoxy" is, for example, OCF3, OCHF2,
OCH2F, CF3CF2O, OCH2CF3 or OCH2CH2CI.
"(C2-C6)Alkenyl" means an unbranched or branched non-cyclic carbon chain having a number of carbon atoms which corresponds to this stated range and which contains at least one double bond which can be located in any position of the respective unsaturated radical. "(C2-C6)Alkenyl" accordingly denotes, for example, the vinyl, allyl, 2-methyl-2-propenyl, 2-butenyl, pentenyl, 2-methylpentenyl or the hexenyl group.
"(C2-C6)Alkynyl" means an unbranched or branched non-cyclic carbon chain having a number of carbon atoms which corresponds to this stated range and which contains one triple bond which can be located in any position of the respective unsaturated radical. "(C2-C6)Alkynyl" accordingly denotes, for example, the propargyl, 1-methyl-2-propynyl, 2-butynyl or 3-butynyl group.
Cycloalkyl groups preferably have from three to seven carbon atoms in the ring and are optionally substituted by halogen or alkyl.
The expression "(Cι-C6)-alkyl-(C3-C7)-cycloalkyr means a (d-C6)alkyl group which is substituted by a (C3-C7)cycloalkyl ring.
The expression "COCH2-(Cι-C )-alkoxy" means for example methoxyacetyi.
In compounds of formula (I) the following examples of radicals are provided:
An example of alkyl substituted by cycloalkyl is cyclopropylmethyl; an example of alkyl substituted by alkoxy is methoxymethyl (CH2OCH3); and an example of alkyl substituted by alkylthio is methylthiomethyl (CH2SCH3).
"CO2-(Cι-C6)-Alkyl" means a (Cι-C6)-alkoxycarbonyl radical.
"CO2-(Cι-C4)-Alkyl-(C3-C7)-cycloalkyl" means a (Cι-C )-alkoxycarbonyl radical which alkoxy moiety is substituted by a (C3-C7)-cycloalkyl radical.
"O(C=O)-(C1-C6)-Alkyl" means a (Cι-C6)-alkylcarbonyloxy radical.
"(Cι-C )-Alkyl-(C3-C )-cycloalkyl" means a (Cι-C4)-alkyl group which is substituted by a (C3-C7)-cycloalkyl ring.
A "heterocyclyl" group can be saturated, unsaturated or heteroaromatic; it preferably contains one or more, in particular 1, 2 or 3, hetero atoms in the heterocyclic ring, preferably selected from the group consisting of N, O and S; it is preferably an aliphatic heterocyclyl radical having 3 to 7 ring atoms or a heteroaromatic radical having 5 to 7 ring atoms. The heterocyclic radical can be, for example, a heteroaromatic radical or ring (heteroaryl) such as, for example, a mono-, bi- or polycyclic aromatic system in which at least 1 ring contains one or more hetero atoms, for example pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, thienyl, thiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, furyl, pyrrolyl, pyrazolyl, imidazolyl and triazolyl, or it is a partially or fully hydrogenated radical such as oxiranyl, oxetanyl, oxolanyl (= tetrahydrofuryl), oxanyl, pyrrolidyl, piperidyl, piperazinyl, dioxolanyl, oxazolinyl, isoxazolinyl, oxazolidinyl, isoxazolidinyl and morpholinyl. The "heterocyclyl" group may be unsubstituted or substituted, preferably by one or more radicals (preferably 1, 2 or 3 radicals) selected from the group consisting of halogen, alkoxy, haloalkoxy, alkylthio, hydroxyl, amino, nitro, carboxyl, cyano, alkoxycarbonyl, alkylcarbonyl, formyl, carbamoyl, mono- and dialkylaminocarbonyl, substituted amino such as acylamino, mono- and dialkylamino, and alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkyl and haloalkyl, and additionally also oxo. The oxo group can also be present at those hetero ring atoms where various oxidation numbers are possible, for example in the case of N and S.
The term pests means arthropod pests (including insects and arachnids), and helminths (including nematodes).
In the following preferred definitions it is generally to be understood that where symbols are not specifically defined they are to be as previously defined in the description.
Preferably R1 is CN or CSNH2 (more preferably R1 is CN).
Preferably W is C-CI or N (more preferably W is C-CI).
Preferably R2 is CI.
Preferably R3 is CF3 or OCF3 (more preferably R3 is CF3).
Preferably X is O.
Preferably Y is a covalent bond.
Preferably R4 is NR7R8.
Preferably R5 and R6 are each independently (C3-C4)-alkenyl, (C3-C )-haloalkenyl,
(C3-C4)-alkynyl, (C3-C4)-haloa!kynyl, (C3-C6)-cycloalkyl, (CH2)qR9 or (CH2)qR10; or are
(Cι-C3)-alkyl unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, (d-C3)-alkoxy, (d-C3)-haloalkoxy, (C3-C4)-alkenyloxy,
(C3-C4)-haloalkenyloxy, (C3-C4)-alkynyloxy, (C3-C )-haloalkyny!oxy, (C3-C6)- cycloalkyl, S(O)pR11, CN, NO2, OH, COR12, NR12R13, S(O)pR9, OR9 and CO2R12. More preferably R5 and R6 are each independently (Cι-C3)-alkyl or (CH2)qR9, wherein q is 0 or 1.
Preferably R7 is H, (C3-C )-alkenyl, (C3-C4)-haloalkenyl, (C3-C )-alkynyl, (C3-
C4)-haloalkynyl, (C3-C6)-cycloalkyl, CO2-(C1-C3)-alkyl, CO2-(C3-C6)-cycloalkyl,
CO2-(C1-C3)-alkyl-(C3-C6)-cycloalkyl, CO2-(C3-C4)-alkenyl, CO2-(CH2)qR9,
CONR12R13, CO2-(CH2)qR10, (CH2)qR9, (CH2)qR10, COR12 or COCH2-(d-C3)-alkoxy; or (CrC6)-alkyl unsubstituted or substituted by one or more R14 radicals.
More preferably R7 is H, (C1-C3)-alkyl unsubstituted or substituted by S(O)p(Cι-C3)- alkyl.
Preferably R8 is H, (C3-C4)-alkynyl, CO2-(d-C3)-alkylr (C3-C6)-cycloalkyl or SO2R15; or (Cι-C3)-alkyl, (C3-C4)-alkenyl or CO-(C C3)-alkyl which last three mentioned groups are unsubstituted or substituted by one or more R14 radicals.
More preferably Rδ is H or (C C3)-alkyl.
A preferred class of compounds of formula (I) are those in which:
R1 is CN or CSNH2 (more preferably R1 is CN);
W is C-CI or N;
R2 is CI;
R3 is CF3 or OCF3 (more preferably R3 is CF3);
R4 is NR7R8;
R5 and R6 are each independently H, (C3-C4)-alkenyl, (C3-C4)-haloalkenyl, (C3-C )- alkynyl, (C3-C4)-haloalkynyl, (C3-C6)-cycloalkyl, (CH2)qR9 or (CH2)qR10; or are (d-
C3)-alkyl unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, (CrC3)-alkoxy, (CrC3)-haloalkoxy, (C3-C )-alkenyloxy,
(C3-C4)-haloalkenyloxy, (C3-C4)-alkynyloxy, (C3-C4)-haloalkynyloxy, (C3-C6)- cycloalkyl, S(O)pR11, CN, NO2, OH, COR12, NR12R13, S(O)pR9, OR9 and CO2R12;
R7 is H, (C3-C4)-alkenyl, (C3-C4)-haloalkenyl, (C3-C4)-alkynyl, (C3-C4)-haloalkynyl,
(C3-C6)-cycloalkyl, CO2-(Cι-C3)-alkyl, CO2-(C3-C6)-cycloalkyl, CO2-(C1-C3)-alkyl-(C3-
C6)-cycloalkyl, CO2-(C3-C4)-alkenyl, CO2-(CH2)qR9, CONR12R13, CO2-(CH2)qR10,
(CH2)qR9, (CH2)qR10, COR12 or COCH2-(d-C3)-alkoxy; or (Cι-C6)-alkyl unsubstituted or substituted by one or more R14 radicals; R8 is H, (C3-C4)-alkynyl, CO2-(d-C3)-alkyl, (C3-C6)-cycloalkyl or SO2R15; or (C1-C3)- alkyl, (C3-C )-alkenyl or CO-(d-C3)-alkyl which last three mentioned groups are unsubstituted or substituted by one or more R14 radicals.
A further preferred class of compounds of formula (I) are those wherein:
R1 is CN or CSNH2 (more preferably R1 is CN);
W is C-CI;
R2 is CI;
R3 is CF3;
R4 is NH2 or NHCH3(more preferably R4 is NHCH3);
X is O or S;
Y and Z are each O, S or a covalent bond; and
R5 and R6 are each independently H, (C3-C4)-alkenyl, (C3-C4)-haloalkenyl, (C3-C4)- alkynyl, (C3-C4)-haloalkynyl, (C3-C6)-cycloalkyl, (CH2)qR9 or (CH2)qR10; or are (d-
C3)-alkyl unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, (d-C3)-alkoxy, (d-C3)-haloa!koxy, (C3-C4)-alkenyioxy,
(C3-C4)-haloalkenyloxy, (Cs-dJ-cycloalkyl, S(O)pR11, CN, COR12, S(O)pR9, OR9 and
CO2R12;
R7 is H, (C3-C4)-alkenyl, (C3-C4)-haloalkenyl, (C3-C4)-alkynyl, (C3-C4)-haloalkynyl,
(C3-C6)-cycloalkyl, CO2-(d-C3)-alkyl, CO2-(C3-C6)-cycloalkyl, CO2-(C1-C3)-alkyl-(C3-
C6)-cycloalkyl, CO2-(C3-C4)-alkenyl, CO2-(CH2)qR9, CONR12R13, CO2-(CH2)qR10,
(CH2)qR9, (CH2)qR10, COR12 or COCH2-(CrC3)-alkoxy; or (C C6)-alkyl unsubstituted or substituted by one or more R14 radicals; and
R8 is H, (C3-C4)-alkynyl, CO2-(d-C3)-alkyl, (C3-C6)-cycloalkyl or SO2R15; or (d-C3)- alkyl, (C3-C4)-alkenyl or CO-(Cι-C3)-alkyl which last three mentioned groups are unsubstituted or substituted by one or more R 4 radicals.
A further preferred class of compounds of formula (I) are those wherein: R1 is CN or CSNH2; W is C-CI; R2 is CI; R3 is CF3; R4 is NH2, NHCHsOr N=CHN-[(d-C6)-alkyl]2; X is O or S;
Y and Z are each O, S or a covalent bond; and
R5 and R6 are each independently H, (d-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-alkynyl, (C3-C7)-cycloalkyl, (d-C6)-alkyl-(C3-C7)-cycloalkyl, (CH2)qR9 or (CH2)qpyridyl.
A further preferred class of compounds of formula (I) are those wherein:
R1 is CN;
W is C-CI;
R2 is CI;
R3 is CF3;
R4 is NR7R8;
X is O;
Y and Z are each a covalent bond;
R5 and R6 are each the same or different (d-C6)-alkyl;
R7 is H, (C2-C6)-aIkenyl, (C2-C6)-alkynyl, (C3-C7)-cycloalkyl, (CH2)qR9 or
(CH2)qpyridyl; or (d-C6)-alkyl unsubstituted or substituted by (C3-C )-cycloalkyl or
S(O)pR11; and
R8 is H, (C2-C6)-alkenyl, (C2-C6)-alkynyl, CO2-(C C6)-alkyl, (C3-C7)-cycloalkyl,
(CH2)qR9, (CH2)qpyridyl or SO2R15; or (C C6)-alkyl unsubstituted or substituted by
(C3-C )-cycloalkyl; and
R15 is (C C6)-alkyl unsubstituted or substituted by R18.
The compounds of general formula (I) can be prepared by the application or adaptation of known methods (i.e. methods heretofore used or described in the chemical literature.
In the following description of processes when symbols appearing in formulae are not specifically defined, it is understood that they are "as defined above" in accordance with the first definition of each symbol in the specification. According to a feature of the invention compounds of formula (I) wherein R4 is N=CHN-[(C1-C6)-a[kyl]2, R5and R6 are as defined above with the exclusion of H, R1 is CN, and R2, R3, W, X , Y and Zare as defined above, may be prepared by the reaction of the corresponding compound of formula (II):
Figure imgf000012_0001
wherein R4 is
Figure imgf000012_0002
and the other values are as defined above, with a compound of formula (III):
Figure imgf000012_0003
wherein R5 and R6 are as defined above with the exclusion of H, and X , Y and Zare as defined above. A base is optionally present in the reaction which is generally performed in an inert solvent such as tetrahydrofuran, dioxan, acetonitrile, toluene, diethyl ether, dichloromethane, dimethylsulfoxide or N.N-dimethylformamide, at a temperature of from 0°C to 150°C, preferably from 20°C to 100°C. The base is generally an alkali metal hydroxide such as potassium hydroxide, an alkali metal hydride such as sodium hydride, an alkali metal carbonate such as potassium carbonate or sodium carbonate, an alkali metal alkoxide such as sodium methoxide, an alkaline earth metal carbonate such as calcium carbonate, or an organic base such as a tertiary amine, for example triethylamine or ethyldiisopropylamine, or pyridine, or 1 ,8-diazabicyclo[5.4.0]undec-7-en (DBU).
According to a further feature of the invention compounds of formula (I) wherein R4 is NH2, R1 is CN, and the other values are as defined above, may be prepared by the hydrolysis of the corresponding compound of formula (I) in which R4 is N=CHN-[(Cr C6)-alkyl]2. The hydrolysis is generally performed using an acid such as hydrochloric acid or 4-toluenesulfonic acid, optionally in a solvent such as dioxan, at a temperature of from 0°C to 100°C.
According to a further feature of he invention compounds of formula (I) wherein R5 and/or R6 is H, Y and Z are each O, S or NRa, R1 is CN, and the other values are as defined above, may be prepared by the hydrolysis of the corresponding compound of formula (I) in which R5 and/or Rδ is (d-C6)-alkyl, benzyl or trialkylsilyl such as trimethylsilyl. The hydrolysis reaction is generally performed using an acid such as trifluoroacetic acid or hydrochloric acid optionally in a solvent such as dioxan.
According to a further feature of the invention compounds of formula (I) wherein R5 and R6 are as defined above with the exclusion of H, R4 is N=CHN-[(Cι-C6)-alkyl]2, X is O, Y and Z are each O, NRa or a covalent bond, R1 is CN, and the other values are as defined above, may be prepared by the reaction of a corresponding compound of formula (IV):
Figure imgf000013_0001
wherein the various values are as defined above, with an oxidant preferably hydrogen peroxide, in an inert solvent for example dichloromethane or dioxan, at a temperature of from 0°C to 50°C.
According to a further feature of the invention compounds of formula (I) wherein R5 and R6 are each H, R4is N=CHN-[(d-C6)-alkyl]2, Y and Z are each O, R1 is CN, and the other values are as defined above, may be prepared by the reaction of the corresponding compound of formula (I) wherein R5 and Rδ are as defined above with the exclusion of H (preferably R5 and R6 are each (d-CδJ-alkyl), and the other values are as defined above, with a trialkylsilyl iodide (preferably trimethylsilyl iodide) of formula (V): R3Si-l (V) wherein R is (d-C6)-alkyl, in a solvent such as acetonitrile, at a temperature of from 0°C to 50°C, followed by hydrolysis with a base such as an alkali metal carbonate or bicarbonate, for example potassium carbonate or sodium bicarbonate, at a temperature of from 0°C to 100°C.
According to a further feature of the invention compounds of formula (I) wherein R5 is as defined above with the exclusion of H, R6 is H, R4is N=CHN-[(C1-C6)-alkyl]2, Y and Z are each O or are each S, R1 is CN, and the other values are as defined above, may be prepared by the reaction of the corresponding compound of formula (I) wherein R5 and R6 are as defined above with the exclusion of H (preferably R5 and/or R6 is (C-ι-C6)-alkyl), and the other values are as defined above, with an alkali metal azide preferably lithium azide, in a solvent such as N,N-dimethylformamide, at a temperature of from 50°C to 150°C (preferably from 70°C to 120°C).
According to a further feature of the invention compounds of formula (I) wherein R1 is CSNH2, and the other values are as defined above, may be prepared by the reaction of the corresponding compound of formula (I) wherein R1 is CN, with an alkali or alkaline earth metal hydrosulfide, such as lithium, potassium, calcium or preferably sodium hydrosulfide, in an inert solvent for example N,N-dimethylformamide, pyridine, dioxan, tetrahydrofuran, sulfolane, dimethyl sulfoxide, methanol or ethanol at a temperature of from -35°C to 50°C preferably 0°C to 30°C. Optionally the hydrosulfide may be generated in situ by treatment with H2S in the presence of an organic base, such as a metal alkoxide or trialkylamine or an inorganic base, such as an alkaline or alkaline earth metal hydroxide or a carbonate, such as sodium, potassium or ammonium carbonate. The use of a metal complexing agent, such as a crown ether, can be of benefit in accelerating the reaction. The reaction of hydrosulfide salt with the compound of formula (I) wherein R1 is CN, can also be conducted in a two-phase water/organic solvent system using a phase transfer catalyst such as a crown ether or a tetraalkylammonium salt such as tetra-n- butylammonium bromide or benzyltrimethylammonium chloride. Organic solvents suitable for use in a two-phase system with water include benzene, toluene, dichloromethane, 1-chlorobutane and methyl tertiary-butyl ether. Alternatively compounds of formula (I) wherein R1 is CSNH2 and the other values are as defined above, may also be prepared from the corresponding compound of formula (1) wherein R1 is CN, by treatment with the reagent Ph2PS2, as described in Tet. Lett., 24 (20), 2059 (1983).
According to a further feature of the invention compounds of formula (I) wherein R1 is CSNH2, and the other values are as defined above, may be prepared by the reaction of the corresponding compound of formula (I) wherein R1 is CN, with a bis(trialkylsilyl)sulfide, preferably bis(trimethylsilyl)sulfide, in the presence of a base generally an alkali metal alkoxide such as sodium methoxide, in a solvent such as N,N-dimethylformamide, at a temperature of from 0°C to 60°C. The procedure is generally described by Lin, Ku and Shiao in Synthesis 1219 (1992).
According to a further feature of the invention compounds of formula (I) wherein R1 is C(=N-H)-S-Q, and Q and the other values are as defined above, may be prepared by the reaction of the corresponding compound of formula (I) wherein R1 is CSNH2 with an alkylating agent of formula (VI) or (VII):
Q-L (VI) Q3O+ BF4- (VII)
wherein Q is as defined above and L is a leaving group, generally halogen and preferably chlorine, bromine or iodine. The reaction is generally performed in the presence of a base, for example an alkali metal hydride such as sodium hydride, or an alkali metal alkoxide such as potassium tert-butoxide, in an inert solvent such as tetrahydrofuran at a temperature from 0 to 60°C. Alternatively an alkali metal carbonate such as potassium carbonate, or an organic base such as a trialkylamine, for example triethylamine or N,N-diisopropylethylamine may be used, in an inert solvent such as acetone, at a temperature from 0°C to the reflux temperature of the solvent. When a compound of formula (VII) such as trimethyloxonium tetrafluoroborate is used as the alkylating agent, the base is preferably an alkali metal bicarbonate such as sodium bicarbonate, the solvent is for example dichloromethane, and the temperature is from 0°C to the reflux temperature of the solvent.
According to a further feature of the present invention compounds of formula (I) wherein R1 is C(=N-V)-S-Q, V is as defined above with the exclusion of H, and Q and the other values are as defined in formula (I), may be prepared by the alkylation, acylation or sulfonylation of the corresponding compound of formula (I) wherein R1 is C(=NH)-S-Q, with a compound of formula (VIII):
V-L (VIII)
wherein V is as defined above with the exclusion of H, and L1 is a leaving group. For alkylation reactions where V is (Cι-C3)-alkyl, (d-C6)-haIoalkyl, (C2-C6)-alkenyl, (C2-C6)-alkynyl or -(CH2)qR9, L1 is preferably halogen, alkylsulfonyloxy or arylsulfonyloxy (more preferably chlorine, bromine, iodine, methylsulfonyloxy or p- toluenesulfonyloxy). The reaction is generally performed in an inert solvent such as tetrahydrofuran, dioxan, acetonitrile, toluene, diethyl ether, dichloromethane, dimethylsulfoxide or N,N-dimethylformamide, at a temperature of from -30°C to 200°C, preferably at 20°C to 100°C. A base is optionally present in the reaction, and when present is preferably an alkali metal hydroxide such as potassium hydroxide, an alkali metal hydride such as sodium hydride, an alkali metal carbonate such as potassium carbonate or sodium carbonate, an alkali metal alkoxide such as sodium methoxide, an alkaline earth metal carbonate such as calcium carbonate, or an organic base such as a tertiary amine, for example triethylamine or ethyldiisopropylamine, or pyridine, or 1 ,8-diazabicyclo[5.4.0]undec-7-en (DBU). For acylations where V is COR20 or CO2-(C1-C6)-alkyl, (VIII) is preferably an acid halide, L1 is preferably chlorine or bromine (more preferably chlorine). The reaction is generally performed using similar bases, solvents and temperatures as are employed for the alkylations.
For sulfonylations where V is SO2R20, (VIII) is preferably a sulfonyl halide and L1 is preferably chlorine or bromine (more preferably chlorine). The reaction is generally performed using similar bases, solvents and temperatures as are employed for the alkylations.
According to a further feature of the invention compounds of formula (I) wherein R4 is NR7R8, one of R7 or R8 is as defined above with the exclusion of H, R1 is CN and the other values are as defined above, may be prepared by the alkylation, acylation or sulfonylation of the corresponding compound of formula (I) in which R4 is NHR7or NHR8, wherein R7 or R8 are as defined above, with a compound of formula (IX) or (X) respectively:
R8-L2 (IX) R7-L3 (X)
wherein R7 and R8 are as defined above with the exclusion of H, and L2 and L3 are each a leaving group.
For alkylations, where R7 is (C2-C6)-alkenyl, (C2-C6)-haloalkenyl, (C2-C6)-alkynyl, (C2- C6)-haloalkynyl, (C3-C7)-cycloalkyl, (CH2)qR9, (CH2)qR10 or (d-C6)-alkyl which last mentioned group is unsubstituted or substituted by one or more R14 radicals; or where R8 is (C2-C6)-alkynyl, (C3-C7)-cycloalkyl, (CH2)qR9, (CH2)qR10, (d-C6)-alkyl or (C2-C6)-alkenyl which last two mentioned groups are unsubstituted or substituted by one or more R14 radicals; L2 and L3 are preferably halogen, alkylsulfonyloxy or arylsulfonyloxy (more preferably chlorine, bromine, iodine, methylsulfonyloxy or p- toluenesulfonyloxy). Alkylation reactions may be performed according to the above alkylation procedure for the preparation of compounds of formula (I) wherein R1 is C(=N-V)-S-Q from compounds of formula (VIII).
For acylations, where R7 is CO2-(d-C6)-alkyl, CO2-(C3-C7)-cycloalkyl, CO2-(C C4)-alkyl-(C3-C7)-cycloalkyl, CO2-(C2-C6)-alkenyl, CO2-(CH2)qR9, CONR12R13, CO2-(CH2)qR10, COR12 or COCH2-(d-C4)-alkoxy; or where R8 is CO2-(d-C6)-alkyl or CO-(Cι-C6)-alkyl which last mentioned group is unsubstituted or substituted by one or more R14 radicals, (IX) or (X) is preferably an acid halide and L2 and L3 is preferably chlorine or bromine (more preferably chlorine). Acylation reactions may be performed according to the above acylation procedure for the preparation of compounds of formula (I) wherein R1 is C(=N-V)-S-Q from compounds of formula (VIII).
For sulfonylations, where R8 is SO2R15, (IX) is preferably a sulfonyl halide where L2 is preferably chlorine or bromine (more preferably chlorine). Sulfonylation reactions may be performed according to the above sulfonylation procedure for the preparation of compounds of formula (I) wherein R1 is C(=N-V)-S-Q from compounds of formula (VIII).
According to a further feature ofthe invention compounds of formula (I) wherein n is 1 or 2 and the other values are as defined above, may be prepared by the oxidation of the corresponding compound in which n is 0 or 1. The oxidation is generally performed using a peracid such as 3-chloroperbenzoic acid in a solvent such as dichloromethane or 1 ,2-dichloroethane, at a temperature of from 0°C to the reflux temperature of the solvent.
According to a further feature of the invention compounds of formula (I) wherein R4 is OH, H, halogen, (C C6)-alkoxy, (d-C6)-alkyl, OCO-(d-C6)-alkyl or S(O)m-(d- C6)-alkyl may be prepared by the adaptation of known methods, for example as described in WO 8703781, WO 0140195 or EP 295117, or references cited therein.
Intermediates of formula (II) may be prepared, for example by the reaction of the corresponding compounds of formula (II) in which R4 is replaced by alkoxymethyleneamino, with dialkylamines according to known methods. The 5- alkoxymethyleneaminopyrazoles may be obtained by methods described in WO 8703781 or EP 295117.
Intermediates of formula (IV) wherein R5 and R6 are as defined above with the exclusion of H, R4is N=CHN-[(Cι-C6)-alkyl]2, Y and Z are each O, and the other values are as defined above, may be prepared by the reaction of a corresponding compound of formula (XI):
Figure imgf000019_0001
wherein the various values are as defined above, with a compound of formula (XII) or (XIII): R5-OH (XII) R6-OH (XIII)
wherein R5 and R6 are as defined above. The reaction is generally performed in the presence of a base such as a trialkylamine for example triethylamine, in a solvent for example ether, at a temperature of from 0°C to 50°C.
Intermediates of formula (IV) wherein R5 and R6 are as defined above with the exclusion of H, R4is N=CHN-[(Cι~C6)-alkyl]2, Y and Z are each a covalent bond, and the other values are as defined above, may be prepared by the reaction of a compound of formula (XI) as defined above with a compound of formula (XIV) or (XV):
R5-Mg-L (XIV) R6-Mg-L (XV)
wherein R5 and R6 are as defined above, and L is a leaving group for example halogen, preferably Br or I, in a solvent for example ether, at a temperature of from -70°C to +30°C.
Intermediates of formula (XI) may be prepared by the reaction of a compound of formula (III) wherein R4 is N=CHN-[(C -C6)-alkyl]2with phosphorus trichloride, in the presence of a base, such as pyridine, at a temperature of from -40°C to +30°C. Collections of compounds of the formula (I) which can be synthesized by the above mentioned process 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 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.
A series of commercially available apparatuses as are offered by, for example, Stem Corporation, Woodrolfe Road, Tollesbury, Essex, CM9 8SE, England or H+P Labortechnik GmbH, Bruckmannring 28, 85764 Oberschleiβheim, Germany or Radleys, Shirehill, Saffron Walden, Essex, England, may be used for the parallel procedure of the reaction and work-up. For the parallel purification of compounds of the formula (I), or of intermediates obtained during the preparation, use may be made, inter alia, of chromatography apparatuses, for example those by ISCO, Inc., 4700 Superior Street, Lincoln, NE 68504, USA.
The apparatuses mentioned lead 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 formula (I) 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 formula (I) in the form of substance collections which are termed libraries. The present invention also relates to libraries which comprise at least two compounds of the formula (I).
Compounds of formula (III), (V), (VI), (VII), (VIII), (IX), (X), (XII), (XIII), (XIV) and (XV) are known or may be prepared by known methods.
The following non-limiting Examples illustrate the preparation of the compounds of formula (I). Chemical Examples
P-31 NMR spectra were run in the solvents stated.
Example 1
Diethyl 1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-5-[(E)- dimethylaminomethylideneamino]pyrazol-4-ylphosphonate
A solution of hydrogen peroxide (50%, 2.5 g) in dry ethanol (40 ml) at -30°C was added to a solution of diethyl 1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-5-[(E)- dimethylaminomethylideneamino]pyrazol-4-ylphosphonite (4.05 g, 0.008 mol) in dry ethanol (5 ml) at -50°C. After 15 minutes the temperature was raised to 20°C, the ethanol evaporated in vacuo without heating, the residue washed with water (4x30 ml), and dried in vacuo. The oily residue was dissolved in hexane (40 ml) at 50°C and the mixture treated with activated carbon and filtered. The filtrate was evaporated to give the title compound as a yellow oil (Compound 11-3, 3.75 g, yield 90%), mp 147°C, NMR δP (hexane) 17.6 ppm.
Example 2
Ethyl hydrogen 1 -(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-5-[(E)- dimethylaminomethylideneamino]pyrazol-4-ylphosphonate
Lithium azide (0.46 g, 0.094 mol) was added to a solution of diethyl 1-(2,6-dichIoro-4- trifluoromethylphenyI)-3-cyano-5-[(E)-dimethylaminomethylideneamino]pyrazol-4- ylphosphonate (0.78 g, 0.0016 mol) in N,N-dimethylformamide (8 ml) and the mixture heated at 95-100°C for 1 hour. After evaporation in vacuo at 90°C, water (5 ml) was added, and the residue extracted with benzene (3x5 ml). The aqueous layer was separated and the pH adjusted to 1 with hydrochloric acid. The solution was evaporated in vacuo at 90°C, and the residue treated with acetonitrile (10 ml), filtrated and evaporated. The crystalline residue was triturated with hot ether and the solid filtered and washed with ether to give the title compound (Compound 11-4, 0.55 g, yield 75%), mp 147°C, NMR δP (acetonitrile) 7.5 ppm.
Example 3
1-(2,6-Dichloro-4-trifluoromethyIphenyl)-5-[(E)-dimethylaminomethylideneamino]-3- cyanopyrazol-4-ylphosphonic acid
Trimethylsilyl iodide (1.02 g, 0.0151 mol) was added to a solution of diethyl 1-(2,6- dichloro-4-trifluoromethylphenyl)-3-cyano-5-[(E)- dimethylaminomethylideneamino]pyrazol-4-ylphosphonate (0.76 g, 0.0015 mol) in acetonitrile (3 ml) and the mixture left for 24 hours at 20°C. The solvent was evaporated in vacuo, the residue extracted with water (4x10 ml) at 50°C and the pH adjusted to 9 with sodium bicarbonate. After 3 days the mixture was filtered, the filtrate was treated with activated carbon, filtrered and evaporated in vacuo. The residue was extracted with hot acetonitrile (10 ml) and filtered hot, then washed with acetonitrile and dried to give the title compound (Compound 11-5, 0.2 g, yield 26%), NMR δP (water) 3.7 ppm.
Example 4
Dimethyl 1~(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-5-[(E)- dimethylaminomethylideneamino]pyrazol-4-yl] phosphine oxide
Hydrogen peroxide (2 ml of 20% solution) was added to a solution of dimethyl 1-(2,6- dichloro-4-trifluoromethyIphenyl)-3-cyano-5-[(E)- dimethylaminomethylideneamino]pyrazol-4-yl] phosphine (2.9 g, 0.0066 mol) in benzene (10 ml) at 0°C. The mixture was shaken periodically and allowed to warm to 20°C, then washed with benzene (2x5 ml). Sodium hydroxide solution (10%) was added and the organic phase separated, washed with water (10 ml) and evaporated. The residue was crystallised from ether (20 ml) to give the title compound (Compound 11-2, 1.5 g, 52% yield), mp 231°C, NMR δP (benzene) 25.2 ppm.
The following Intermediate Examples illustrate the preparation of intermediates used in the synthesis of the above Examples.
Intermediate Example 1
Figure imgf000024_0001
11-1
1-(2,6-Dichloro-4-trifluoromethylphenyl)-3-cyano-5-[(E)- dimethylaminomethylideneamino]pyrazol-4-ylphosphonous dichloride
Phosphorus trichloride (2.74 g, 0.02 mol) was added to a solution of 1-(2,6-dichloro- 4-trifluoromethylphenyl)-3-cyano-5-[(E)-(dimethylamino)methylideneamino]pyrazole (4.8 g, 0.013 mol) in pyridine (10 ml) at -30°C. After 15 minutes the temperature was raised to 15°C. After 2 hours triethylamine (2.73 g, 0.027 mol) was added and the mixture stirred for 1 hour. The precipitated solid was separated under an argon atmosphere, and washed with ether (2x10 ml). The filtrate was evaporated in vacuo and the residue extracted with ether (3x10 ml), concentrated and the residue recrystallised from hexane to give the title compound (5.01 g, yield 80%).
Intermediate Example 2
Diethyl 1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-5-[(E)~ dimethylaminomethylideneamino]pyrazol-4-ylphosphonite
A mixture of dry ethanol (1.15 g, 0.025 mol) and triethylamine (2.93 g, 0.029 mol) in ether (40 ml) was added dropwise during 20 minutes to a solution of 1-(2,6-dichloro- 4-trifluoromethylphenyl)-3-cyano-5-[(E)-dimethylaminomethylideneamino]pyrazol-4- ylphosphonous dichloride (4.45 g, 0.01 mol) in ether (40 ml) at 0°C. The reaction mixture was warmed to 20°C and left for 24 hours. The residue was separated under an argon atmosphere, and washed with ether (2x20 ml). The filtrate was evaporated to give the title compound as an oil (4.2 g, yield 91%), NMR δP (ether) 158.2 ppm.
Intermediate Example 3
Dimethyl 1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-5-[(E)- dimethylaminomethylideneamino]pyrazoi-4-yl] phosphine
A solution of methylmagnesium bromide (2.2 ml) was added during 15 minutes to a solution of 1 -(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-5-[(E)- dimethylaminomethylideneamino]pyrazol-4-ylphosphonous dichloride (4.5 g, 0.0092 mol) in ether (100 ml) at -70°C, during which the temperature increased to 20°C. The solution was cooled to -60°C and a saturated solution of ammonium chloride (30 ml) added. The mixture was warmed to 20°C, the ethereal layer separated under an argon atmosphere and the solvent evaporated. The residue was extracted with benzene (10 ml), filtered under an argon atmosphere and evaporated in vacuo to give the title compound (2.9 g, yield 70%), NMR δP (benzene) 73.6 ppm.
The following preferred compounds shown in Tables 1 to 11 also form part of the present invention, and were or may be prepared in accordance with, or analogously to, the above-mentioned Examples 1 to 4 or the above-described general methods. In the Tables Ph means phenyl and SO2(2,4-Et-Ph)means 2,4-diethylphenylsulfonyl. "Cpd Number" means Compound numbers, which are given for reference purposes only. In Tables 1 to 9 the carbon atom on the left side of the R5 and R6 values is bonded to Y and Z respectively. In Table 10 the carbon atom on the left side of the R7 and R8 values is bonded to the N atom of the NR7R8 group.
Table I: Compounds of formula (I) in which the substituents have the following meanings:
R1 is CN; R2 is CI; W is C-CI; R3 is CF3; R4 is NH2; X is O; and Z and Y are covalent bonds.
Figure imgf000026_0001
Table 2: Compounds of formula (I) in which R1 is CN; R2 is CI; W is C-CI; R3 is CF3; R4 is NHCH3; X is O; and Z and Y are covalent bonds.
Figure imgf000026_0002
Figure imgf000027_0001
Table 3: Compounds of formula (I) in which R1 is C(S)NH2; R2 is CI; W is C-CI; R3 is CF3; R4 is NHCH3; X is O; and Z and Y are covalent bonds.
Figure imgf000027_0002
Figure imgf000028_0001
Table 4: Compounds of formula (I) in which R1 is C(S)NH2; R2 is CI; W is C-CI; R3 is CF3; R4 is NH2; X is O; and Z and Y are covalent bonds.
Figure imgf000028_0002
Figure imgf000029_0001
Table 5: Compounds of formula (I) in which R1 is C(S)NH2; R2 is CI; W is C-CI; R3 is CF3; R4 is NHCH3; X is S; and Z and Y are covalent bonds.
Figure imgf000029_0002
Figure imgf000030_0001
Table 6: Compounds of formula (I) in which R1 is CN; R2 is CI; W is C-CI; R3 is CF3; R4 is NHCH3; X is S; and Z and Y are covalent bonds.
Figure imgf000030_0002
Figure imgf000031_0001
Table 7: Compounds of formula (I) in which R1 is CN; R2 is CI; W is C-CI; R3 is CF3; R4 is NH2; X is S; and Z and Y are covalent bonds.
Figure imgf000031_0002
Figure imgf000032_0001
Table 8: Compounds of formula (I) in which R1 is CN; R2 is CI; W is C-CI; R3 is CF3; R4 is NHCH3; and X, Y and Z are O.
Figure imgf000032_0002
Figure imgf000033_0001
Table 9: Compounds of formula (I) in which R1 is CN; R2 is CI; W is C-CI; R3 is CF3; R4 is NHCH3; X is O; Y and Z are S.
Figure imgf000033_0002
Figure imgf000034_0001
Table 10: Compounds of formula (I) in which R1 is CN; R2 is CI; W is C-CI; R3 is CF3; R4 is NR7R8; X is O; Y and Z are each a covalent bond; and R5 and R6 are each CH3.
Figure imgf000034_0002
Figure imgf000035_0001
Table 11: Compounds of formula (I) in which R2 is CI; W is C-CI; X is O; and R3 is CF3.
Figure imgf000035_0002
According to a further feature of the present invention there is provided a method for the control of pests at a locus which comprises applying thereto an effective amount of a compound of formula (I) or a salt thereof. For this purpose, the said compound is normally used in the form of a pesticidal composition (i.e. in association with compatible diluents or carriers and/or surface active agents suitable for use in pesticidal compositions), for example as hereinafter described.
The term "compound of the invention" as used hereinafter embraces a 4- phosphorylpyrazole derivatives of formula (I) as defined above and a pesticidally acceptable salt thereof.
One aspect of the present invention as defined above is a method for the control of pests at a locus. The locus includes, for example, the pest itself, the place (plant, field, forest, orchard, waterway, soil, plant product, or the like) where the pest resides or feeds, or a place susceptible to future infestation by the pest. The compound of the invention may therefore be applied directly to the pest, to the place where the pest resides or feeds, or to the place susceptible to future infestation by the pest. As is evident from the foregoing pesticidal uses, the present invention provides pesticidally active compounds and methods of use of said compounds for the control of a number of pest species which includes: arthropods, especially insects or mites, or plant nematodes. The compound of the invention may thus be advantageously employed in practical uses, for example, in agricultural or horticultural crops, in forestry, in veterinary medicine or livestock husbandry, or in public health. The compounds ofthe invention may be used for example in the following applications and on the following pests:
For the control of soil insects, such as corn rootworm, termites (especially for protection of structures), root maggots, wireworms, root weevils, stalkborers, cutworms, root aphids, or grubs. They may also be used to provide activity against plant pathogenic nematodes, such as root-knot, cyst, dagger, lesion, or stem or bulb nematodes, or against mites. For the control of soil pests, for example corn rootworm, the compounds are advantageously applied to or incorporated at an effective rate into the soil in which crops are planted or to be planted or to the seeds or growing plant roots.
In the area of public health, the compounds are especially useful in the control of many insects, especially filth flies or other Dipteran pests, such as houseflies, stableflies, soldierflies, hornflies, deerflies, horseflies, midges, punkies, blackflies, or mosquitoes.
In the protection of stored products, for example cereals, including grain or flour, groundnuts, animal feedstuffs, timber or household goods, e.g. carpets and textiles, compounds of the invention are useful against attack by arthropods, more especially beetles, including weevils, moths or mites, for example Ephestia spp. (flour moths),
Anthrenus spp. (carpet beetles), Tribolium spp. (flour beetles), Sitophilus spp. (grain weevils) or Acarus spp. (mites).
In the control of cockroaches, ants or termites or similar arthropod pests in infested domestic or industrial premises or in the control of mosquito larvae in waterways, wells, reservoirs or other running or standing water.
For the treatment of foundations, structures or soil in the prevention of the attack on building by termites, for example, Reticulitermes spp., Heterotermes spp.,
Coptotermes spp..
In agriculture against adults, larvae and eggs of Lepidoptera (butterflies and moths), e.g. Heliothis spp. such as Heliothis virescens (tobacco budworm), Heliothis armigera and Heliothis zea. Against adults and larvae of Coleoptera (beetles) e.g.
Anthonomus spp. e.g. grandis (cotton boll weevil), Leptinotarsa decemlineata
(Colorado potato beetle), Diabrotica spp. (corn rootworms). Against Heteroptera
(Hemiptera and Homoptera) e.g. Psylla spp., Bemisia spp., Trialeurodes spp., Aphis spp., Myzus spp., Megoura viciae, Phylloxera spp., Nephotettix spp. (rice leaf hoppers), Nilaparvata spp..
Against Diptera e.g. Musca spp.. Against Thysanoptera such as Thrips tabaci.
Against Orthoptera such as Locusta and Schistocerca spp., (locusts and crickets) e.g. Gryllus spp., and Acheta spp. for example, Blatta orientalis, Periplaneta americana, Blatella germanica, Locusta migratoria migratorioides, and Schistocerca gregaria. Against Collembola e.g. Periplaneta spp. and Blatella spp. (roaches).
Against arthropods of agricultural significance such as Acari (mites) e.g. Tetranychus spp., and Panonychus spp..
Against nematodes which attack plants or trees of importance to agriculture, forestry or horticulture either directly or by spreading bacterial, viral, mycoplasma or fungal diseases of the plants. For example root-knot nematodes such as Meloidogyne spp. (e.g. M. incognita).
In the field of veterinary medicine or livestock husbandry or in the maintenance of public health against arthropods which are parasitic internally or externally upon vertebrates, particularly warm-blooded vertebrates, for example domestic animals, e.g. cattle, sheep, goats, equines, swine, poultry, dogs or cats, for example Acarina, including ticks (e.g. soft-bodied ticks including Argasidae spp. e.g. Argas spp. and Ornithodorus spp. (e.g. Ornithodorus moubata); hard-bodied ticks including Ixodidae spp., e.g. Boophilus spp. e.g. Boophilus microplus, Rhipicephalus spp. e.g. Rhipicephalus appendiculatus and Rhipicephalus sanguineus; mites (e.g. Damalinia spp.); fleas (e.g. Ctenocephalides spp. e.g. Ctenocephalides felis (cat flea) and Ctenocephalides canis (dog flea)); lice e.g. Menopon spp.; Diptera (e.g. Aedes spp., Anopheles spp., Musca spp., Hypoderma spp.); Hemiptera.; Dictyoptera (e.g. Periplaneta spp., Blatella spp.); Hymenoptera; for example against infections of the gastro-intestinal tract caused by parasitic nematode worms, for example members of the family Trichostrongylidae.
In a preferred aspect of the invention the compounds of formula (I) are used for the control of parasites of animals. Preferably the animal to be treated is a domestic companion animal such as a dog or a cat.
In a further aspect of the invention the compounds of formula (I) or salts or compositions thereof are used for the preparation of a veterinary medicament.
A further feature of the invention thus relates to the use of a compound of formula (I) or a salt thereof, or of a composition thereof, for the control of pests.
In practical use for the control of arthropods, especially insects or mites, or helminths, especially nematode pests of plants, a method, for example, comprises applying to the plants or to the medium in which they grow an effective amount of a compound of the invention. For such a method, the compound of the invention is generally applied to the locus in which the arthropod or nematode infestation is to be controlled at an effective rate in the range of about 2g to about 1 kg of the active compound per hectare of locus treated. Under ideal conditions, depending on the pest to be controlled, a lower rate may offer adequate protection. On the other hand, adverse weather conditions, resistance of the pest or other factors may require that the active ingredient be used at higher rates. The optimum rate depends usually upon a number of factors, for example, the type of pest being controlled, the type or the growth stage of the infested plant, the row spacing or also the method of application. Preferably an effective rate range of the active compound is from about 10g/ha to about 400g/ha, more preferably from about 50g/ha to about 200 g/ha. When a pest is soil-borne, the active compound generally in a formulated composition, is distributed evenly over the area to be treated (ie, for example broadcast or band treatment) in any convenient manner and is applied at rates from about 10g/ha to about 400g ai/ha, preferably from about 50g/ha to about 200 g ai/ha. When applied as a root dip to seedlings or drip irrigation to plants the liquid solution or suspension contains from about 0.075 to about 1000 mg ai/l, preferably from about 25 to about 200 mg ai/l. Application may be made, if desired, to the field or crop-growing area generally or in close proximity to the seed or plant to be protected from attack. The compound of the invention can be washed into the soil by spraying with water over the area or can be left to the natural action of rainfall. During or after application, the formulated compound can, if desired, be distributed mechanically in the soil, for example by ploughing, disking, or use of drag chains. Application can be prior to planting, at planting, after planting but before sprouting has taken place, or after sprouting.
The compound of the invention and methods of control of pests therewith are of particular value in the protection of field, forage, plantation, glasshouse, orchard or vineyard crops, of ornamentals, or of plantation or forest trees, for example: cereals (such as wheat or rice), cotton, vegetables (such as peppers), field crops (such as sugar beets, soybeans or oil seed rape), grassland or forage crops (such as maize or sorghum), orchards or groves (such as of stone or pit fruit or citrus), ornamental plants, flowers or vegetables or shrubs under glass or in gardens or parks, or forest trees (both deciduous and evergreen) in forests, plantations or nurseries. They are also valuable in the protection of timber (standing, felled, converted, stored or structural) from attack, for example, by sawflies or beetles or termites. They have applications in the protection of stored products such as grains, fruits, nuts, spices or tobacco, whether whole, milled or compounded into products, from moth, beetle, mite or grain weevil attack. Also protected are stored animal products such as skins, hair, wool or feathers in natural or converted form (e.g. as carpets or textiles) from moth or beetle attack as well as stored meat, fish or grains from beetle, mite or fly attack.
Additionally, the compound of the invention and methods of use thereof are of particular value in the control of arthropods or helminths which are injurious to, or spread or act as vectors of diseases of domestic animals, for example those hereinbefore mentioned, and more especially in the control of ticks, mites, lice, fleas, midges, or biting, nuisance or myiasis flies. The compounds of the invention are particularly useful in controlling arthropods or helminths which are present inside domestic host animals or which feed in or on the skin or suck the blood of the animal, for which purpose they may be administered orally, parenterally, percutaneously or topically.
The compositions hereinafter described for application to growing crops or crop growing loci or as a seed dressing may, in general, alternatively be employed in the protection of stored products, household goods, property or areas of the general environment. Suitable means of applying the compounds of the invention include: to growing crops as foliar sprays (for example as an in-furrow spray), dusts, granules, fogs or foams or also as suspensions of finely divided or encapsulated compositions as soil or root treatments by liquid drenches, dusts, granules, smokes or foams; to seeds of crops via application as seed dressings, e.g. by liquid slurries or dusts; to animals infested by or exposed to infestation by arthropods or helminths, by parenteral, oral or topical application of compositions in which the active ingredient exhibits an immediate and/or prolonged action over a period of time against the arthropods or helminths, for example by incorporation in feed or suitable orally- ingestible pharmaceutical formulations, edible baits, salt licks, dietary supplements, pour-on formulations, sprays, baths, dips, showers, jets, dusts, greases, shampoos, creams, wax smears or livestock self-treatment systems; to the environment in general or to specific locations where pests may lurk, including stored products, timber, household goods, or domestic or industrial premises, as sprays, fogs, dusts, smokes, wax-smears, lacquers, granules or baits, or in tricklefeeds to waterways, wells, reservoirs or other running or standing water.
The compounds of formula (I) are particularly useful for the control of parasites of animals when applied orally, and in a further preferred aspect of the invention the compounds of formula (I) are used for the control of parasites of animals by oral application. The compounds of the formula (I) or salts thereof may be administered before, during or after meals. The compounds of the formula (I) or salts thereof may be mixed with a carrier and/or foodstuff.
The compound of the formula (I) or salt thereof is administered orally in a dose to the animal in a dose range generally from 0.1 to 500 mg/kg of the compound of the formula (I) or salt thereof per kilogram of animal body weight (mg/kg). The frequency of treatment of the animal, preferably the domestic animal to be treated by the compound of the formula (I) or salt thereof is generally from about once per week to about once per year, preferably from about once every two weeks to once every three months.
The compounds of the invention may be administered most advantageously with another parasiticidally effective material, such as an endoparasiticide, and/or an ectoparasiticide, and/or an endectoparasiticide. For example, such compounds include macrocyclic lactones such as avermectins or milbemycins e.g., ivermectin, pyratel or an insect growth regulator such as lufenuron or methoprene.
The compounds of the formula (I) 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. Thus, transgenic plants are known where the starch content is increased, or the starch quality is altered, or where the harvested material has a different fatty acid composition.
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 formula (I) for controlling harmful organisms in transgenic crop plants.
According to a further feature of the present invention there is provided a pesticidal composition comprising one or more compounds of the invention as defined above, in association with, and preferably homogeneously dispersed in one or more compatible pesticidally acceptable diluents or carriers and/or surface active agents [i.e. diluents or carriers and/or surface active agents of the type generally accepted in the art as being suitable for use in pesticidal compositions and which are compatible with compounds of the invention].
In practice, the compounds of the invention most frequently form parts of compositions. These compositions can be employed to control arthropods, especially insects, or plant nematodes or mites. The compositions may be of any type known in the art suitable for application to the desired pest in any premises or indoor or outdoor area. These compositions contain at least one compound of the invention as the active ingredient in combination or association with one or more other compatible components which are for example, solid or liquid carriers or diluents, adjuvants, surface-active-agents, or the like appropriate for the intended use and which are agronomically or medicinally acceptable. These compositions, which may be prepared by any manner known in the art, likewise form a part of this invention.
The compounds of the invention, in their commercially available formulations and in the use forms prepared from these formulations may be present in mixtures with other active substances such as insecticides, attractants, sterilants, acaricides, nematicides, fungicides, 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, flupyrazofos, fonofos, formothion, fosthiazate, 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-furylmethy! (E)- (1R)-cis-2,2-dimethyl- 3-(2-oxothiolan-3-ylidenemethyl)cyclopropanecarboxylate, beta-cyfluthrin, alpha- cypermethrin, beta-cypermethrin, bioallethrin, bioallethrin ((S)-cyclopentylisomer), bioresmethrin, bifenthrin, (RS)-1-cyano-1-(6-phenoxy-2-pyridyl)methyl (1RS)-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 (® isomer), prallethrin, pyrethrins (natural products), resmethrin, tefluthrin, tetramethrin, theta-cypermethrin, 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, acequinocyl, Anagrapha falcitera, AKD-1022, AKD-3059, ANS-118, azadirachtin, Bacillus thuringiensis, Beauveria bassianea, bensultap, bifenazate, binapacryl, BJL-932, bromopropylate, BTG-504, BTG-505, buprofezin, camphechlor, cartap, chlorobenzilate, chlorfenapyr, chlorfluazuron, 2- (4-chlorophenyl)-4,5-diphenylthiophene (UBI-T 930), chlorfentezine, chlorproxyfen, chromafenozide, clothianidine, 2-naphthylmethyl cyclopropanecarboxylate (Ro12- 0470), cyromazin, diacloden (thiamethoxam), diafenthiuron, DBI-3204, ethyl 2- chloro-N-(3,5-dich!oro-4-(1 , 1 ,2,3,3, 3-hexafluoro-1-propyloxy)phenyl)carbamoyl)-2- carboximidate, DDT, dicofol, diflubenzuron, N-(2,3-dihydro-3-methyl-1 ,3-thiazol-2- ylidene)-2,4-xylidine, dihydroxymethyldihydroxypyrrolidine, dinobuton, dinocap, diofenolan, emamectin benzoate, endosulfan, ethiprole (sulfethiprole), ethofenprox, etoxazole, fenazaquin, fenoxycarb, fipronil, flonicamid (IKI-220), fluazuron, flumite (flufenzine, SZI-121), 2-fluoro-5-(4-(4-ethoxyphenyI)-4-methyl-1-pentyl)diphenyl ether (MTI 800), granulosis and nuclear polyhedrosis viruses, fenpyroximate, fenthiocarb, fluacrypyrim, flubenzimine, flubrocythrinate, flucycloxuron, flufenoxuron, flufenzine, flufenprox, fluproxyfen, gamma-HCH, halfenozide, halofenprox, hexaflumuron (DE_473), hexythiazox, HOI-9004, hydramethylnon (AC 217300), indoxacarb, ivermectin, L-14165, imidacloprid, indoxacarb (DPX-MP062), kanemite (AKD-2023), lufenuron, M-020, M-020, methoxyfenozide, milbemectin, NC-196, neemgard, nidinoterfuran, nitenpyram, 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), novaluron, pirydaryl, propargite, protrifenbute, pymethrozine, pyridaben, pyrimidifen, pyriproxyfen, NC-196, NC-1111 , NNI-9768, novaluron (MCW-275), OK-9701 , OK-9601, OK-9602, OK-9802, R-195, RH-0345, RH-2485, RYI-210, S-1283, S-1833, SI-8601, silafluofen, silomadine (CG-177), spinosad, spirodiclofen, SU-9118, tebufenozide, tebufenpyrad, teflubenzuron, tetradifon, tetrasul, thiacloprid, thiocyclam, thiamethoxam, tolfenpyrad, triazamate, triethoxyspinosyn A, triflumuron, verbutin, vertalec (mykotal), YI-5301.
The abovementioned components for combinations are known active substances, many of which are described in Ch.R Worthing, S.B. Walker, The Pesticide Manual, 12th Edition, British Crop Protection Council, Farnham 2000.
The effective use doses of the compounds employed in the invention can vary within wide limits, particularly depending on the nature of the pest to be eliminated or degree of infestation, for example, of crops with these pests. In general, the compositions according to the invention usually contain about 0.05 to about 95% (by weight) of one or more active ingredients according to the invention, about 1 to about 95% of one or more solid or liquid carriers and, optionally, about 0.1 to about 50% of one or more other compatible components, such as surface-active agents or the like. In the present account, the term "carrier" denotes an organic or inorganic ingredient, natural or synthetic, with which the active ingredient is combined to facilitate its application, for example, to the plant, to seeds or to the soil. This carrier is therefore generally inert and it must be acceptable (for example, agronomically acceptable, particularly to the treated plant).
The carrier may be a solid, for example, clays, natural or synthetic silicates, silica, resins, waxes, solid fertilizers (for example ammonium salts), ground natural minerals, such as kaolins, clays, talc, chalk, quartz, attapulgite, montmorillonite, bentonite or diatomaceous earth, or ground synthetic minerals, such as silica, alumina, or silicates especially aluminium or magnesium silicates. As solid carriers for granules the following are suitable: crushed or fractionated natural rocks such as calcite, marble, pumice, sepiolite and dolomite; synthetic granules of inorganic or organic meals; granules of organic material such as sawdust, coconut shells, corn cobs, corn husks or tobacco stalks; kieselguhr, tricalcium phosphate, powdered cork, or absorbent carbon black; water soluble polymers, resins, waxes; or solid fertilizers. Such solid compositions may, if desired, contain one or more compatible wetting, dispersing, emulsifying or colouring agents which, when solid, may also serve as a diluent.
The carrier may also be liquid, for example: water; alcohols, particularly butanol or glycol, as well as their ethers or esters, particularly methylglycol acetate; ketones, particularly acetone, cyclohexanone, methylethyl ketone, methylisobutylketone, or isophorone; petroleum fractions such as paraffinic or aromatic hydrocarbons, particularly xylenes or alkyl naphthalenes; mineral or vegetable oils; aliphatic chlorinated hydrocarbons, particularly trichloroethane or methylene chloride; aromatic chlorinated hydrocarbons, particularly chlorobenzenes; water-soluble or strongly polar solvents such as dimethylformamide, dimethyl sulphoxide, or N- methylpyrrolidone; liquefied gases; or the like or a mixture thereof. The surface-active agent may be an emulsifying agent, dispersing agent or wetting agent of the ionic or non-ionic type or a mixture of such surface-active agents. Amongst these are e.g., salts of polyacrylic acids, salts of lignosulphonic acids, salts of phenolsulphonic or naphthalenesulphonic acids, polycondensates of ethylene oxide with fatty alcohols or fatty acids or fatty esters or fatty amines, substituted phenols (particularly alkylphenols or arylphenols), salts of sulphosuccinic acid esters, taurine derivatives (particularly alkyltaurates), phosphoric esters of alcohols or of polycondensates of ethylene oxide with phenols, esters of fatty acids with polyols, or sulphate, sulphonate or phosphate functional derivatives of the above compounds. The presence of at least one surface-active agent is generally essential when the active ingredient and/or the inert carrier are only slightly water soluble or are not water soluble and the carrier agent of the composition for application is water. Compositions of the invention may further contain other additives such as adhesives or colorants. Adhesives such as carboxymethylcellulose or natural or synthetic polymers in the form of powders, granules or lattices, such as arabic gum, polyvinyl alcohol or polyvinyl acetate, natural phospholipids, such as cephalins or lecithins, or synthetic phospholipids can be used in the formulations. It is possible to use colorants such as inorganic pigments, for example: iron oxides, titanium oxides or Prussian Blue; organic dyestuffs, such as alizarin dyestuffs, azo dyestuffs or metal phthalocyanine dyestuffs; or trace nutrients such as salts of iron, manganese, boron, copper, cobalt, molybdenum or zinc.
For their agricultural application, the compounds of the invention are therefore generally in the form of compositions, which are in various solid or liquid forms. Solid forms of compositions which can be used are dusting powders (with a content of the compound of the invention, ranging up to 80%), wettable powders or granules (including water dispersible granules), particularly those obtained by extrusion, compacting, impregnation of a granular carrier, or granulation starting from a powder (the content of the compound of the invention, in these wettable powders or granules being between about 0.5 and about 80%). Solid homogenous or heterogenous compositions containing one or more compounds of the invention, for example granules, pellets, briquettes or capsules, may be used to treat standing or running water over a period of time. A similar effect may be achieved using trickle or intermittent feeds of water dispersible concentrates as described herein. Liquid compositions, for example, include aqueous or non-aqueous solutions or suspensions (such as emulsifiable concentrates, emulsions, flowables, dispersions, or solutions) or aerosols. Liquid compositions also include, in particular, emulsifiable concentrates, dispersions, emulsions, flowables, aerosols, wettable powders (or powder for spraying), dry flowables or pastes as forms of compositions which are liquid or intended to form liquid compositions when applied, for example as aqueous sprays (including low and ultra-low volume) or as fogs or aerosols. Liquid compositions, for example, in the form of emulsifiable or soluble concentrates most frequently comprise about 5 to about 80% by weight of the active ingredient, while the emulsions or solutions which are ready for application contain, in their case, about 0.01 to about 20% of the active ingredient. Besides the solvent, the emulsifiable or soluble concentrates may contain, when required, about 2 to about 50% of suitable additives, such as stabilizers, surface-active agents, penetrating agents, corrosion inhibitors, colorants or adhesives. Emulsions of any required concentration, which are particularly suitable for application, for example, to plants, may be obtained from these concentrates by dilution with water. These compositions are included within the scope of the compositions which may be employed in the present invention. The emulsions may be in the form of water-in-oil or oil-in-water type and they may have a thick consistency. The liquid compositions of this invention may, in addition to normal agricultural use applications be used for example to treat substrates or sites infested or liable to infestation by arthropods (or other pests controlled by compounds of this invention) including premises, outdoor or indoor storage or processing areas, containers or equipment or standing or running water.
All these aqueous dispersions or emulsions or spraying mixtures can be applied, for example, to crops by any suitable means, chiefly by spraying, at rates which are generally of the order of about 100 to about 1 ,200 liters of spraying mixture per hectare, but may be higher or lower (eg. low or ultra-low volume) depending upon the need or application technique. The compound or compositions according to the invention are conveniently applied to vegetation and in particular to roots or leaves having pests to be eliminated. Another method of application of the compounds or compositions according to the invention is by chemigation, that is to say, the addition of a formulation containing the active ingredient to irrigation water. This irrigation may be sprinkler irrigation for foliar pesticides or it can be ground irrigation or underground irrigation for soil or for systemic pesticides.
The concentrated suspensions, which can be applied by spraying, are prepared so as to produce a stable fluid product which does not settle (fine grinding) and usually contain from about 10 to about 75% by weight of active ingredient, from about 0.5 to about 30% of surface-active agents, from about 0.1 to about 10% of thixotropic agents, from about 0 to about 30% of suitable additives, such as anti-foaming agents, corrosion inhibitors, stabilizers, penetrating agents, adhesives and, as the carrier, water or an organic liquid in which the active ingredient is poorly soluble or insoluble Some organic solids or inorganic salts may be dissolved in the carrier to help prevent settling or as antifreezes for water.
The wettable powers (or powder for spraying) are usually prepared so that they contain from about 10 to about 80% by weight of active ingredient, from about 20 to about 90% of a solid carrier, from about 0 to about 5% of a wetting agent, from about 3 to about 10% of a dispersing agent and, when necessary, from about 0 to about 80% of one or more stabilizers and/or other additives, such as penetrating agents, adhesives, anti-caking agents, colorants, or the like. To obtain these wettable powders, the active ingredient is thoroughly mixed in a suitable blender with additional substances which may be impregnated on the porous filler and is ground using a mill or other suitable grinder. This produces wettable powders, the wettability and the suspendability of which are advantageous. They may be suspended in water to give any desired concentration and this suspension can be employed very advantageously in particular for application to plant foliage. The "water dispersible granules (WG)" (granules which are readily dispersible in water) have compositions which are substantially close to that of the wettable powders. They may be prepared by granulation of formulations described for the wettable powders, either by a wet route (contacting finely divided active ingredient with the inert filler and a little water, e.g. 1 to 20% by weight, or with an aqueous solution of a dispersing agent or binder, followed by drying and screening), or by a dry route (compacting followed by grinding and screening). The rates and concentrations of the formulated compositions may vary according to the method of application or the nature of the compositions or use thereof. Generally speaking, the compositions for application to control arthropod or plant nematode pests usually contain from about 0.00001% to about 95%, more particularly from about 0.0005% to about 50% by weight of one or more compounds of the invention, or of total active ingredients (that is to say the compounds of the invention, together with other substances toxic to arthropods or plant nematodes, synergists, trace elements or stabilizers). The actual compositions employed and their rate of application will be selected to achieve the desired effect(s) by the farmer, livestock producer, medical or veterinary practitioner, pest control operator or other person skilled in the art.
Solid or liquid compositions for application topically to animals, timber, stored products or household goods usually contain from about 0.00005% to about 90%, more particularly from about 0.001% to about 10%, by weight of one or more compounds of the invention. For administration to animals orally or parenterally, including percutaneously solid or liquid compositions, these normally contain from about 0.1 % to about 90% by weight of one or more compounds of the invention. Medicated feedstuffs normally contain from about 0.001% to about 3% by weight of one or more compounds of the invention. Concentrates or supplements for mixing with feedstuffs normally contain from about 5% to about 90%, preferably from about 5% to about 50%, by weight of one or more compounds of the invention. Mineral salt licks normally contain from about 0.1% to about 10% by weight of one or more compounds of formula (I) or pesticidally acceptable salts thereof. Dusts or liquid compositions for application to livestock, goods, premises or outdoor areas may contain from about 0.0001% to about 15%, more especially from about 0.005% to about 2.0%, by weight, of one or more compounds of the invention. Suitable concentrations in treated waters are between about 0.0001 ppm and about 20 ppm, more particularly about 0.001 ppm to about 5.0 ppm. of one or more compounds of the invention, and may be used therapeutically in fish farming with appropriate exposure times. Edible baits may contain from about 0.01 % to about 5%, preferably from about 0.01% to about 1.0%, by weight, of one or more compounds of the invention. When administered to vertebrates parenterally, orally or by percutaneous or other means, the dosage of compounds of the invention, will depend upon the species, age, or health of the vertebrate and upon the nature and degree of its actual or potential infestation by arthropod or helminth pests. A single dose of about 0.1 to about 100 mg, preferably about 2.0 to about 20.0 mg, per kg body weight of the animal or doses of about 0.01 to about 20.0 mg, preferably about 0.1 to about 5.0 mg, per kg body weight of the animal per day, for sustained medication, are generally suitable by oral or parenteral administration. By use of sustained release formulations or devices, the daily doses required over a period of months may be combined and administered to animals on a single occasion. The following composition EXAMPLES 2A - 2M illustrate compositions for use against arthropods, especially mites or insects, or plant nematodes, which comprise, as active ingredient, compounds of the invention, such as those described in preparative examples. The compositions described in EXAMPLES 2A - 2M can each be diluted to give a sprayable compositon at concentrations suitable for use in the field. Generic chemical descriptions of the ingredients (for which all of the following percentages are in weight percent), used in the composition EXAMPLES 2A - 2M exemplified below, are as follows: Trade Name Chemical Description
Ethylan BCP Nonylphenol ethylene oxide condensate
Soprophor BSU Tristyrylphenol ethylene oxide condensate
Arylan CA A 70% w/v solution of calcium dodecylbenzenesulfonate
Solvesso 150 Light C10 aromatic solvent
Arylan S Sodium dodecylbenzenesulfonate
Darvan NO2 Sodium lignosulphonate
Celite PF Synthetic magnesium silicate carrier
Sopropon T36 Sodium salts of polycarboxylic acids
Rhodigel 23 Polysaccharide xanthan gum
Bentone 38 Organic derivative of magnesium montmorillonite Aerosil Microfine silicon dioxide EXAMPLE 2A
A water soluble concentrate is prepared with the composition as follows: Active ingredient 7% Ethylan BCP 10% N-methylpyrrolidone 83%
To a solution of Ethylan BCP dissolved in a portion of N-methylpyrrolidone is added the active ingredient with heating and stirring until dissolved. The resulting solution is made up to volume with the remainder of the solvent.
EXAMPLE 2B
An emulsifiable concentrate (EC) is prepared with the composition as follows: Active ingredient 25%(max) Soprophor BSU 10% Arylan CA 5% N-methylpyrrolidone 50% Solvesso 150 10%
The first three components are dissolved in N-methylpyrrolidone and to this is then added the Solvesso 150 to give the final volume.
EXAMPLE 2C
A wettable powder (WP) is prepared with the composition as follows: Active ingredient 40% Arylan S 2% Darvan NO2 5% Celite PF 53%
The ingredients are mixed and ground in a hammer-mill to a powder with a particle size of less than 50 microns.
EXAMPLE 2D
An aqueous-flowable formulation is prepared with the composition as follows: Active ingredient 40.00% Ethylan BCP 1.00% Sopropon T360. 0.20% Ethylene glycol 5.00% Rhodigel 230. 0.15% Water 53.65%
The ingredients are intimately mixed and are ground in a bead mill until a mean particle size of less than 3 microns is obtained.
EXAMPLE 2E
An emulsifiable suspension concentrate is prepared with the composition as follows: Active ingredient 30.0% Ethylan BCP 10.0% Bentone 38 0.5% Solvesso 150 59.5%
The ingredients are intimately mixed and ground in a beadmill until a mean particle size of less than 3 microns is obtained.
EXAMPLE 2F
A water dispersible granule is prepared with the composition as follows: Active ingredient 30% Darvan No 2 15% Arylan S 8% Celite PF 47%
The ingredients are mixed, micronized in a fluid-energy mill and then granulated in a rotating pelletizer by spraying with water (up to 10%). The resulting granules are dried in a fluid-bed drier to remove excess water.
EXAMPLE 2G
A dusting powder is prepared with the composition as follows: Active ingredient 1 to 10% Talc powder-superfine 99 to 90% The ingredients are intimately mixed and further ground as necessary to achieve a fine powder. This powder may be appplied to a locus of arthropod infestation, for example refuse dumps, stored products or household goods or animals infested by, or at risk of infestation by, arthropods to control the arthropods by oral ingestion. Suitable means for distributing the dusting powder to the locus of arthropod infestation include mechanical blowers, handshakers or livestock self treatment devices.
EXAMPLE 2H
An edible bait is prepared with the composition as follows: Active ingredient 0.1 to 1.0% Wheat flour 80% Molasses 19.9 to 19%
The ingredients are intimately mixed and formed as required into a bait form. This edible bait may be distributed at a locus, for example domestic or industrial premises, e.g. kitchens, hospitals or stores, or outdoor areas, infested by arthropods, for example ants, locusts, cockroaches or flies, to control the arthropods by oral ingestion.
EXAMPLE 2I
A solution formulation is prepared with a composition as follows: Active ingredient 15% Dimethyl sulfoxide 85%
The active ingredient is dissolved in dimethyl sulfoxide with mixing and or heating as required. This solution may be applied percutaneously as a pour-on application to domestic animals infested by arthropods or, after sterilization by filtration through a polytetrafluoroethylene membrane (0.22 micrometer pore size), by parenteral injection, at a rate of application of from 1.2 to 12 ml of solution per 100 kg of animal body weight.
EXAMPLE 2J
A wettable powder is prepared with the composition as follows: Active ingredient 50% Ethylan BCP 5% Aerosil 5% Celite PF 40%
The Ethylan BCP is absorbed onto the Aerosil which is then mixed with the other ingredients and ground in a hammer-mill to give a wettable powder, which may be diluted with water to a concentration of from 0.001% to 2% by weight of the active compound and applied to a locus of infestation by arthropods, for example, dipterous larvae or plant nematodes, by spraying, or to domestic animals infested by, or at risk of infection by arthropods, by spraying or dipping, or by oral administration in drinking water, to control the arthropods.
EXAMPLE 2K
A slow release bolus composition is formed from granules containing the following components in varying percentages(similar to those described for the previous compositions) depending upon need: Active ingredient Density agent Slow-release agent Binder The intimately mixed ingredients are formed into granules which are compressed into a bolus with a specific gravity of 2 or more. This can be administered orally to ruminant domestic animals for retention within the reticulo-rumen to give a continual slow release of active compound over an extended period of time to control infestation of the ruminant domestic animals by arthropods.
EXAMPLE 2L
A slow release composition in the form of granules, pellets, brickettes or the like can be prepared with compositions as follows: Active ingredient 0.5 to 25% Polyvinyl chloride 75 to 99.5% Dioctyl phthalate (plasticizer) The components are blended and then formed into suitable shapes by melt-extrusion or molding. These composition are useful, for example, for addition to standing water or for fabrication into collars or eartags for attachment to domestic animals to control pests by slow release.
EXAMPLE 2M
A water dispersible granule is prepared with the composition as follows: Active ingredient 85%(max) Polyvinylpyrrolidone 5% Attapulgite clay 6% Sodium lauryl sulfate 2% Glycerine 2%
The ingredients are mixed as a 45% slurry with water and wet milled to a particle size of 4 microns, then spray-dried to remove water.
METHODS OF PESTICIDAL USE The following representative test procedure, using compounds of the invention, was conducted to determine the parasiticidal activity of compounds of the invention.
METHOD A: Screening method to test systemicity of compounds against Ctenocephalides felis (Cat flea)
A test container was filled with 10 adults of Ctenocephalides felis. A glass cylinder was closed on one end with parafilm and placed on top of the test container. The test compound solution was then pipetted into bovine blood and added to the glass cylinder. The treated Ctenocephalides felis were held in this artificial dog test (blood 37 °C, 40-60 % relative humidity; Ctenocephalides felis 20-22°C, 40-60 % relative humidity) and assessment performed at 24 and 48 hours after application.
METHOD B: Diabrotica undecimpunctata (southern corn rootworm) screen Two days before application, seeds of maize were soaked in water under warm conditions to elicit fast germination. One day before application, eggs of Diabrotica undecimpunctata were transferred to one half of a Japanese filter paper placed in a plastic petri dish. Afterwards, a sprouted maize seed was placed on a moistened pad beside the filter paper. Three drops of 200 microlitres of test compound solution were carefully pipetted onto the egg. The remainder of the solution was placed on the maize and then the Petri dish was closed. The treated eggs in the Petri dishes were held in a climate chamber for 6 days. The compound efficacy (percentage of dead eggs and/or larvae in comparison to untreated control) was assessed 6 days after application using a binocular microscope.
METHOD C: Nephotettix Cinciceps (rice leafhopper) screen
The leaves of 12 rice plants having a stem length of 8 cm were dipped for 5 seconds into an aqueous solution of the formulated test compound. After the solution had run off, the rice plants treated in this manner were placed in a Petri dish and populated with about 20 larvae (L3 stage) of Nephotettix cincticeps. The Petri dish was closed and then stored in a climate chamber (16 hours of light/day, 25°C, 40-60% relative humidity). After 6 days storage, the percentage mortality of leafhopper larvae was determined.
METHOD D: Screening method to test contact activity against Ctenocephalides felis (Cat flea)
Solutions of the test compounds were dropped onto filter paper, dried and the filter paper placed into test tubes and infested with 10 adults of Ctenocephalides felis. The treated Ctenocephalides felis were held in a climate chamber (26°C, 80% RH) and the percentage efficacy assessed 24 hours and 48 hours after application in comparison with the untreated control.
METHOD E: Screening method to test contact activity against Rhipicephalus sanguineus (Brown dog tick)
Solutions of the test compounds were dropped onto filter paper, dried and the filter paper placed into test tubes and infested with 20-30 larvae (L1 ) of Rhipicephalus sanguineus and the tubes closed with a clip. The treated Rhipicephalus sanguineus were held in a climate chamber (25°C, 90% RH) and the percentage efficacy assessed 24 hours after application in comparison with the untreated control.
Compound number 1-2 was active in one or more of the above test methods.

Claims

A compound of formula (I):
Figure imgf000059_0001
wherein:
R1 is CN, CSNH2or C(=N-V)-S(O)r-Q;
W is C-halogen, C-CH3 or N;
R2 is hydrogen, halogen, CH3,
Figure imgf000059_0002
or N[(Cι-Cβ)-alky1]2;
R3 is (CrC3)-haloalkyl, (CrC3)-haloalkoxy or SF5;
X is O or S;
Y and Z are each independently O, S, NRa or a covalent bond;
Ra is H or (Cι-C6)-alkyl;
R4 is NR7R8, OH, H, halogen, (d-CeJ-alkoxy, (C-ι-C6)-alkyl. OCO-(Cι-Cβ)-alkyl,
S(O)m-(C Cβ)-alkyl or N=CHN-[(C1-C6)-alkyl]2;
R5 and R6 are each independently H, (C2-C6)-alkenyl, (C2-C6)-haloalkenyl, (C2-C6)- alkynyl, (C2-C6)-haloalkynyl, (C3-C7)-cycloalkyl, (CH2)qR9 or (CH2)qR10; or are (C
C6)-alkyl unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, (CrC6)-alkoxy, (CrC6)-haloalkoxy, (C3-C6)-alkenyloxy,
(C3-C6)-haloalkenyloxy, (C3-C6)-alkynyloxy, (C3-C6)-haloalkynyloxy, (C3-C7)- cycloalkyl, S(O)pR11, CN, NO2, OH, COR12, NR12R13, S(O)pR9, OR9 and CO2R12;
R7 is H, (C2-C6)-alkenyl, (C2-C6)-haloalkenyl, (C2-C6)-alkynyl, (C2-C6)-haloalkynyl,
(C3-C7)-cycloaIkyl, CO2-(C1-C6)-aIkyl, CO2-(C3-C7)-cycloalkyl, CO2-(C1-C4)-alkyl-(C3-
C7)-cycloalkyl, CO2-(C2-C6)-aIkenyl, CO2-(CH2)qR9, CONR12R13, CO2-(CH2)qR10, (CH2)qR9, (CH2)qR10, COR12 or COCH2-(Cι-C4)-alkoxy; or (C C6)-alkyl unsubstituted or substituted by one or more R14 radicals;
R8 is H, (C2-C6)-alkynyl, CO2-(d-C6)-alkyl, (C3-C7)-cycloalkyl, (CH2)qR9, (CH2)qR10, or SO2R15; or (C C6)-alkyl, (C2-C6)-alkenyl or CO-(Cι-C6)-alkyl which last three mentioned groups are unsubstituted or substituted by one or more R14 radicals;
R9 is phenyl unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, (Cι-C6)-alkyl, (Cι-C6)-haloalkyl, (C-i-CβV-alkoxy, (d-C6)- haloalkoxy, CN, NO2, S(O)pR11 and NR13R16;
R10 is heterocyclyl unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, (d-C )-alkyl, (C-ι-C4)-haloalkyl, (C-ι-C4)-alkoxy,
S(O)pR11, OH and oxo;
R11 is (Cι-C6)-alkyl, (d-C6)-haloalkyl, (C2-C6)-alkenyl, (C2-C6)-haloalkenyl, (C2-
C6)-alkynyl, (C2-C6)-haloalkynyl or (C3-C7)-cycloalkyl;
R12 is H, (d-C6)-alkyl, (Cι-C6)-haloalkyl, (C3-C7)-cycloalkyl, (C1-C6)-alkyl-(C3-C7)- cycloalkyl, (CH2)qR9 or (CH2)qR10;
R13 and R16are each independently H, (C C6)-alkyl, (d-C6)-haloalkyl, (C3-
C )-cycloalkyl or (C1-C6)-alkyl-(C3-C7)-cycloalkyl; or
R12 and R 3 together with the attached N atom form a five- or six-membered saturated ring which optionally contains an additional hetero atom in the ring which is selected from O, S and N, the ring being unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, (d-C6)-alkyl, (d-C6)- haloalkyl and halogen;
R14 is halogen, (C1-C6)-alkoxy, (C1-C6)-haloalkoxy, (C3-C7)-cycloalkyl, S(O)pR11,
CO2-(d-C6)-alkyl, O(C=O)-(d-C6)-alkyl, CO-(d-C6)-alkyl, CO-(d-C6)-haloalkyl,
NR 2R13, CONR12R13, SO2NR12R13, OH, CN, NO2, OR9, NR12COR16, NR12SO2R11 or
OR10;
R15 is (C3-C7)-cycloalkyl, (C2-C6)-alkenyl, (C2-C6)-haloalkenyl or R10; or phenyl unsubstituted or substituted by one or more radicals selected from R17; or is (d-
CεJ-alkyl unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, (d-C6)-alkoxy, (d-C6)-haloalkoxy, (C2-C6)-alkenyloxy,
(C2-C6)-haloalkenyloxy, (C2-C6)-alkynyloxy, (C2-C6)-haloalkynyloxy, (C3-C7)- cycloalkyl, S(O)pR9, S(O)pR10, S(O)pR11, CN, NO2, OH, COR12, NR12COR16,
NR12SO2R11, CONR12R13, NR12R13, OR9, OR10, R18, R10 and CO2R12;
R17 is halogen, (Cι-C6)-alkyl, (Cι-C6)-haloalkyl, (d-C6)-alkoxy, (Cι-C6)-haloalkoxy,
CN, NO2, S(O)pR11, NR12R13, COR11, COR9, CONR12R13, SO2NR12R13, R9, SF5, OH,
OR9, R19, OR19, SO3H or (C C6)-alkylideneimino;
R18 is phenyl unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, (d-C6)-alkyl, (CrCβJ-haloalkyl, (C C6)-alkoxy, (d-Cβ)- haloalkoxy, CN, NO2, S(O)pR11, NR12R13, COR11, COR9, CONR12R13, SO2NR12R13,
OH, SO3H and (Cι-C6)-alkylideneimino;
R19 is a heteroaromatic radical selected from the group consisting of pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, thienyl, thiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, furyl, pyrrolyl, pyrazolyl, imidazolyl and triazolyl, which groups are unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, (Cι-C6)-alkyl, (Ci-CβJ-haloalkyl and (CrC6)-alkoxy;
V is H, (C C6)-alkyl, (Cι-C6)-haloalkyl, (C2-C6)-alkenyl, (C2-C6)-alkynyl, (CH2)qR9,
COR20, CO2-(d-C6)-alkyl or S(O)pR20;
Q is (d-C6)-alkyl or CH2R9;
R20 is (d-C6)-alkyl or (d-C6)-haloalkyl; m, n, p and r are each independently zero, one or two; q is 0 or 1 to 4; and each heterocyclyl in the above-mentioned radicals is independently a heterocyclic radical having 3 to 6 ring atoms and 1 , 2 or 3 hetero atoms in the ring selected from the group consisting of N, O and S; or a pesticidally acceptable salt thereof.
2. A compound or a salt thereof as claimed in claim 1 wherein R1 is CN or CSNH2.
3. A compound or a salt thereof as claimed in claim 1 or 2 wherein R is CI
4. A compound or a salt thereof as claimed in claim 1 , 2 or 3 wherein R1 is CN or CSNH2; W is C-CI;
R2 is CI;
R3 is CF3;
R4 is NH2, NHCH3or N=CHN-[(d-C6)-alkyl]2;
X is O or S;
Y and Z are each O, S or a covalent bond; and
R5 and R6 are each independently H, (C1-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-alkynyl, (C3-C7)-cycloalkyl, (C1-C6)-alkyl-(C3-C7)-cycloalkyl, (CH2)qR9 or (CH2)qpyridyl.
5. A compound or a salt thereof as claimed in any one of claims 1 to 4 wherein R1 is CN;
W is C-CI; R2 is CI; R3 is CF3; R4 is NR7R8; X is O;
Y and Z are each a covalent bond;
R5 and R6 are each the same or different (d-C6)-alkyl;
R7 is H, (C2-C6)-alkenyl, (C2-C6)-alkynyl, (C3-C7)-cycloaIkyl, (CH2)qR9 or
(CH2)qpyridyl; or (Cι-C6)-alkyl unsubstituted or substituted by (C3-C )-cycloalkyl or
S(O)pR11; and
R8 is H, (C2-C6)-alkenyl, (C2-C6)-alkynyl, CO2-(C1-C6)-alkyl, (C3-C7)-cycloalkyl,
(CH2)qR9, (CH2)qpyridyl or SO2R15; or (d-C6)-aIkyl unsubstituted or substituted by
(C3-C )-cycIoalkyl; and
R15 is (d-C6)-alkyl unsubstituted or substituted by R18.
6. A process for the preparation of a compound of formula (I) or a salt thereof as defined in any one of claims 1 to 5, which process comprises: a) where R4 is N=CHN-[(C1-C6)-alkyl]2, R5 and R6 are as defined in claim 1 with the exclusion of H, R1 is CN, and R2, R3, W, X , Y and Zare as defined in claim 1 , reacting the corresponding compound of formula (II):
Figure imgf000063_0001
wherein R4 is N=CHN-[(d-C6)-alkyl]2 and the other values are as defined in claim 1 , with a compound of formula (III):
Figure imgf000063_0002
wherein R5and R6are as defined in claim 1 with the exclusion of H, and X , Y and Z are as defined in claim 1 ; or b) where R4 is NH2, R1 is CN, and the other values are as defined in claim 1 , hydrolysing the corresponding compound of formula (I) in which R4 is N=CHN-[(Cr C6)-alkyl]2; or c) where R5 and/or R6 is H, Y and Z are each O, S or NRa, R1 is CN, and the other values are as defined in claim 1, hydrolysing the corresponding compound of formula (I) in which R5 and/or R6 is (Cι-C6)-alkyl, benzyl or trialkylsilyl; or d) where R5 and R6 are as defined in claim 1 with the exclusion of H, R4 is N=CHN-[(Cι-C6)-alkyl]2, X is O, Y and Z are each O, NRa or a covalent bond, R1 is CN, and the other values are as defined in claim 1 , oxidising a corresponding compound of formula (IV):
Figure imgf000064_0001
or e) where R5 and R6 are each H, R4 is N=CHN-[(d-C6)-alkyl]2, Y and Z are each
0, R1 is CN, and the other values are as defined in claim 1, reacting the corresponding compound of formula (I) wherein R5 and R6 are as defined in claim 1 with the exclusion of H, with a trialkylsilyl iodide of formula (V): R3Si-l (V) wherein R is (Ci-CβJ-alkyl; or f) where R5 is as defined in claim 1 with the exclusion of H, R6 is H, R4 is N=CHN-[(C1-C6)-alkyl]2, Y and Z are each O or are each S, R1 is CN, and the other values are as defined in claim 1 , reacting the corresponding compound of formula (I) wherein R5 and R6 are as defined in claim 1 with the exclusion of H, with an alkali metal azide; or g) where R1 is CSNH2, and the other values are as defined in claim 1, reacting the corresponding compound of formula (I) wherein R1 is CN, with an alkali or alkaline earth metal hydrosulfide, or with H2S in the presence of an organic base, or with the reagent Ph2PS2; or h) where R1 is CSNH2, and the other values are as defined in claim 1, reacting the corresponding compound of formula (I) wherein R1 is CN, with a bis(trialkylsilyl)sulfide in the presence of a base; or i) where R1 is C(=N-H)-S-Q, and Q and the other values are as defined in claim
1, reacting the corresponding compound of formula (I) wherein R1 is CSNH2 with an alkylating agent of formula (VI) or (VII):
Q-L (VI) Q3O+ BF4- (VII) where Q is as defined in claim 1 and L is a leaving group; or j) where R1 is C(=N-V)-S-Q, V is as defined in claim 1 with the exclusion of H, and Q and the other values are as defined in claim 1 , alkylating, acylating or sulfonylating the corresponding compound of formula (I) wherein R1 is C(=NH)-S-Q, with a compound of formula (VIII):
V-L1 (VIII)
wherein V is as defined in claim 1 with the exclusion of H, and L1 is a leaving group; or k) where R4 is NR7R8, one of R7 or R8 is as defined in claim 1 with the exclusion of H, R1 is CN and the other values are as defined in claim 1 , alkylating, acylating or sulfonylating the corresponding compound of formula (I) in which R4 is NHR7 or
NHR8, wherein R7 or R8 are as defined in claim 1, with a compound of formula (IX) or
(X) respectively:
Figure imgf000065_0001
wherein R7 and R8 are as defined in claim 1 with the exclusion of H, and L2 and L3 are each a leaving group; or
I) where n is 1 or 2 and the other values are as defined in claim 1, oxidising the corresponding compound in which n is 0 or 1 ; and m) if desired, converting a resulting compound of formula (I) into a pesticidally acceptable salt thereof.
7. A pesticidal composition comprising a compound of formula (I) or a pesticidally acceptable salt thereof as defined in any one of claims 1 to 5, in association with a pesticidally acceptable diluent or carrier and/or surface active agent.
8. The use of a compound of formula (I) or a salt thereof according to any one of claims 1 to 5 or of a composition according to claim 7, for the preparation of a veterinary medicament.
9. The use of a compound of formula (I) or a salt thereof according to any one of claims 1 to 5 or of a composition according to claim 7, for the control of pests.
10. A method for controlling pests at a locus which comprises applying thereto an effective amount of a compound of formula (I) or a salt thereof as claimed in any one of claims 1 to 5 or of a composition according to claim 7.
PCT/EP2005/000581 2004-02-26 2005-01-21 4-phosphorylpyrazole derivatives for pesticidal use WO2005082917A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP04004318 2004-02-26
EP04004318.4 2004-02-26

Publications (1)

Publication Number Publication Date
WO2005082917A1 true WO2005082917A1 (en) 2005-09-09

Family

ID=34895955

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2005/000581 WO2005082917A1 (en) 2004-02-26 2005-01-21 4-phosphorylpyrazole derivatives for pesticidal use

Country Status (2)

Country Link
AR (1) AR048071A1 (en)
WO (1) WO2005082917A1 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115703806A (en) * 2021-08-06 2023-02-17 香港理工大学深圳研究院 Phosphine ligand with pyrazole-amide skeleton and preparation method and application thereof

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0154115A1 (en) * 1984-01-24 1985-09-11 Bayer Ag Herbicidal compositions based on derivatives of pyrazoles
DE4139849A1 (en) * 1990-12-07 1992-06-11 Ciba Geigy Ag New insecticidal and acaricidal 1-aryl-4-pyrazolyl-phosphorous cpds. - useful esp. for protection of cotton, vegetable and fruit crops against sucking insects
WO1993006089A1 (en) * 1991-09-27 1993-04-01 Zeneca Limited N-phenylphrazoles as insecticides and acaricides
EP0659745A1 (en) * 1993-12-22 1995-06-28 Bayer Ag Substituted 1-aryl pyrazoles
WO1996039389A1 (en) * 1995-06-05 1996-12-12 Rhone-Poulenc Agrochimie Pesticidal sulfur compounds

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0154115A1 (en) * 1984-01-24 1985-09-11 Bayer Ag Herbicidal compositions based on derivatives of pyrazoles
DE4139849A1 (en) * 1990-12-07 1992-06-11 Ciba Geigy Ag New insecticidal and acaricidal 1-aryl-4-pyrazolyl-phosphorous cpds. - useful esp. for protection of cotton, vegetable and fruit crops against sucking insects
WO1993006089A1 (en) * 1991-09-27 1993-04-01 Zeneca Limited N-phenylphrazoles as insecticides and acaricides
EP0659745A1 (en) * 1993-12-22 1995-06-28 Bayer Ag Substituted 1-aryl pyrazoles
WO1996039389A1 (en) * 1995-06-05 1996-12-12 Rhone-Poulenc Agrochimie Pesticidal sulfur compounds

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
MILLER P C ET AL: "One-pot synthesis of dimethyl [1-substituted-5-hydroxy-1H-pyrazol 4-yl]phosphonates", ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL, ORGANIC PREPARATION AND PROCEDURES CO., NEWTON HIGHLANDS, MA, US, vol. 31, no. 3, 1999, pages 295 - 304, XP000910413, ISSN: 0030-4948 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115703806A (en) * 2021-08-06 2023-02-17 香港理工大学深圳研究院 Phosphine ligand with pyrazole-amide skeleton and preparation method and application thereof

Also Published As

Publication number Publication date
AR048071A1 (en) 2006-03-29

Similar Documents

Publication Publication Date Title
EP1483245B1 (en) 5-substituted-alkylaminopyrazole derivatives as pesticides
WO2004049803A1 (en) Pesticidal 5- (acylamino) pyrazole derivatives
EP1692939A1 (en) Pesticidal substituted piperidines
EP1727805B1 (en) 1-phenyl and 1-pyridylpyrazole derivatives and their use as pesticides
ZA200503742B (en) Pesticidal sulphonylaminopyrazoles
US7576107B2 (en) 5-substituted-alkylaminopyrazole derivatives as pesticides
WO2005090312A1 (en) 5-aminoalkylpyrazole derivatives as pesticidal agents
EP1599451A1 (en) Pesticidal 1-ayl-3-amidoxime-pyrazole derivatives
WO2005082916A1 (en) 5-phosphorylaminopyrazole derivatives and their use as pesticides
EP1663985B1 (en) Pesticides
EP1663986B1 (en) Pesticidal 5-substituted-oxyalkylamino-1-arylpyrazole derivatives
WO2005082917A1 (en) 4-phosphorylpyrazole derivatives for pesticidal use
EP1671967A1 (en) 1-Arylpyrazoles and their use as pesticides
MXPA06010447A (en) 1-phenyl and 1-pyridylpyrazole derivatives and their use as pesticides

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BW BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE EG ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NA NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SM SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): BW GH GM KE LS MW MZ NA SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LT LU MC NL PL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
122 Ep: pct application non-entry in european phase