WO2001055144A1 - Isothiazole derivatives and their use as pesticides - Google Patents

Isothiazole derivatives and their use as pesticides Download PDF

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Publication number
WO2001055144A1
WO2001055144A1 PCT/GB2001/000338 GB0100338W WO0155144A1 WO 2001055144 A1 WO2001055144 A1 WO 2001055144A1 GB 0100338 W GB0100338 W GB 0100338W WO 0155144 A1 WO0155144 A1 WO 0155144A1
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WIPO (PCT)
Prior art keywords
optionally substituted
alkyl
alkoxy
haloalkyl
cyano
Prior art date
Application number
PCT/GB2001/000338
Other languages
French (fr)
Inventor
Sarah Armstrong
Nigel John Barnes
Susan Patricia Barnett
Eric Daniel Clarke
Patrick Jelf Crowley
Torquil Eoghan Macleod Fraser
David John Hughes
Christopher John Mathews
Roger Salmon
Stephen Christopher Smith
Russell Viner
William Guy Whittingham
John Williams
Alan John Whittle
William Roderick Mound
Christopher John Urch
Brian Leslie Pilkington
Original Assignee
Syngenta Limited
PILKINGTON, Joan
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
Priority claimed from GB0002037A external-priority patent/GB0002037D0/en
Priority claimed from GB0027571A external-priority patent/GB0027571D0/en
Application filed by Syngenta Limited, PILKINGTON, Joan filed Critical Syngenta Limited
Priority to EP01902500A priority Critical patent/EP1265892B1/en
Priority to US10/182,425 priority patent/US6703347B2/en
Priority to DE60116732T priority patent/DE60116732T2/en
Priority to JP2001561003A priority patent/JP2003523355A/en
Priority to AU2001230358A priority patent/AU2001230358A1/en
Publication of WO2001055144A1 publication Critical patent/WO2001055144A1/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/80—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,2

Definitions

  • the present invention relates to azole derivatives, to processes for preparing them, to fungicidal, insecticidal, acaricidal, molluscicidal and nematicidal compositions comprising them, to methods of using them to combat fungal diseases (especially fungal diseases of plants) and to methods of using them to combat and control insect, acarine, mollusc and nematode pests.
  • Azole and azine derivatives are disclosed in WO95/31448, WO97/18198, WO98/02424, WO98/05670 and WO98/17630.
  • the present invention provides a compound of formula (I):
  • A is optionally substituted alkylene, optionally substituted C 2 . 6 alkenylene, optionally substituted C 2 - 6 alkynylene, optionally substituted cycloalkylene, optionally substituted Cj . - 6 alkylenoxy, optionally substituted oxy(C 1 - 6 )alkylene, optionally substituted .
  • R 1 is hydrogen, halogen, optionally substituted Ct- 6 alkyl, optionally substituted C 2 _ 6 alkenyl, optionally substituted C 2 . 6 alkynyl, optionally substituted _ 6 alkoxy, optionally substituted C ⁇ - 6 alkylthio, optionally substituted C 3 .
  • R 4 , R 5 and R 6 are, independently, hydrogen, halogen, optionally substituted Q- 6 alkyl, optionally substituted Q- 6 alkoxy, optionally substituted Q- 6 alkylthio, optionally substituted Q- 6 alkylsulfinyl, optionally substituted Q.
  • R 7 is hydrogen, halogen, cyano, optionally substituted Q- 2 o alkyl, optionally substituted C 2 - 20 alkenyl, optionally substituted C - 20 alkynyl, optionally substituted C 3 - cycloalkyl, optionally substituted C 5 - 6 cycloalkenyl, formyl, optionally substituted Q- 2 o alkoxycarbonyl, optionally substituted Q.
  • R 9 is hydrogen, cyano, nitro, optionally substituted Q- 6 alkyl, optionally substituted C 3 - 7 cycloalkyl, optionally substituted (C 2 - 6 )alkenyl(Q- 6 )alkyl, optionally substituted (C 2 - 6 )alkynyl(Q- 6 )alkyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted Q- 6 alkylcarbonyl, optionally substituted Q-6 alkoxycarbonyl, optionally substituted
  • R 10 is hydrogen, cyano, optionally substituted Q_ 8 alkyl, optionally substituted [C - 6 alkenyl(Q- 6 )alkyl], optionally substituted [C 2 .
  • R ⁇ and R 18 are, independently, hydrogen, optionally substituted phenyl (Q.
  • R 12 and R 19 are, independently, hydrogen, optionally substituted phenyl or optionally substituted Q- 6 alkyl
  • R 13 and R 14 are, independently, optionally substituted Q- 6 alkyl
  • R 13 and R 14 together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one or two further heteroatoms selected from O, N and S and which is optionally substituted by one or two independently selected Q- 6 alkyl groups
  • R 15 is hydrogen, optionally substituted Q- 2 o alkyl, optionally substituted [C .
  • R 16 and R are, independently, hydrogen, optionally substituted Q- 20 alkyl, optionally substituted C 3 - 7 cycloalkyl, optionally substituted [C 2 - 20 alkenyl(C 1 - 6 )alkyl], optionally substituted [C 2 - 20 alkynyl(Q- 6 )alkyl], optionally substituted Q- 2 o alkoxycarbonyl, optionally substituted phenoxycarbonyl, formyl, optionally substituted Q_ 2 o alkylcarbonyl, optionally substituted Q- 2 o alkylsulfonyl or optionally substituted phenylsulfonyl.
  • One group of preferred compounds of formula (I) is a group wherein A is optionally substituted Q-6 alkylene, optionally substituted C 2 . 6 alkenylene, optionally substituted C 2 - 6 alkynylene, optionally substituted Q-6 alkylenoxy, optionally substituted oxy(Q- 6 )alkylene, optionally substituted Q- 6 alkylenethio, optionally substituted thio(C 1 - 6 )alkylene, optionally substituted Q- 6 alkylenamino, optionally substituted amino-(Q. 6 )alkylene, optionally substituted [Q.
  • R 4 , R 5 and R 6 are, independently, hydrogen, halogen, optionally substituted Q- 6 alkyl, optionally substituted Q-6 alkoxy, optionally substituted Q_ 6 alkylthio, optionally substituted Q- 6 alkylsulfinyl, optionally substituted Q- 6 alkylsulfonyl, cyano, nitro, optionally substituted Q_ 6 alkylcarbonyl, optionally substituted Q- 6 alkoxycarbonyl or SF 5 ; R 7 is hydrogen, halogen, cyano, optionally substituted Q.
  • alkyl optionally substituted C 2 - 20 alkenyl, optionally substituted C _ 2 o alkynyl, optionally substituted C 3 - 7 cycloalkyl, optionally substituted C 5 . 6 cycloalkenyl, formyl, optionally substituted Q- 0 alkoxycarbonyl, optionally substituted Q.
  • alkylcarbonyl aminocarbonyl, optionally substituted Q- 2 o alkylaminocarbonyl, optionally substituted di(Q- 2 o)alkylaminocarbonyl, optionally substituted aryloxycarbonyl, optionally substituted arylcarbonyl, optionally substituted arylaminocarbonyl, optionally substituted N-alkyl-N-arylaminocarbonyl, optionally substituted diarylaminocarbonyl, optionally substituted heteroaryloxycarbonyl, optionally substituted heteroarylcarbonyl, optionally substituted heteroarylaminocarbonyl, optionally substituted alkylheteroarylaminocarbonyl, optionally substituted diheteroarylaminocarbonyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted heterocyclyl, R 15 O, HS, optionally substituted Q- 2 o alkylthio, optionally substituted Q.
  • alkylsulfinyl optionally substituted Q.
  • R 1 is hydrogen, halogen, optionally substituted Q.
  • R 2 is hydrogen, halogen, optionally substituted Q- 6 alkyl, optionally substituted C 2 - 6 alkenyl, optionally substituted C 2 -6 alkynyl, optionally substituted Q_ 6 alkoxy, optionally substituted Q- alkylthio, optionally substituted C 3 - 7 cycloalkyl, cyano, nitro or SF 5 ;
  • R 2 is hydrogen, halogen, optionally substituted Q- 6 alkyl, optionally substituted C 2 - 6 alkenyl, optionally substituted C 2 - 6 alkynyl, optionally substituted Q.
  • R 1 and R 2 together with the atoms to which they are attached may be joined to form a five, six or seven-membered saturated or unsaturated ring carbocylic or heterocyclic ring which may contain one or two heteroatoms selected from O, N or S and which may be optionally substituted by Q_ 6 alkyl, Q_ 6 haloalkyl or halogen;
  • R 9 is hydrogen, cyano, nitro, optionally substituted Q_ 6 alkyl, optionally substituted C 3 - 7 cycloalkyl, optionally substituted (C 2 _ 6 )alken
  • R 10 is hydrogen, cyano, optionally substituted Q_ 8 alkyl, optionally substituted [C 2 - 6 alkenyl(Q- 6 )alkyl], optionally substituted [C 2 _ 6 alkynyl
  • R 8 is hydrogen, halogen, nitro, cyano, optionally substituted Q- 8 alkyl, optionally substituted C 2 - 6 alkenyl, optionally substituted C 2 - 6 alkynyl, optionally substituted C 3 - 7 cycloalkyl, optionally substituted Q- 6 alkoxycarbonyl, optionally substituted Q.
  • R 13 and R 14 are, independently, optionally substituted Q- 6 alkyl or R 13 and R 14 together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one or two further heteroatoms selected from O, N or S and which may be optionally substituted by one or two Q- 6 alkyl groups;
  • R 15 is hydrogen, optionally substituted Q- 20 alkyl, optionally substituted [C 2 - 2 o alkenyl(Q-6)alkyl], optionally substituted [C 2 - 2 o alkynyl(Q- 6 )alkyl], optionally substituted C 3 - 7 cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted [
  • R 16 and R 17 together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one or two further heteroatoms selected from O, N or S and which may be optionally substituted by one or two Q_ alkyl groups;
  • R 19 and R 12 are independently hydrogen, optionally substituted phenyl or optionally substituted Q- 6 alkyl; and
  • R 18 and R u are, independently, hydrogen, optionally substituted phenyl (Q. 2 )alkyl or optionally substituted Q_ 2 o alkyl.
  • the compounds of formula (I) may exist in different geometric or optical isomers or tautomeric forms. This invention covers all such isomers and tautomers and mixtures thereof in all proportions as well as isotopic forms such as deuterated compounds.
  • R 20 is Q- 6 alkyl, C ⁇ - 6 haloalkyl, OR 23 or NR 24 R 25 ;
  • R 21 and R 22 are, independently, hydrogen, Q- 6 alkyl, Q- 6 alkoxy, Q- 6 haloalkyl, cyano, Q- 6 alkoxycarbonyl, Q- 6 alkylcarbonyl or NR 26 R 27 ;
  • R 23 is Q- 6 alkyl, Q- 6 haloalkyl or phenyl(Q- 2 )alkyl;
  • R 24 and R 25 are, independently, hydrogen, Q_ 8 alkyl, C 3 - 7 cycloalkyl, C 2 - 6 alkenyl(Q- 6 )alkyl, C 2 - 6 alkynyl(Q- 6 )alkyl, C 2
  • R 26 and R 27 are, independently, hydrogen, Q- 8 alkyl, C 3 - 7 cycloalkyl, C - 6 alkenyl(Q- 6 )alkyl, C 2 - 6 alkynyl(Q- 6 )alkyl, C 2 - 6 haloalkyl, Q- 6 alkoxy(Q- 6 )alkyl, Q- 6 alkoxycarbonyl(Q- 6 )alkyl
  • R 26 and R 27 together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one or two further heteroatoms selected from O, N or S and which is optionally substituted by one or two Q- 6 alkyl groups.
  • Each alkyl moiety is a straight or branched chain and is, for example, methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, wo-propyl, n-butyl, sec-butyl, iso-butyl, tert-butyl or neo-pentyl.
  • the optional substituents on an alkyl moiety include one or more of halogen, nitro, cyano, NCS-, C 3 - 7 cycloalkyl (itself optionally substituted with Q- 6 alkyl or halogen), C 5 - 7 cycloalkenyl (itself optionally substituted with Q.
  • Alkenyl and alkynyl moieties can be in the form of straight or branched chains, and the alkenyl moieties, where appropriate, can be of either the (E) ⁇ or ⁇ -configuration. Examples are vinyl, allyl and propargyl.
  • the optional substituents on alkenyl or alkynyl include those optional substituents given above for an alkyl moiety.
  • acyl is optionally substituted Q- 6 alkylcarbonyl (for example acetyl), optionally substituted C 2 - 6 alkenylcarbonyl, optionally substituted C 2 - 6 alkynylcarbonyl, optionally substituted arylcarbonyl (for example benzoyl) or optionally substituted heteroarylcarbonyl.
  • Halogen is fluorine, chlorine, bromine or iodine.
  • Haloalkyl groups are alkyl groups which are substituted with one or more of the same or different halogen atoms and are, for example, CF 3 , CF 2 C1, CF 3 CH 2 or CHF 2 CH 2 .
  • Aryl includes naphthyl, anthracyl, fluorenyl and indenyl but is preferably phenyl.
  • heteroaryl refers to an aromatic ring containing up to 10 atoms including one or more heteroatoms (preferably one or two heteroatoms) selected from O, S and N.
  • Such rings include pyridine, pyrimidine, furan, quinoline, quinazoline, pyrazole, thiophene, thiazole, oxazole and isoxazole.
  • heterocycle and heterocyclyl refer to a non-aromatic ring containing up to 10 atoms including one or more (preferably one or two) heteroatoms selected from O, S and N.
  • examples of such rings include 1,3-dioxolane, tetrahydrofuran and morpholine.
  • heterocyclyl When present, the optional substituents on heterocyclyl include Q- 6 alkyl as well as those optional substituents given above for an alkyl moiety.
  • Cycloalkyl includes cyclopropyl, cyclopentyl and cyclohexyl.
  • Cycloalkenyl includes cyclopentenyl and cyclohexenyl.
  • cycloalkyl or cycloalkenyl include Q- alkyl as well as those optional substituents given above for an alkyl moiety.
  • Carbocyclic rings include aryl, cycloalkyl and cycloalkenyl groups.
  • the optional substituents on aryl or heteroaryl are selected, independently, from halogen, nitro, cyano, NCS-, Q-6 alkyl, Q- 6 haloalkyl, Q- 6 alkoxy(Q- 6 )alkyl, C 2 - 6 alkenyl, C 2 -6 haloalkenyl, C 2 -6 alkynyl, C 3 - 7 cycloalkyl (itself optionally substituted with Q- 6 alkyl or halogen), C 5 .
  • substituents are independently selected from halogen, Q- 6 alkyl, Q- 6 haloalkyl, Q- 6 alkoxy(Q- 6 )alkyl, Q- 6 alkoxy, Q- 6 haloalkoxy, Q- 6 alkylthio, Q-6 haloalkylthio, Q- 6 alkylsulfinyl, Q_ 6 haloalkylsulfinyl, Q- 6 alkylsulfonyl, Q.
  • Haloalkenyl groups are alkenyl groups which are substituted with one or more of the same or different halogen atoms.
  • dialkylamino substituents include those where the dialkyl groups together with the N atom to which they are attached form a five, six or seven- membered heterocyclic ring which may contain one or two further heteroatoms selected from O, N or S and which is optionally substituted by one or two independently selected (Q- 6 )alkyl groups.
  • heterocyclic rings are formed by joining two groups on an N atom, the resulting rings are suitably pyrrolidine, piperidine, thiomorpholine and morpholine each of which may be substituted by one or two independently selected (Q- 6 ) alkyl groups.
  • the optional substituents on an alkyl moiety include one or more of halogen, nitro, cyano, HO 2 C, C ⁇ o alkoxy (itself optionally substituted by Q- 10 alkoxy), aryl(Q- 4 )alkoxy, .io alkylthio, Q-io alkylcarbonyl, Q-io alkoxycarbonyl, Q- 6 alkylaminocarbonyl, di(Q-6 alkylaminocarbonyl, (Q- 6 )alkylcarbonyloxy, optionally substituted phenyl, heteroaryl, aryloxy, arylcarbonyloxy, heteroaryloxy, heterocyclyl, heterocyclyloxy, C 3 - 7 cycloalkyl (itself optionally substituted with (Q- 6 )alkyl or halogen), C 3 - 7 cycloalkyloxy, C 5 .
  • the optional substituents on alkenyl or alkynyl include one or more of halogen, aryl and C 3 - 7 cycloalkyl.
  • heterocyclyl is optionally substituted by Q- 6 alkyl.
  • the optional substituents for cycloalkyl include halogen, cyano and Q_ 3 alkyl.
  • the optional substituents for cycloalkenyl include Q- 3 alkyl, halogen and cyano.
  • the present invention provides a compound of formula (IA): wherein A, B, Y, Z, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 7 are as defined above for a compound of formula (I).
  • More preferred compounds of formula (IA) are those wherein R 1 is hydrogen, halogen, Q- 6 alkyl, C 2 - 6 alkenyl, C 2 - 6 alkynyl, Q- 6 cyanoalkyl, Q- 6 haloalkyl, Q- 6 alkoxy, Q- 6 haloalkoxy, Q- 6 alkylthio, Q- 6 haloalkylthio, C 3 _ 6 cycloalkyl, C 3 - 7 cycloalkyl(Q- 4 )alkyl, Q- 6 alkoxy(Q- 6 )alkyl, cyano, nitro or SF 5 ;
  • A is Q-6 alkylene, Q- 6 alkenylene , Q- 6 alkylenoxy, oxy(Q- 6 )alkylene, Q- alkylenamino or Q- 6 alkylenethio, each of which is optionally substituted by Q- 3 alkyl, Q- 3 haloalkyl,
  • A is more preferably Q- 4 alkylene (optionally substituted by halogen, Q- 3 alkyl or Q- 3 alkoxy, -C(O)- or Q- 4 alkyleneoxy (which may be optionally substituted by Q- 3 alkyl); provided that A is not CH or CH 2 O.
  • A is Q- 2 alkyl-substituted Q- 4 alkylene, fluoro- substituted C ⁇ alkylene, methoxy-substituted Q- 4 alkylene, -C(O)- or Q- 4 alkyleneoxy; still more preferably A is Q- alkyl-substituted Q- 4 alkylene, fluoro-substituted Q- 4 alkylene or methoxy-substituted C ⁇ alkylene.
  • A is CH(CH 3 )CH 2 , CH 2 CH(CH 3 ), CH(CH 3 ), CHF, CH(OCH 3 ) or CH(CH 3 )O; further preferred that A is CH(CH 3 )CH 2 , CH 2 CH(CH 3 ), CH(CH 3 ), CHF or CH(CH 3 )O; it is especially preferred that A is CHF, CH(OCH 3 ) or CH(CH 3 ); and most preferably A is CHF or CH(CH 3 ).
  • A is optionally fluoro-substituted
  • B is preferably N.
  • Y is preferably O or S.
  • Y is more preferably O.
  • Z is preferably O or S.
  • Z is more preferably O.
  • R 1 is hydrogen, halogen, Q- ⁇ alkyl, Q- 6 cyanoalkyl, Ci- 6 haloalkyl, C 3 _ 7 cycloalkyl(Q- )alkyl, Q- 6 alkoxy(Q- 6 )alkyl, - 6 alkenyl, Q- 6 alkynyl, Q- 6 alkoxy, Q- 6 haloalkoxy, Q- 6 alkylthio, Q-6 haloalkylthio, Q- 6 cycloalkyl, cyano, nitro or SF 5 .
  • R 1 is more preferably hydrogen, halogen, Q- 6 alkyl, - 6 alkenyl, Q- 6 haloalkyl, Q- 6 alkoxy, Ci- 6 haloalkoxy, Q-6 alkylthio, Q- 6 haloalkylthio, C 3 - 6 cycloalkyl, cyano, nitro or SF 5 .
  • R 1 is hydrogen, halogen, Q- 6 alkyl, Q- 6 haloalkyl, Q- 6 alkoxy(Q- 6 )alkyl, - 6 alkenyl, Q- 6 alkoxy, Q- 6 haloalkoxy, Q- 6 alkylthio, Q- 6 haloalkylthio, Q- 6 cycloalkyl or cyano.
  • R 1 is halogen, Q- 6 alkyl, Q- haloalkyl, Q- 6 alkoxy or Q- 6 haloalkoxy.
  • R is hydrogen, halogen, Ci- 6 alkyl, Ci- 6 haloalkyl, Q- 6 alkoxy (Q- 6 )alkyl, Ci-6 alkoxy, Q-6 haloalkoxy, Ci-6 alkylthio or SF 5 ; or R 1 and R 2 together with the atoms to which they are attached form a cyclopentane or benzene ring optionally substituted by Q- 6 alkyl, Q-6 haloalkyl or halogen.
  • R 2 is even more preferably hydrogen, halogen, Q- 6 alkyl, Q- 6 haloalkyl, Q- 6 alkoxy,
  • R 2 is hydrogen, halogen, Ci- 6 alkyl, Q-e haloalkyl, Q- 6 alkoxy(Q- 6 )alkyl, Q- 6 alkoxy, Q-6 haloalkoxy, or R 1 and R 2 together with the atoms to which they are attached form a cyclopentane ring optionally substituted by Ci- 6 alkyl, Ci- 6 haloalkyl or halogen.
  • R 2 is most preferably halogen, Q-6 alkyl, Ci-6 haloalkyl, Q- 6 alkoxy, Ci- 6 alkoxy(Q- 6 )alkyl or Ci-6 haloalkoxy. It is preferred that R 3 is hydrogen, Q- 10 alkyl, Q- 6 alkylcarbonyloxy(Q- 6 )alkyl, benzoyloxymethyl (where the phenyl ring is optionally substituted with halogen or Q- 4 alkyl), Ci- alkoxy(Q- 6 )alkyl (where the alkyl group is optionally substituted by aryl or Q- 4 alkoxycarbonyl), - 6 alkenyloxy(Q- 4 )alkyl, -6 alkynyloxy(Q- 4 )alkyl, benzyloxy(Q- 4 )alkyl (where the phenyl ring is optionally substituted with halogen or C alkyl), Q- 7 cycloalkyl(C 1 -
  • R 3 is hydrogen, Q-6 alkyl, Q- 6 alkylcarbonyloxymethyl, benzoyloxymethyl (where the phenyl ring is optionally substituted with halogen or C M alkyl), Q- 6 alkoxymethyl, Q-6 alkenyloxymefhyl, Q-6 alkynyloxymethyl, benzyloxymethyl (where the phenyl ring is optionally substituted with halogen or Q- 4 alkyl), Q- 6 alkynyl(Q_ 6 )alkyl (especially propargyl) or Q-io alkylcarbonyl.
  • R 3 is more preferably hydrogen, Q- 6 alkyl, Q- 6 alkoxy(Q- 6 )alkyl, benzyloxymethyl or benzoyloxymethyl; or alternatively R 3 may be Q- 6 alkylcarbonyloxymethyl.
  • R 3 is hydrogen, Q_ 6 alkyl, Q_ 6 alkylcarbonyloxymethyl or Ci- alkoxymethyl. It is preferred that R 4 , R 5 and R 6 are, independently, hydrogen, halogen, Q- 6 alkyl, Q- 6 haloalkyl, Q- 6 alkoxy, Ci-6 haloalkoxy, Q-6 alkylthio, Ci-6 haloalkylthio, Ci-6 alkylsulfinyl, Ci- 6 haloalkylsulfinyl, Q- 6 alkylsulfonyl, Q- 6 haloalkylsulfonyl, cyano, nitro, Ci- 6 alkylcarbonyl or Ci- 6 alkoxycarbonyl. It is more preferred that R 4 , R 5 and R 6 are, independently, hydrogen, halogen or Q- 3 alkyl.
  • R 4 , R 5 and R 6 are, independently, hydrogen or halogen (especially fluorine).
  • R 7 is cyano, Q- 8 alkyl, Q- 8 haloalkyl, Q- cyanoalkyl, Q- 7 cycloalkyl (Q- 6 )alkyl, C 5 - 6 cycloalkenyl(Q- 6 )alkyl, Q- 6 alkoxy(Q- 6 )alkyl, C 3 - 6 alkenyloxy(C ⁇ - 6 )alkyl, C 3 -6 alkynyloxy(Q.6)alkyl, aryloxy(C ⁇ -6)alkyl, Ci- 6 carboxyalkyl, C ⁇ - 6 alkylcarbonyl(Q- 6 )alkyl, - 6 alkenylcarbonyl(C ⁇ - 6 )alkyl, C 2 - 6 alkynylcarbonyl(Q- 6 )alkyl, Ci- 6 alkoxycarbonyl(Q- 6 )alkyl, C 3 - 6 alkenyloxycarbonyl(Ci-
  • R 7 is more preferably Q- 8 alkyl, Ci-6 haloalkyl, Ci- 6 cyanoalkyl, - 6 alkenyl, - 6 alkynyl, Q- 7 cycloalkyl, Q- 7 halocycloalkyl, Q- 7 cyanocycloalkyl, Q- 3 alkyl(Q- 7 )cycloalkyl, Q- 3 alkyl(C 3 - 7 )halocycloalkyl, -6 cycloalkenyl, Q- 7 cycloalkyl(Q- 6 )alkyl, - 6 cycloalkenyl(Q- 6 )alkyl, - 6 haloalkenyl, Ci- cyanoalkenyl, Q- 6 alkoxy(Q- 6 )alkyl, Q- 6 alkenyloxy(Q- 6 )alkyl, - 6 alkynyloxy(Q-6)alkyl, aryloxy(Q- 6 )
  • R 7 is Q- 8 alkyl, Q- 8 haloalkyl, Q_ 8 cyanoalkyl, Q- 7 cycloalkyl(Q- 6 )alkyl, Q- 6 cycloalkenyl (Q-6)alkyl, Q- 6 alkoxy(Q- 6 )alkyl, Q- 6 alkenyloxy(Q- 6 )alkyl, Q- 6 alkynyloxy(Q- 6 )alkyl, aryloxy(Q- 6 )alkyl, Q- 6 carboxyalkyl, Q- 6 alkylcarbonyl(Q- 6 )alkyl, Q- 6 alkenylcarbonyl (Q- 6 )alkyl, Q-6 alkynylcarbonyl(Q- 6 )alkyl, Q_ 6 alkoxycarbonyl(Q- 6 )alkyl, Q-6 alkenyloxycarbonyl(Q-6)alkyl, Q-6 alkynyloxycarbonyl
  • heteroaryl(Q- 4 )alkyl wherein the heteroaryl group is optionally substituted by halo, nitro, cyano, Q- 6 alkyl, Ci- 6 haloalkyl, Q- 6 alkoxy or Q- 6 haloalkoxy), heterocyclyl (Q.
  • R 7 is Q- 8 alkyl, Q- 8 haloalkyl, Q- 8 cyanoalkyl, Q- 6 alkoxy (Ci- 6 ) alkyl, Q- 7 cycloalkyl, Q- alkyl (Q_ 7 ) cycloalkyl, heterocyclyl (optionally substituted by halo, nitro, cyano, Q- alkyl, Q-6 haloalkyl, Q-6 alkoxy or Q- haloalkoxy) or di(C i - )alkylamino.
  • R is Q- 8 alkyl, Q- 8 haloalkyl, Q- 8 cyanoalkyl, Q- 6 alkoxy (Q- 6 ) alkyl, Q- 7 cycloalkyl, Q- 3 alkyl (Q. 7 ) cycloalkyl, heterocyclyl (optionally substituted by Q- 6 alkyl) or di(Q- 8 )alkylamino.
  • R 7 is most preferably Q- 8 alkyl, Q- 8 haloalkyl, Q_ 8 cyanoalkyl, Q- cycloalkyl, Q- 3 alkyl(C 3 - 7 )cycloalkyl, Q- 6 alkoxy(Q- 6 )alkyl or R 16 R 17 N; where R 16 andR 17 are, independently, Q_ 8 alkyl or together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one further heteroatom selected from O, N or S and which may be optionally substituted by one or two Q. 6 alkyl groups.
  • R 8 is hydrogen, halogen, nitro, cyano, Q- 8 alkyl, Q- 6 haloalkyl, Q- 6 cyanoalkyl, Q- 7 cycloalkyl(Q- 6 )alkyl, Q- 6 alkoxy(C !
  • R 8 is hydrogen, halogen, Q- 8 alkyl or Q- 6 haloalkyl. It is preferred that R 9 is cyano, nitro, Ci- 6 alkyl, Q- 6 haloalkyl, Q- cycloalkyl(Q- 6 )alkyl, Q- 7 cycloalkyl, CH 2 (C 2 - 6 )alkenyl, CH 2 (Q- 6 )alkynyl, phenyl (optionally substituted by halo, nitro, cyano, Q- 6 alkyl, Q-6 haloalkyl, Q- 6 alkoxy or Q- 6 haloalkoxy), heteroaryl (optionally substituted by halo, nitro, cyano, Q-6 alkyl, Ci- 6 haloalkyl, Q- 6 alkoxy or Ci- 6 haloalkoxy), Ci- 6 alkylcarbonyl, Ci- 6 alkoxycarbonyl, Q- 6 alkylamino,
  • R 10 is hydrogen, Q- 8 alkyl, Ci-6 haloalkyl, Q- 6 cyanoalkyl, Q_ 6 alkenyl, Q- 6 haloalkenyl, - 6 alkynyl, Q- 7 cycloalkyl, Q_ 7 cycloalkyl(Q- 6 )alkyl, Q- 6 alkoxy(Q- 6 )alkyl, Ci- 6 alkoxycarbonyl, Q- 6 alkylcarbonyl, Q- 6 alkylaminocarbonyl, di(Q- 6 )alkylaminocarbonyl, phenyl (optionally substituted by halo, nitro, cyano, Ci- alkyl, Ci- haloalkyl, Q- 6 alkoxy or Q- 6 haloalkoxy) or heteroaryl (optionally substituted by halo, nitro, cyano, Q- 6 alkyl, Ci- 6 haloalkyl, Ci- 6 alkoxy or Q
  • R 10 is hydrogen, Q- 8 alkyl or Q- 6 haloalkyl.
  • Tables 1-102 illustrate compounds of the invention.
  • Table 1 provides 160 compounds of formula (1) wherein R 1 , R 3 and R 7 are defined in Table 1.
  • Table 2 provides 160 compounds of formula (2)
  • Table 3 provides 160 compounds of formula (3)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 4 provides 160 compounds of formula (4)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 5 provides 160 compounds of formula (5)
  • w ere n R , R an are as e ine n a e .
  • Table 6 provides 160 compounds of formula (6) wherein R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 7 provides 160 compounds of formula (7)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 8 provides 160 compounds of formula (8)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 9 provides 160 compounds of formula (9)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 10 provides 160 compounds of formula (10)
  • Table 11 provides 160 compounds of formula (11)
  • Table 12 provides 160 compounds of formula (12)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 13 Table 13 provides 160 compounds of formula (13)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 14 Table 14 provides 160 compounds of formula (14)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 15 provides 160 compounds of formula (15) wherein R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 16 Table 16 provides 160 compounds of formula (16)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 17 provides 160 compounds of formula (17)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 18 Table 18 provides 160 compounds of formula (18)
  • Table 19 provides 160 compounds of formula (19)
  • Table 20 provides 160 compounds of formula (20)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 21 Table 21 provides 160 compounds of formula (21)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 22 Table 22 provides 160 compounds of formula (22)
  • Table 23 provides 160 compounds of formula (23)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 24 Table 24 provides 160 compounds of formula (24)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 25 Table 25 provides 160 compounds of formula (25)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 26 Table 26 provides 160 compounds of formula (26)
  • Table 27 provides 160 compounds of formula (27)
  • Table 28 provides 160 compounds of formula (28)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 29 provides 160 compounds of formula (29)
  • Table 30 provides 160 compounds of formula (30)
  • Table 31 provides 160 compounds of formula (31)
  • Table 32 provides 160 compounds of formula (32)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 33 Table 33 provides 160 compounds of formula (33)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 34 Table 34 provides 160 compounds of formula (34)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 35 provides 160 compounds of formula (35)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 36 Table 36 provides 160 compounds of formula (36)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 37 Table 37 provides 160 compounds of formula (37)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 38 provides 160 compounds of formula (38)
  • R 1 , , R 3 and R 7 are as defined in Table 1.
  • Table 39 provides 160 compounds of formula (39)
  • Table 40 provides 160 compounds of formula (40)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 41 Table 41 provides 160 compounds of formula (41)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 42 Table 42 provides 160 compounds of formula (42)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 43 Table 43 provides 160 compounds of formula (43)
  • R ⁇ l , r R> 3 and R are as defined in Table 1.
  • Table 44 provides 160 compounds of formula (44)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 45 Table 45 provides 160 compounds of formula (45)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 46 Table 46 provides 160 compounds of formula (46)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 47 provides 160 compounds of formula (47)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 48 Table 48 provides 160 compounds of formula (48)
  • Table 49 provides 160 compounds of formula (49)
  • Table 50 provides 160 compounds of formula (50)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 51 Table 51 provides 160 compounds of formula (51)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 52 Table 52 provides 160 compounds of formula (52)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 53 provides 160 compounds of formula (53)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 54 Table 54 provides 160 compounds of formula (54)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 55 Table 55 provides 160 compounds of formula (55)
  • Table 56 provides 160 compounds of formula (56)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 57 provides 160 compounds of formula (57)
  • Table 58 provides 160 compounds of formula (58)
  • Table 59 provides 160 compounds of formula (59)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 60 Table 60 provides 160 compounds of formula (60)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 61 provides 160 compounds of formula (61)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 62 provides 160 compounds of formula (62)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 63 provides 160 compounds of formula (63)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 64 Table 64 provides 160 compounds of formula (64)
  • Table 65 provides 160 compounds of formula (65)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 66 provides 160 compounds of formula (66)
  • Table 67 provides 160 compounds of formula (67)
  • Table 68 provides 160 compounds of formula (68)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 69 provides 160 compounds of formula (69)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 70 provides 160 compounds of formula (70)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 71 provides 160 compounds of formula (71)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 72 Table 72 provides 160 compounds of formula (72)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 73 provides 160 compounds of formula (73)
  • Table 74 provides 160 compounds of formula (74)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 75 Table 75 provides 160 compounds of formula (75)
  • Table 76 provides 160 compounds of formula (76)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 77 provides 160 compounds of formula (77)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 78 provides 160 compounds of formula (78)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 79 provides 160 compounds of formula (79)
  • Table 80 provides 160 compounds of formula (80)
  • Table 81 provides 160 compounds of formula (81)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 82 provides 160 compounds of formula (82)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 83 provides 160 compounds of formula (83)
  • Table 84 provides 160 compounds of formula (84)
  • Table 85 provides 160 compounds of formula (85)
  • Table 86 provides 160 compounds of formula (86)
  • R , 1 , R and R are as defined in Table 1.
  • Table 87 provides 160 compounds of formula (87)
  • R 1 , R 3 and R 7 are as defined in Table 1 Table 88
  • Table 88 provides 160 compounds of formula (88)
  • Table 89 provides 160 compounds of formula (89)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 90 Table 90 provides 160 compounds of formula (90)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 91 provides 160 compounds of formula (91)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 92 provides 160 compounds of formula (92)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 93 provides 160 compounds of formula (93)
  • R 1 , R 3 and R 7 are as defined in Table 1.
  • Table 94 provides 160 compounds of formula (94)
  • R 3 and R 7 are defined in Table 95.
  • Table 96 provides 80 compounds of formula (96)
  • R 3 and R 7 are as defined in Table 95.
  • Table 97 provides 80 compounds of formula (97)
  • Table 98 provides 80 compounds of formula (98)
  • R 3 and R 7 are as defined in Table 95.
  • Table 99 Table 99 provides 80 compounds of formula (99)
  • R 3 and R 7 are as defined in Table 95.
  • Table 100 provides 80 compounds of formula (100)
  • R 3 and R 7 are as defined in Table 95.
  • Table 101 provides 80 compounds of formula (101)
  • R 3 and R 7 are as defined in Table 95.
  • Table 102 provides 80 compounds of formula (102) wherein R 3 and R 7 are as defined in Table 95.
  • Table 103 shows selected melting point and selected NMR data, all with CDC1 3 as the solvent (unless otherwise stated; if a mixture of solvents is present, this is indicated as, for example, (CDC1 3 / VDMSO)), (no attempt is made to list all characterising data in all cases) for compounds of Tables 1-102.
  • the compounds of the invention may be made in a variety of ways.
  • a compound of formula (I) which is a compound of formula (A) (where A, B, Z, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 7 are as defined above for a compound of formula (I) except that R 3 is not H) may be made from a compound of formula (B) (where A, B, Z, R 1 , R 2 , R 4 , R 5 , R 6 and R 7 are as defined above for a compound of formula (I)) by treatment with an alkylating agent (such as an alkyl halide, dialkyl sulfate or trialkyloxonium salt), an acylating agent (such as an acid chloride) or a similar reagent (such as a carbamoyl chloride or sulfenyl chloride), optionally in the presence of a base.
  • an alkylating agent such as an alkyl halide, dialkyl sulfate or trialkyloxonium salt
  • a compound of formula (A) may be separated from a compound of formula (C) and purified by routine techniques (such as recrystallisation, chromatography or trituration with a suitable solvent).
  • a compound of formula (A) (where A, B, Z, R 1 , R 2 , R 4 , R 5 , R 6 and R 7 are as defined above for a compound of formula (I) and where R 3 is alkoxyalkyl or acyloxyalkyl) may also be prepared from a compound of formula (B) (where A, B, Z, R 1 , R 2 , R 4 , R 5 , R 6 and R 7 are as defined above for a compound of formula (I)) by sequential reaction with formaldehyde and an alkylating or acylating agent.
  • a compound of formula (B) (where B, Z, R 1 , R 2 , R 4 , R 5 , R 6 and R 7 are as defined above for a compound of formula (I) and A is optionally substituted alkylene, alkenylene, alkynylene, alkylenoxy, alkylenamino or alkylenethio) may be prepared by reacting a compound of formula (IT) (where R 1 and R 2 are as defined above for a compound of formula (I)) either with an appropriate compound of formula (DI) (where B, Z, R 4 , R 5 , R 6 and R 7 are as defined above for a compound of formula (I); A is optionally substituted alkylene, alkenylene, alkynylene, alkylenoxy, alkylenamino or alkylenethio; and X is OH) preferably in the presence of a suitable coupling reagent (such as 1,3-dicyclohexylcarbodiimide, 1,3-diis
  • a compound of formula (B) (where B, Z, R 4 , R 5 , R 6 and R 7 are as defined above for a compound of formula (I); and A is optionally substituted oxyalkylene) may be prepared in an analogous manner starting from a compound of formula (II) (where R and R ⁇ are as defined above for a compound of formula (I)) and a suitable compound of formula (HI) (where B, Z, R 4 , R 5 , R 6 and R 7 are as defined above for a compound of formula (I); A is optionally substituted oxyalkylene; and X is chloro).
  • a compound of formula (IH) (where A, B, Z, R 4 , R 5 , R 6 and R 7 are as defined above for a compound of formula (I) and X is - 6 alkoxy [optionally substituted by halogen, C ⁇ - 3 alkoxy, C 1 - 3 alkylthio, tri(C 1 - 3 )alkylsilyl or aryl (itself optionally substituted by C 1 - 3 alkyl, - 3 alkoxy, halogen, cyano or nitro)]) may be prepared in a number of ways; the preferred method is dependent on the nature of its fused benzheterocyclic ring and on the nature of its moiety A-C(O)-X (where A and X are as defined above).
  • a suitable reagent Y-C(O)-X (where X is Q- alkoxy [optionally substituted by halogen, Q- 3 alkoxy, Q- 3 alkylthio, tri(Q- 3 )alkylsilyl or aryl (itself optionally substituted by Q- 3 alkyl, Q- 3 alkoxy, halogen, cyano or nitro)]) and Y is a suitably reactive moiety, such as one of those described below) can be attached to a preformed fused heterocyclic ring.
  • a compound of formula (Ula) [where J is a single bond or a suitable alkylene moiety (such as CH 2 )] may be reacted with a suitable base (such as lithium diisopropylamide, sodium hydride or lithium hexamethyldisilazide) in a suitable solvent (such as tetrahydrofuran) and then treated with an electrophilic reagent such as an alkylating agent (for example an alkyl halide, alkenylalkyl halide or arylalkyl halide), a halogenating agent (for example N-fluorobenzenesulfonimide) or a further compound with the general formula R f -LG (where LG designates a suitable leaving group, such as a halide and R f is, for example, a sulfenyl or acyl moiety) to introduce R as a new substituent.
  • a suitable base such as lithium diisopropylamide, sodium
  • a compound of formula (HI) bearing fragments which are sufficiently chemically reactive, undergoes reactions typical of those fragments.
  • a compound of formula (Hid) [where B, Z, R , R 5 , R 6 and R 7 are as defined above for a compound of formula (I), X is Q- alkoxy (optionally substituted by halogen, Q- 3 alkoxy, Q- 3 alkylthio, tri(Q- 3 )alkylsilyl or aryl (itself optionally substituted by Q- 3 alkyl, Q- 3 alkoxy, halogen, cyano or nitro)) and J is a single bond or a suitable alkylene moiety (such as CH 2 )] will undergo certain reactions typical of ⁇ -ketoesters; for instance, reduction by a metal hydride (such as sodium borohydride) in a suitable solvent (such as ethanol) to give a corresponding alcohol:
  • the benzofused heterocyclic ring may be formed by ring synthesis from a suitably substituted benzene of formula (VII) (where Q and G are suitable precursors (atoms or groups) for the formation of the desired heterocyclic ring, A, R 4 , R 5 and R 6 are as defined above for a compound of formula (I) and X is hydroxy or Q- 6 alkoxy [optionally substituted by halogen, Q- 3 alkoxy, Q- 3 alkylthio, tri(Q- 3 )alkylsilyl or aryl (itself optionally substituted by Q- 3 alkyl, Q-3 alkoxy, halogen, cyano or nitro)]) the benzofused heterocyclic ring may be formed by ring synthesis from a suitably substituted benzene of formula (VII) (where Q and G are suitable precursors (atoms or groups) for the formation of the desired heterocyclic ring, A, R 4 , R 5 and R 6 are as defined above for
  • acylating agent such as an acid chloride or anhydride
  • a suitable base such as triethylamine, potassium carbonate or pyridine
  • an acid preferably in the presence of a coupling agent (such as 1,3- dicyclohexyl-carbodiimide, 1 ,3-diisopropylcarbodiimide, 1 -(3-dimethylaminopropyl)-3- ethyl-carbodiimide or l, -carbonyldiimidazole)) followed by cyclisation, optionally catalysed by an acid (such as r ⁇ -toluenesulfonic acid), gives a benzoxazole:
  • a benzofuran may be made from an ⁇ rt7- ⁇ -halophenol, as described by Henning Lutjens and Peter J Scammells (Tetrahedron Letters 39 (1998), 6581-6584); Terence C Owen et al, (Tetrahedron Letters 30, No 13, 1597 (1989)); and Fred G Schreiber and Robert Stevenson (J.C.S. Perkin 1, 90, 1977).
  • An indole may be made from an ⁇ rt/z ⁇ -haloaniline according to the methods of Cheng-yi Chen et al. (J. Org. Chem. 1997, 62, 2676); Takao Sakamoto et al., (J. Org. Chem. 1997, 62, 6507); and Alan D. Adams et al. (WO9827974).
  • a compound of formula (I) (where A, B, Z, R 1 , R 2 , R 4 , R 5 , R 6 and R 7 are as defined above, Y is S and R 3 is H) may be prepared by reacting a compound of formula (I) (where A, B, Z, R 1 , R 2 , R 4 , R 5 , R 6 and R 7 are as defined above, Y is O and R 3 is H) with a suitable thionating agent (such as 2,4-bis(4-methoxyphenyl)-l,3-dithia-2,4-diphosphetane-2,4- disulfide (Lawesson's reagent), 2,4-bis(methylthio)-l,3-dithia-2,4-diphosphetane-2,4- disulfide (Davy reagent methyl), 2,4-bis(p ⁇ r ⁇ -tolyl)-l,3-dithia-2,4-diphosphetane
  • a compound of formula (DC) (where B, Z, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 7 are as defined above for a compound of formula (I)) may be made by reacting a compound of formula (X) (where B, Z, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 7 are as defined above) with N,N- dimethyl-formamide dialkyl acetal in a suitable solvent (such as toluene or N,N- dimethylformamide). Frequently this reaction produces a mixture of E- and Z-isomers which are sometimes separable by standard techniques (such as flash column chromatography and recrystallisation).
  • a compound of formula (X) ((where B, Z, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 7 are as defined for a compound of formula (I)) may be treated in an analogous manner with a trialkylorthoformate to afford a compound of formula (XI) (where B, Z, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 7 are as defined for a compound of formula (I) and R d is Q- 6 alkyl).
  • a compound of formula (IX) (where B, Z, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 7 are as defined above for a compound of formula (I)) may be treated with an amine of formula (HNR 26 R 27 ) (where R 26 and R 27 are as defined for a compound of formula (I)) to give a compound of formula (XII) (where B, Z, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 26 and R 27 are as defined above for a compound of formula (I)).
  • a compound of formula (DC) (where B, Z, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 7 are as defined above for a compound of formula (I)) may be oxidised to a compound of formula (XIH) (where B, Z, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 7 are as defined above for a compound of formula (I)) under known conditions.
  • a compound of formula (I) (where Y is S, R 3 is H and A, B, Z, R 1 , R 2 , R 4 , R 5 , R 6 and R 7 are as defined above for a compound of formula (I)) may be treated with an electrophile (such as an alkyl halide, dialkyl sulfate, chloromethyl ether or trialkyloxonium salt) optionally in the presence of a base to give a compound of formula (XIV) (where R 32 is alkyl, alkenylalkyl, alkynylalkyl, cycloalkyl, alkoxyalkyl and A, B, Z, R 1 , R 2 , R 4 , R 5 , R 6 and R 7 are as defined above for a compound of formula (I)).
  • an electrophile such as an alkyl halide, dialkyl sulfate, chloromethyl ether or trialkyloxonium salt
  • Such a compound may be further treated with a compound of formula R 9 -NH 2 (where R 9 is as defined above for a compound of formula (I)) optionally in the presence of a mercuric salt (such as mercuric chloride), according to known procedures to give a compound of formula (XV) (where R 3 is H and A, B, Z, R 1 , R 2 , R 4 , R 5 , R 6 and R 7 are as defined above for a compound of formula (I)).
  • a compound of formula (XV) where R 3 is H and A, B, Z, R 1 , R 2 , R 4 , R 5 , R 6 and R 7 are as defined above for a compound of formula (I)).
  • Such a compound may be treated with an alkylating agent, an acylating agent or similar electrophile to give a compound of formula (XV) [where A, B, Z, R 1 , R 2 , R 4 , R 5 , R 6 and R 7 are as defined above for a compound of formula (I) and R is as defined above for a compound of formula (I) (except that R 3 is not H)] in an analogous manner to that previously described for the formation of a compound of formula (A) from a compound of formula (B).
  • the compounds of formula (I) can be used to combat and control infestations of insect pests such as Lepidoptera, Diptera, Hemiptera, Thysanoptera, Orthoptera, Dictyoptera, Coleoptera, Siphonaptera, Hymenoptera and Isoptera and also other invertebrate pests, for example, acarine, nematode and mollusc pests. Insects, acarines, nematodes and molluscs are hereinafter collectively referred to as pests.
  • the pests which may be combated and controlled by the use of the invention compounds include those pests associated with agriculture (which term includes the growing of crops for food and fibre products), horticulture and animal husbandry, companion animals, forestry and the storage of products of vegetable origin (such as fruit, grain and timber); those pests associated with the damage of man-made structures and the transmission of diseases of man and animals; and also nuisance pests (such as flies).
  • pest species which may be controlled by the compounds of formula (I) include: Myzus persicae (aphid), Aphis gossypii (aphid), Aphis fabae (aphid), Lygus spp. (capsids), Dysdercus spp. (capsids), Nilaparvata lugens (planthopper), Nephotettixc incticeps (leafhopper), Nezara spp. (stinkbugs), Euschistus spp. (stinkbugs), Leptocorisa spp. (stinkbugs), Frankliniella occidentalis (thrip), Thrips spp.
  • Brevipalpus spp. flat mites
  • Boophilus microplus cattle tick
  • Dermacentor variabilis American dog tick
  • Ctenocephalides felis cat flea
  • Liriomyza spp. leaf miner
  • Musca domestica housefly
  • Aedes aegypti mosquito
  • Anopheles spp. mosquitoes
  • Culex spp. mosquitoes
  • Termitidae for example Globitermes sulphur eus
  • Solenopsis geminata fire ant
  • Monomorium pharaonis pharaoh's ant
  • Damalinia spp. Linognathus spp. (biting and sucking lice)
  • Meloidogyne spp. root knot nematodes
  • Globodera spp. Globodera spp.
  • Heterodera spp. cyst nematodes
  • Pratylenchus spp. lesion nematodes
  • the compounds of formula (I) are also active fungicides and may be used to control one or more of the following pathogens: Pyricularia oryzae (Magnaporthe grisea) on rice and wheat and other Pyricularia spp. on other hosts; Puccinia recondita, Puccinia striiformis and other rusts on wheat, Puccinia hordei, Puccinia striiformis and other rusts on barley, and rusts on other hosts (for example turf, rye, coffee, pears, apples, peanuts, sugar beet, vegetables and ornamental plants); Erysiphe cichoracearum on cucurbits (for example melon); Erysiphe graminis (powdery mildew) on barley, wheat, rye and turf and other powdery mildews on various hosts, such as Sphaerotheca macularis on hops, Sphaerotheca fusca (Sphaerothe
  • Botrytis cinerea grey mould
  • Botrytis cinerea grey mould
  • Alternaria spp. on vegetables (for example carrots), oil-seed rape, apples, tomatoes, potatoes, cereals (for example wheat) and other hosts
  • Venturia spp. including Venturia inaequalis (scab)) on apples, pears, stone fruit, tree nuts and other hosts
  • Cladosporium spp. on a range of hosts including cereals (for example wheat) and tomatoes
  • a compound of formula (I) may move acropetally, basipetally or locally in plant tissue to be active against one or more fungi. Moreover, a compound of formula (I) may be volatile enough to be active in the vapour phase against one or more fungi on the plant.
  • the invention therefore provides a method of combating and controlling insects, acarines, nematodes or molluscs which comprises applying an insecticidally, acaricidally, nematicidally or molluscicidally effective amount of a compound of formula (I), or a composition containing a compound of formula (I), to a pest, a locus of pest, or to a plant susceptible to attack by a pest, and a method of combating and controlling fungi which comprises applying a fungicidally effective amount of a compound of formula (I), or a composition containing a compound of formula (I), to a plant, to a seed of a plant, to the locus of the plant or seed, to soil or to any other growth medium (for example a nutrient solution).
  • a method of combating and controlling insects, acarines, nematodes or molluscs which comprises applying an insecticidally, acaricidally, nematicidally or mol
  • the compounds of formula (I) are preferably used against insects, acarines, nematodes or fungi.
  • plant as used herein includes seedlings, bushes and trees.
  • fungicidal method of the invention includes protectant, curative, systemic, eradicant and antisporulant treatments.
  • the compounds of formula (I) are preferably used for agricultural, horticultural and turfgrass purposes in the form of a composition.
  • a compound of formula (I) is usually formulated into a composition which includes, in addition to the compound of formula (I), a suitable inert diluent or carrier and, optionally, a surface active agent (SFA).
  • SFAs are chemicals which are able to modify the properties of an interface (for example, liquid/solid, liquid/air or liquid/liquid interfaces) by lowering the interfacial tension and thereby leading to changes in other properties (for example dispersion, emulsification and wetting). It is preferred that all compositions (both solid and liquid formulations) comprise, by weight, 0.0001 to 95%, more preferably 1 to 85%, for example 5 to 60%, of a compound of formula (I).
  • the composition is generally used for the control of pests or fungi such that a compound of formula (I) is applied at a rate of from O.lg to 10kg per hectare, preferably from lg to 6kg per hectare, more preferably from lg to 1kg per hectare.
  • a compound of formula (I) When used in a seed dressing, a compound of formula (I) is used at a rate of 0.0001 g to lOg (for example O.OOlg or 0.05g), preferably 0.005g to lOg, more preferably 0.005g to 4g, per kilogram of seed.
  • the present invention provides an insecticidal, acaricidal, nematicidal, molluscicidal or fungicidal composition
  • an insecticidal, acaricidal, nematicidal, molluscicidal or fungicidal composition comprising an insecticidally, acaricidally, nematicidally, molluscicidally or fungicidally effective amount of a compound of formula (I) and a suitable carrier or diluent therefor.
  • the composition is preferably an insecticidal, acaricidal, nematicidal or fungicidal composition.
  • the invention provides a method of combating and controlling pests or fungi at a locus which comprises treating the pests or fungi or the locus of the pests or fungi with an insecticidally, acaricidally, nematicidally, molluscicidally or fungicidally effective amount of a composition comprising a compound of formula (I).
  • the compounds of formula (I) are preferably used against insects, acarines, nematodes or fungi.
  • compositions can be chosen from a number of formulation types, including dustable powders (DP), soluble powders (SP), water soluble granules (SG), water dispersible granules (WG), wettable powders (WP), granules (GR) (slow or fast release), soluble concentrates (SL), oil miscible liquids (OL), ultra low volume liquids (UL), emulsifiable concentrates (EC), dispersible concentrates (DC), emulsions (both oil in water (EW) and water in oil (EO)), micro-emulsions (ME), suspension concentrates (SC), aerosols, fogging/smoke formulations, capsule suspensions (CS) and seed treatment formulations.
  • DP dustable powders
  • SP soluble powders
  • SG water soluble granules
  • WP water dispersible granules
  • GR granules
  • SL soluble concentrates
  • OL oil miscible liquids
  • UL ultra
  • Dustable powders may be prepared by mixing a compound of formula (I) with one or more solid diluents (for example natural clays, kaolin, pyrophyllite, bentonite, alumina, montmorillonite, kieselguhr, chalk, diatomaceous earths, calcium phosphates, calcium and magnesium carbonates, sulphur, lime, flours, talc and other organic and inorganic solid carriers) and mechanically grinding the mixture to a fine powder.
  • solid diluents for example natural clays, kaolin, pyrophyllite, bentonite, alumina, montmorillonite, kieselguhr, chalk, diatomaceous earths, calcium phosphates, calcium and magnesium carbonates, sulphur, lime, flours, talc and other organic and inorganic solid carriers
  • Soluble powders may be prepared by mixing a compound of formula (I) with one or more water-soluble inorganic salts (such as sodium bicarbonate, sodium carbonate or magnesium sulphate) or one or more water-soluble organic solids (such as a polysaccharide) and, optionally, one or more wetting agents, one or more dispersing agents or a mixture of said agents to improve water dispersibility/solubility. The mixture is then ground to a fine powder. Similar compositions may also be granulated to form water soluble granules (SG).
  • water-soluble inorganic salts such as sodium bicarbonate, sodium carbonate or magnesium sulphate
  • water-soluble organic solids such as a polysaccharide
  • WP Wettable powders
  • WG Water dispersible granules
  • Granules may be formed either by granulating a mixture of a compound of formula (I) and one or more powdered solid diluents or carriers, or from pre-formed blank granules by absorbing a compound of formula (I) (or a solution thereof, in a suitable agent) in a porous granular material (such as pumice, attapulgite clays, fuller's earth, kieselguhr, diatomaceous earths or ground corn cobs) or by adsorbing a compound of formula (I) (or a solution thereof, in a suitable agent) on to a hard core material (such as sands, silicates, mineral carbonates, sulphates or phosphates) and drying if necessary.
  • a hard core material such as sands, silicates, mineral carbonates, sulphates or phosphates
  • Agents which are commonly used to aid absorption or adsorption include solvents (such as aliphatic and aromatic petroleum solvents, alcohols, ethers, ketones and esters) and sticking agents (such as polyvinyl acetates, polyvinyl alcohols, dextrins, sugars and vegetable oils).
  • solvents such as aliphatic and aromatic petroleum solvents, alcohols, ethers, ketones and esters
  • sticking agents such as polyvinyl acetates, polyvinyl alcohols, dextrins, sugars and vegetable oils.
  • One or more other additives may also be included in granules (for example an emulsifying agent, wetting agent or dispersing agent).
  • DC Dispersible Concentrates
  • a compound of formula (I) may be prepared by dissolving a compound of formula (I) in water or an organic solvent, such as a ketone, alcohol or glycol ether. These solutions may contain a surface active agent (for example to improve water dilution or prevent crystallisation in a spray tank).
  • Emulsifiable concentrates (EC) or oil-in-water emulsions (EW) may be prepared by dissolving a compound of formula (I) in an organic solvent (optionally containing one or more wetting agents, one or more emulsifying agents or a mixture of said agents).
  • Suitable organic solvents for use in ECs include aromatic hydrocarbons (such as alkylbenzenes or alkylnaphthalenes, exemplified by SOLVESSO 100, SOLVESSO 150 and SOLVESSO 200; SOLVESSO is a Registered Trade Mark), ketones (such as cyclohexanone or methylcyclohexanone) and alcohols (such as benzyl alcohol, furfuryl alcohol or butanol),
  • aromatic hydrocarbons such as alkylbenzenes or alkylnaphthalenes, exemplified by SOLVESSO 100, SOLVESSO 150 and SOLVESSO 200; SOLVESSO is a Registered Trade Mark
  • ketones such as cyclohexanone or methylcyclohexanone
  • alcohols such as benzyl alcohol, furfuryl alcohol or butanol
  • N-alkylpyrrolidones such as N-methylpyrrolidone or N-octylpyrrolidone
  • dimethyl amides of fatty acids such as C 8 -Qo fatty acid dimethylamide
  • chlorinated hydrocarbons such as C 8 -Qo fatty acid dimethylamide
  • Preparation of an EW involves obtaining a compound of formula (I) either as a liquid (if it is not a liquid at room temperature, it may be melted at a reasonable temperature, typically below 70°C) or in solution (by dissolving it in an appropriate solvent) and then emulsifiying the resultant liquid or solution into water containing one or more SFAs, under high shear, to produce an emulsion.
  • Suitable solvents for use in EWs include vegetable oils, chlorinated hydrocarbons (such as chlorobenzenes), aromatic solvents (such as alkylbenzenes or alkylnaphthalenes) and other appropriate organic solvents which have a low solubility in water.
  • Microemulsions may be prepared by mixing water with a blend of one or more solvents with one or more SFAs, to produce spontaneously a thermodynamically stable isotropic liquid formulation.
  • a compound of formula (I) is present initially in either the water or the solvent/SFA blend.
  • Suitable solvents for use in MEs include those hereinbefore described for use in in ECs or in EWs.
  • An ME may be either an oil-in-water or a water-in-oil system (which system is present may be determined by conductivity measurements) and may be suitable for mixing water-soluble and oil-soluble pesticides in the same formulation.
  • An ME is suitable for dilution into water, either remaining as a microemulsion or forming a conventional oil-in-water emulsion.
  • SC Suspension concentrates
  • SCs may comprise aqueous or non-aqueous suspensions of finely divided insoluble solid particles of a compound of formula (I).
  • SCs may be prepared by ball or bead milling the solid compound of formula (I) in a suitable medium, optionally with one or more dispersing agents, to produce a fine particle suspension of the compound.
  • One or more wetting agents may be included in the composition and a suspending agent may be included to reduce the rate at which the particles settle.
  • a compound of formula (I) may be dry milled and added to water, containing agents hereinbefore described, to produce the desired end product.
  • Aerosol formulations comprise a compound of formula (I) and a suitable propellant (for example n-butane).
  • a compound of formula (I) may also be dissolved or dispersed in a suitable medium (for example water or a water miscible liquid, such as «-propanol) to provide compositions for use in non-pressurised, hand-actuated spray pumps.
  • a compound of formula (I) may be mixed in the dry state with a pyrotechnic mixture to form a composition suitable for generating, in an enclosed space, a smoke containing the compound.
  • Capsule suspensions may be prepared in a manner similar to the preparation of EW formulations but with an additional polymerisation stage such that an aqueous dispersion of oil droplets is obtained, in which each oil droplet is encapsulated by a polymeric shell and contains a compound of formula (I) and, optionally, a carrier or diluent therefor.
  • the polymeric shell may be produced by either an interfacial polycondensation reaction or by a coacervation procedure.
  • the compositions may provide for controlled release of the compound of formula (I) and they may be used for seed treatment.
  • a compound of formula (I) may also be formulated in a biodegradable polymeric matrix to provide a slow, controlled release of the compound.
  • a composition may include one or more additives to improve the biological performance of the composition (for example by improving wetting, retention or distribution on surfaces; resistance to rain on treated surfaces; or uptake or mobility of a compound of formula (I)).
  • additives include surface active agents, spray additives based on oils, for example certain mineral oils or natural plant oils (such as soy bean and rape seed oil), and blends of these with other bio-enhancing adjuvants (ingredients which may aid or modify the action of a compound of formula (I)).
  • a compound of formula (I) may also be formulated for use as a seed treatment, for example as a powder composition, including a powder for dry seed treatment (DS), a water soluble powder (SS) or a water dispersible powder for slurry treatment (WS), or as a liquid composition, including a flowable concentrate (FS), a solution (LS) or a capsule suspension (CS).
  • DS powder for dry seed treatment
  • SS water soluble powder
  • WS water dispersible powder for slurry treatment
  • CS capsule suspension
  • the preparations of DS, SS, WS, FS and LS compositions are very similar to those of, respectively, DP, SP, WP, SC and DC compositions described above.
  • Compositions for treating seed may include an agent for assisting the adhesion of the composition to the seed (for example a mineral oil or a film-forming barrier).
  • Wetting agents, dispersing agents and emulsifying agents may be surface SFAs of the cationic, anionic, amphoteric or non-ionic type.
  • Suitable SFAs of the cationic type include quaternary ammonium compounds (for example cetyltrimethyl ammonium bromide), imidazolines and amine salts.
  • Suitable anionic SFAs include alkali metals salts of fatty acids, salts of aliphatic monoesters of sulphuric acid (for example sodium lauryl sulphate), salts of sulphonated aromatic compounds (for example sodium dodecylbenzenesulphonate, calcium dodecylbenzenesulphonate, butylnaphthalene sulphonate and mixtures of sodium di-isopropyl- and tri-w propyl-naphthalene sulphonates), ether sulphates, alcohol ether sulphates (for example sodium laureth-3-sulphate), ether carboxylates (for example sodium laureth-3-carboxylate), phosphate esters (products from the reaction between one or more fatty alcohols and phosphoric acid (predominately mono-esters) or phosphorus pentoxide (predominately di-esters), for example the reaction between lauryl alcohol and tetraphosphoric acid; additionally these
  • Suitable SFAs of the amphoteric type include betaines, propionates and glycinates.
  • Suitable SFAs of the non-ionic type include condensation products of alkylene oxides, such as ethylene oxide, propylene oxide, butylene oxide or mixtures thereof, with fatty alcohols (such as oleyl alcohol or cetyl alcohol) or with alkylphenols (such as octylphenol, nonylphenol or octylcresol); partial esters derived from long chain fatty acids or hexitol anhydrides; condensation products of said partial esters with ethylene oxide; block polymers (comprising ethylene oxide and propylene oxide); alkanolamides; simple esters (for example fatty acid polyethylene glycol esters); amine oxides (for example lauryl dimethyl amine oxide); and lecithins.
  • Suitable suspending agents include hydrophilic colloids (such as polysaccharides, polyvinylpyrrolidone or sodium carb
  • a compound of formula (I) may be applied by any of the known means of applying pesticidal or fungicidal compounds. For example, it may be applied, formulated or unformulated, to the pests or to a locus of the pests (such as a habitat of the pests, or a growing plant liable to infestation by the pests) or to any part of the plant, including the foliage, stems, branches or roots, to the seed before it is planted or to other media in which plants are growing or are to be planted (such as soil surrounding the roots, the soil generally, paddy water or hydroponic culture systems), directly or it may be sprayed on, dusted on, applied by dipping, applied as a cream or paste formulation, applied as a vapour or applied through distribution or incorporation of a composition (such as a granular composition or a composition packed in a water-soluble bag) in soil or an aqueous environment.
  • a locus of the pests such as a habitat of the pests, or a growing plant liable to infestation by the pest
  • a compound of formula (I) may also be injected into plants or sprayed onto vegetation using electrodynamic spraying techniques or other low volume methods, or applied by land or aerial irrigation systems.
  • compositions for use as aqueous preparations are generally supplied in the form of a concentrate containing a high proportion of the active ingredient, the concentrate being added to water before use.
  • These concentrates which may include DCs, SCs, ECs, EWs, MEs SGs, SPs, WPs, WGs and CSs, are often required to withstand storage for prolonged periods and, after such storage, to be capable of addition to water to form aqueous preparations which remain homogeneous for a sufficient time to enable them to be applied by conventional spray equipment.
  • Such aqueous preparations may contain varying amounts of a compound of formula (I) (for example 0.0001 to 10%, by weight) depending upon the purpose for which they are to be used.
  • a compound of formula (I) may be used in mixtures with fertilisers (for example nitrogen-, potassium- or phosphorus-containing fertilisers).
  • fertilisers for example nitrogen-, potassium- or phosphorus-containing fertilisers.
  • Suitable formulation types include granules of fertiliser.
  • the mixtures suitably contain up to 25% by weight of the compound of formula (I).
  • the invention therefore also provides a fertiliser composition
  • a fertiliser composition comprising a fertiliser and a compound of formula (I).
  • the compositions of this invention may contain other compounds having biological activity, for example micronutrients or compounds having similar or complementary fungicidal activity or which possess plant growth regulating, herbicidal, insecticidal, nematicidal or acaricidal activity.
  • the resulting composition may have a broader spectrum of activity or a greater level of intrinsic activity than the compound of formula (I) alone. Further the other fungicide may have a synergistic effect on the fungicidal activity of the compound of formula (I).
  • the compound of formula (I) may be the sole active ingredient of the composition or it may be admixed with one or more additional active ingredients such as a pesticide, fungicide, synergist, herbicide or plant growth regulator where appropriate.
  • An additional active ingredient may: provide a composition having a broader spectrum of activity or increased persistence at a locus; synergise the activity or complement the activity (for example by increasing the speed of effect or overcoming repellency) of the compound of formula (I); or help to overcome or prevent the development of resistance to individual components.
  • the particular additional active ingredient will depend upon the intended utility of the composition.
  • Suitable pesticides include the following: a) Pyrethroids, such as permethrin, cypermethrin, fenvalerate, esfenvalerate, deltamethrin, cyhalothrin (in particular lambda-cyhalothrin), bifenthrin, fenpropathrin, cyfluthrin, tefluthrin, fish safe pyrethroids (for example ethofenprox), natural pyrethrin, tetramethrin, s-bioallethrin, fenfluthrin, prallethrin or 5-benzyl-3-furylmethyl-(E)-(lR,3S)-2,2-dimethyl- 3-(2-oxothiolan-3-ylidenemethyl)cyclopropane carboxylate; b) Organophosphates, such as, profenofos, sulprofos, acephat
  • pesticides having particular targets may be employed in the composition, if appropriate for the intended utility of the composition.
  • selective insecticides for particular crops for example stemborer specific insecticides (such as cartap) or hopper specific insecticides (such as buprofezin) for use in rice may be employed.
  • insecticides or acaricides specific for particular insect species/stages may also be included in the compositions (for example acaricidal ovo-larvicides, such as clofentezine, flubenzimine, hexythiazox or tetradifon; acaricidal motilicides, such as dicofol or propargite; acaricides, such as bromopropylate or chlorobenzilate; or growth regulators, such as hydramethylnon, cyromazine, methoprene, chlorfluazuron or diflubenzuron).
  • acaricidal ovo-larvicides such as clofentezine, flubenzimine, hexythiazox or tetradifon
  • acaricidal motilicides such as dicofol or propargite
  • acaricides such as bromopropylate or chlorobenzilate
  • growth regulators such
  • fungicidal compounds which may be included in the composition of the invention are (E)-N-methyl-2-[2-(2,5-dimethylphenoxymethyl)phenyl]-2-methoxy- iminoacetamide (SSF-129), 4-bromo-2-cyano-N,N-dimethyl-6-trifluoromethylbenzimidazole- 1 -sulphonamide, ⁇ -[N-(3 -chloro-2,6-xylyl)-2-methoxyacetamido] - ⁇ -butyrolactone, 4-chloro- 2-cyano-N,N-dimethyl-5-/?-tolylimidazole-l -sulfonamide (IKF-916, cyamidazosulfamid), 3-5-dichloro-N-(3-chloro- 1 -ethyl- 1 -methyl-2-oxopropyl)-4-methylbenzamide (RH-7281 , zoxamide
  • synergists for use in the compositions include piperonyl butoxide, sesamex, safroxan and dodecyl imidazole.
  • Suitable herbicides and plant-growth regulators for inclusion in the compositions will depend upon the intended target and the effect required.
  • An example of a rice selective herbicide which may be included is propanil.
  • An example of a plant growth regulator for use in cotton is PDCTM.
  • Some mixtures may comprise active ingredients which have significantly different physical, chemical or biological properties such that they do not easily lend themselves to the same conventional formulation type.
  • other formulation types may be prepared.
  • one active ingredient is a water insoluble solid and the other a water insoluble liquid
  • the resultant composition is a suspoemulsion (SE) formulation.
  • Step 4 Preparation of methyl (3-amino-4-hydroxyphenyl)acetate.
  • Methyl (4-hydroxy-3-nitrophenyl)acetate [from step 3] (48.9g, 0.23mole) and 5% palladium on carbon were suspended in methanol and the resulting mixture was hydrogenated until all the starting material had been consumed.
  • the reaction mixture was filtered to remove the catalyst and the filter-cake was washed with methanol.
  • the combined filtrate and washings were concentrated in vacuo, affording methyl (3-amino-4- hydroxyphenyl)acetate as a solid (41. Og).
  • Methyl [(2,2-dimethylpropyl)benzoxazol-5-yl]acetate [from step 6] (5.00g, 0.0185mole) was dissolved in methanol (5ml) and then a solution of sodium hydroxide (0.8 lg, 0.0204mole) in water (5ml) was added slowly over 20minutes, maintaining the temperature below 25°C by external cooling. Once the addition was complete, the mixture was allowed to stir at room temperature for lhour. The reaction mixture was poured slowly into water (50ml) and concentrated hydrochloride acid was added until the pH of the mixture was below pH6. The mixture was stirred for lhour then filtered and the solid was washed thoroughly with water and dried.
  • N-(4-Chloro-3-methylisothiazol-5-yl)-(2-[2,2-dimethylpropyl]benzoxazol-5- yl)acetamide [prepared as in Example 1] (0.38g) in dry NN-dimethylformamide (3ml) under an atmosphere of nitrogen was stirred at ambient temperature then sodium hydride (0.200g, 80% dispersion in mineral oil) was added. The mixture was stirred for 15minutes then chloromethyl pivalate (0.166g) was added. The mixture was heated to 80-85°C for 3hours, further sodium hydride (0.1 OOg, 80% dispersion in mineral oil ) was added, the mixture was heated for a further 3hours and then cooled to ambient temperature.
  • the solution was diluted with water (50ml), acidified with dilute hydrochloric acid to give a fawn solid which was filtered from solution and then sucked to dryness.
  • the solid was fractionated by HPLC (silica, hexane/ethyl acetate at 5:1 by volume) to give the required product as a colourless solid (0.050g).
  • EXAMPLE 6 This Example illustrates the preparation of Compound No. 7 of Table No. 15.
  • Methyl iodide 38.4g, 0.27mole was added dropwise, at such a rate that the reaction temperature was maintained below -60°C, and once the addition was complete the mixture was stirred for lhour. The cooling bath was removed and the mixture was stirred for 3hours, allowed to warm to room temperature, at which it was kept overnight. The reaction was quenched with water, acidified with dilute aqueous hydrochloric acid and extracted with ethyl acetate. The organic extract was dried over anhydrous magnesium sulfate, filtered and the filtrate evaporated in vacuo.
  • Lithium diisopropylamide (2.0 molar solution in tetrahydrofuran / ethylbenzene / heptane, 1.46ml, 0.0029mole) was added dropwise to a chilled solution of 5-amino-4-chloro- 3-methylisothiazole (0.44 g, 0.0029mole) [preparation as in Example 1, Step 1] in tetrahydrofuran (20ml) and the solution was stirred at 0°C for lhour.
  • 5-Amino-4-chloro-3-methylisothiazole (0.4 lg, 0.0028mol) was added to a suspension of sodium methoxide (0.34g, 0.0063mol) in tetrahydrofuran (5ml) and the mixture was stirred at room temperature for 30minutes.
  • a solution of methyl [2-(2,2-dimethylpropyl) benzoxazol-5-yl]fluoroacetate (0.70g, 0.0025mol) in tetrahydrofuran (3ml) was added dropwise and the mixture was stirred at room temperature for 3days.
  • the mixture was diluted with water, neutralised with saturated aqueous ammonium chloride solution and extracted with ethyl acetate.
  • 5-Amino-4-chloro-3-methylisothiazole (7.4g, 0.050mol) was added to a suspension of sodium methoxide (6.1g, 0.112mol) in tetrahydrofuran (160ml) and the mixture was stirred at room temperature for 20minutes.
  • a solution of methyl 2-(4-methoxyphenyl) propionate (8.8g, 0.045mol) in tetrahydrofuran (40ml) was added dropwise and the mixture was stirred for 3hours at room temperature. The reaction was quenched with water, acidified with dilute aqueous hydrochloric acid and extracted with ethyl acetate.
  • NN-dimethylformamide (100 ml) was hydrogenated at 15bar (15xl0 5 ⁇ m ⁇ 2 ) for 6 hours at room temperature.
  • the catalyst was removed by filtration and the filtrate evaporated in vacuo to give N-(4-chloro-3-methylisothiazol-5-yl)-2-(3-amino-4- hydroxyphenyl)propionamide (9.0g) as an off-white solid, m.p.222-223°C.
  • EXAMPLE 10 This Example illustrates the preparation of Compound No. 78 of Table No. 1.
  • a solution of N,O-bis(trimethylsilyl)acetamide (0.141g, 0.0007mol) in dichloromethane (1ml) was added to a solution of N-(4-chloro-3-methylisothiazol-5-yl)-2-[2- (2,2,2-trifluoroethyl)benzoxazol-5-yl]propionamide (0.236g, O.OOO ⁇ mol) in dichloromethane (4ml) and the mixture was stirred at room temperature for 15minutes.
  • Chloromethylethyl ether (0.1 lg, O.OOlmol) was added and stirring was continued for 24hours.
  • Step l Preparation of methyl (3-heptafluorobutyramido-4-hydroxyphenyl)acetate Sodium bicarbonate (51g, 0.607mol) was suspended in 1,2-dimethoxyethane (180ml), and methyl (3-amino-4-hydroxyphenyl)acetate (58.26g, 0.32mol) was added, followed by a further quantity of 1,2-dimethoxyethane (75ml). To this mixture was added, dropwise, a solution of heptafluorobutyryl chloride (112.5g, 0.48mol) in 1,2-dimethoxyethane (140ml), at such a rate that the reaction temperature was maintained at 19-20°C.
  • Racemic N-(4-chloro-3-methylisothiazol-5-yl)-2-[(2-heptafluoropropyl)benzoxazol- 5-yl]propionamide (0.05 g) was dissolved in 60ml of 2-methylpentane : propan-2-ol 90:10 and loaded onto a Chiralcel OTTM column (0.46cm x 25cm) in aliquots of c ⁇ .0.008ml. The chromatographic system was equilibrated and run using a mobile phase of 2-methylpentane : propan-2-ol (95:5) at 2ml min and fractions were collected and assesed by analytical HPLC under the conditions described immediately above.
  • Enantiomer A (0.029g) eluted first; enantiomer B (0.016g) eluted second. Fractions containing mixtures of enantiomers were discarded.
  • EXAMPLE 12 This Example illustrates the preparation of Compound No. 80 of Table No. 1.
  • a solution of N,0-bis(trimethylsilyl)acetamide (0.50 g, 0.00245 moi) was added to a solution of N-(4-chloro-3-methylisothiazol-5-yl)-2-[2-heptafluoropropylbenzoxazol-5- yl]propionamide (l.OOg, 0.002mol) in dichloromethane (10ml) and the mixture was stirred at room temperature for 15minutes.
  • Chloromethylethyl ether (0.386g, 0.004mol) was added and stirring was continued for 48hours.
  • the reaction mixture was diluted with dichloromethane and poured into water.
  • 5-Amino-4-chloro-3-methylisothiazole (0.225g, 0.00152mol) was added to a suspension of sodium methoxide (0197g, 0.00365mol) in tetrahydrofuran (8ml) and the mixture was stirred at room temperature for 20minutes.
  • a solution of ethyl 3-[2-(2,2-dimethylpropyl)benzoxazol-5-yl]propanoate (0.400g, 0.00138mol) in tetrahydrofuran (2ml) was added dropwise and the mixture was then stirred at room temperature for 20hours.
  • the mixture was diluted with water, acidified with saturated aqueous ammonium chloride solution and extracted with ethyl acetate.
  • Iron powder (8.1g) was added to a solution of methyl 4-fluoro-3-nitrophenylacetate (27.24g, 0.128mol) in a mixture of concentrated hydrochloric acid (1.5ml), isopropanol (265ml) and water (26.5ml) and the mixture was stirred at room temperature for lhour. A second portion of iron powder (8.1g) was added and the mixture was heated to reflux for lhour. A further quantity of concentrated hydrochloric acid was added and the mixture was refluxed for a further lhour.
  • the cooling bath was removed and the mixture was allowed to warm to room temperature over a period of lhour.
  • the mixture was diluted with water, acidified with 2M aqueous hydrochloric acid and extracted with ethyl acetate.
  • the organic extract was dried over anhydrous magnesium sulfate, filtered and the filtrate evaporated in vacuo to give methyl 2-[2-(2-methylpropyl)benzothiazol-5-yl]propionate (1.15g) which was used without further purification in the next step.
  • EXAMPLE 15 This Example illustrates the preparation of Compound No. 156 of Table No. 39.
  • the reaction mixture was diluted with dichloromethane and washed with saturated aqueous sodium bicarbonate solution.
  • the organic phase was dried over anhydrous magnesium sulfate, filtered and the filtrate was evaporated in vacuo.
  • the residue was purified by column chromatography on silica gel, eluting with ethyl acetate : hexane 1 : 4, to give the desired product (0.278g).
  • EXAMPLE 17 This Example illustrates the pesticidal insecticidal properties of compounds of formula (I).
  • the activities of individual compounds of formula (I) were determined using a variety of pests.
  • the pests were treated with a liquid composition containing 500 parts per million (ppm) by weight of a compound of formula (I).
  • Each composition was made by dissolving the compound in an acetone and ethanol (50:50 by volume) mixture and diluting the solution with water containing 0.05% by volume of a wetting agent, SYNPERONIC NP8, until the liquid composition contained the required concentration of the compound.
  • SYNPERONIC is a registered trade mark.
  • test procedure adopted with regard to each pest was essentially the same and comprised supporting a number of the pests on a medium, which was usually a substrate, a host plant or a foodstuff on which the pests feed, and treating either or both the medium and the pests with a composition. Pest mortality was assessed usually between two and five days after treatment.
  • EXAMPLE 18 This Example illustrates the fungicidal properties of compounds of formula (I).
  • the compounds were tested against a variety of foliar fungal diseases of plants. The technique employed was as follows. Plants were grown in John Innes Potting Compost (No.l or 2) in 4cm diameter, 3.5cm depth minipots. The test compounds were individually formulated as a solution either in acetone or acetone/ethanol (1:1 by volume) which was diluted in deionised water to a concentration of lOOppm (that is, lmg of compound in a final volume of 10ml) immediately before use. When foliar sprays were applied to monocotyledonous crops, TWEEN 20 (0.1% by volume) was added. TWEEN is a registered trade mark.
  • PRCO 100 - ⁇ Mean disease level for treatment A ⁇ x 100 ⁇ Mean disease level on untreated controls ⁇
  • the PRCO is then rounded to the nearest whole number; therefore, in this particular example, the PRCO result is 71. It is possible for negative PRCO values to be obtained.
  • Results are displayed in Table 105.
  • PHYTIN Phytophthora infestans lycopersici
  • PYRIOR Pyricularia oryzae
  • This Example illustrates the fungicidal properties of compounds of formula (I).
  • the compounds were tested against a variety of foliar fungal diseases of plants. The techniques employed were as follows.
  • Test compounds were individually formulated as a solution either in acetone or acetone/ethanol (1:1 by volume) which was diluted in reverse osmosis water to a concentration of lOOppm (that is, lmg of compound in a final volume of 10ml) immediately before use.
  • lOOppm concentration of lmg of compound in a final volume of 10ml
  • the plants were incubated under high humidity conditions and then put into an appropriate environment to allow infection to proceed, until the disease was ready for assessment.
  • the Blumeria graminis f.sp. tritici plants were inoculated using a 'shake' inoculation technique.
  • the plants were reincubated under high humidity conditions for 24hours prior to assessment.
  • the time period between chemical application and assessment varied from five to nine days according to the disease and environment. However, each individual disease was assessed after the same time period for all the compounds tested against that particular disease.
  • the disease level present (that is, the percentage leaf area covered by actively sporulating disease) was assessed visually. For each treatment, the assessed values for all its replicates were meaned to provide mean disease values. Untreated control plants were assessed in the same manner. The data were then processed by either of two alternative methods, described below, each providing its own PRCO (Percentage Reduction from Control) value. All assessments on plants grown on cellulose media (and some grown in soil) used method 1. METHOD 1 This method uses banded assessment values.
  • the mean disease values are banded in the manner shown below. If the disease level value falls exactly mid-way between two of the points, the result will be the lower of the two points.
  • METHOD 2 This method uses unhanded assessment values (that is, the mean disease values are used in the PRCO calculation without a banding step).
  • PRCO 100 - ⁇ Mean disease level for treatment A ⁇ x 100 ⁇ Mean disease level on untreated controls ⁇
  • the PRCO is then rounded to the nearest whole number; therefore, in this particular example, the PRCO result is 71.
  • ERYSGT Blumeria graminis f.sp. tritici
  • PLASVI Plasmopara viticola
  • PHYTIN Phytophthora infestans lycopersici
  • PUCCRT Puccinia recondita

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Abstract

A compound of formula (I), where A is optionally substituted alkylene, alkenylene, alkynylene, cycloalkylene, alkylenoxy, oxy(C1-6)alkylene, alkylenethio, thio(C1-6)alkylene, C1-6alkylenamino, amino(C1-6)alkylene, [C1-6alkyleneoxy(C1-6)alkylene], [C1-6alkylenethio(c1-6)alkylene], [1-6alkylenesulfinyl(c1-6)alkylene],[c1-6alkylenesulfonyl(C1-6)alkylene] or [C1-6alkyleneamino(C1-6)alkylene]; provided that A is not CH2 or CH2O; B is N, N-oxide or CR8; Y is O, S or NR9; Z is O, S or NR?10; and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10¿ are specified radicals; compositions containing them; processes for making them; and their use as insecticides or fungicides.

Description

ISOTHIAZOLE DERIVATIVES AND THEIR USE AS PESTICIDES
The present invention relates to azole derivatives, to processes for preparing them, to fungicidal, insecticidal, acaricidal, molluscicidal and nematicidal compositions comprising them, to methods of using them to combat fungal diseases (especially fungal diseases of plants) and to methods of using them to combat and control insect, acarine, mollusc and nematode pests.
Azole and azine derivatives are disclosed in WO95/31448, WO97/18198, WO98/02424, WO98/05670 and WO98/17630. The present invention provides a compound of formula (I):
Figure imgf000003_0001
where A is optionally substituted
Figure imgf000003_0002
alkylene, optionally substituted C2.6 alkenylene, optionally substituted C2-6 alkynylene, optionally substituted cycloalkylene, optionally substituted Cj.-6 alkylenoxy, optionally substituted oxy(C1-6)alkylene, optionally substituted .6 alkylenethio, optionally substituted thio(C1-6)alkylene, optionally substituted C^ alkylenamino, optionally substituted amino(Cι_6)alkylene, optionally substituted [Cι_6 alkyleneoxy(C1_6)alkylene], optionally substituted [C^ alkylenethio(Cι-6)alkylene], optionally substituted [ -ό alkylenesulfinyl(C1.6)alkylene], optionally substituted [Cι- alkylenesulfonyl(C1.6)alkylene] or optionally substituted [C e alkyleneamino(Cι_ )alkylene]; provided that A is not CH2 or CH2O; B is N, N-oxide or CR8; Y is O, S or NR9; Z is O, S or NR10; R1 is hydrogen, halogen, optionally substituted Ct-6 alkyl, optionally substituted C2_6 alkenyl, optionally substituted C2.6 alkynyl, optionally substituted _6 alkoxy, optionally substituted Cι-6 alkylthio, optionally substituted C3.7 cycloalkyl, cyano, nitro or SF5; R2 is hydrogen, halogen, optionally substituted Cι-6 alkyl, optionally substituted C2. alkenyl, optionally substituted C2.6 alkynyl, optionally substituted Cι_6 alkoxy, optionally substituted Cι- alkylthio, optionally substituted Cι-6 alkylsulfinyl, optionally substituted Cι_6 alkylsulfonyl, cyano, nitro, formyl, optionally substituted Cι_6 alkylcarbonyl, optionally substituted Cj_6 alkoxycarbonyl, SF5 or RnON=C(R12); or R1 and R2 together with the atoms to which they are attached may be joined to form a five, six or seven-membered saturated or unsaturated, carbocylic or heterocyclic ring which may contain one or two heteroatoms selected from O, N or S and which is optionally substituted by Q-6 alkyl, Q-6 haloalkyl or halogen; R3 is hydrogen, optionally substituted Q-10 alkyl, optionally substituted [C2.6 alkenyl(C1-6)alkyl], optionally substituted [C2-6 alkynyl(Q-6)alkyl], optionally substituted C3-7 cycloalkyl, optionally substituted C O alkylcarbonyl, optionally substituted C O alkoxycarbonyl, formyl, optionally substituted CMO alkylaminocarbonyl, optionally substituted di(C1.1o)alkylaminocarbonyl, optionally substituted phenoxycarbonyl, optionally substituted Cι-6 alkylthio, optionally substituted Q_6 alkylsulfinyl, optionally substituted Q-6 alkylsulfonyl, optionally substituted -6 arylthio, optionally substituted -6 arylsulfinyl, optionally substituted Q-6 arylsulfonyl or R13R14NS(O)p; p is 0, 1 or 2; R4, R5 and R6 are, independently, hydrogen, halogen, optionally substituted Q-6 alkyl, optionally substituted Q-6 alkoxy, optionally substituted Q-6 alkylthio, optionally substituted Q-6 alkylsulfinyl, optionally substituted Q.6 alkylsulfonyl, cyano, nitro, optionally substituted Q- alkylcarbonyl, optionally substituted Q-6 alkoxycarbonyl or SF5; R7 is hydrogen, halogen, cyano, optionally substituted Q-2o alkyl, optionally substituted C2-20 alkenyl, optionally substituted C -20 alkynyl, optionally substituted C3- cycloalkyl, optionally substituted C5-6 cycloalkenyl, formyl, optionally substituted Q-2o alkoxycarbonyl, optionally substituted Q.2o alkylcarbonyl, aminocarbonyl, optionally substituted Q- o alkylaminocarbonyl, optionally substituted di(Q_2o)alkylaminocarbonyl, optionally substituted aryloxycarbonyl, optionally substituted arylcarbonyl, optionally substituted arylaminocarbonyl, optionally substituted N-(Q-6)alkyl-N-arylaminocarbonyl, optionally substituted diarylaminocarbonyl, optionally substituted heteroaryloxycarbonyl, optionally substituted heteroarylcarbonyl, optionally substituted heteroarylaminocarbonyl, optionally substituted N-(Q-6)alkyl- N-heteroarylaminocarbonyl, optionally substituted diheteroarylaminocarbonyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted heterocyclyl, SH, optionally substituted Q-2o alkylthio, optionally substituted Q-20 alkylsulfinyl, optionally substituted Q_2o alkylsulfonyl, optionally substituted arylthio, optionally substituted arylsulfinyl, optionally substituted arylsulfonyl, R15O, R16R17N or R18ON=C(R19); R8 is hydrogen, halogen, nitro, cyano, optionally substituted Q-8 alkyl, optionally substituted C2.6 alkenyl, optionally substituted C2_6 alkynyl, optionally substituted C3.7 cycloalkyl, optionally substituted Q-6 alkoxycarbonyl, optionally substituted Q_6 alkylcarbonyl, optionally substituted Q-6 alkylaminocarbonyl, optionally substituted di(Q-6)alkylaminocarbonyl, optionally substituted phenyl or optionally substituted heteroaryl; R9 is hydrogen, cyano, nitro, optionally substituted Q-6 alkyl, optionally substituted C3-7 cycloalkyl, optionally substituted (C2-6)alkenyl(Q-6)alkyl, optionally substituted (C2-6)alkynyl(Q-6)alkyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted Q-6 alkylcarbonyl, optionally substituted Q-6 alkoxycarbonyl, optionally substituted Q-6 alkylamino, optionally substituted di(Q.6)alkylamino, optionally substituted Q-6 alkylcarbonylamino, optionally substituted Q-6 alkoxycarbonylamino, optionally substituted Q-6 alkoxy, optionally substituted Q-6 alkylthio, optionally substituted Q.6 alkylsulfinyl, optionally substituted Q-6 alkylsulfonyl, optionally substituted arylthio, optionally substituted arylsulfinyl, optionally substituted arylsulfonyl or Q-6 alkylcarbonyloxy; R10 is hydrogen, cyano, optionally substituted Q_8 alkyl, optionally substituted [C -6 alkenyl(Q-6)alkyl], optionally substituted [C2.6 alkynyl (Q-6)alkyl], optionally substituted C3-7 cycloalkyl, optionally substituted [C3_7 cycloalkyl(Q-6)alkyl], Q-6 alkoxy(C1.6)alkyl, optionally substituted Q-6 alkoxycarbonyl, optionally substituted Q-6 alkylcarbonyl, optionally substituted Q-6 alkylaminocarbonyl, optionally substituted di(Q-6)alkylaminocarbonyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted alkylsulfonyl or optionally substituted arylsulfonyl; Rπ and R18 are, independently, hydrogen, optionally substituted phenyl (Q.2)alkyl or optionally substituted Q-2o alkyl; R12 and R19 are, independently, hydrogen, optionally substituted phenyl or optionally substituted Q-6 alkyl; R13 and R14 are, independently, optionally substituted Q-6 alkyl; or R13 and R14 together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one or two further heteroatoms selected from O, N and S and which is optionally substituted by one or two independently selected Q-6 alkyl groups; R15 is hydrogen, optionally substituted Q-2o alkyl, optionally substituted [C .2o alkenyl(Q-6)alkyl], optionally substituted [Q_20 alkynyl(Q-6) alkyl], optionally substituted C3-7 cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, (Q-6)alkylCH=N, optionally substituted arylCH=N, optionally substituted [aryl(Q_6)alkyl]CH=N, optionally substituted heteroarylCH=N, optionally substituted [heterocyclyl(Q_6)alkyl]CH=N, optionally substituted arylC(CH3)=N, optionally substituted heteroarylC(CH3)=N or optionally substituted di(Q.6)alkylC=N; and R16 and R are, independently, hydrogen, optionally substituted Q-20 alkyl, optionally substituted C3-7 cycloalkyl, optionally substituted [C2-20 alkenyl(C1-6)alkyl], optionally substituted [C2-20 alkynyl(Q-6)alkyl], optionally substituted Q-2o alkoxycarbonyl, optionally substituted phenoxycarbonyl, formyl, optionally substituted Q_2o alkylcarbonyl, optionally substituted Q-2o alkylsulfonyl or optionally substituted phenylsulfonyl.
One group of preferred compounds of formula (I) is a group wherein A is optionally substituted Q-6 alkylene, optionally substituted C2.6 alkenylene, optionally substituted C2-6 alkynylene, optionally substituted Q-6 alkylenoxy, optionally substituted oxy(Q-6)alkylene, optionally substituted Q-6 alkylenethio, optionally substituted thio(C1-6)alkylene, optionally substituted Q-6 alkylenamino, optionally substituted amino-(Q.6)alkylene, optionally substituted [Q.6 alkyleneoxy(C1-6)alkylene], optionally substituted [Cι-6 alkylenethio(C1-ό)alkylene], optionally substituted [Q_6 alkylenesulfιnyl(Q-6)alkylene], optionally substituted [Q-6 alkylenesulfonyl(Q_6)alkylene] or optionally substituted [Q-6 alkyleneamino(C1-6)alkylene], provided that A is not CH2 or CH2O; B is N, N-oxide or CR8; Y is O, S or NR9; Z is O, S or NR10; R3 is hydrogen, optionally substituted Q-ι0 alkyl, optionally substituted [C2-6 alkenyl(Q_6)alkyl], optionally substituted [C2-6 alkynyl(C1-6)alkyl], optionally substituted C3-7 cycloalkyl, optionally substituted C O alkylcarbonyl, optionally substituted Cι-ιo alkoxycarbonyl, formyl, optionally substituted Q-10 alkylaminocarbonyl, optionally substituted di(Q.ιo)alkylaminocarbonyl, optionally substituted phenoxycarbonyl, optionally substituted Q.6 alkylthio, optionally substituted Q_6 alkylsulfinyl, optionally substituted Q-6 alkylsulfonyl, optionally substituted Q.6 arylthio, optionally substituted Q_6 arylsulfinyl, optionally substituted Q_6 arylsulfonyl or R13R14NS; R4, R5 and R6 are, independently, hydrogen, halogen, optionally substituted Q-6 alkyl, optionally substituted Q-6 alkoxy, optionally substituted Q_6 alkylthio, optionally substituted Q-6 alkylsulfinyl, optionally substituted Q-6 alkylsulfonyl, cyano, nitro, optionally substituted Q_6 alkylcarbonyl, optionally substituted Q-6 alkoxycarbonyl or SF5; R7 is hydrogen, halogen, cyano, optionally substituted Q. 0 alkyl, optionally substituted C2-20 alkenyl, optionally substituted C _2o alkynyl, optionally substituted C3-7 cycloalkyl, optionally substituted C5.6 cycloalkenyl, formyl, optionally substituted Q- 0 alkoxycarbonyl, optionally substituted Q. o alkylcarbonyl, aminocarbonyl, optionally substituted Q-2o alkylaminocarbonyl, optionally substituted di(Q-2o)alkylaminocarbonyl, optionally substituted aryloxycarbonyl, optionally substituted arylcarbonyl, optionally substituted arylaminocarbonyl, optionally substituted N-alkyl-N-arylaminocarbonyl, optionally substituted diarylaminocarbonyl, optionally substituted heteroaryloxycarbonyl, optionally substituted heteroarylcarbonyl, optionally substituted heteroarylaminocarbonyl, optionally substituted alkylheteroarylaminocarbonyl, optionally substituted diheteroarylaminocarbonyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted heterocyclyl, R15O, HS, optionally substituted Q-2o alkylthio, optionally substituted Q.20 alkylsulfinyl, optionally substituted Q. o alkylsulfonyl, optionally substituted arylthio, optionally substituted arylsulfinyl, optionally substituted arylsulfonyl, RI6R17N or R18ON=C(R19); R1 is hydrogen, halogen, optionally substituted Q.6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, optionally substituted Q_6 alkoxy, optionally substituted Q- alkylthio, optionally substituted C3-7 cycloalkyl, cyano, nitro or SF5; R2 is hydrogen, halogen, optionally substituted Q-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, optionally substituted Q.6 alkoxy, optionally substituted Q-6 alkylthio, optionally substituted Q-6 alkylsulfinyl, optionally substituted Q-6 alkylsulfonyl, cyano, nitro, formyl, RuON=C(R12), optionally substituted Q-6 alkylcarbonyl, optionally substituted Q-6 alkoxycarbonyl or SF5; or R1 and R2 together with the atoms to which they are attached may be joined to form a five, six or seven-membered saturated or unsaturated ring carbocylic or heterocyclic ring which may contain one or two heteroatoms selected from O, N or S and which may be optionally substituted by Q_6 alkyl, Q_6 haloalkyl or halogen; R9 is hydrogen, cyano, nitro, optionally substituted Q_6 alkyl, optionally substituted C3-7 cycloalkyl, optionally substituted (C2_6)alkenyl(Q_6)alkyl, optionally substituted (C2-6)alkynyl(Q-6)alkyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted Q-6 alkylcarbonyl, optionally substituted Q- alkoxycarbonyl, optionally substituted Q_6 alkylamino, optionally substituted di(Q-6)alkylamino, optionally substituted Q-6 alkylcarbonylamino, optionally substituted Q-6 alkoxycarbonylamino, optionally substituted Q- alkoxy, optionally substituted Q_6 alkylthio, optionally substituted Q-6 alkylsulfinyl, optionally substituted Q.6 alkylsulfonyl, optionally substituted arylthio, optionally substituted arylsulfinyl, optionally substituted arylsulfonyl or Q.6 acyloxy; R10 is hydrogen, cyano, optionally substituted Q_8 alkyl, optionally substituted [C2-6 alkenyl(Q-6)alkyl], optionally substituted [C2_6 alkynyl
(Q.6)alkyl], optionally substituted C3-7 cycloalkyl, optionally substituted [Q_7 cycloalkyl (C1-6>alkyl], Q-6 alkoxy(Q-6)alkyl, optionally substituted C!-6 alkoxycarbonyl, optionally substituted Q-6 alkylcarbonyl, optionally substituted Q- alkylaminocarbonyl, optionally substituted di(Q-6)alkylaminocarbonyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted alkylsulfonyl or optionally substituted arylsulfonyl; R8 is hydrogen, halogen, nitro, cyano, optionally substituted Q-8 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, optionally substituted C3-7 cycloalkyl, optionally substituted Q-6 alkoxycarbonyl, optionally substituted Q.6 alkylcarbonyl, optionally substituted Q_6 alkylaminocarbonyl, optionally substituted di(Q-6)alkylaminocarbonyl, optionally substituted phenyl or optionally substituted heteroaryl; R13 and R14 are, independently, optionally substituted Q-6 alkyl or R13 and R14 together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one or two further heteroatoms selected from O, N or S and which may be optionally substituted by one or two Q-6 alkyl groups; R15 is hydrogen, optionally substituted Q-20 alkyl, optionally substituted [C2-2o alkenyl(Q-6)alkyl], optionally substituted [C2-2o alkynyl(Q-6)alkyl], optionally substituted C3-7 cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted [heterocyclyl(Q-6)alkylCH=N] or di(Q-6)alkylC=N; R16 and R17 are, independently, hydrogen, optionally substituted Q-2o alkyl, optionally substituted C3-7 cycloalkyl, optionally substituted [C2-2o alkenyl(Q-6)alkyl], optionally substituted [C2-2o alkynyl(Q-6)alkyl], optionally substituted Q.2o alkoxycarbonyl, optionally substituted phenoxycarbonyl, formyl, optionally substituted Q-2o alkylcarbonyl, optionally substituted Q-2o alkylsulfonyl or optionally substituted phenylsulfonyl; or R16 and R17 together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one or two further heteroatoms selected from O, N or S and which may be optionally substituted by one or two Q_ alkyl groups; R19 and R12 are independently hydrogen, optionally substituted phenyl or optionally substituted Q-6 alkyl; and R18 and Ru are, independently, hydrogen, optionally substituted phenyl (Q.2)alkyl or optionally substituted Q_2o alkyl.
The compounds of formula (I) may exist in different geometric or optical isomers or tautomeric forms. This invention covers all such isomers and tautomers and mixtures thereof in all proportions as well as isotopic forms such as deuterated compounds.
When present, optional substituents on alkylene, alkenylene or alkynylene moieties include (subject to valency constraints) one or more of hydroxy, halogen, Q_6 alkyl, Q-6 haloalkyl, Q-6 cyanoalkyl, Q-6 alkoxy(Q-6) alkyl, Q- alkoxy, cyano, =O, =NR20 and =CR21R22; and, especially, one or more of halogen, Q-6 alkyl, Q-6 haloalkyl, Q.6 cyanoalkyl, Q-6 alkoxy(Q-6) alkyl, Q-6 alkoxy, cyano, =O, =NR20 and =CR21R22; wherein R20 is Q-6 alkyl, Cι-6 haloalkyl, OR23 or NR24R25; where R21 and R22 are, independently, hydrogen, Q-6 alkyl, Q-6 alkoxy, Q-6 haloalkyl, cyano, Q-6 alkoxycarbonyl, Q-6 alkylcarbonyl or NR26R27; R23 is Q-6 alkyl, Q-6 haloalkyl or phenyl(Q-2)alkyl; R24 and R25 are, independently, hydrogen, Q_8 alkyl, C3-7 cycloalkyl, C2-6 alkenyl(Q-6)alkyl, C2-6 alkynyl(Q-6)alkyl, C2.6 haloalkyl, Cι-6 alkoxy(Cι-6)alkyl, Q-6 alkoxycarbonyl(Q-6)alkyl, carboxy(Q-6)alkyl or phenyl(Cι-2)alkyl; or R24 and R25 together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one or two further hetero atoms selected from O, N or S and which is optionally substituted by one or two Q-6 alkyl groups; R26 and R27 are, independently, hydrogen, Q-8 alkyl, C3-7 cycloalkyl, C -6 alkenyl(Q-6)alkyl, C2-6 alkynyl(Q-6)alkyl, C2-6 haloalkyl, Q-6 alkoxy(Q-6)alkyl, Q-6 alkoxycarbonyl(Q-6)alkyl, carboxy(C1-6)alkyl or phenyl(C!-2)alkyl; or R26 and R27 together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one or two further heteroatoms selected from O, N or S and which is optionally substituted by one or two Q-6 alkyl groups.
Each alkyl moiety is a straight or branched chain and is, for example, methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, wo-propyl, n-butyl, sec-butyl, iso-butyl, tert-butyl or neo-pentyl.
When present, the optional substituents on an alkyl moiety include one or more of halogen, nitro, cyano, NCS-, C3-7 cycloalkyl (itself optionally substituted with Q-6 alkyl or halogen), C5-7 cycloalkenyl (itself optionally substituted with Q.6 alkyl or halogen), hydroxy, Q-ϊo alkoxy, CMO alkoxy(Q-1o)alkoxy, tri(Q-4)alkylsilyl(Q-6)alkoxy, Q-6 alkoxycarbonyl(C1-1o)alkoxy, C|.ιo haloalkoxy, aryl(Q-4)alkoxy (where the aryl group is optionally substituted), C3-7 cycloalkyloxy (where the cycloalkyl group is optionally substituted with Q-6 alkyl or halogen), Q-io alkenyloxy, Q-io alkynyloxy, SH, CMO alkylthio, Q-10 haloalkylthio, aryl(Q-4)alkylthio (where the aryl group is optionally substituted), C3.7 cycloalkylthio (where the cycloalkyl group is optionally substituted with Q-6 alkyl or halogen), tri(Q-4)alkylsilyl(Q-6)alkylthio, arylthio (where the aryl group is optionally substituted), Q-6 alkylsulfonyl, Q-6 haloalkylsulfonyl, Q-6 alkylsulfinyl, Q_6 haloalkylsulfinyl, arylsulfonyl (where the aryl group may be further optionally substituted), -ri(Q- )alkylsilyl, aryldi(C1- )alkylsilyl, (C1-4)alkyldiarylsilyl, triarylsilyl, Q-10 alkylcarbonyl, HO C, Q-io alkoxycarbonyl, aminocarbonyl, Q-6 alkylaminocarbonyl, di(Q-6 alkylaminocarbonyl, N-(Q-3 alkyl)-N-(Q-3 alkoxy)aminocarbonyl, Q-6 alkylcarbonyloxy, arylcarbonyloxy (where the aryl group is optionally substituted), di(Q-6)alkylaminocarbonyloxy, aryl (itself optionally substituted), heteroaryl (itself optionally substituted), heterocyclyl (itself optionally substituted with Q-6 alkyl or halogen), aryloxy (where the aryl group is optionally substituted), heteroaryloxy, (where the heteroaryl group is optionally substituted), heterocyclyloxy (where the heterocyclyl group is optionally substituted with Q-6 alkyl or halogen), amino, Q- alkylamino, di (CMalkylamino, Q-6 alkylcarbonylamino and N-(Q-6)alkylcarbonyl-N-(Q-6)alkylamino.
Alkenyl and alkynyl moieties can be in the form of straight or branched chains, and the alkenyl moieties, where appropriate, can be of either the (E)~ or ©-configuration. Examples are vinyl, allyl and propargyl.
When present, the optional substituents on alkenyl or alkynyl include those optional substituents given above for an alkyl moiety.
In the context of this specification acyl is optionally substituted Q-6 alkylcarbonyl (for example acetyl), optionally substituted C2-6 alkenylcarbonyl, optionally substituted C2-6 alkynylcarbonyl, optionally substituted arylcarbonyl (for example benzoyl) or optionally substituted heteroarylcarbonyl. Halogen is fluorine, chlorine, bromine or iodine.
Haloalkyl groups are alkyl groups which are substituted with one or more of the same or different halogen atoms and are, for example, CF3, CF2C1, CF3CH2 or CHF2CH2.
Aryl includes naphthyl, anthracyl, fluorenyl and indenyl but is preferably phenyl. The term heteroaryl refers to an aromatic ring containing up to 10 atoms including one or more heteroatoms (preferably one or two heteroatoms) selected from O, S and N.
Examples of such rings include pyridine, pyrimidine, furan, quinoline, quinazoline, pyrazole, thiophene, thiazole, oxazole and isoxazole.
The terms heterocycle and heterocyclyl refer to a non-aromatic ring containing up to 10 atoms including one or more (preferably one or two) heteroatoms selected from O, S and N. Examples of such rings include 1,3-dioxolane, tetrahydrofuran and morpholine.
When present, the optional substituents on heterocyclyl include Q-6 alkyl as well as those optional substituents given above for an alkyl moiety. Cycloalkyl includes cyclopropyl, cyclopentyl and cyclohexyl. Cycloalkenyl includes cyclopentenyl and cyclohexenyl.
When present, the optional substituents on cycloalkyl or cycloalkenyl include Q- alkyl as well as those optional substituents given above for an alkyl moiety. Carbocyclic rings include aryl, cycloalkyl and cycloalkenyl groups.
When present, the optional substituents on aryl or heteroaryl are selected, independently, from halogen, nitro, cyano, NCS-, Q-6 alkyl, Q-6 haloalkyl, Q-6 alkoxy(Q-6)alkyl, C2-6 alkenyl, C2-6 haloalkenyl, C2-6 alkynyl, C3-7 cycloalkyl (itself optionally substituted with Q-6 alkyl or halogen), C5.7 cycloalkenyl (itself optionally substituted with Q-6 alkyl or halogen), hydroxy, Q-10 alkoxy, Q-10 alkoxy(Q-10)alkoxy, tri(Q- )alkylsilyl(Q-6)alkoxy, Q- alkoxycarbonyl(Q-10)alkoxy, Q-10 haloalkoxy, aryl(Q.4)alkoxy (where the aryl group is optionally substituted), C3.7 cycloalkyloxy (where the cycloalkyl group is optionally substituted with Q-6 alkyl or halogen), Q-io alkenyloxy, Q-w alkynyloxy, SH, Q-10 alkylthio, Q-io haloalkylthio, aryl(Q-4)alkylthio (where the aryl group may be further optionally substituted), C3-7 cycloalkylthio (where the cycloalkyl group is optionally substituted with Q-6 alkyl or halogen), tri(Q- )alkylsilyl(Q-6)alkylthio, arylthio (where the aryl group is optionally substituted), Q-6 alkylsulfonyl, Q-6 haloalkylsulfonyl, Q-6 alkylsulfinyl, Q-6 haloalkylsulfinyl, arylsulfonyl (where the aryl group is optionally substituted), tri(Q.4)alkylsilyl, aryldi(Q-4)alkylsilyl, (Q-4)alkyldiarylsilyl, triarylsilyl, Q_10 alkylcarbonyl, HO2C, Q-10 alkoxycarbonyl, aminocarbonyl, Q-6 alkylaminocarbonyl, di(Q.6 alkylaminocarbonyl, N-(C!-3 alkyl)-N-(C!-3 alkoxy)aminocarbonyl, Q-6 alkylcarbonyloxy, arylcarbonyloxy (where the aryl group is optionally substituted), di(Q-6)alkylamino- carbonyloxy, aryl (itself optionally substituted), heteroaryl (which itself may be further optionally substituted), heterocyclyl (itself optionally substituted with Q-6 alkyl or halogen), aryloxy (where the aryl group is optionally substituted), heteroaryloxy (where the heteroaryl group is optionally substituted), heterocyclyloxy (where the heterocyclyl group is optionally substituted with Q_6 alkyl or halogen), amino, Q-6 alkylamino, di(Q-6)alkylamino, Q-6 alkylcarbonylamino and N-(C1_6)alkylcarbonyl-N-(C1_6)alkylamino.
For substituted phenyl moieties, heterocyclyl and heteroaryl groups it is preferred that one or more substituents are independently selected from halogen, Q-6 alkyl, Q-6 haloalkyl, Q-6 alkoxy(Q-6)alkyl, Q-6 alkoxy, Q-6 haloalkoxy, Q-6 alkylthio, Q-6 haloalkylthio, Q-6 alkylsulfinyl, Q_6 haloalkylsulfinyl, Q-6 alkylsulfonyl, Q.6 haloalkylsulfonyl, C -6 alkenyl, C2-6 haloalkenyl, C2-6 alkynyl, C3-7 cycloalkyl, nitro, cyano, CO2H, Q-6 alkylcarbonyl, Q-6 alkoxycarbonyl, R28R29N or R30R31NC(O); wherein R28, R29, R30 and R31 are, independently, hydrogen or Q-6 alkyl.
Haloalkenyl groups are alkenyl groups which are substituted with one or more of the same or different halogen atoms.
It is to be understood that dialkylamino substituents include those where the dialkyl groups together with the N atom to which they are attached form a five, six or seven- membered heterocyclic ring which may contain one or two further heteroatoms selected from O, N or S and which is optionally substituted by one or two independently selected (Q-6)alkyl groups. When heterocyclic rings are formed by joining two groups on an N atom, the resulting rings are suitably pyrrolidine, piperidine, thiomorpholine and morpholine each of which may be substituted by one or two independently selected (Q-6) alkyl groups.
Preferably the optional substituents on an alkyl moiety include one or more of halogen, nitro, cyano, HO2C, C^o alkoxy (itself optionally substituted by Q-10 alkoxy), aryl(Q-4)alkoxy, .io alkylthio, Q-io alkylcarbonyl, Q-io alkoxycarbonyl, Q-6 alkylaminocarbonyl, di(Q-6 alkylaminocarbonyl, (Q-6)alkylcarbonyloxy, optionally substituted phenyl, heteroaryl, aryloxy, arylcarbonyloxy, heteroaryloxy, heterocyclyl, heterocyclyloxy, C3-7 cycloalkyl (itself optionally substituted with (Q-6)alkyl or halogen), C3-7 cycloalkyloxy, C5. cycloalkenyl, Q-6 alkylsulfonyl, Q-6 alkylsulfinyl, tri(Q-4)alkylsilyl, tri(Q-4)alkylsilyl(Q-6)alkoxy, aryldi(Q-4)alkylsilyl, (Q-4)alkyldiarylsilyl and triarylsilyl.
Preferably the optional substituents on alkenyl or alkynyl include one or more of halogen, aryl and C3-7 cycloalkyl.
It is more preferred that heterocyclyl is optionally substituted by Q-6 alkyl.
Preferably the optional substituents for cycloalkyl include halogen, cyano and Q_3 alkyl.
Preferably the optional substituents for cycloalkenyl include Q-3 alkyl, halogen and cyano.
In a further aspect, the present invention provides a compound of formula (IA):
Figure imgf000013_0001
wherein A, B, Y, Z, R1, R2 , R3, R4, R5, R6 and R7 are as defined above for a compound of formula (I).
More preferred compounds of formula (IA) are those wherein R1 is hydrogen, halogen, Q-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Q-6 cyanoalkyl, Q-6 haloalkyl, Q-6 alkoxy, Q-6 haloalkoxy, Q-6 alkylthio, Q-6 haloalkylthio, C3_6 cycloalkyl, C3-7 cycloalkyl(Q-4)alkyl, Q-6 alkoxy(Q-6)alkyl, cyano, nitro or SF5; A is Q-6 alkylene, Q-6 alkenylene , Q-6 alkylenoxy, oxy(Q-6)alkylene, Q- alkylenamino or Q-6 alkylenethio, each of which is optionally substituted by Q-3 alkyl, Q-3 haloalkyl, Q-3 cyanoalkyl, halogen, Q-3 alkoxy, Q-6 alkoxycarbonyl, cyano, =O, =NR20 or =CR21R22, provided that A is not CH2 or CH2O; B is N or CR8; Y is O, S or NR9; Z is O, S or NR10; R3 is hydrogen, Q-ι0 alkyl, benzyloxymethyl, benzoyloxymethyl, Q-6alkoxy(Q-6)alkyl, C2-6 alkenyl(Q-6)alkyl (especially allyl), C2-6 alkynyl(C1-6)alkyl (especially propargyl), C^o alkylcarbonyl or Q-10 alkoxycarbonyl (especially wobutoxycarbonyl); R4, R5 and R are independently selected from hydrogen, halogen, Q-6 alkyl, Q- alkoxy, Q-6 haloalkoxy, Q-6 alkylthio, Q-6 haloalkylthio, Q-6 alkylsulfinyl, Q-6 haloalkylsulfinyl, Q-6 alkylsulfonyl, Q-6 haloalkylsulfonyl, Q-6 haloalkyl, cyano, nitro, Q-6 alkylcarbonyl, Q-6 alkoxycarbonyl or SF5; R7 is cyano, Q-8 alkyl, Q-6 haloalkyl, Q-6 cyanoalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C3-7 halocycloalkyl, C3-7 cyanocycloalkyl, Q-3 alkyl(C3-7)cycloalkyl, Q-3 alkyl(C3-7)halocycloalkyl, C5-6 cycloalkenyl, C3-7 cycloalkyl(Q-6)alkyl, C5-6 cycloalkenyl(Q-6)alkyl, C2-6 haloalkenyl, Q-6 cyanoalkenyl, Q-6 alkoxy(C1-6)alkyl, C3-6 alkenyloxy(Q-6)alkyl, C3-6 alkynyloxy(C1-6)alkyl, aryloxy(C1-6)alkyl, formyl, Q-6 carboxyalkyl, Q-6 alkylcarbonyl(Q-6)alkyl, C -6 alkenylcarbonyl(Q-6)alkyl, C2-6 alkynylcarbonyl(C1-6)alkyl, Cι-6 alkoxycarbonyl(Cι-6)alkyl, -6 alkenyloxycarbonyl(Q-6)alkyl, C3-6 alkynyloxycarbonyl(Q-6)alkyl, aryloxycarbonyl(C1-6)alkyl, Q-6 alkylthio(C1-6)alkyl, C1-6 alkylsulfιnyl(Q-6)alkyl, Q-6 alkylsulfonyl(Q-6)alkyl, aminocarbonyl(Q-6)alkyl, aminocarbonyl(C -6)alkenyl, aminocarbonyl(C -6)alkynyl, Q-6 alkylaminocarbonyl (Q-6)alkyl, di(C 1.6)alkylaminocarbonyl(C 1 -6)alkyl, C 1 -6 alkylaminocarbonyl (C 1 -6)alkenyl, di(Cι-6)alkylaminocarbonyl(Cι-6)alkenyl, alkylaminocarbonyl(Q-6)alkynyl, di(C1-6)alkylaminocarbonyl(Cι-6)alkynyl, Q-6 alkoxycarbonyl, C]-6 alkylcarbonyl, aminocarbonyl, Q-6 alkylaminocarbonyl, di(Q_6)alkylaminocarbonyl, phenyl (optionally substituted by halo, nitro, cyano, Q-6 alkyl, Q-6 haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy), phenyl(Q-4)alkyl (wherein the phenyl group is optionally substituted by halo, nitro, cyano, Ci-6 alkyl, Q-6 haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy), phenyl(C2-4)alkenyl, (wherein the phenyl group is optionally substituted by halo, nitro, cyano, Q-6 alkyl, Q-6 haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy), heteroaryl (optionally substituted by halo, nitro, cyano, Ci-6 alkyl, Ci-6 haloalkyl, Ci-6 alkoxy or Q-6 haloalkoxy), heterocyclyl (optionally substituted by halo, nitro, cyano, Q-6 alkyl, Q-6 haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy), heteroaryl (Q-4)alkyl (where the heteroaryl may be substituted by halo, nitro, cyano, Q-6 alkyl, Q-6 haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy), heterocyclyl(Q-4)alkyl (where the heterocyclyl may be substituted by halo, cyano, Q-6 alkyl, Q-6 haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy), R15O, Q-8 alkylthio, R16R17N or R18ON=C(R19); R2 is hydrogen, halogen, Q-6 alkyl, C2-6 alkenyl, Ci-6 alkynyl, Ci-6 haloalkyl, Q-6 alkoxy, Q-6 alkoxy (Q-6)alkyl, Q-6 haloalkoxy, Q-6 alkylthio, Q-6 haloalkylthio, Q-6 alkylsulfinyl, Q-6 haloalkylsulfinyl, Q-6 alkylsulfonyl, Q-6 haloalkylsulfonyl, Q-6 haloalkyl, cyano, nitro, formyl, CH=NORn, Ci-6 alkylcarbonyl, Ci-6 alkoxycarbonyl or SF5; or together R1 and R2 together with the atoms to which they are attached may be joined to form a five, six or seven-membered saturated or unsaturated ring carbocylic or heterocyclic ring which may contain one or two hetero atoms selected from O, N or S and which may be optionally substituted by Q_6 alkyl, Ci-6 haloalkyl or halogen; R9 is cyano, nitro, Q-6 alkyl, Q-6 haloalkyl, C3_7 cycloalkyl, C3-7 cycloalkyl(Q-6)alkyl, CH2 - (C2-6) alkenyl, CH2(C2-6)alkynyl, phenyl (optionally substituted by halo, nitro, cyano, Ci- alkyl, Q-6 haloalkyl, Q-6 alkoxy or Ci-6 haloalkoxy) heteroaryl (optionally substituted by halo, nitro, cyano, Q-6 alkyl, Q-6 haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy), Q-6 alkylcarbonyl, Q-6 alkoxycarbonyl, Q-6 alkylamino, di(Q-6)alkylamino, Q-6 alkylcarbonylamino, Q-6 alkoxycarbonylamino, Q-6 alkoxy, Q-6 alkylthio, Q-6 alkylsulfinyl, Ci-6 alkylsulfonyl, Q-6 haloalkylthio, Q-6 haloalkylsulfinyl, Q_6 haloalkylsulfonyl, arylthio, arylsulfinyl, arylsulfonyl or OCO(Cι-6)alkyl; R10 is hydrogen, Q_8 alkyl, Q-6 haloalkyl, Q-6 cyanoalkyl, C2-6 alkenyl, C2_6 alkynyl, C3_7 cycloalkyl, C2-6 haloalkenyl, Q_7 cycloalkyl(Q-6)alkyl, Q-6 alkoxy(Q_6)alkyl, Q-6 alkoxycarbonyl, Q_6 alkylcarbonyl, Q_6 alkylaminocarbonyl, di(Cι_6)alkylaminocarbonyl, phenyl (optionally substituted by halo, nitro, cyano, Q-6 alkyl, Ci-6 haloalkyl, Q-6 alkoxy or Cι-6 haloalkoxy) or heteroaryl (optionally substituted by halo, nitro, cyano, Ci-6 alkyl, Q-6 haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy); R20 is Q-6 alkyl, OR23 or NR24R25; R21 is hydrogen, Q-6 alkyl or Q-6 haloalkyl; R22 is hydrogen, Q-6 alkyl, Ci-6 haloalkyl, Q-6 alkoxy, cyano, Q-6 alkoxycarbonyl, Q_6 alkylcarbonyl or NR26R27; R8 is hydrogen, halogen, nitro, cyano, Q-8 alkyl, Q-6 haloalkyl, C1-6 cyanoalkyl, -6 alkenyl, -6 alkynyl, Q-7 cycloalkyl, Q-6 haloalkenyl, C3-7 cycloalkyl(Q-6)alkyl, Ci-6 alkoxy(Ci-6)alkyl, Ci-6 alkoxycarbonyl, Q-6 alkylcarbonyl, Ci-6 alkylaminocarbonyl, di(Q-6)alkylaminocarbonyl, Q-6 alkoxycarbonyl(Q-6)alkyl, Ci-6 alkylcarbonyl(Ci-6)alkyl, Ci-6 alkylaminocarbonyl(Q-6)alkyl, di(Ci-6)alkylaminocarbonyl(Ci-6)alkyl, phenyl (optionally substituted by halo, nitro, cyano, Ci-6 alkyl, Q-6 haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy), phenyl(Q-6)alkyl (wherein the phenyl group is optionally substituted by halo, nitro, cyano, Q-6 alkyl, Q-6 haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy), heteroaryl (optionally substituted by halo, nitro, cyano, Q-6 alkyl, Q-6 haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy) or heteroaryl(Q-6)alkyl (wherein the heteroaryl group is optionally substituted by halo, nitro, cyano, Q-6 alkyl, Ci-6 haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy); R23 is Ci-6 alkyl or optionally substituted phenyl(Q-2)alkyl; R24 and R25 are, independently, hydrogen, Q-8 alkyl or phenyl (optionally substituted by halo, nitro, cyano, Q-6 alkyl, Q-6 haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy); R15 is hydrogen, Q-8 alkyl, Q-6 haloalkyl, Q-6 cyanoalkyl, C2-6 alkenyl, C2-6 alkynyl, Q-6 alkoxy(Q-6)alkyl, phenyl (Q-4)alkyl (wherein the phenyl group is optionally substituted by halo, nitro, cyano, Ci-6 alkyl, Q-6 haloalkyl, Ci-6 alkoxy or Q-6 haloalkoxy), heteroaryl(Q-4)alkyl (wherein the heteroaryl group is optionally substituted by halo, nitro, cyano, Q-6 alkyl, Q-6 haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy), heterocyclyl (optionally substituted by halo, nitro, cyano, Q-6 alkyl, Ci-6 haloalkyl, Q-6 alkoxy or Ci-6 haloalkoxy), heterocyclyl(Q-4)alkyl (wherein the heterocyclyl group is optionally substituted by halo, nitro, cyano, Q-6 alkyl, Q-6 haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy), Ci-6 alkoxycarbonyl(Q-6)alkyl or N=C(CH3)2; R19 is Q-6 alkyl, Ci- haloalkyl or phenyl (optionally substituted by halo, nitro, cyano, Q-6 alkyl, Q-6 haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy); R16 and R17 are, independently, hydrogen, Q-8 alkyl, C3-7 cycloalkyl, Q-6 alkenyl, Q-6 alkynyl, Q-7 cycloalkyl(Q-4)alkyl, C2-6 haloalkyl, Q- 6 alkoxy(Q-6)alkyl, Q-6 alkoxycarbonyl, or R16 and R17 together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one or two further hetero atoms selected from O, N or S and which may be optionally substituted by one or two Ci-6 alkyl groups; R18 and R11 are, independently, Ci-6 alkyl or phenyl(Q-2)alkyl (wherein the phenyl group is optionally substituted by halo, nitro, cyano, Q-6 alkyl, Ci-6 haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy); and R26 and R27 are, independently, hydrogen, Q-8 alkyl, C3-7 cycloalkyl, - alkenyl, - alkynyl, -6 haloalkyl, Q-6 alkoxy(Q-6)alkyl, Q-6 alkoxycarbonyl(Q-6)alkyl, carboxy(Q-6)alkyl or phenyl(Q- )alkyl; or R26 and R27 together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one or two further heteroatoms selected from O, N or S and which may be optionally substituted by one or two Q-6 alkyl groups. It is preferred that A is Q-6 alkylene, Ci-6 alkenylene, Q-6 alkylenoxy, oxy(Q-6)alkylene or Q-6 alkylenaniino, each of which is optionally substituted by Q-3 alkyl, Q-3 haloalkyl, Q-3 cyanoalkyl, halogen, Q-3 alkoxy, Q-6 alkoxycarbonyl, cyano, =O, =NR20 or =CR21R22; where R20 is Q-6 alkyl, OR23 or NR24R25; R23 is Q-6 alkyl or phenyl(Q-2)alkyl (where the phenyl group is optionally substituted by halo, nitro, cyano, Q-6 alkyl, Ci-6 haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy); R24 and R25 are, independently, hydrogen, Q-8 alkyl or phenyl (which may be optionally substituted by halo, nitro, cyano, Ci-6 alkyl, Q-6 haloalkyl, Q-6 alkoxy or Ci-6 haloalkoxy); R21 is hydrogen, Ci-6 alkyl or Q-6 haloalkyl; R22 is hydrogen, Q-6 alkyl, Q-6 haloalkyl, Ci-6 alkoxy, cyano, Q-6 alkoxycarbonyl, Q-6 alkylcarbonyl or NR R ; and R and R are, independently, hydrogen, Q-8 alkyl, C3-7 cycloalkyl, Q-6 alkenyl, Q-6 alkynyl, Q-6 haloalkyl, Q-6 alkoxy(Q-6)alkyl, Q-6 alkoxycarbonyl(Q-6)alkyl, carboxy(Q-6)alkyl or phenyl(Q- )alkyl; or R26 and R27 together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one or two further heteroatoms selected from O, N or S and which may be optionally substituted by one or two Q-6 alkyl groups; provided that A is not CH2 or CH2O.
A is more preferably Q-4 alkylene (optionally substituted by halogen, Q-3 alkyl or Q-3 alkoxy, -C(O)- or Q-4 alkyleneoxy (which may be optionally substituted by Q-3 alkyl); provided that A is not CH or CH2O.
It is even more preferred that A is Q-2 alkyl-substituted Q-4 alkylene, fluoro- substituted Cμ alkylene, methoxy-substituted Q-4 alkylene, -C(O)- or Q-4 alkyleneoxy; still more preferably A is Q- alkyl-substituted Q-4 alkylene, fluoro-substituted Q-4 alkylene or methoxy-substituted Cμ alkylene. It is further preferred that A is CH(CH3)CH2, CH2CH(CH3), CH(CH3), CHF, CH(OCH3) or CH(CH3)O; further preferred that A is CH(CH3)CH2, CH2CH(CH3), CH(CH3), CHF or CH(CH3)O; it is especially preferred that A is CHF, CH(OCH3) or CH(CH3); and most preferably A is CHF or CH(CH3). One group of preferred compounds is that where A is optionally fluoro-substituted
Q-4 alkylene, -C(O)- or C2-4 alkyleneoxy; provided that A is not CH2.
B is preferably N.
Y is preferably O or S.
Y is more preferably O. Z is preferably O or S.
Z is more preferably O.
It is preferred that R1 is hydrogen, halogen, Q-β alkyl, Q-6 cyanoalkyl, Ci-6 haloalkyl, C3_7 cycloalkyl(Q- )alkyl, Q-6 alkoxy(Q-6)alkyl, -6 alkenyl, Q-6 alkynyl, Q-6 alkoxy, Q-6 haloalkoxy, Q-6 alkylthio, Q-6 haloalkylthio, Q-6 cycloalkyl, cyano, nitro or SF5. R1 is more preferably hydrogen, halogen, Q-6 alkyl, -6 alkenyl, Q-6 haloalkyl, Q-6 alkoxy, Ci-6 haloalkoxy, Q-6 alkylthio, Q-6 haloalkylthio, C3-6 cycloalkyl, cyano, nitro or SF5.
It is even more preferred that R1 is hydrogen, halogen, Q-6 alkyl, Q-6 haloalkyl, Q-6 alkoxy(Q-6)alkyl, -6 alkenyl, Q-6 alkoxy, Q-6 haloalkoxy, Q-6 alkylthio, Q-6 haloalkylthio, Q-6 cycloalkyl or cyano.
It is most preferred that R1 is halogen, Q-6 alkyl, Q- haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy.
It is preferred that R2 is hydrogen, halogen, Q-6 alkyl, Q-6 haloalkyl, Ci-6 alkoxy(Q-6)alkyl, -6 alkenyl, Q-6 alkynyl, Q-6 alkoxy, Q-6 haloalkoxy, Q-6 alkylthio, Q_6 haloalkylthio, Q-6 alkylsulfinyl, Ci-6 haloalkylsulfinyl, Q-6 alkylsulfonyl, Ci-6 haloalkylsulfonyl, cyano, nitro, formyl, Q-6 alkylcarbonyl, Ci-6 alkoxycarbonyl or CH=NORπ or SF5; or R1 and R2 together with the atoms to which they are attached may be joined to form a five, six or seven-membered saturated or unsaturated, carbocylic or heterocyclic ring which may contain one or two heteroatoms selected from O, N or S and which is optionally substituted by Q-6 alkyl, Q_6 haloalkyl or halogen; where R1 ' is phenyl(Q-2)alkyl (wherein the phenyl group is optionally substituted by halo, nitro, cyano, Q-6 alkyl, Q_6 haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy) or Q-6 alkyl. It is more preferred that R is hydrogen, halogen, Ci-6 alkyl, Ci-6 haloalkyl, Q-6 alkoxy (Q-6)alkyl, Ci-6 alkoxy, Q-6 haloalkoxy, Ci-6 alkylthio or SF5; or R1 and R2 together with the atoms to which they are attached form a cyclopentane or benzene ring optionally substituted by Q-6 alkyl, Q-6 haloalkyl or halogen. R2 is even more preferably hydrogen, halogen, Q-6 alkyl, Q-6 haloalkyl, Q-6 alkoxy,
Q-6 haloalkoxy, Q-6 alkoxy(Q-6)alkyl, Q-6 alkylthio or SF5; or R1 and R2 together with the atoms to which they are attached form a benzene ring optionally substituted by Q-6 alkyl, Q-6 haloalkyl or halogen; or alternatively the ring may be a cyclopentane ring.
It is further preferred that R2 is hydrogen, halogen, Ci-6 alkyl, Q-e haloalkyl, Q-6 alkoxy(Q-6)alkyl, Q-6 alkoxy, Q-6 haloalkoxy, or R1 and R2 together with the atoms to which they are attached form a cyclopentane ring optionally substituted by Ci-6 alkyl, Ci-6 haloalkyl or halogen.
R2 is most preferably halogen, Q-6 alkyl, Ci-6 haloalkyl, Q-6 alkoxy, Ci-6 alkoxy(Q-6)alkyl or Ci-6 haloalkoxy. It is preferred that R3 is hydrogen, Q-10 alkyl, Q-6 alkylcarbonyloxy(Q-6)alkyl, benzoyloxymethyl (where the phenyl ring is optionally substituted with halogen or Q-4 alkyl), Ci- alkoxy(Q-6)alkyl (where the alkyl group is optionally substituted by aryl or Q-4 alkoxycarbonyl), -6 alkenyloxy(Q-4)alkyl, -6 alkynyloxy(Q-4)alkyl, benzyloxy(Q-4)alkyl (where the phenyl ring is optionally substituted with halogen or C alkyl), Q-7 cycloalkyl(C1-4)alkyl, heteroaryl (Q-3)alkyl (where the heteroaryl group is optionally substituted with halogen), tri(Q-4)alkylsilyl(Q-6)alkyl, -6 alkenyl(Q-6)alkyl (especially allyl), -6 haloalkenyl(Q-6)alkyl, CM alkoxycarbonyl(Q-6)alkenyl(Q-6)alkyl, -6 alkynyl(Q-6)alkyl, tri(Q-4)alkylsilyl(C2-6)alkynyl(Q-6)alkyl or Q-10 alkylcarbonyl.
It is further preferred that R3 is hydrogen, Q-6 alkyl, Q-6 alkylcarbonyloxymethyl, benzoyloxymethyl (where the phenyl ring is optionally substituted with halogen or CM alkyl), Q-6 alkoxymethyl, Q-6 alkenyloxymefhyl, Q-6 alkynyloxymethyl, benzyloxymethyl (where the phenyl ring is optionally substituted with halogen or Q-4 alkyl), Q-6 alkynyl(Q_6)alkyl (especially propargyl) or Q-io alkylcarbonyl.
R3 is more preferably hydrogen, Q-6 alkyl, Q-6 alkoxy(Q-6)alkyl, benzyloxymethyl or benzoyloxymethyl; or alternatively R3 may be Q-6 alkylcarbonyloxymethyl.
It is most preferred that R3 is hydrogen, Q_6 alkyl, Q_6 alkylcarbonyloxymethyl or Ci- alkoxymethyl. It is preferred that R4, R5 and R6 are, independently, hydrogen, halogen, Q-6 alkyl, Q-6 haloalkyl, Q-6 alkoxy, Ci-6 haloalkoxy, Q-6 alkylthio, Ci-6 haloalkylthio, Ci-6 alkylsulfinyl, Ci-6 haloalkylsulfinyl, Q-6 alkylsulfonyl, Q-6 haloalkylsulfonyl, cyano, nitro, Ci-6 alkylcarbonyl or Ci-6 alkoxycarbonyl. It is more preferred that R4, R5 and R6 are, independently, hydrogen, halogen or Q-3 alkyl.
It is even more preferred that R4, R5 and R6 are, independently, hydrogen or halogen (especially fluorine).
It is preferred that R7 is cyano, Q-8 alkyl, Q-8 haloalkyl, Q- cyanoalkyl, Q-7 cycloalkyl (Q-6)alkyl, C5-6 cycloalkenyl(Q-6)alkyl, Q-6 alkoxy(Q-6)alkyl, C3-6 alkenyloxy(Cι-6)alkyl, C3-6 alkynyloxy(Q.6)alkyl, aryloxy(Cι-6)alkyl, Ci-6 carboxyalkyl, Cι-6 alkylcarbonyl(Q-6)alkyl, -6 alkenylcarbonyl(Cι-6)alkyl, C2-6 alkynylcarbonyl(Q-6)alkyl, Ci-6 alkoxycarbonyl(Q-6)alkyl, C3-6 alkenyloxycarbonyl(Ci-6)alkyl, C3-6 alkynyloxycarbonyl(Q-6)alkyl, aryloxycarbonyl(Ci-6)alkyl, Q-6 alkyl thio(Q-6)alkyl, Ci-6 alkylsulfinyl(Q-6)alkyl, Ci-6 alkylsulfonyl(Q-6)alkyl, aminocarbonyl(Cι-6)alkyl, Q-6 alkylaminocarbonyl(C i -6)alkyl, di(Q -6)alkylaminocarbonyl(Q -6)alkyl, phenyl (C i -4)alkyl (wherein the phenyl group is optionally substituted by halo, nitro, cyano, Ci-6 alkyl, Ci-6 haloalkyl, Ci-6 alkoxy or Q-6 haloalkoxy), heteroaryl(Q-4)alkyl (where the heteroaryl group is optionally substituted by halo, nitro, cyano, Q-6 alkyl, Ci-6 haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy), heterocyclyl(Q- )alkyl (where the heterocyclyl group is optionally substituted by halo, cyano, Ci-6 alkyl, Q-6 haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy), -6 alkenyl, -6 haloalkenyl, Q-6 cyanoalkenyl, -6 cycloalkenyl, aminocarbonyl(Q-6)alkenyl, Q-6 alkylaminocarbonyl(Q-6)alkenyl, di(Q-6)alkylaminocarbonyl(Q-6)alkenyl, phenyl(Q-4)alkenyl (wherein the phenyl group is optionally substituted by halo, nitro, cyano, Q-6 alkyl, Ci-6 haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy), Q-6 alkynyl, aminocarbonyl-
(Q-6)alkynyl, alkylaminocarbonyl (Q-6)alkynyl, di(Q-6)alkylaminocarbonyl(Q-6)alkynyl, Q- η cycloalkyl, Q-7 halocycloalkyl, Q_7 cyanocycloalkyl, Q-3 alkyl(Q-7)cycloalkyl, Q-3 alkyl(Q-7)halocycloalkyl, C5-6 cycloalkenyl, formyl, Q-6 alkoxycarbonyl, Q-6 alkylcarbonyl, aminocarbonyl, Q_6 alkylaminocarbonyl, di(C1-6)alkylaminocarbonyl, phenyl (optionally substituted by halo, nitro, cyano, Q-6 alkyl, Q-6 haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy), heteroaryl (optionally substituted by halo, nitro, cyano, Q-6 alkyl, Q_6 haloalkyl, Q.6 alkoxy or Q.6 haloalkoxy), heterocyclyl (optionally substituted by halo, nitro, cyano, Q-6 alkyl, -6 haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy), Q-8 alkylthio, R15O, R16R17N or R18ON=C(R19); where R15 is hydrogen, Q-8 alkyl, Ci- haloalkyl, Ci-6 cyanoalkyl, Q-6 alkoxy(Q-6)alkyl, phenyl (Q-^alkyl, (wherein the phenyl group is optionally substituted by halo, nitro, cyano, Q-6 alkyl, Ci-6 haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy), heteroaryl(Q-4)alkyl (wherein the heteroaryl group is optionally substituted by halo, nitro, cyano, Ci-6 alkyl, Q-6 haloalkyl, Q-6 alkoxy or Ci- haloalkoxy), heterocyclyl(Q-4)alkyl (wherein the heterocyclyl group is optionally substituted by halo, nitro, cyano, Q-6 alkyl, Q-6 haloalkyl, Ci-6 alkoxy or Q-6 haloalkoxy), Ci-6 alkoxycarbonyl(Q-6)alkyl, Q-6 alkenyl, -6 alkynyl or N=C(CH3)2; R19 is phenyl (optionally substituted by halo, nitro, cyano, Q-6 alkyl, Ci-6 haloalkyl, Q-6 alkoxy or Ci-6 haloalkoxy), Ci-6 alkyl or Q-6 haloalkyl; R16 and R17 are, independently, hydrogen, Q-8 alkyl, Q-7cycloalkyl(Q-4)alkyl, -6 haloalkyl, Q-6 alkoxy(Q-6)alkyl, C3-7 cycloalkyl, -6 alkenyl, - alkynyl or Q-6 alkoxycarbonyl; and R18 is phenyl(Q-2)alkyl (wherein the phenyl group is optionally substituted by halo, nitro, cyano, Q-6 alkyl, Q-6 haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy) or Ci-6 alkyl. R7 is more preferably Q-8 alkyl, Ci-6 haloalkyl, Ci-6 cyanoalkyl, -6 alkenyl, -6 alkynyl, Q-7 cycloalkyl, Q-7 halocycloalkyl, Q-7 cyanocycloalkyl, Q-3 alkyl(Q-7)cycloalkyl, Q-3 alkyl(C3-7)halocycloalkyl, -6 cycloalkenyl, Q-7 cycloalkyl(Q-6)alkyl, -6 cycloalkenyl(Q-6)alkyl, -6 haloalkenyl, Ci- cyanoalkenyl, Q-6 alkoxy(Q-6)alkyl, Q-6 alkenyloxy(Q-6)alkyl, -6 alkynyloxy(Q-6)alkyl, aryloxy(Q-6)alkyl, Q-6 carboxyalkyl, Q-6 alkylcarbonyl(Q-6)alkyl, C2-6 alkenylcarbonyl(Q-6)alkyl, Q-6 alkynylcarbonyl(Q-6)alkyl, Q-6 alkoxycarbonyl(Q-6)alkyl, Q-6 alkenyloxycarbonyl(Q-6)alkyl, C3-6 alkynyloxycarbonyl(Q-6)alkyl, aryloxycarbonyl(Ci-6)alkyl, Q-6 alkylthio(Q-6)alkyl, Q-6 alkylsulfinyl(Q-6)alkyl, Ci-6 alkylsulfonyl (Q-6)alkyl, aminocarbonyl(Q-6)alkyl, aminocarbonyl(C2-6)alkenyl, aminocarbonyl(C2-6)alkynyl, Q-6 alkylaminocarbonyl(Q-6)alkyl, di(Ci-6)alkylaminocarbonyl(Cι-6)alkyl, Q-6 alkylaminocarbonyl(Q-6)alkenyl, di(C i -6)alkylaminocarbonyl(C i -6)alkenyl, alkylaminocarbonyl (C i-6)alkynyl, di(Q-6)alkylaminocarbonyl(Q-6)alkynyl, phenyl (optionally substituted by halo, nitro, cyano, Ci-6 alkyl, Q-6 haloalkyl, Q-6 alkoxy or Ci-6 haloalkoxy), phenyl(Q-4)alkyl (wherein the phenyl group is optionally substituted by halo, nitro, cyano, Ci-6 alkyl, Q-6 haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy), phenyl(Q-4)alkenyl, (wherein the phenyl group is optionally substituted by halo, nitro, cyano, Q-6 alkyl, Q-6 haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy), heteroaryl (optionally substituted by halo, nitro, cyano, Q-6 alkyl, Q-6 haloalkyl, Q-6 alkoxy or Ci-6 haloalkoxy), heterocyclyl (wherein the heterocyclyl group is optionally substituted by halo, nitro, cyano, Q-6 alkyl, Q-6 haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy), heteroaryl (C1-4)alkyl (wherein the heteroaryl group is optionally substituted by halo, nitro, cyano, Ci-6 alkyl, Ci-6 haloalkyl, Q-6 alkoxy or Ci-6 haloalkoxy), heterocyclyl (Q-^alkyl (wherein the heterocyclyl group is optionally substituted by halo, nitro, cyano, Q-6 alkyl, Q-6 haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy), R15O, Q-8 alkylthio, R16R17N or R18ON=C(R19); where R15 is Q-8 alkyl, Ci-6 haloalkyl; R19 is Ci-6 alkyl, Q-6 haloalkyl or phenyl (optionally substituted by halo, nitro, cyano, Q-6 alkyl, Ci-6 haloalkyl, Ci-6 alkoxy or Q-6 haloalkoxy); R16 and R17 are, independently, hydrogen, Q-8 alkyl, Q-7 cycloalkyl, Q-6 alkenyl, Q-6 alkynyl, Q-7 cycloalkyl(Q--Oalkyl, Q-6 haloalkyl, Q-6 alkoxy(Q-6)alkyl, Q-6 alkoxycarbonyl, or R16 and R17 together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one or two further heteroatoms selected from O, N or S and which may be optionally substituted by one or two Q-6 alkyl groups; and R18 is Ci-6 alkyl or phenyl(Q-2)alkyl (wherein the phenyl group is optionally substituted by halo, nitro, cyano, Ci-6 alkyl, Ci-6 haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy); and R7 is more preferably Q-8 alkyl, Q-8 haloalkyl, Q-8 cyanoalkyl, Q-7 cycloalkyl, Q-3 alkyl(Q-7)cycloalkyl, Q-6 alkoxy(Q-6)alkyl, heterocyclyl (wherein the heterocyclyl group is optionally substituted by halo, nitro, cyano, Q-6 alkyl, Q-6 haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy) or R16R17N; where R16 andR17 are, independently, Q-8 alkyl or together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one or two further heteroatoms selected from O, N or S and which may be optionally substituted by one or two Q-6 alkyl groups.
It is further preferred that R7 is Q-8 alkyl, Q-8 haloalkyl, Q_8 cyanoalkyl, Q-7 cycloalkyl(Q-6)alkyl, Q-6 cycloalkenyl (Q-6)alkyl, Q-6 alkoxy(Q-6)alkyl, Q-6 alkenyloxy(Q-6)alkyl, Q-6 alkynyloxy(Q-6)alkyl, aryloxy(Q-6)alkyl, Q-6 carboxyalkyl, Q-6 alkylcarbonyl(Q-6)alkyl, Q-6 alkenylcarbonyl (Q-6)alkyl, Q-6 alkynylcarbonyl(Q-6)alkyl, Q_6 alkoxycarbonyl(Q-6)alkyl, Q-6 alkenyloxycarbonyl(Q-6)alkyl, Q-6 alkynyloxycarbonyl- (Q-6)alkyl, aryloxycarbonyl(Q-6)alkyl, Q-6 alkyl thio(Q-6)alkyl, Ci-6 alkylsulfinyl(Cι-6)alkyl, Ci-6 alkylsulfonyl(Q-6)alkyl, aminocarbonyl(Q-6)alkyl, Q_6 alkylaminocarbonyl(Q-6)alkyl, di(Ci-6)alkylaminocarbonyl(Q-6)alkyl, phenyl(Cj- )alkyl (wherein the phenyl group is optionally substituted by halo, nitro, cyano, Q.6 alkyl, Q-6 haloalkyl, Q-6 alkoxy or Q_6 haloalkoxy), heteroaryl(Q-4)alkyl (wherein the heteroaryl group is optionally substituted by halo, nitro, cyano, Q-6 alkyl, Ci-6 haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy), heterocyclyl (Q. 4)alkyl (wherein the heterocyclyl group is optionally substituted by halo, nitro, cyano, Ci-6 alkyl, Ci-6 haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy), Q-6 alkenyl, Q-6 haloalkenyl, Ci-6 cyanoalkenyl, -6 cycloalkenyl, aminocarbonyl(Q-6)alkenyl, Q-6 alkylaminocarbonyl(Q- 6)alkenyl, di(Q6)alkylaminocarbonyl(Q-6)alkenyl, phenyl(Q-4)alkenyl (wherein the phenyl group is optionally substituted by halo, nitro, cyano, Q- alkyl, Q-6 haloalkyl, Q-6 alkoxy or Ci-6 haloalkoxy), -6 alkynyl, aminocarbonyl(Q-6)alkynyl, alkylaminocarbonyl(Q-6)alkynyl, di(Q-6)alkylaminocarbonyl(Q-6)alkynyl, Q-7 cycloalkyl, Q-7 halocycloalkyl, Q- cyanocycloalkyl, Ci-3 alkyl(Q-7)cycloalkyl, Q-3 alkyl(C3-7)halocycloalkyl, phenyl (optionally substituted by halo, nitro, cyano, Q-6 alkyl, Q-6 haloalkyl, Ci-6 alkoxy or Q-6 haloalkoxy), heteroaryl (optionally substituted by halo, nitro, cyano, Q-6 alkyl, Q-6 haloalkyl, Ci-6 alkoxy or Q-6 haloalkoxy), heterocyclyl (optionally substituted by halo, nitro, cyano, Ci-6 alkyl, Q-6 haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy), Q-8 alkylthio, R,5O, R16R17N or RI8ON=C(R19); where R15 is Q-8 alkyl or Q-6 haloalkyl; R19 is phenyl (optionally substituted by halo, nitro, cyano, Ci-6 alkyl, Q-6 haloalkyl, Q-6 alkoxy or Ci-6 haloalkoxy), Q-6 alkyl or Ci-6 haloalkyl; R16 and R17 are, independently, hydrogen, Q-8 alkyl, Q-7 cycloalkyl (Q-4)alkyl, Q-6 haloalkyl, Q-6 alkoxy(Q-6)alkyl, Q-7 cycloalkyl, -6 alkenyl, Q-6 alkynyl or Q-6 alkoxycarbonyl; and R18 is phenyl(Q-2)alkyl (wherein the phenyl group is optionally substituted by halo, nitro, cyano, Q-6 alkyl, Q-6 haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy) or Q-6 alkyl.
It is even more preferred that R7 is Q-8 alkyl, Q-8 haloalkyl, Q-8 cyanoalkyl, Q-6 alkoxy (Ci-6) alkyl, Q-7 cycloalkyl, Q- alkyl (Q_7) cycloalkyl, heterocyclyl (optionally substituted by halo, nitro, cyano, Q- alkyl, Q-6 haloalkyl, Q-6 alkoxy or Q- haloalkoxy) or di(C i - )alkylamino. It is yet more preferred that R is Q-8 alkyl, Q-8 haloalkyl, Q-8 cyanoalkyl, Q-6 alkoxy (Q-6) alkyl, Q-7 cycloalkyl, Q-3 alkyl (Q.7) cycloalkyl, heterocyclyl (optionally substituted by Q-6 alkyl) or di(Q-8)alkylamino.
R7 is most preferably Q-8 alkyl, Q-8 haloalkyl, Q_8 cyanoalkyl, Q- cycloalkyl, Q-3 alkyl(C3-7)cycloalkyl, Q-6 alkoxy(Q-6)alkyl or R16R17N; where R16 andR17 are, independently, Q_8 alkyl or together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one further heteroatom selected from O, N or S and which may be optionally substituted by one or two Q.6 alkyl groups. It is preferred that R8 is hydrogen, halogen, nitro, cyano, Q-8 alkyl, Q-6 haloalkyl, Q-6 cyanoalkyl, Q-7 cycloalkyl(Q-6)alkyl, Q-6 alkoxy(C!-6)alkyl, Ci-6 alkoxycarbonyl(Q-6)alkyl, Ci-6 alkylcarbonyl(Ci-6)alkyl, Ci-6 alkylaminocarbonyl(Ci-6)alkyl, di(Cι-6)alkylamino-carbonyl(C1-6)alkyl, phenyl(Q-6)alkyl (wherein the phenyl group is optionally substituted by halo, nitro, cyano, Q-6 alkyl, Q-6 haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy), heteroaryl(Q-6)alkyl (wherein the heteroaryl group is optionally substituted by halo, nitro, cyano, Ci-6 alkyl, Ci-6 haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy), -6 alkenyl, -6 haloalkenyl, -6 alkynyl, Q-7 cycloalkyl, Ci-6 alkoxycarbonyl, Q-6 alkylcarbonyl, Q-6 alkylaminocarbonyl, di(Q-6)alkylaminocarbonyl, phenyl (optionally substituted by halo, nitro, cyano, Ci-6 alkyl, Q-6 haloalkyl, Ci-6 alkoxy or Q-6 haloalkoxy) or heteroaryl
(optionally substituted by halo, nitro, cyano, Q-6 alkyl, Q-6 haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy).
It is more preferred that R8 is hydrogen, halogen, Q-8 alkyl or Q-6 haloalkyl. It is preferred that R9 is cyano, nitro, Ci-6 alkyl, Q-6 haloalkyl, Q- cycloalkyl(Q-6)alkyl, Q-7 cycloalkyl, CH2(C2-6)alkenyl, CH2(Q-6)alkynyl, phenyl (optionally substituted by halo, nitro, cyano, Q-6 alkyl, Q-6 haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy), heteroaryl (optionally substituted by halo, nitro, cyano, Q-6 alkyl, Ci-6 haloalkyl, Q-6 alkoxy or Ci-6 haloalkoxy), Ci-6 alkylcarbonyl, Ci-6 alkoxycarbonyl, Q-6 alkylamino, di(Q-6)alkylamino, Ci-6 alkylcarbonylamino, Ci-6 alkoxycarbonylamino, Q-6 alkoxy, Q-6 alkylthio, Ci-6 haloalkylthio, Q-6 alkylsulfinyl, Q-6 haloalkylsulfinyl, Ci-6 alkylsulfonyl, Q-6 haloalkylsulfonyl, arylthio, arylsulfinyl, arylsulfonyl or (Q-6)alkylcarbonyloxy.
It is preferred that R10 is hydrogen, Q-8 alkyl, Ci-6 haloalkyl, Q-6 cyanoalkyl, Q_6 alkenyl, Q-6 haloalkenyl, -6 alkynyl, Q-7 cycloalkyl, Q_7 cycloalkyl(Q-6)alkyl, Q-6 alkoxy(Q-6)alkyl, Ci-6 alkoxycarbonyl, Q-6 alkylcarbonyl, Q-6 alkylaminocarbonyl, di(Q-6)alkylaminocarbonyl, phenyl (optionally substituted by halo, nitro, cyano, Ci- alkyl, Ci- haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy) or heteroaryl (optionally substituted by halo, nitro, cyano, Q-6 alkyl, Ci-6 haloalkyl, Ci-6 alkoxy or Q-6 haloalkoxy).
It is more preferred that R10 is hydrogen, Q-8 alkyl or Q-6 haloalkyl. The compounds in Tables 1-102 illustrate compounds of the invention. Table 1 provides 160 compounds of formula (1)
Figure imgf000024_0001
wherein R1, R3 and R7 are defined in Table 1.
Table 1
Compound No. R1 R3 R7
1 CH3 H CH3
2 CH3 H CH2CH3
3 CH3 H CH2CH2CH3
4 CH3 H CH(CH3)2
5 CH3 H C(CH3)3
6 CH3 H CH2CH(CH3)2
7 CH3 H CH2C(CH3)3
8 CH3 H CH2CF3
9 CH3 H CF2CF3
10 CH3 H CF2CF2CF3
11 CH3 CH3 CH3
12 CH3 CH3 CH2CH3
13 CH3 CH3 CH CH2CH3
14 CH3 CH3 CH(CH3)2
15 CH3 CH3 C(CH3)3
16 CH3 CH3 CH2CH(CH3)2
17 CH3 CH3 CH2C(CH3)3
18 CH3 CH3 CH2CF3
19 CH3 CH3 CF2CF3
20 CH3 CH3 CF2CF2CF3
21 CH3 CH2CH3 CH3
22 CH3 CH2CH3 CH2CH3
23 CH3 CH2CH3 CH2CH2CH3
24 CH3 CH2CH3 CH(CH3)2
25 CH3 CH2CH3 C(CH3)3
26 CH3 CH2CH3 CH2CH(CH3)2
27 CH3 CH2CH3 CH2C(CH3)3
28 CH3 CH2CH3 CH2CF3
29 CH3 CH2CH3 CF2CF3
30 CH3 CH2CH3 CF2CF2CF3
31 CH3 CH CH2CH3 CH3
32 CH3 CH2CH2CH3 CH2CH3
33 CH3 CH2CH2CH3 CH CH2CH3
34 CH3 CH2CH2CH3 CH(CH3)2
35 CH3 CH2CH CH3 C(CH3)3
36 CH3 CH2CH CH3 CH2CH(CH3)2
37 CH3 CH2CH2CH3 CH2C(CH3)3
38 CH3 CH CH2CH3 CH2CF3
Figure imgf000025_0001
ffi ffi ffi ffi a a a a a a en en en m en en en en en u υ u II u W HH hH HH W W W W HH H S H w S ffi H ffi
II u II υ II u II υ II υ II u II u II u II πM πy π π π π^ π πU πU U πn fii n
X X u κ tuf u ffiuuuuuuu u u aaaaaaaaaauuuuuuuuuu o o o o o o o o uuuuuυuuuu a a a X a a x X uuuuuuuu uuuuu auuu au ( u u uuu uuuuuuuuuu H
en cn cn co cn en cn en cn en cn en eo cn en cn en co cn en cn en en eo m cn en cn cn cn en en c a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a
U U U U U U U U U U U U U U U U UU UUU UU UU U U U U UUU
CO
Figure imgf000025_0002
o
Figure imgf000026_0001
en en en en en en en cs cs cs cs cs es c cN en en en en en en en en cn en u HH yHH uHH yMH. yHH. uMH W yH yH.H yH yHH a y y a y y y y aaaa II y II y II u g aaaaaaaaaa U U U U U U U U U U a a a II a a a a < II II II y
UUUUUUUUUU ffi E a ffi tti a a a a a a a ϋ ϋ
S Ϊ S S K S S K K K
U r i r u ui rui rui rui rui rui Iffi--!"*u bffi-ii*uuuuuuuuuuuuuuuuuu u nu ru ffiK --____-*a >a—.'aa ^'a ^a'a _^a M _a_____*a Ma ^a "a CJa °*a ^a iuii ^u uuuuuuuuuuuuuuuuuuuu
CN
K M uu
MM M
Figure imgf000026_0002
u HH huH HuHuI^ HuH Iu^uHHuI^ luJH |uJH HuHu|JH HuHuI^ Auul^ %uuuuuuuuuuuuuuuuuuuuuuuuuuuuuu
Cms" c
M oo oo
Figure imgf000026_0003
O
O
Figure imgf000027_0001
-i co cn m -i rn ro co c". en en en en en en
U U U U U U U U uuuuu e csU csU u „,u -.,u «,u _,uuQGu .o ouuuuu - .o u - .oo - .oo - .oo .o ^o ^ a a a a a a a »,u ..,o - .o - aaaaaaaaa X X ffi ffi a a o UoUoUoUoUoU UooUoUoU
U U U U U U U U U U U U U U U U ffi ffi a a a a a a a a
U U U U U U U U U U
CM
en en co co ro ^ co co rn ro co co ro cn co cn ro co co tn rn cn uuuuuuuuuuuuuuuuuuuuuuuuuu uuuuuuuuuuuuuuuuuuuuuuuuuu
τ h oo oo oN 'H co i- in r~ x) C
Figure imgf000027_0002
Figure imgf000027_0003
f
IΛ e o
Table 2
Table 2 provides 160 compounds of formula (2)
Figure imgf000028_0001
wherein R1, R3 and R7 are as defined in Table 1. Table 3
Table 3 provides 160 compounds of formula (3)
Figure imgf000028_0002
wherein R1, R3 and R7 are as defined in Table 1.
Table 4
Table 4 provides 160 compounds of formula (4)
Figure imgf000028_0003
wherein R1, R3 and R7 are as defined in Table 1.
Table 5 Table 5 provides 160 compounds of formula (5)
Figure imgf000028_0004
w ere n R , R an are as e ine n a e .
Table 6 Table 6 provides 160 compounds of formula (6)
Figure imgf000029_0001
wherein R1, R3 and R7 are as defined in Table 1.
Table 7 Table 7 provides 160 compounds of formula (7)
Figure imgf000029_0002
wherein R1, R3 and R7 are as defined in Table 1.
Table 8
Table 8 provides 160 compounds of formula (8)
Figure imgf000029_0003
wherein R1, R3 and R7 are as defined in Table 1.
Table 9 Table 9 provides 160 compounds of formula (9)
Figure imgf000029_0004
wherein R1, R3 and R7 are as defined in Table 1.
Table 10
Table 10 provides 160 compounds of formula (10)
Figure imgf000029_0005
wherein R1, R3 and R7 are as defined in Table 1. Table 11
Table 11 provides 160 compounds of formula (11)
Figure imgf000030_0001
wherein R1, R3 and R7 are as defined in Table 1. Table 12
Table 12 provides 160 compounds of formula (12)
Figure imgf000030_0002
wherein R1, R3 and R7 are as defined in Table 1.
Table 13 Table 13 provides 160 compounds of formula (13)
Figure imgf000030_0003
wherein R1, R3 and R7 are as defined in Table 1.
Table 14 Table 14 provides 160 compounds of formula (14)
Figure imgf000030_0004
wherein R1, R3 and R7 are as defined in Table 1.
Table 15
Table 15 provides 160 compounds of formula (15)
Figure imgf000031_0001
wherein R1, R3 and R7 are as defined in Table 1.
Table 16 Table 16 provides 160 compounds of formula (16)
Figure imgf000031_0002
wherein R1, R3 and R7 are as defined in Table 1.
Table 17
Table 17 provides 160 compounds of formula (17)
Figure imgf000031_0003
wherein R1, R3 and R7 are as defined in Table 1.
Table 18 Table 18 provides 160 compounds of formula (18)
Figure imgf000031_0004
wherein R1, R3 and R7 are as defined in Table 1. Table 19
Table 19 provides 160 compounds of formula (19)
Figure imgf000032_0001
wherein R1, R3 and R7 are as defined in Table 1. Table 20
Table 20 provides 160 compounds of formula (20)
Figure imgf000032_0002
wherein R1, R3 and R7 are as defined in Table 1.
Table 21 Table 21 provides 160 compounds of formula (21)
Figure imgf000032_0003
wherein R1, R3 and R7 are as defined in Table 1.
Table 22 Table 22 provides 160 compounds of formula (22)
Figure imgf000032_0004
wherein R1, R3 and R7 are as defined in Table 1. Table 23
Table 23 provides 160 compounds of formula (23)
Figure imgf000033_0001
wherein R1, R3 and R7 are as defined in Table 1.
Table 24 Table 24 provides 160 compounds of formula (24)
Figure imgf000033_0002
wherein R1, R3 and R7 are as defined in Table 1.
Table 25 Table 25 provides 160 compounds of formula (25)
Figure imgf000033_0003
wherein R1, R3 and R7 are as defined in Table 1.
Table 26 Table 26 provides 160 compounds of formula (26)
Figure imgf000033_0004
wherein R1, R3 and R7 are as defined in Table 1. Table 27
Table 27 provides 160 compounds of formula (27)
Figure imgf000034_0001
wherein R1, R3 and R7 are as defined in Table 1. Table 28
Table 28 provides 160 compounds of formula (28)
Figure imgf000034_0002
wherein R1, R3 and R7 are as defined in Table 1.
Table 29 Table 29 provides 160 compounds of formula (29)
Figure imgf000034_0003
Table 30 provides 160 compounds of formula (30)
Figure imgf000034_0004
wherein R1, R3 and R7 are as defined in Table 1. Table 31
Table 31 provides 160 compounds of formula (31)
Figure imgf000035_0001
wherein R1, R3 and R7 are as defined in Table 1. Table 32
Table 32 provides 160 compounds of formula (32)
Figure imgf000035_0002
wherein R1, R3 and R7 are as defined in Table 1.
Table 33 Table 33 provides 160 compounds of formula (33)
Figure imgf000035_0003
wherein R1, R3 and R7 are as defined in Table 1.
Table 34 Table 34 provides 160 compounds of formula (34)
Figure imgf000035_0004
wherein R1, R3 and R7 are as defined in Table 1.
Table 35
Table 35 provides 160 compounds of formula (35)
Figure imgf000035_0005
wherein R1, R3 and R7 are as defined in Table 1.
Table 36 Table 36 provides 160 compounds of formula (36)
Figure imgf000036_0001
wherein R1, R3 and R7 are as defined in Table 1.
Table 37 Table 37 provides 160 compounds of formula (37)
Figure imgf000036_0002
wherein R1, R3 and R7 are as defined in Table 1.
Table 38
Table 38 provides 160 compounds of formula (38)
Figure imgf000036_0003
wherein R1, , R3 and R7 are as defined in Table 1.
Table 39 1
Table 39 provides 160 compounds of formula (39)
Figure imgf000036_0004
wherein R1, R3 and R7 are as defined in Table 1. Table 40
Table 40 provides 160 compounds of formula (40)
Figure imgf000037_0001
wherein R1, R3 and R7 are as defined in Table 1.
Table 41 Table 41 provides 160 compounds of formula (41)
Figure imgf000037_0002
wherein R1, R3 and R7 are as defined in Table 1.
Table 42 Table 42 provides 160 compounds of formula (42)
Figure imgf000037_0003
wherein R1, R3 and R7 are as defined in Table 1.
Table 43 Table 43 provides 160 compounds of formula (43)
Figure imgf000037_0004
wherein R ι l , r R> 3 and R are as defined in Table 1.
Table 44
Table 44 provides 160 compounds of formula (44)
Figure imgf000037_0005
wherein R1, R3 and R7 are as defined in Table 1.
Table 45 Table 45 provides 160 compounds of formula (45)
Figure imgf000038_0001
wherein R1, R3 and R7 are as defined in Table 1.
Table 46 Table 46 provides 160 compounds of formula (46)
Figure imgf000038_0002
wherein R1, R3 and R7 are as defined in Table 1.
Table 47 Table 47 provides 160 compounds of formula (47)
Figure imgf000038_0003
wherein R1, R3 and R7 are as defined in Table 1.
Table 48 Table 48 provides 160 compounds of formula (48)
Figure imgf000038_0004
wherein R1 , R3 and R7 are as defined in Table 1. Table 49
Table 49 provides 160 compounds of formula (49)
Figure imgf000039_0001
wherein R1, R3 and R7 are as defined in Table 1. Table 50
Table 50 provides 160 compounds of formula (50)
Figure imgf000039_0002
wherein R1, R3 and R7 are as defined in Table 1.
Table 51 Table 51 provides 160 compounds of formula (51)
Figure imgf000039_0003
wherein R1, R3 and R7 are as defined in Table 1.
Table 52 Table 52 provides 160 compounds of formula (52)
Figure imgf000039_0004
wherein R1, R3 and R7 are as defined in Table 1.
Table 53
Table 53 provides 160 compounds of formula (53)
Figure imgf000039_0005
wherein R1, R3 and R7 are as defined in Table 1.
Table 54 Table 54 provides 160 compounds of formula (54)
Figure imgf000040_0001
wherein R1, R3 and R7 are as defined in Table 1.
Table 55 Table 55 provides 160 compounds of formula (55)
Figure imgf000040_0002
wherein R1, R3 and R7 are as defined in Table 1. Table 56
Table 56 provides 160 compounds of formula (56)
Figure imgf000040_0003
wherein R1, R3 and R7 are as defined in Table 1.
Table 57 Table 57 provides 160 compounds of formula (57)
Figure imgf000040_0004
wherein R1, R3 and R7 are as defined in Table 1. Table 58
Table 58 provides 160 compounds of formula (58)
Figure imgf000041_0001
wherein R1, R3 and R7 are as defined in Table 1. Table 59
Table 59 provides 160 compounds of formula (59)
Figure imgf000041_0002
wherein R1, R3 and R7 are as defined in Table 1.
Table 60 Table 60 provides 160 compounds of formula (60)
Figure imgf000041_0003
wherein R1, R3 and R7 are as defined in Table 1.
Table 61 Table 61 provides 160 compounds of formula (61)
Figure imgf000041_0004
wherein R1, R3 and R7 are as defined in Table 1.
Table 62
Table 62 provides 160 compounds of formula (62)
Figure imgf000041_0005
wherein R1, R3 and R7 are as defined in Table 1.
Table 63 Table 63 provides 160 compounds of formula (63)
Figure imgf000042_0001
wherein R1, R3 and R7 are as defined in Table 1.
Table 64 Table 64 provides 160 compounds of formula (64)
Figure imgf000042_0002
wherein R1, R3 and R7 are as defined in Table 1. Table 65
Table 65 provides 160 compounds of formula (65)
Figure imgf000042_0003
wherein R1, R3 and R7 are as defined in Table 1.
Table 66 Table 66 provides 160 compounds of formula (66)
Figure imgf000042_0004
wherein R1, R3 and R7 are as defined in Table 1. Table 67
Table 67 provides 160 compounds of formula (67)
Figure imgf000043_0001
wherein R1, R3 and R7 are as defined in Table 1. Table 68
Table 68 provides 160 compounds of formula (68)
Figure imgf000043_0002
wherein R1, R3 and R7 are as defined in Table 1.
Table 69 Table 69 provides 160 compounds of formula (69)
Figure imgf000043_0003
wherein R1, R3 and R7 are as defined in Table 1.
Table 70 Table 70 provides 160 compounds of formula (70)
Figure imgf000043_0004
wherein R1, R3 and R7 are as defined in Table 1.
Table 71
Table 71 provides 160 compounds of formula (71)
Figure imgf000043_0005
wherein R1, R3 and R7 are as defined in Table 1.
Table 72 Table 72 provides 160 compounds of formula (72)
Figure imgf000044_0001
wherein R1, R3 and R7 are as defined in Table 1.
Table 73 Table 73 provides 160 compounds of formula (73)
Figure imgf000044_0002
wherein R1, R3 and R7 are as defined in Table 1. Table 74
Table 74 provides 160 compounds of formula (74)
Figure imgf000044_0003
wherein R1, R3 and R7 are as defined in Table 1.
Table 75 Table 75 provides 160 compounds of formula (75)
Figure imgf000044_0004
wherein R1, R3 and R7 are as defined in Table 1. Table 76
Table 76 provides 160 compounds of formula (76)
Figure imgf000045_0001
wherein R1, R3 and R7 are as defined in Table 1.
Table 77 Table 77 provides 160 compounds of formula (77)
Figure imgf000045_0002
wherein R1, R3 and R7 are as defined in Table 1.
Table 78 Table 78 provides 160 compounds of formula (78)
Figure imgf000045_0003
wherein R1, R3 and R7 are as defined in Table 1.
Table 79 Table 79 provides 160 compounds of formula (79)
Figure imgf000045_0004
wherein R1, R3 and R7 are as defined in Table 1. Table 80
Table 80 provides 160 compounds of formula (80)
Figure imgf000046_0001
wherein R1, R3 and R7 are as defined in Table 1. Table 81
Table 81 provides 160 compounds of formula (81)
Figure imgf000046_0002
wherein R1, R3 and R7 are as defined in Table 1.
Table 82 Table 82 provides 160 compounds of formula (82)
Figure imgf000046_0003
wherein R1, R3 and R7 are as defined in Table 1.
Table 83
Table 83 provides 160 compounds of formula (83)
Figure imgf000046_0004
wherein R1, R3 and R7 are as defined in Table 1. Table 84
Table 84 provides 160 compounds of formula (84)
Figure imgf000047_0001
wherein R1, R3 and R7 are as defined in Table 1. Table 85
Table 85 provides 160 compounds of formula (85)
Figure imgf000047_0002
wherein R , 1 , R >3 a „„nd, R are as defined in Table 1.
Table 86 Table 86 provides 160 compounds of formula (86)
Figure imgf000047_0003
wherein R , 1 , R and R are as defined in Table 1.
Table 87 Table 87 provides 160 compounds of formula (87)
Figure imgf000047_0004
wherein R1, R3 and R7 are as defined in Table 1 Table 88
Table 88 provides 160 compounds of formula (88)
Figure imgf000048_0001
wherein R1, R3 and R7 are as defined in Table 1. Table 89
Table 89 provides 160 compounds of formula (89)
Figure imgf000048_0002
wherein R1, R3 and R7 are as defined in Table 1.
Table 90 Table 90 provides 160 compounds of formula (90)
Figure imgf000048_0003
wherein R1, R3 and R7 are as defined in Table 1.
Table 91 Table 91 provides 160 compounds of formula (91)
Figure imgf000048_0004
wherein R1, R3 and R7 are as defined in Table 1.
Table 92 Table 92 provides 160 compounds of formula (92)
Figure imgf000048_0005
wherein R1, R3 and R7 are as defined in Table 1.
Table 93 Table 93 provides 160 compounds of formula (93)
Figure imgf000049_0001
wherein R1, R3 and R7 are as defined in Table 1.
Table 94 Table 94 provides 160 compounds of formula (94)
Figure imgf000049_0002
wherein R1, R3 and R7 are as defined in Table 1. Table 95 provides 80 compounds of formula (95)
Figure imgf000049_0003
wherein R3 and R7 are defined in Table 95.
Table 95
Compound No. R3 R7
1 H CH3
2 H CH2CH3
3 H CH2CH CH3
4 H CH(CH3)2
5 H C(CH3)3
6 H CH2CH(CH3)2
7 H CH2C(CH3)3
8 H CH2CF3
9 H CF2CF3
10 H CF2CF2CF3
11 CH3 CH3
12 CH3 CH2CH3
13 CH3 CH2CH2CH3
14 CH3 CH(CH3)2
15 CH3 C(CH3)3 16 CH3 CH2CH(CH3)2
17 CH3 CH2C(CH3)3
18 CH3 CH2CF3
19 CH3 CF2CF3
20 CH3 CF2CF2CF3
21 CH2CH3 CH3
22 CH2CH3 CH2CH3
23 CH2CH3 CH2CH2CH3
24 CH2CH3 CH(CH3)2
25 CH2CH3 C(CH3)3
26 CH2CH3 CH2CH(CH3)2
27 CH2CH3 CH2C(CH3)3
28 CH2CH3 CH2CF3
29 CH2CH3 CF2CF3
30 CH2CH3 CF2CF2CF3
31 CH2CH2CH3 CH3
32 CH2CH2CH3 CH2CH3
33 CH2CH2CH3 CH2CH2CH3
34 CH2CH2CH3 CH(CH3)2
35 CH CH2CH3 C(CH3)3
36 CH2CH2CH3 CH2CH(CH3)2
37 CH2CH2CH3 CH2C(CH3)3
38 CH2CH2CH3 CH2CF3
39 CH2CH2CH3 CF2CF3
40 CH2CH CH3 CF2CF2CF3
41 CH2CH=CH2 CH3
42 CH2CH=CH2 CH2CH3
43 CH2CH=CH2 CH2CH2CH3
44 CH2CH=CH2 CH(CH3)2
45 CH2CH=CH2 C(CH3)3
46 CH2CH=CH2 CH2CH(CH3)2
47 CH2CH=CH2 CH2C(CH3)3
48 CH2CH=CH2 CH2CF3
49 CH2CH=CH2 CF2CF3
50 CH2CH=CH2 CF2CF2CF3
51 CH2C.CH CH3
52 CH2C.CH CH2CH3
53 CH2C.CH CH2CH2CH3
54 CH2C.CH CH(CH3)2
55 CH2C.CH C(CH3)3
56 CH2C.CH CH2CH(CH3)2
57 CH2C.CH CH2C(CH3)3
58 CH2C.CH CH2CF3
59 CH2C.CH CF2CF3
60 CH2C.CH CF2CF2CF3
61 CH2OCH3 CH3
62 CH2OCH3 CH2CH3
63 CH2OCH3 CH2CH CH3 64 CH2OCH3 CH(CH3)2
65 CH2OCH3 C(CH3)3
66 CH2OCH3 CH2CH(CH3)2
67 CH2OCH3 CH2C(CH3)3
68 CH2OCH3 CH2CF3
69 CH2OCH3 CF2CF3
70 CH2OCH3 CF2CF2CF3
71 CH2OCH2CH3 CH3
72 CH2OCH2CH3 CH2CH3
73 CH2OCH2CH3 CH CH2CH3
74 CH2OCH2CH3 CH(CH3)2
75 CH2OCH2CH3 C(CH3)3
76 CH2OCH2CH3 CH2CH(CH3)2
77 CH2OCH2CH3 CH2C(CH3)3
78 CH2OCH2CH3 CH2CF3
79 CH2OCH2CH3 CF2CF3
80 CH2OCH2CH3 CF2CF2CF3
Table 96
Table 96 provides 80 compounds of formula (96)
Figure imgf000051_0001
wherein R3 and R7 are as defined in Table 95.
Table 97 Table 97 provides 80 compounds of formula (97)
Figure imgf000051_0002
wherein R3 and R7 are as defined in Table 95. Table 98
Table 98 provides 80 compounds of formula (98)
Figure imgf000052_0001
wherein R3 and R7 are as defined in Table 95.
Table 99 Table 99 provides 80 compounds of formula (99)
Figure imgf000052_0002
wherein R3 and R7 are as defined in Table 95.
Table 100
Table 100 provides 80 compounds of formula (100)
Figure imgf000052_0003
wherein R3 and R7 are as defined in Table 95.
Table 101 Table 101 provides 80 compounds of formula (101)
Figure imgf000052_0004
wherein R3 and R7 are as defined in Table 95.
Table 102 Table 102 provides 80 compounds of formula (102)
Figure imgf000053_0001
wherein R3 and R7 are as defined in Table 95.
The following abbreviations are used throughout this description: m.p. = melting point ppm = parts per million s = singlet b = broad d = doublet dd = doublet of doublets t = triplet q = quartet m = multiplet
Table 103 shows selected melting point and selected NMR data, all with CDC13 as the solvent (unless otherwise stated; if a mixture of solvents is present, this is indicated as, for example, (CDC13 / VDMSO)), (no attempt is made to list all characterising data in all cases) for compounds of Tables 1-102.
TABLE 103
Figure imgf000053_0002
Figure imgf000054_0001
Figure imgf000055_0001
Figure imgf000056_0001
Figure imgf000057_0001
Figure imgf000058_0001
The compounds of the invention may be made in a variety of ways.
For example, a compound of formula (I) which is a compound of formula (A) (where A, B, Z, R1, R2, R3, R4, R5, R6 and R7 are as defined above for a compound of formula (I) except that R3 is not H) may be made from a compound of formula (B) (where A, B, Z, R1, R2, R4, R5, R6 and R7 are as defined above for a compound of formula (I)) by treatment with an alkylating agent (such as an alkyl halide, dialkyl sulfate or trialkyloxonium salt), an acylating agent (such as an acid chloride) or a similar reagent (such as a carbamoyl chloride or sulfenyl chloride), optionally in the presence of a base. Frequently these reactions give rise to a mixture of a compound of formula (A) with a compound of formula (C) as an isomeric product. A compound of formula (A) may be separated from a compound of formula (C) and purified by routine techniques (such as recrystallisation, chromatography or trituration with a suitable solvent).
Figure imgf000059_0001
(B) (A) (C)
A compound of formula (A) (where A, B, Z, R1, R2, R4, R5, R6 and R7 are as defined above for a compound of formula (I) and where R3 is alkoxyalkyl or acyloxyalkyl) may also be prepared from a compound of formula (B) (where A, B, Z, R1, R2, R4, R5, R6 and R7 are as defined above for a compound of formula (I)) by sequential reaction with formaldehyde and an alkylating or acylating agent.
A compound of formula (B) (where B, Z, R1, R2, R4, R5, R6 and R7 are as defined above for a compound of formula (I) and A is optionally substituted alkylene, alkenylene, alkynylene, alkylenoxy, alkylenamino or alkylenethio) may be prepared by reacting a compound of formula (IT) (where R1 and R2 are as defined above for a compound of formula (I)) either with an appropriate compound of formula (DI) (where B, Z, R4, R5, R6 and R7 are as defined above for a compound of formula (I); A is optionally substituted alkylene, alkenylene, alkynylene, alkylenoxy, alkylenamino or alkylenethio; and X is OH) preferably in the presence of a suitable coupling reagent (such as 1,3-dicyclohexylcarbodiimide, 1,3-diisopropylcarbodiimide, l-(3-dimethylaminopropyl)-3-ethylcarbodiimide or l,l'-carbonyldiimidazole) or with a suitable compound of formula (HI) (where B, Z, R4, R5, R6 and R7 are as defined above for a compound of formula (I); A is optionally substituted alkylene, alkenylene, alkynylene, alkylenoxy, alkylenamino or alkylenethio; and X is halogen, acyloxy, alkoxy (especially methoxy), substituted alkoxy or aryloxy) optionally in the presence of a base (such as triethylamine or sodium methoxide) and in a suitable solvent (such as 1,1,2,2-tetrachloroethane, tetrahydrofuran, N,N-dimethylacetamide or mesitylene). A compound of formula (B) (where B, Z, R4, R5, R6 and R7 are as defined above for a compound of formula (I); and A is optionally substituted oxyalkylene) may be prepared in an analogous manner starting from a compound of formula (II) (where R and R~ are as defined above for a compound of formula (I)) and a suitable compound of formula (HI) (where B, Z, R4, R5, R6 and R7 are as defined above for a compound of formula (I); A is optionally substituted oxyalkylene; and X is chloro).
Figure imgf000060_0001
(ID (III) (B)
1 7
Compounds of formula (H) (where R and R are as defined above for a compound of formula (I)) are known compounds or may be made from known compounds by known methods.
A compound of formula (IH) (where A, B, Z, R4, R5, R6 and R7 are as defined above for a compound of formula (I) and X is -6 alkoxy [optionally substituted by halogen, Cι-3 alkoxy, C1-3 alkylthio, tri(C1-3)alkylsilyl or aryl (itself optionally substituted by C1-3 alkyl, -3 alkoxy, halogen, cyano or nitro)]) may be prepared in a number of ways; the preferred method is dependent on the nature of its fused benzheterocyclic ring and on the nature of its moiety A-C(O)-X (where A and X are as defined above). For example, a suitable reagent Y-C(O)-X (where X is Q- alkoxy [optionally substituted by halogen, Q-3 alkoxy, Q-3 alkylthio, tri(Q-3)alkylsilyl or aryl (itself optionally substituted by Q-3 alkyl, Q-3 alkoxy, halogen, cyano or nitro)]) and Y is a suitably reactive moiety, such as one of those described below) can be attached to a preformed fused heterocyclic ring. Examples of such procedures include, but are not restricted to, the following: (i) Coupling a compound of formula (IV) (where B, Z, R4, R5, R6 and R7 are as defined above for a compound of formula (I) and T is hydroxy) with a compound of formula (V) [where X is Q-6 alkoxy (optionally substituted by halogen, Q-3 alkoxy, Q-3 alkylthio, tri(Q-3)alkylsilyl or aryl (itself optionally substituted by Q-3 alkyl, Q-3 alkoxy, halogen, cyano or nitro)), Y1 is optionally substituted Q-6 alkylene and Hal is chloro, bromo or iodo] under basic conditions to give a compound of formula (HI'):
Figure imgf000060_0002
(V) (IV) (ii) Coupling a suitably functionalised alkane (such as a malonate), alkene (such as an acrylate) or alkyne with a suitable fused heterocyclic halide (especially bromide or iodide) under transition-metal (especially Cu or Pd) mediated cross-coupling conditions. An example of this type of transformation is the reaction between a compound of formula (VI) [where Rx and Ry are as defined above for substituents on alkenylene, Y2 is a single bond or is optionally substituted Q-4 alkylene and X is Q-6 alkoxy (optionally substituted by halogen, Q-3 alkoxy, Q-3 alkylthio, tri(Q-3)alkylsilyl or aryl (itself optionally substituted by Q-3 alkyl, Q-3 alkoxy, halogen, cyano or nitro))] and a compound of formula (IV) (where B, Z, R4, R5, R6 and R7 are as defined above for a compound of formula (I) and T is chlorine, bromine or iodine) under Pd(0) catalysis to give a compound of formula (DI"):
Figure imgf000061_0001
(VI) (IV) (III") and
(iii) Direct alkylation or acylation under, for example, Friedel-Craft conditions. Certain compounds of formula (ITf) are amenable to modification to give further analogues. For example, a compound of formula (DT) (where B, Z, R4, R5, R6 and R7 are as defined above for a compound of formula (I), X is Q-6 alkoxy [optionally substituted by halogen, Q-3 alkoxy, Q- alkylthio, tri(Q-3)alkylsilyl or aryl (itself optionally substituted by Q-3 alkyl, Q-3 alkoxy, halogen, cyano or nitro)] and A is Q-6 alkylene) undergoes reactions typical of aliphatic esters. Thus a compound of formula (Ula) [where J is a single bond or a suitable alkylene moiety (such as CH2)] may be reacted with a suitable base (such as lithium diisopropylamide, sodium hydride or lithium hexamethyldisilazide) in a suitable solvent (such as tetrahydrofuran) and then treated with an electrophilic reagent such as an alkylating agent (for example an alkyl halide, alkenylalkyl halide or arylalkyl halide), a halogenating agent (for example N-fluorobenzenesulfonimide) or a further compound with the general formula Rf-LG (where LG designates a suitable leaving group, such as a halide and Rf is, for example, a sulfenyl or acyl moiety) to introduce R as a new substituent. This procedure may be repeated to introduce a second substituent, Rε (which may be the same or different to Rf):
Figure imgf000062_0001
x R9 f- R3έtB
(lllc)
As expected, a compound of formula (HI), bearing fragments which are sufficiently chemically reactive, undergoes reactions typical of those fragments. For example, a compound of formula (Hid) [where B, Z, R , R5, R6 and R7 are as defined above for a compound of formula (I), X is Q- alkoxy (optionally substituted by halogen, Q-3 alkoxy, Q-3 alkylthio, tri(Q-3)alkylsilyl or aryl (itself optionally substituted by Q-3 alkyl, Q-3 alkoxy, halogen, cyano or nitro)) and J is a single bond or a suitable alkylene moiety (such as CH2)] will undergo certain reactions typical of α-ketoesters; for instance, reduction by a metal hydride (such as sodium borohydride) in a suitable solvent (such as ethanol) to give a corresponding alcohol:
Figure imgf000062_0002
(llld) (llle)
In an alternative preparation of a compound of formula (D ) (where A, B, Z, R4, R5, R6 and R7 are as defined above for a compound of formula (I) and X is hydroxy or Q-6 alkoxy [optionally substituted by halogen, Q-3 alkoxy, Q-3 alkylthio, tri(Q-3)alkylsilyl or aryl (itself optionally substituted by Q-3 alkyl, Q-3 alkoxy, halogen, cyano or nitro)]) the benzofused heterocyclic ring may be formed by ring synthesis from a suitably substituted benzene of formula (VII) (where Q and G are suitable precursors (atoms or groups) for the formation of the desired heterocyclic ring, A, R4, R5 and R6 are as defined above for a compound of formula (I) and X is hydroxy or Q-6 alkoxy [optionally substituted by halogen, Q-3 alkoxy, Q-3 alkylthio, tri(C!-3)alkylsilyl or aryl (itself optionally substituted by Q-3 alkyl, Q-3 alkoxy, halogen, cyano or nitro)]):
ring synthesis
Figure imgf000063_0001
Figure imgf000063_0002
This methodology may be extended to the following transformation
ring synthesis
Figure imgf000063_0003
Figure imgf000063_0004
(VIII) (B) where A, B, Z, R1, R2, R4, R5, R6 and R7 are as defined above for a compound of formula (I) and Q and G are suitable precursors (atoms or groups) for the formation of the desired heterocyclic ring. For example, when Q is hydroxy and G is amino, treatment of a compound of formula (VIII) either with an acylating agent [such as an acid chloride or anhydride] optionally in the presence of a suitable base (such as triethylamine, potassium carbonate or pyridine) or with an acid (preferably in the presence of a coupling agent (such as 1,3- dicyclohexyl-carbodiimide, 1 ,3-diisopropylcarbodiimide, 1 -(3-dimethylaminopropyl)-3- ethyl-carbodiimide or l, -carbonyldiimidazole)) followed by cyclisation, optionally catalysed by an acid (such as rα-toluenesulfonic acid), gives a benzoxazole:
Figure imgf000063_0005
2. Cyclisation
Figure imgf000063_0006
Similar reactions (where G is amino and Q is SH or amino) lead to a benzothiazole or a benzimidazole respectively. Indeed, the synthesis of a substituted benzimidazole, benzoxazole or benzothiazole from a substituted benzene is well known [see for example, Alan R.Katritzky and Charles W.Rees (Comprehensive Heterocyclic Chemistry, Vol. 6, Pergamon Press, 1984); Helmut M.Hugel, Synth. Commun. Q5 (12), 1075-1080, (1985)); J.Scheigetz, R.Zamboni and B.Roy, Synth. Commun., 25 (18), 2791-2806, (1995); David W. Dunwell, Delme Evans, Terence A. Hicks (J. Med. Chem., 1975, 18, No. 1, 53); Abdou O. Abdelhamid, Cyril Parkanyi, S.M. Khaledur Rashid and Winston D. Lloyd (J. Heterocyclic Chem., 25, 403, (1988)); Teruyuki Kondo, Sungbong Yang, Keun-Tae Huh, Masanobu Kobayashi, Shinju Kotachi and Yoshihisa Watanabe (Chemistry Letters, 1275, 1991); and Dale L. Boger (J. Org. Chem., 43, No 11, 2296, 1978)] and similar processes may be utilised in the synthesis of a compound of formula (HI) (where A, B, Z, R4, R5, R6 and R7 are as defined above for a compound of formula (1) and X is hydroxy, halogen, acyloxy, alkoxy, substituted alkoxy or aryloxy) from appropriate starting materials. A benzothiophene may be made from an appropriate thiophenol by a process similar to those described by Robert D Schuetz and Richard L Titus (J. Heterocycl. Chem., 4, No 4, 465 (1967); suitable thiophenols are known compounds or may be prepared by known methods from known compounds. A benzofuran may be made from an ørt7-σ-halophenol, as described by Henning Lutjens and Peter J Scammells (Tetrahedron Letters 39 (1998), 6581-6584); Terence C Owen et al, (Tetrahedron Letters 30, No 13, 1597 (1989)); and Fred G Schreiber and Robert Stevenson (J.C.S. Perkin 1, 90, 1977). An indole may be made from an ørt/zø-haloaniline according to the methods of Cheng-yi Chen et al. (J. Org. Chem. 1997, 62, 2676); Takao Sakamoto et al., (J. Org. Chem. 1997, 62, 6507); and Alan D. Adams et al. (WO9827974).
A compound of formula (I) (where A, B, Z, R1, R2, R4, R5, R6 and R7 are as defined above, Y is S and R3 is H) may be prepared by reacting a compound of formula (I) (where A, B, Z, R1, R2, R4, R5, R6 and R7 are as defined above, Y is O and R3 is H) with a suitable thionating agent (such as 2,4-bis(4-methoxyphenyl)-l,3-dithia-2,4-diphosphetane-2,4- disulfide (Lawesson's reagent), 2,4-bis(methylthio)-l,3-dithia-2,4-diphosphetane-2,4- disulfide (Davy reagent methyl), 2,4-bis(pαrα-tolyl)-l,3-dithia-2,4-diphosphetane-2,4- disulfide (Davy reagent -tolyl) or phosphorus pentasulfide) in a suitable solvent (such as toluene or fluorobenzene). A compound of formula (DC) (where B, Z, R1, R2, R3, R4, R5, R6 and R7 are as defined above for a compound of formula (I)) may be made by reacting a compound of formula (X) (where B, Z, R1, R2, R3, R4, R5, R6 and R7 are as defined above) with N,N- dimethyl-formamide dialkyl acetal in a suitable solvent (such as toluene or N,N- dimethylformamide). Frequently this reaction produces a mixture of E- and Z-isomers which are sometimes separable by standard techniques (such as flash column chromatography and recrystallisation).
Figure imgf000065_0001
A compound of formula (X) ((where B, Z, R1, R2, R3, R4, R5, R6 and R7 are as defined for a compound of formula (I)) may be treated in an analogous manner with a trialkylorthoformate to afford a compound of formula (XI) (where B, Z, R1, R2, R3, R4, R5, R6 and R7 are as defined for a compound of formula (I) and Rd is Q-6 alkyl).
Figure imgf000065_0002
A compound of formula (IX) (where B, Z, R1, R2, R3, R4, R5, R6 and R7 are as defined above for a compound of formula (I)) may be treated with an amine of formula (HNR26R27) (where R26 and R27 are as defined for a compound of formula (I)) to give a compound of formula (XII) (where B, Z, R1, R2, R3, R4, R5, R6, R7, R26 and R27are as defined above for a compound of formula (I)).
A compound of formula (DC) (where B, Z, R1, R2, R3, R4, R5, R6 and R7 are as defined above for a compound of formula (I)) may be oxidised to a compound of formula (XIH) (where B, Z, R1, R2, R3, R4, R5, R6 and R7 are as defined above for a compound of formula (I)) under known conditions.
Figure imgf000065_0003
(XIII)
A compound of formula (I) (where Y is S, R3 is H and A, B, Z, R1, R2, R4, R5, R6 and R7 are as defined above for a compound of formula (I)) may be treated with an electrophile (such as an alkyl halide, dialkyl sulfate, chloromethyl ether or trialkyloxonium salt) optionally in the presence of a base to give a compound of formula (XIV) (where R32 is alkyl, alkenylalkyl, alkynylalkyl, cycloalkyl, alkoxyalkyl and A, B, Z, R1, R2, R4, R5, R6 and R7 are as defined above for a compound of formula (I)). Such a compound may be further treated with a compound of formula R9-NH2 (where R9 is as defined above for a compound of formula (I)) optionally in the presence of a mercuric salt (such as mercuric chloride), according to known procedures to give a compound of formula (XV) (where R3 is H and A, B, Z, R1, R2, R4, R5, R6 and R7 are as defined above for a compound of formula (I)). Such a compound may be treated with an alkylating agent, an acylating agent or similar electrophile to give a compound of formula (XV) [where A, B, Z, R1, R2, R4, R5, R6 and R7 are as defined above for a compound of formula (I) and R is as defined above for a compound of formula (I) (except that R3 is not H)] in an analogous manner to that previously described for the formation of a compound of formula (A) from a compound of formula (B).
Figure imgf000066_0001
(XIV) (XV) The compounds of formula (I) can be used to combat and control infestations of insect pests such as Lepidoptera, Diptera, Hemiptera, Thysanoptera, Orthoptera, Dictyoptera, Coleoptera, Siphonaptera, Hymenoptera and Isoptera and also other invertebrate pests, for example, acarine, nematode and mollusc pests. Insects, acarines, nematodes and molluscs are hereinafter collectively referred to as pests. The pests which may be combated and controlled by the use of the invention compounds include those pests associated with agriculture (which term includes the growing of crops for food and fibre products), horticulture and animal husbandry, companion animals, forestry and the storage of products of vegetable origin (such as fruit, grain and timber); those pests associated with the damage of man-made structures and the transmission of diseases of man and animals; and also nuisance pests (such as flies).
Examples of pest species which may be controlled by the compounds of formula (I) include: Myzus persicae (aphid), Aphis gossypii (aphid), Aphis fabae (aphid), Lygus spp. (capsids), Dysdercus spp. (capsids), Nilaparvata lugens (planthopper), Nephotettixc incticeps (leafhopper), Nezara spp. (stinkbugs), Euschistus spp. (stinkbugs), Leptocorisa spp. (stinkbugs), Frankliniella occidentalis (thrip), Thrips spp. (thrips), Leptinotarsa decemlineata (Colorado potato beetle), Anthonomus grandis (boll weevil), Aonidiella spp. (scale insects), Trialeurodes spp. (white flies), Bemisia tabaci (white fly), Ostrinia nubilalis (European corn borer), Spodoptera littoralis (cotton leafworm), Heliothis virescens (tobacco budworm), Helicoverpa armigera (cotton bollworm), Helicoverpa zea (cotton bollworm), Sylepta derogata (cotton leaf roller), Pieris brassicae (white butterfly), Plutella xylostella (diamond back moth), Agrotis spp. (cutworms), Chilo suppressalis (rice stem borer), Locusta_ migratoria (locust), Chortiocetes terminifera (locust), Diabrotica spp. (rootworms), Panonychus ulmi (European red mite), Panonychus citri (citrus red mite), Tetranychus urticae (two-spotted spider mite), Tetranychus cinnabarinus (carmine spider mite), Phyllocoptruta oleivora (citrus rust mite), Polyphagotarsonemus latus (broad mite),
Brevipalpus spp. (flat mites), Boophilus microplus (cattle tick), Dermacentor variabilis (American dog tick), Ctenocephalides felis (cat flea), Liriomyza spp. (leaf miner), Musca domestica (housefly), Aedes aegypti (mosquito), Anopheles spp. (mosquitoes), Culex spp. (mosquitoes), Lucillia spp. (blowflies), Blattella germanica (cockroach), Periplaneta americana (cockroach), Blatta orientalis (cockroach), termites of the Mastotermitidae (for example Mastotermes spp.), the Kalotermitidae (for example Neotermes spp.), the Rhinotermitidae (for example Coptotermes formosanus, Reticulitermes flavipes, R. speratu, R. virginicus, R. hesperus, and R. santonensis) and the Termitidae (for example Globitermes sulphur eus), Solenopsis geminata (fire ant), Monomorium pharaonis (pharaoh's ant), Damalinia spp. and Linognathus spp. (biting and sucking lice), Meloidogyne spp. (root knot nematodes), Globodera spp. and Heterodera spp. (cyst nematodes), Pratylenchus spp. (lesion nematodes), Rhodopholus spp. (banana burrowing nematodes), Tylenchulus spp.(citrus nematodes), Haemonchus contortus (barber pole worm), Caenorhabditis elegans_ (vinegar eelworm), Trichostrongylus spp. (gastro intestinal nematodes) and Deroceras reticulatum (slug).
The compounds of formula (I) are also active fungicides and may be used to control one or more of the following pathogens: Pyricularia oryzae (Magnaporthe grisea) on rice and wheat and other Pyricularia spp. on other hosts; Puccinia recondita, Puccinia striiformis and other rusts on wheat, Puccinia hordei, Puccinia striiformis and other rusts on barley, and rusts on other hosts (for example turf, rye, coffee, pears, apples, peanuts, sugar beet, vegetables and ornamental plants); Erysiphe cichoracearum on cucurbits (for example melon); Erysiphe graminis (powdery mildew) on barley, wheat, rye and turf and other powdery mildews on various hosts, such as Sphaerotheca macularis on hops, Sphaerotheca fusca (Sphaerotheca fuliginea) on cucurbits (for example cucumber), Leveillula taurica on tomatoes, aubergine and green pepper, Podosphaera leucotricha on apples and Uncinula necator on vines; Cochliobolus spp., Helminthospoήum spp., Drechslera spp. (Pyrenophora spp.), Rhynchosporium spp., Mycosphaerella graminicola (Septoria tritici) and Phaeosphaeria nodorum (Stagonospora nodorum or Septoria nodorum), Pseudocercosporella herpotrichoides and Gaeumannomyces graminis on cereals (for example wheat, barley, rye), turf and other hosts; Cercospora arachidicola and Cercosporidium personatum on peanuts and other Cercospora spp. on other hosts, for example sugar beet, bananas, soya beans and rice; Botrytis cinerea (grey mould) on tomatoes, strawberries, vegetables, vines and other hosts and other Botrytis spp. on other hosts; Alternaria spp. on vegetables (for example carrots), oil-seed rape, apples, tomatoes, potatoes, cereals (for example wheat) and other hosts; Venturia spp. (including Venturia inaequalis (scab)) on apples, pears, stone fruit, tree nuts and other hosts; Cladosporium spp. on a range of hosts including cereals (for example wheat) and tomatoes; Monilinia spp. on stone fruit, tree nuts and other hosts; Didymella spp. on tomatoes, turf, wheat, cucurbits and other hosts; Phoma spp. on oil-seed rape, turf, rice, potatoes, wheat and other hosts; Aspergillus spp. and Aureobasidium spp. on wheat, lumber and other hosts; Ascochyta spp. on peas, wheat, barley and other hosts; Stemphylium spp. (Pleospora spp.) on apples, pears, onions and other hosts; summer diseases (for example bitter rot (Glomerella cingulata), black rot or frogeye leaf spot (Botryosphaeria obtusa), Brooks fruit spot (Mycosphaerella pomϊ), Cedar apple rust (Gymnosporangiumjuniperi-virginianae), sooty blotch (Gloeodes pomigena), flyspeck (Schizothyrium pomϊ) and white rot (Botryosphaeria dothidea)) on apples and pears; Plasmopara viticola on vines; other downy mildews, such as Bremia lactucae on lettuce, Peronospora spp. on soybeans, tobacco, onions and other hosts, Pseudoperonospora humuli on hops and Pseudoperonospora cubensis on cucurbits; Pythium spp. (including Pythium ultimum) on turf and other hosts; Phytophthora infestans on potatoes and tomatoes and other Phytophthora spp. on vegetables, strawberries, avocado, pepper, ornamentals, tobacco, cocoa and other hosts; Thanatephorus cucumeris on rice and turf and other Rhizoctonia spp. on various hosts such as wheat and barley, peanuts, vegetables, cotton and turf; Sclerotinia spp. on turf, peanuts, potatoes, oil-seed rape and other hosts; Sclerotium spp. on turf, peanuts and other hosts; Gibberella fujikuroi on rice; Colletotrichum spp. on a range of hosts including turf, coffee and vegetables; Laetisaria fuciformis on turf; Mycosphaerella spp. on bananas, peanuts, citrus, pecans, papaya and other hosts; Diaporthe spp. on citrus, soybean, melon, pears, lupin and other hosts; Elsinoe spp. on citrus, vines, olives, pecans, roses and other hosts; Verticillium spp. on a range of hosts including hops, potatoes and tomatoes; Pyrenopeziza spp. on oil-seed rape and other hosts; Oncobasidium theobromae on cocoa causing vascular streak dieback; Fusarium spp., Typhula spp., Microdochium nivale, Ustilago spp., Urocystis spp., Tilletia spp. and Claviceps purpurea on a variety of hosts but particularly wheat, barley, turf and maize; Ramularia spp. on sugar beet, barley and other hosts; post-harvest diseases particularly of fruit (for example Penicillium digitatum, Penicillium italicum and Trichoderma viride on oranges, Colletotrichum musae and
Gloeosporium musarum on bananas and Botrytis cinerea on grapes); other pathogens on vines, notably Eutypa lata, Guignardia bidwellii, Phellinus igniarus, Phomopsis viticola, Pseudopeziza tracheiphila and Stereum hirsutum; other pathogens on trees (for example Lophodermium seditiosum) or lumber, notably Cephaloascus fragrans, Ceratocystis spp., Ophiostoma piceae, Penicillium spp., Trichoderma pseudokoningii, Trichoderma viride, Trichoderma harzianum, Aspergillus niger, Leptographium lindbergi and Aureobasidium pullulans; and fungal vectors of viral diseases (for example Polymyxa graminis on cereals as the vector of barley yellow mosaic virus (B YMV) and Polymyxa betae on sugar beet as the vector of rhizomania). A compound of formula (I) may move acropetally, basipetally or locally in plant tissue to be active against one or more fungi. Moreover, a compound of formula (I) may be volatile enough to be active in the vapour phase against one or more fungi on the plant. The invention therefore provides a method of combating and controlling insects, acarines, nematodes or molluscs which comprises applying an insecticidally, acaricidally, nematicidally or molluscicidally effective amount of a compound of formula (I), or a composition containing a compound of formula (I), to a pest, a locus of pest, or to a plant susceptible to attack by a pest, and a method of combating and controlling fungi which comprises applying a fungicidally effective amount of a compound of formula (I), or a composition containing a compound of formula (I), to a plant, to a seed of a plant, to the locus of the plant or seed, to soil or to any other growth medium (for example a nutrient solution). The compounds of formula (I) are preferably used against insects, acarines, nematodes or fungi. The term "plant" as used herein includes seedlings, bushes and trees. Furthermore, the fungicidal method of the invention includes protectant, curative, systemic, eradicant and antisporulant treatments.
As fungicides, the compounds of formula (I) are preferably used for agricultural, horticultural and turfgrass purposes in the form of a composition.
In order to apply a compound of formula (I) as an insecticide, acaricide, nematicide or molluscicide to a pest, a locus of pest, or to a plant susceptible to attack by a pest, or, as a fungicide to a plant, to a seed of a plant, to the locus of the plant or seed, to soil or to any other growth medium, a compound of formula (I) is usually formulated into a composition which includes, in addition to the compound of formula (I), a suitable inert diluent or carrier and, optionally, a surface active agent (SFA). SFAs are chemicals which are able to modify the properties of an interface (for example, liquid/solid, liquid/air or liquid/liquid interfaces) by lowering the interfacial tension and thereby leading to changes in other properties (for example dispersion, emulsification and wetting). It is preferred that all compositions (both solid and liquid formulations) comprise, by weight, 0.0001 to 95%, more preferably 1 to 85%, for example 5 to 60%, of a compound of formula (I). The composition is generally used for the control of pests or fungi such that a compound of formula (I) is applied at a rate of from O.lg to 10kg per hectare, preferably from lg to 6kg per hectare, more preferably from lg to 1kg per hectare. When used in a seed dressing, a compound of formula (I) is used at a rate of 0.0001 g to lOg (for example O.OOlg or 0.05g), preferably 0.005g to lOg, more preferably 0.005g to 4g, per kilogram of seed.
In another aspect the present invention provides an insecticidal, acaricidal, nematicidal, molluscicidal or fungicidal composition comprising an insecticidally, acaricidally, nematicidally, molluscicidally or fungicidally effective amount of a compound of formula (I) and a suitable carrier or diluent therefor. The composition is preferably an insecticidal, acaricidal, nematicidal or fungicidal composition.
In a still further aspect the invention provides a method of combating and controlling pests or fungi at a locus which comprises treating the pests or fungi or the locus of the pests or fungi with an insecticidally, acaricidally, nematicidally, molluscicidally or fungicidally effective amount of a composition comprising a compound of formula (I). The compounds of formula (I) are preferably used against insects, acarines, nematodes or fungi. The compositions can be chosen from a number of formulation types, including dustable powders (DP), soluble powders (SP), water soluble granules (SG), water dispersible granules (WG), wettable powders (WP), granules (GR) (slow or fast release), soluble concentrates (SL), oil miscible liquids (OL), ultra low volume liquids (UL), emulsifiable concentrates (EC), dispersible concentrates (DC), emulsions (both oil in water (EW) and water in oil (EO)), micro-emulsions (ME), suspension concentrates (SC), aerosols, fogging/smoke formulations, capsule suspensions (CS) and seed treatment formulations. The formulation type chosen in any instance will depend upon the particular purpose envisaged and the physical, chemical and biological properties of the compound of formula (I). Dustable powders (DP) may be prepared by mixing a compound of formula (I) with one or more solid diluents (for example natural clays, kaolin, pyrophyllite, bentonite, alumina, montmorillonite, kieselguhr, chalk, diatomaceous earths, calcium phosphates, calcium and magnesium carbonates, sulphur, lime, flours, talc and other organic and inorganic solid carriers) and mechanically grinding the mixture to a fine powder. Soluble powders (SP) may be prepared by mixing a compound of formula (I) with one or more water-soluble inorganic salts (such as sodium bicarbonate, sodium carbonate or magnesium sulphate) or one or more water-soluble organic solids (such as a polysaccharide) and, optionally, one or more wetting agents, one or more dispersing agents or a mixture of said agents to improve water dispersibility/solubility. The mixture is then ground to a fine powder. Similar compositions may also be granulated to form water soluble granules (SG). Wettable powders (WP) may be prepared by mixing a compound of formula (I) with one or more solid diluents or carriers, one or more wetting agents and, preferably, one or more dispersing agents and, optionally, one or more suspending agents to facilitate the dispersion in liquids. The mixture is then ground to a fine powder. Similar compositions may also be granulated to form water dispersible granules (WG).
Granules (GR) may be formed either by granulating a mixture of a compound of formula (I) and one or more powdered solid diluents or carriers, or from pre-formed blank granules by absorbing a compound of formula (I) (or a solution thereof, in a suitable agent) in a porous granular material (such as pumice, attapulgite clays, fuller's earth, kieselguhr, diatomaceous earths or ground corn cobs) or by adsorbing a compound of formula (I) (or a solution thereof, in a suitable agent) on to a hard core material (such as sands, silicates, mineral carbonates, sulphates or phosphates) and drying if necessary. Agents which are commonly used to aid absorption or adsorption include solvents (such as aliphatic and aromatic petroleum solvents, alcohols, ethers, ketones and esters) and sticking agents (such as polyvinyl acetates, polyvinyl alcohols, dextrins, sugars and vegetable oils). One or more other additives may also be included in granules (for example an emulsifying agent, wetting agent or dispersing agent).
Dispersible Concentrates (DC) may be prepared by dissolving a compound of formula (I) in water or an organic solvent, such as a ketone, alcohol or glycol ether. These solutions may contain a surface active agent (for example to improve water dilution or prevent crystallisation in a spray tank). Emulsifiable concentrates (EC) or oil-in-water emulsions (EW) may be prepared by dissolving a compound of formula (I) in an organic solvent (optionally containing one or more wetting agents, one or more emulsifying agents or a mixture of said agents). Suitable organic solvents for use in ECs include aromatic hydrocarbons (such as alkylbenzenes or alkylnaphthalenes, exemplified by SOLVESSO 100, SOLVESSO 150 and SOLVESSO 200; SOLVESSO is a Registered Trade Mark), ketones (such as cyclohexanone or methylcyclohexanone) and alcohols (such as benzyl alcohol, furfuryl alcohol or butanol),
N-alkylpyrrolidones (such as N-methylpyrrolidone or N-octylpyrrolidone), dimethyl amides of fatty acids (such as C8-Qo fatty acid dimethylamide) and chlorinated hydrocarbons. An EC product may spontaneously emulsify on addition to water, to produce an emulsion with sufficient stability to allow spray application through appropriate equipment. Preparation of an EW involves obtaining a compound of formula (I) either as a liquid (if it is not a liquid at room temperature, it may be melted at a reasonable temperature, typically below 70°C) or in solution (by dissolving it in an appropriate solvent) and then emulsifiying the resultant liquid or solution into water containing one or more SFAs, under high shear, to produce an emulsion. Suitable solvents for use in EWs include vegetable oils, chlorinated hydrocarbons (such as chlorobenzenes), aromatic solvents (such as alkylbenzenes or alkylnaphthalenes) and other appropriate organic solvents which have a low solubility in water.
Microemulsions (ME) may be prepared by mixing water with a blend of one or more solvents with one or more SFAs, to produce spontaneously a thermodynamically stable isotropic liquid formulation. A compound of formula (I) is present initially in either the water or the solvent/SFA blend. Suitable solvents for use in MEs include those hereinbefore described for use in in ECs or in EWs. An ME may be either an oil-in-water or a water-in-oil system (which system is present may be determined by conductivity measurements) and may be suitable for mixing water-soluble and oil-soluble pesticides in the same formulation. An ME is suitable for dilution into water, either remaining as a microemulsion or forming a conventional oil-in-water emulsion.
Suspension concentrates (SC) may comprise aqueous or non-aqueous suspensions of finely divided insoluble solid particles of a compound of formula (I). SCs may be prepared by ball or bead milling the solid compound of formula (I) in a suitable medium, optionally with one or more dispersing agents, to produce a fine particle suspension of the compound. One or more wetting agents may be included in the composition and a suspending agent may be included to reduce the rate at which the particles settle. Alternatively, a compound of formula (I) may be dry milled and added to water, containing agents hereinbefore described, to produce the desired end product.
Aerosol formulations comprise a compound of formula (I) and a suitable propellant (for example n-butane). A compound of formula (I) may also be dissolved or dispersed in a suitable medium (for example water or a water miscible liquid, such as «-propanol) to provide compositions for use in non-pressurised, hand-actuated spray pumps.
A compound of formula (I) may be mixed in the dry state with a pyrotechnic mixture to form a composition suitable for generating, in an enclosed space, a smoke containing the compound.
Capsule suspensions (CS) may be prepared in a manner similar to the preparation of EW formulations but with an additional polymerisation stage such that an aqueous dispersion of oil droplets is obtained, in which each oil droplet is encapsulated by a polymeric shell and contains a compound of formula (I) and, optionally, a carrier or diluent therefor. The polymeric shell may be produced by either an interfacial polycondensation reaction or by a coacervation procedure. The compositions may provide for controlled release of the compound of formula (I) and they may be used for seed treatment. A compound of formula (I) may also be formulated in a biodegradable polymeric matrix to provide a slow, controlled release of the compound. A composition may include one or more additives to improve the biological performance of the composition (for example by improving wetting, retention or distribution on surfaces; resistance to rain on treated surfaces; or uptake or mobility of a compound of formula (I)). Such additives include surface active agents, spray additives based on oils, for example certain mineral oils or natural plant oils (such as soy bean and rape seed oil), and blends of these with other bio-enhancing adjuvants (ingredients which may aid or modify the action of a compound of formula (I)). A compound of formula (I) may also be formulated for use as a seed treatment, for example as a powder composition, including a powder for dry seed treatment (DS), a water soluble powder (SS) or a water dispersible powder for slurry treatment (WS), or as a liquid composition, including a flowable concentrate (FS), a solution (LS) or a capsule suspension (CS). The preparations of DS, SS, WS, FS and LS compositions are very similar to those of, respectively, DP, SP, WP, SC and DC compositions described above. Compositions for treating seed may include an agent for assisting the adhesion of the composition to the seed (for example a mineral oil or a film-forming barrier).
Wetting agents, dispersing agents and emulsifying agents may be surface SFAs of the cationic, anionic, amphoteric or non-ionic type. Suitable SFAs of the cationic type include quaternary ammonium compounds (for example cetyltrimethyl ammonium bromide), imidazolines and amine salts.
Suitable anionic SFAs include alkali metals salts of fatty acids, salts of aliphatic monoesters of sulphuric acid (for example sodium lauryl sulphate), salts of sulphonated aromatic compounds (for example sodium dodecylbenzenesulphonate, calcium dodecylbenzenesulphonate, butylnaphthalene sulphonate and mixtures of sodium di-isopropyl- and tri-w propyl-naphthalene sulphonates), ether sulphates, alcohol ether sulphates (for example sodium laureth-3-sulphate), ether carboxylates (for example sodium laureth-3-carboxylate), phosphate esters (products from the reaction between one or more fatty alcohols and phosphoric acid (predominately mono-esters) or phosphorus pentoxide (predominately di-esters), for example the reaction between lauryl alcohol and tetraphosphoric acid; additionally these products may be ethoxylated), sulphosuccinamates, paraffin or olefine sulphonates, taurates and lignosulphonates.
Suitable SFAs of the amphoteric type include betaines, propionates and glycinates. Suitable SFAs of the non-ionic type include condensation products of alkylene oxides, such as ethylene oxide, propylene oxide, butylene oxide or mixtures thereof, with fatty alcohols (such as oleyl alcohol or cetyl alcohol) or with alkylphenols (such as octylphenol, nonylphenol or octylcresol); partial esters derived from long chain fatty acids or hexitol anhydrides; condensation products of said partial esters with ethylene oxide; block polymers (comprising ethylene oxide and propylene oxide); alkanolamides; simple esters (for example fatty acid polyethylene glycol esters); amine oxides (for example lauryl dimethyl amine oxide); and lecithins. Suitable suspending agents include hydrophilic colloids (such as polysaccharides, polyvinylpyrrolidone or sodium carboxymethylcellulose) and swelling clays (such as bentonite or attapulgite).
A compound of formula (I) may be applied by any of the known means of applying pesticidal or fungicidal compounds. For example, it may be applied, formulated or unformulated, to the pests or to a locus of the pests (such as a habitat of the pests, or a growing plant liable to infestation by the pests) or to any part of the plant, including the foliage, stems, branches or roots, to the seed before it is planted or to other media in which plants are growing or are to be planted (such as soil surrounding the roots, the soil generally, paddy water or hydroponic culture systems), directly or it may be sprayed on, dusted on, applied by dipping, applied as a cream or paste formulation, applied as a vapour or applied through distribution or incorporation of a composition (such as a granular composition or a composition packed in a water-soluble bag) in soil or an aqueous environment.
A compound of formula (I) may also be injected into plants or sprayed onto vegetation using electrodynamic spraying techniques or other low volume methods, or applied by land or aerial irrigation systems.
Compositions for use as aqueous preparations (aqueous solutions or dispersions) are generally supplied in the form of a concentrate containing a high proportion of the active ingredient, the concentrate being added to water before use. These concentrates, which may include DCs, SCs, ECs, EWs, MEs SGs, SPs, WPs, WGs and CSs, are often required to withstand storage for prolonged periods and, after such storage, to be capable of addition to water to form aqueous preparations which remain homogeneous for a sufficient time to enable them to be applied by conventional spray equipment. Such aqueous preparations may contain varying amounts of a compound of formula (I) (for example 0.0001 to 10%, by weight) depending upon the purpose for which they are to be used. A compound of formula (I) may be used in mixtures with fertilisers (for example nitrogen-, potassium- or phosphorus-containing fertilisers). Suitable formulation types include granules of fertiliser. The mixtures suitably contain up to 25% by weight of the compound of formula (I).
The invention therefore also provides a fertiliser composition comprising a fertiliser and a compound of formula (I). The compositions of this invention may contain other compounds having biological activity, for example micronutrients or compounds having similar or complementary fungicidal activity or which possess plant growth regulating, herbicidal, insecticidal, nematicidal or acaricidal activity.
By including another fungicide, the resulting composition may have a broader spectrum of activity or a greater level of intrinsic activity than the compound of formula (I) alone. Further the other fungicide may have a synergistic effect on the fungicidal activity of the compound of formula (I).
The compound of formula (I) may be the sole active ingredient of the composition or it may be admixed with one or more additional active ingredients such as a pesticide, fungicide, synergist, herbicide or plant growth regulator where appropriate. An additional active ingredient may: provide a composition having a broader spectrum of activity or increased persistence at a locus; synergise the activity or complement the activity (for example by increasing the speed of effect or overcoming repellency) of the compound of formula (I); or help to overcome or prevent the development of resistance to individual components. The particular additional active ingredient will depend upon the intended utility of the composition. Examples of suitable pesticides include the following: a) Pyrethroids, such as permethrin, cypermethrin, fenvalerate, esfenvalerate, deltamethrin, cyhalothrin (in particular lambda-cyhalothrin), bifenthrin, fenpropathrin, cyfluthrin, tefluthrin, fish safe pyrethroids (for example ethofenprox), natural pyrethrin, tetramethrin, s-bioallethrin, fenfluthrin, prallethrin or 5-benzyl-3-furylmethyl-(E)-(lR,3S)-2,2-dimethyl- 3-(2-oxothiolan-3-ylidenemethyl)cyclopropane carboxylate; b) Organophosphates, such as, profenofos, sulprofos, acephate, methyl parathion, azinphos-methyl, demeton-s-methyl, heptenophos, thiometon, fenamiphos, monocrotophos, profenofos, triazophos, methamidophos, dimethoate, phosphamidon, malathion, chlorpyrifos, phosalone, terbufos, fensulfothion, fonofos, phorate, phoxim, pirimiphos-methyl, pirimiphos-ethyl, fenitrothion, fosthiazate or diazinon; c) Carbamates (including aryl carbamates), such as pirimicarb, triazamate, cloethocarb, carbofuran, furathiocarb, ethiofencarb, aldicarb, thiofurox, carbosulfan, bendiocarb, fenobucarb, propoxur, methomyl or oxamyl; d) Benzoyl ureas, such as diflubenzuron, triflumuron, hexaflumuron, flufenoxuron or chlorfluazuron; e) Organic tin compounds, such as cyhexatin, fenbutatin oxide or azocyclotin; f) Pyrazoles, such as tebufenpyrad and fenpyroximate; g) Macrolides, such as avermectins or milbemycins, for example abamectin, emamectin benzoate, ivermectin, milbemycin, spinosad or azadirachtin; h) Hormones or pheromones; i) Organochlorine compounds such as endosulfan, benzene hexachloride, DDT, chlordane or dieldrin; j) Amidines, such as chlordimeform or amitraz; k) Fumigant agents, such as chloropicrin, dichloropropane, methyl bromide or metam; 1) Chloronicotinyl compounds such as imidacloprid, thiacloprid, acetamiprid, nitenpyram or thiamethoxam; m) Diacylhydrazines, such as tebufenozide, chromafenozide or methoxyfenozide; n) Diphenyl ethers, such as diofenolan or pyriproxifen; o) Indoxacarb; p) Chlorfenapyr; or q) Pymetrozine.
In addition to the major chemical classes of pesticide listed above, other pesticides having particular targets may be employed in the composition, if appropriate for the intended utility of the composition. For instance, selective insecticides for particular crops, for example stemborer specific insecticides (such as cartap) or hopper specific insecticides (such as buprofezin) for use in rice may be employed. Alternatively insecticides or acaricides specific for particular insect species/stages may also be included in the compositions (for example acaricidal ovo-larvicides, such as clofentezine, flubenzimine, hexythiazox or tetradifon; acaricidal motilicides, such as dicofol or propargite; acaricides, such as bromopropylate or chlorobenzilate; or growth regulators, such as hydramethylnon, cyromazine, methoprene, chlorfluazuron or diflubenzuron). Examples of fungicidal compounds which may be included in the composition of the invention are (E)-N-methyl-2-[2-(2,5-dimethylphenoxymethyl)phenyl]-2-methoxy- iminoacetamide (SSF-129), 4-bromo-2-cyano-N,N-dimethyl-6-trifluoromethylbenzimidazole- 1 -sulphonamide, α-[N-(3 -chloro-2,6-xylyl)-2-methoxyacetamido] -γ-butyrolactone, 4-chloro- 2-cyano-N,N-dimethyl-5-/?-tolylimidazole-l -sulfonamide (IKF-916, cyamidazosulfamid), 3-5-dichloro-N-(3-chloro- 1 -ethyl- 1 -methyl-2-oxopropyl)-4-methylbenzamide (RH-7281 , zoxamide), N-allyl-4,5,-dimethyl-2-trimethylsilylthiophene-3-carboxamide (MOΝ65500), N-( 1 -cyano- 1 ,2-dimethylpropyl)-2-(2,4-dichlorophenoxy)propionamide (AC382042), N-(2-methoxy-5-pyridyl)-cyclopropane carboxamide, acibenzolar (CGA245704), alanycarb, aldimorph, anilazine, azaconazole, azoxystrobin, benalaxyl, benomyl, biloxazol, bitertanol, blasticidin S, bromuconazole, bupirimate, captafol, captan, carbendazim, carbendazim chlorhydrate, carboxin, carpropamid, carvone, CGA41396, CGA41397, chinomethionate, chlorothalonil, chlorozolinate, clozylacon, copper containing compounds such as copper oxychloride, copper oxyquinolate, copper sulphate, copper tallate and Bordeaux mixture, cymoxanil, cyproconazole, cyprodinil, debacarb, di-2-pyridyl disulphide 1,1 '-dioxide, dichlofluanid, diclomezine, dicloran, diethofencarb, difenoconazole, difenzoquat, diflumetorim, O,O-di- 5o-propyl-S-benzyl thiophosphate, dimefluazole, dimetconazole, dimethomorph, dimethirimol, diniconazole, dinocap, dithianon, dodecyl dimethyl ammonium chloride, dodemorph, dodine, doguadine, edifenphos, epoxiconazole, ethirimol, ethyl(Z)-N-benzyl-N([methyl(methyl-thioethylideneaminooxycarbonyl)amino]thio)-
-β-alaninate, etridiazole, famoxadone, fenamidone (RPA407213), fenarimol, fenbuconazole, fenfuram, fenhexamid (KBR2738), fenpiclonil, fenpropidin, fenpropimorph, fentin acetate, fentin hydroxide, ferbam, ferimzone, fluazinam, fludioxonil, flumetover, fluoroimide, fluquinconazole, flusilazole, flutolanil, flutriafol, folpet, fuberidazole, furalaxyl, furametpyr, guazatine, hexaconazole, hydroxyisoxazole, hymexazole, imazalil, imibenconazole, iminoctadine, iminoctadine triacetate, ipconazole, iprobenfos, iprodione, iprovalicarb (SZX0722), isopropanyl butyl carbamate, isoprothiolane, kasugamycin, kresoxim-methyl, LY186054, LY211795, LY248908, mancozeb, maneb, mefenoxam, mepanipyrim, mepronil, metalaxyl, metconazole, metiram, metiram-zinc, metominostrobin, myclobutanil, neoasozin, nickel dimethyldithiocarbamate, nitrothal-z.sOpropyl, nuarimol, ofurace, organomercury compounds, oxadixyl, oxasulfuron, oxolinic acid, oxpoconazole, oxycarboxin, pefurazoate, penconazole, pencycuron, phenazin oxide, phosetyl-Al, phosphorus acids, phthalide, picoxystrobin (ZA1963), polyoxin D, polyram, probenazole, prochloraz, procymidone, propamocarb, propiconazole, propineb, propionic acid, pyrazophos, pyrifenox, pyrimethanil, pyroquilon, pyroxyfur, pyrrolnitrin, quaternary ammonium compounds, quinomethionate, quinoxyfen, quintozene, sipconazole (F-155), sodium pentachlorophenate, spiroxamine, streptomycin, sulphur, tebuconazole, tecloftalam, tecnazene, tetraconazole, thiabendazole, thifluzamid, 2-(thiocyanomethylthio)benzothiazole, thiophanate-methyl, thiram, timibenconazole, tolclofos-methyl, tolylfluanid, triadimefon, triadimenol, triazbutil, triazoxide, tricyclazole, tridemorph, trifloxystrobin (CGA279202), triforine, triflumizole, triticonazole, validamycin A, vapam, vinclozolin, zineb and ziram. The compounds of formula (I) may be mixed with soil, peat or other rooting media for the protection of plants against seed-borne, soil-borne or foliar fungal diseases.
Examples of suitable synergists for use in the compositions include piperonyl butoxide, sesamex, safroxan and dodecyl imidazole.
Suitable herbicides and plant-growth regulators for inclusion in the compositions will depend upon the intended target and the effect required.
An example of a rice selective herbicide which may be included is propanil. An example of a plant growth regulator for use in cotton is PDC™.
Some mixtures may comprise active ingredients which have significantly different physical, chemical or biological properties such that they do not easily lend themselves to the same conventional formulation type. In these circumstances other formulation types may be prepared. For example, where one active ingredient is a water insoluble solid and the other a water insoluble liquid, it may nevertheless be possible to disperse each active ingredient in the same continuous aqueous phase by dispersing the solid active ingredient as a suspension (using a preparation analogous to that of an SC) but dispersing the liquid active ingredient as an emulsion (using a preparation analogous to that of an EW). The resultant composition is a suspoemulsion (SE) formulation.
The invention is illustrated by the following Examples:
EXAMPLE 1 This Example illustrates the preparation of N-(4-chloro-3-methylisothiazol-5-yl)-
[2-(2,2-dimethylpropyl)benzoxazol-5-yl]acetamide. Step 1 Preparation of 5-amino-4-chloro-3-methylisothiazole. 5-Amino-3-methylisothiazole hydrochloride (250g, 1.66 mole) was suspended in dichloromethane(1.251) and stirred at 8°C. Sulfuryl chloride(146.8ml, 1.83 mole) was added dropwise over lhour and during this addition the temperature of the reaction mixture was maintained between 10 and 15°C. As the sulfuryl chloride was added the suspended particles dissolved and a dark oil began to fall out of solution. The resultant two-phase mixture was stirred at 10°C for 15minutes. The mixture was cooled to below 10°C and quenched by careful addition of aqueous potassium carbonate solution (367.3g, 2.66 mole, of potassium carbonate in 11 of water). The two phases were separated and the aqueous layer extracted with dichloromethane (600ml+400ml). The combined organic layers were dried over anhydrous magnesium sulfate, filtered and the filtrate was concentrated in vacuo. The residue was slurried in hexane (~500ml) for lhour, filtered and dried to give 5-amino-4- chloro-3-methylisothiazole as a red-brown-solid (228.7g, 93%), m.p. 69-71°C.
1H NMR (CDC13) δ: 2.3 (3H,s); 4.6(2H, bs)ppm. Step 2 Preparation of methyl (4-hydroxyphenyl)acetate.
Hydrogen chloride was bubbled through a solution of (4-hydroxyphenyl) acetic acid (25g , O.lόmole) in methanol (100ml) at room temperature. An exotherm resulted in the solution refluxing for about lOminutes. The mixture was allowed to cool to room temperature and the solvent was evaporated in vacuo to afford methyl (4-hydroxyphenyl) acetate as a yellow oil (27.5g) which crystallised on seeding, m.p. 46-52°C.
1H NMR (CDCI3) δ: 3.57(2H,s); 3.71(3H,s); 6.0(lH,b); 6.76 (2H,m); 7.10(2H,m)ppm. Step 3 Preparation of methyl (4-hydroxy-3-nitrophenyI)acetate. Nitric acid (69% by weight, 16M, 20ml) was added dropwise to a solution of methyl
(4-hydroxyphenyl)acetate [from step 2] (50.0g, 0.3mole) in acetic acid (500ml), maintaining the temperature of the reaction below 15°C by external cooling. (An induction period was observed for this reaction.) Once gas chromatographic analysis had confirmed that the reaction was complete, the mixture was carefully quenched into water (21) with vigorous stirring. An emulsion formed which subsequently crystallised. After filtration, washing with water and drying, the desired product was obtained as a yellow powder. 1H NMR (CDCI3) δ: 3.63(2H,s); 3.72(3H,s); 7.14(lH,d); 7.52(lH,dd); 8.02(lH,d); 10.5(lH,s)ρpm. Step 4 Preparation of methyl (3-amino-4-hydroxyphenyl)acetate. Methyl (4-hydroxy-3-nitrophenyl)acetate [from step 3] (48.9g, 0.23mole) and 5% palladium on carbon were suspended in methanol and the resulting mixture was hydrogenated until all the starting material had been consumed. The reaction mixture was filtered to remove the catalyst and the filter-cake was washed with methanol. The combined filtrate and washings were concentrated in vacuo, affording methyl (3-amino-4- hydroxyphenyl)acetate as a solid (41. Og).
1H NMR (d6-DMSO) δ: 3.51(2H,s); 4.45(2H,b); 6.20(lH,dd); 6.40(lH,d); 6.49(lH,d); 8.87(lH,b)ppm. Step 5 Preparation of methyl [3-(2,2-dimethylpropionamido)-4-hydroxyphenyl]acetate._ Sodium hydrogen carbonate (19g, 0.23 moi) was suspended in 1,2-dimethoxyethane
(180ml), and methyl (3-amino-4-hydroxyphenyl)acetate [from step 4] (26.3g, 0.145mole) was added. To this mixture was added, dropwise, a solution of tert-butylacetyl chloride in 1,2-dimethoxyethane (45ml), over 2hours. Once the addition was complete, the mixture was stirred at room temperature for lhour. The mixture was filtered, the inorganic solid washed with ethyl acetate (3x50ml) and the filtrate and washings were combined and concentrated. Trituration of the product with hexane gave methyl [3-(2,2-dimethylpropionamido)-4- hydroxyphenyl] acetate (40.1g) as an off-white solid, m.p. 112 - 113°C.
1H NMR (CDCI3) δ: l.l(9H,s); 2.30(2H,s); 3.51(2H,s); 3.70(3H,s); 6.9-7.0(3H,m); 7.55(lH,b); 8.85(lH,b)ppm. Step 6
Preparation of methyl [(2,2-dimethyIpropyl)benzoxazol-5-yl]acetate. ra-Toluenesulphonic acid (1.5g) in toluene (120ml) was stirred and heated to reflux with a Dean & Stark™ assembly fitted to remove water. After lhour at reflux the solution was cooled to ~80°C and methyl [3-(2,2-dimethylpropionamido)-4- hydroxyphenyl] acetate [from step 5] (20.0g, 0.07mole) was added portionwise. The reaction mixture was then heated at reflux for όhours, cooled, diluted with hexane (200ml) and filtered through a plug of silica gel, eluting with ethyl acetate. The filtrate was evaporated in vacuo to give methyl [(2,2-dimethylpropyl)benzoxazol-5yl]acetate (17.5 g) as an oil.
1H NMR (CDC13) δ: l.l(9H,s); 2.8(2H,s); 3.7(3H,s); 3.74(2H,s); 7.4(3H,m)ppm. Step 7 Preparation of [(2,2-dimethylpropyl)benzoxazol-5-yl]acetic acid.
Methyl [(2,2-dimethylpropyl)benzoxazol-5-yl]acetate [from step 6] (5.00g, 0.0185mole) was dissolved in methanol (5ml) and then a solution of sodium hydroxide (0.8 lg, 0.0204mole) in water (5ml) was added slowly over 20minutes, maintaining the temperature below 25°C by external cooling. Once the addition was complete, the mixture was allowed to stir at room temperature for lhour. The reaction mixture was poured slowly into water (50ml) and concentrated hydrochloride acid was added until the pH of the mixture was below pH6. The mixture was stirred for lhour then filtered and the solid was washed thoroughly with water and dried. Trituration with hexane gave [(2,2-dimethylpropyl)- benzoxazol-5yl]acetic acid (4.51g) as a white solid, m.p. 108-109°C. 1H NMR (CDCI3) δ: 1.05(9H,s); 2.80(2H,s); 3.77(2H,s); 7.42(3H,m)ppm.
Step 8
Preparation of N-(4-chloro-3-methylisothiazol-5-yl)-[2-(2,2-dimethylpropyl)- benzoxazol-5-yl]acetamide.
[2-(2,2-Dimethylpropyl)benzoxazol-5-yl]acetic acid [from step 7] (0.800g, 0.003mole) was suspended in dichloromethane (10ml) and N,N-dimethylformamide (one drop) and oxalyl chloride (0.45 lg, 0.004mole) were added sequentially. The mixture was stirred for 2hour and then the solvent was removed in vacuo. The residue was taken up in xylene (10ml), 5-amino-4-chloro-3-methylisothiazole [from step 1] (0.829g, 0.006mole) was added and then the mixture was heated under reflux for 2hours. The mixture was cooled to room temperature, diluted with ethyl acetate and washed with brine. The organic solution was dried over anhydrous magnesium sulfate, filtered and the filtrate was evaporated in vacuo. The residue was further purified by flash column chromatography on silica gel, eluting with a 2:1 mixture of hexane: ethyl acetate, to give Ν-(4-chloro-3-methylisothiazol-5- yl)-[2-(2,2-dimethylpropyl)benzoxazol-5-yl]acetamide (0.325g) as a pale orange solid, m.p. 144-145°C.
'H NMR (CDCI3) δ: l.l(9H,s); 2.35(3H,s); 2.85(2H,s); 3.95(2H,s); 7.25(lH,dd); 7.55(lH,d); 7.65(lH,d); 8.1(lH,b)ppm. EXAMPLE 2 This Example illustrates the preparation of Compound No. 7 of Table No. 11. N-(4-Chloro-3-methylisothiazol-5-yl)-(2-[2,2-dimethylpropyl]benzoxazol-5- yl)acetamide [prepared as in Example 1] (0.38g) in dry NN-dimethylformamide (3ml) under an atmosphere of nitrogen was stirred at ambient temperature then sodium hydride (0.200g, 80% dispersion in mineral oil) was added. The mixture was stirred for 15minutes then chloromethyl pivalate (0.166g) was added. The mixture was heated to 80-85°C for 3hours, further sodium hydride (0.1 OOg, 80% dispersion in mineral oil ) was added, the mixture was heated for a further 3hours and then cooled to ambient temperature. The solution was diluted with water (50ml), acidified with dilute hydrochloric acid to give a fawn solid which was filtered from solution and then sucked to dryness. The solid was fractionated by HPLC (silica, hexane/ethyl acetate at 5:1 by volume) to give the required product as a colourless solid (0.050g).
EXAMPLE 3 This Example illustrates the preparation of Compound No. 7 of Table No. 22.
To a stirred solution of N-(4-chloro-3-methylisothiazol-5-yl)-(2-[2,2-dimethylpropyl] benzoxazol-5-yl)acetamide (0.2 lg) [prepared as in Example 1] in dry NN-dimethylformamide (2.5ml) under an atmosphere of nitrogen at ambient temperature was added sodium hydride (0.2 lg, 80% dispersion in mineral oil). The mixture was stirred for 0.5hour then 1-methylethylsulfenyl chloride (0.078g) was added dropwise. The mixture was stirred for 2hours then the solvent was evaporated under reduced pressure. The residue was fractionated by chromatography (silica, hexane/ethyl acetate 2: 1 by volume) to give the required product (0.021g), as a pale yellow gum.
EXAMPLE 4 This Example illustrates the preparation of Compound No. 7 of Table No. 10.
To a stirred solution of N-(4-chloro-3-methylisothiazol-5-yl)-(2-[2,2-dimethylpropyl] benzoxazol-5-yl)acetamide (0.25g) [prepared as in Example 1] in dry NN-dimethylformamide (2.5ml) under an atmosphere of nitrogen at ambient temperature was added sodium hydride (0.2 lg, 80% dispersion in mineral oil). The mixture was stirred for 0.2hour, morpholine sulfenyl chloride [ref. EP 216423] (0.1 lg) was added dropwise over 0.2hour and then the mixture was stirred for a further 4.5hours. The solvent was evaporated under reduced pressure and the residue was fractionated by chromatography (silica, hexane/ethyl acetate 2: 1 by volume) to give the required product, 0.057g, as a yellow solid.
EXAMPLE 5 This Example illustrates the preparation of Compound No. 7 of Table No. 14. N-(4-Chloro-3-methylisothiazol-5-yl)-[2-(2,2-dimethylpropyl)-benzoxazol-5- yl]acetamide (2.5g, 0.0066mole) [prepared as in Example 1] and NN-dimethylformamide dimethylacetal (1.5g, 0.013 mole) were added to a mixture of NN-dimethylformamide (5ml) and toluene (20ml) and the resulting mixture was heated to 110°C for 4hours. The mixture was cooled to room temperature and the solvent was evaporated in vacuo. The residue was taken up in ethyl acetate and washed sequentially with brine and water, dried over anhydrous magnesium sulfate, filtered and the filtrate evaporated in vacuo. The residue was further purified by flash column chromatography, eluting with ethyl acetate : hexane at 1:1 by volume. Further flash column chromatography, eluting with ethyl acetate : dichloromethane at 1:9 by volume gave N-(4-chloro-3-methylisothiazol-5-yl)-α-[(dimethylamino)methylene]- [2-(2,2-dimethylpropyl)benzoxazol-5-yl]acetamide (0.78g) as a single geometrical isomer.
EXAMPLE 6 This Example illustrates the preparation of Compound No. 7 of Table No. 15. A mixture of N-(4-chloro-3-methylisothiazol-5-yl)-α-[(dimethylamino)methylene]- [2-(2,2-dimethylpropyl)benzoxazol-5-yl]acetamide (0.20g, 0.00046mole) [from Example 5] and ethylamine hydrochloride (0.0225g, 0.0028mole) in tetrahydrofuran (4ml) and water (lml) was heated for 24hours at 60°C. The mixture was cooled to room temperature, the solvent was evaporated in vacuo and the residue partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution. The organic extract was dried over anhydrous magnesium sulfate, filtered and the filtrate was evaporated in vacuo. Further purification by flash column chromatography, eluting with ethyl acetate : hexane at 2:3 by volume, gave N-(4-chloro-3-methylisothiazol-5-yl)-α-[(ethylamino)methylene]-[2-(2,2- dimeth-ylpropyl)benzoxazol-5-yl]acetamide as a colourless solid (0.17g). Analysis by 1H ΝMR showed the product comprised a mixture of E- and Z-isomers.
By similar procedures, Compound No. 7 of Table No. 16 (E- and Z-isomers), Compound No. 7 of Table No. 17 and Compound No. 7 of Table No. 19 (E- and Z-isomers) were each made individually. EXAMPLE 7 This Example illustrates the preparation of Compound No. 7 of Table No. 1. Step l Preparation of methyl 2-[2-(2,2-dimethylpropyl)benzoxazol-5-yl]propionate. Methyl [2-(2,2-dimethylpropyl)benzoxazol-5-yl]acetate (8.0g, 0.031mole) [prepared as in Example 1, step 6] was dissolved in dry tetrahydrofuran (200ml) and the solution was cooled to -78°C. Lithium diisopropylamide (2.0 molar solution in tetrahydrofuran / ethylbenzene / heptane, 15.4ml, 0.031 mole) was added dropwise, maintaining the reaction temperature below -60°C, and once the addition was complete the mixture was stirred for lhour. Methyl iodide (38.4g, 0.27mole) was added dropwise, at such a rate that the reaction temperature was maintained below -60°C, and once the addition was complete the mixture was stirred for lhour. The cooling bath was removed and the mixture was stirred for 3hours, allowed to warm to room temperature, at which it was kept overnight. The reaction was quenched with water, acidified with dilute aqueous hydrochloric acid and extracted with ethyl acetate. The organic extract was dried over anhydrous magnesium sulfate, filtered and the filtrate evaporated in vacuo. Further purification by flash column chromatography, eluting with ethyl acetate : hexane at 1:7 by volume gave methyl 2-[2-(2,2-dimethylpropyl) benzoxazol-5-yl]propionate (6.6 g).
1H NMR (CDC13) δ: 1.08(9H,s); 1.54(3H,d); 2.81(2H,s); 3.6 (3H,s); 3.84(lH,q); 7.26(lH,dd); 7.43(lH,d); 7.62(lH,d)ppm. Step 2
Preparation of N-(4-Chloro-3-methylisothiazol-5-yl)-2-[2-(2,2-dimethylpropyl)- benzoxazol-5-yl]propionamide.
Lithium diisopropylamide (2.0 molar solution in tetrahydrofuran / ethylbenzene / heptane, 1.46ml, 0.0029mole) was added dropwise to a chilled solution of 5-amino-4-chloro- 3-methylisothiazole (0.44 g, 0.0029mole) [preparation as in Example 1, Step 1] in tetrahydrofuran (20ml) and the solution was stirred at 0°C for lhour. A solution of methyl 2-[2-(2,2-dimethylpropyl)benzoxazol-5-yl]propionate (0.80g, 0.0029mole) [from previous step] in tetrahydrofuran (5ml) was added dropwise and once the addition was complete the mixture was stirred at 0°C for 30minutes and then at room temperature overnight. The mixture was quenched with water, acidified with aqueous ammonium chloride solution and extracted with ethyl acetate. The organic extract was dried over anhydrous magnesium sulfate, filtered and the filtrate evaporated in vacuo. Further purification by flash column chromatography, eluting with ethyl acetate : hexane at 1: 4 by volume gave N-(4-chloro-3- methylisothiazol-5-yl)-2-[2-(2,2-dimethylpropyl)benzoxazol-5-yl]propionamide as a colourless solid. By similar procedures, Compound No. 7 of Table No. 3, Compound No. 7 of Table
No. 4 and Compound No. 7 of Table No. 18 were each made individually.
EXAMPLE 8 This Example illustrates the preparation of Compound No. 7 of Table No. 5. Step l Preparation of methyl [2-(2,2-dimethylpropyl)benzoxazol-5-yI]fluoroacetate.
A solution of lithium diisopropylamide (2.0M solution in tetrahydrofuran /ethyl benzene / heptane, 3.85ml, 0.0077mol) was added dropwise to a solution of methyl [2-(2,2-dimethylpropyl)benzoxazol-5-yl]acetate (2.0g, 0.0077mol) in tetrahydrofuran (40ml) at -78°C under a nitrogen atmosphere and the mixture was stirred at -78°C for lhour. A solution of N-fluorobenzenesulfonimide (2.42g, 0.0077mol) in tetrahydrofuran (10ml) was added dropwise and the mixture was stirred at -70°C for a further lhour. The cooling bath was removed and the mixture allowed to warm to room temperature over a period of 20hours. The reaction mixture was diluted with water, acidified with dilute aqueous hydrochloric acid and extracted with ethyl acetate. The organic extracts were combined, washed with water, dried over anhydrous magnesium sulfate, filtered and the filtrate was evaporated in vacuo. The residue was purified by flash column chromatography on silica gel, eluting with ethyl acetate : dichloromethane 5 : 95, and was further purified by column chromatography on silica gel, eluting with ethyl acetate : hexane 1 : 3, to give methyl [2-(2,2-dimethylpropyl)benzoxazol-5-yl]fluoroacetate (1.4g). 1H ΝMR (CDC13) δ: 1.08(s,9H); 2.83(s,2H); 3.79(s,3H); 5.90(d,lH); 7.43(dd,lH);
7.53(d,lH); 7.80(d,lH)ppm. Step 2
5-Amino-4-chloro-3-methylisothiazole (0.4 lg, 0.0028mol) was added to a suspension of sodium methoxide (0.34g, 0.0063mol) in tetrahydrofuran (5ml) and the mixture was stirred at room temperature for 30minutes. A solution of methyl [2-(2,2-dimethylpropyl) benzoxazol-5-yl]fluoroacetate (0.70g, 0.0025mol) in tetrahydrofuran (3ml) was added dropwise and the mixture was stirred at room temperature for 3days. The mixture was diluted with water, neutralised with saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The organic extracts were combined, dried over anhydrous magnesium sulfate, filtered and the filtrate was evaporated in vacuo. The residue was purified by flash column chromatography on silica gel, eluting with ethyl acetate : hexane 1 : 1 , to give the desired product (0.48g).
EXAMPLE 9 This Example illustrates the preparation of Compound No. 8 of Table No. 1. Step l Preparation of methyl 4-methoxyphenylacetate A solution of methyl 4-hydroxyphenylacetate (25.0g, 0.147mol) in tetrahydrofuran
(50ml) was added dropwise to a stirred suspension of sodium hydride (4.45g of an 80% dispersion in oil, 0.147mol) in tetrahydrofuran (150ml) and the mixture was stirred for 90minutes. A solution of methyl iodide (20.9g, 0.47mol) in tetrahydrofuran (50ml) was added dropwise and the mixture was stirred overnight at room temperature. The solvent was removed in vacuo, and the residue was partitioned between water and ethyl acetate. The organic extract was washed with brine, dried over anhydrous magnesium sulfate, filtered and the filtrate was evaporated in vacuo. The residue was purified by chromatography on silica gel, eluting with ethyl acetate : hexane 1 : 9, to give methyl 4-methoxyphenylacetate (22.0g) as a colourless oil. 1H NMR (CDC13) δ: 3.57(s,2H); 3.68(s,3H); 3.8(s,3H); 6.87(m,2H);
7.20(m,2H)ppm. Step 2 Preparation of methyl 2-(4-methoxyphenyl)propionate
A solution of lithium diisopropylamide (2.0M solution in tetrahydrofuran /ethyl benzene / heptane, 34.0ml, 0.0667mol) was added dropwise to a solution of methyl
4-methoxyphenylacetate (12.0g, 0.0667 moi) in tetrahydrofuran (150ml) at -70°C under a nitrogen atmosphere and the mixture was stirred at -70 °C for lhour. A solution of methyl iodide (9.5g, 0.0667mol) in tetrahydrofuran (20ml) was added dropwise and the mixture was stirred at -70°C for a further lhour. The cooling bath was removed and the mixture was allowed to warm to room temperature overnight. The reaction was quenched with water, acidified with dilute aqueous hydrochloric acid and extracted with ethyl acetate. The organic extract was washed with brine, dried over anhydrous magnesium sulfate, filtered and the filtrate was evaporated in vacuo. The residue was purified by flash column chromatography on silica gel, eluting with ethyl acetate : hexane 1 : 9, to give methyl 2-(4-methoxyphenyl) propionate (8.8g) as a colourless oil.
1H NMR (CDC13) δ: 1.48(d,3H); 3.67(s,3H); 3.69(q,lH); 3.79(s,3H); 6.86(m,2H); 7.22(m,2H)ppm. Step 3 Preparation of N-(4-chloro-3-methylisothiazol-5-yl)-2-(4-methoxyphenyl)propionamide
5-Amino-4-chloro-3-methylisothiazole (7.4g, 0.050mol) was added to a suspension of sodium methoxide (6.1g, 0.112mol) in tetrahydrofuran (160ml) and the mixture was stirred at room temperature for 20minutes. A solution of methyl 2-(4-methoxyphenyl) propionate (8.8g, 0.045mol) in tetrahydrofuran (40ml) was added dropwise and the mixture was stirred for 3hours at room temperature. The reaction was quenched with water, acidified with dilute aqueous hydrochloric acid and extracted with ethyl acetate. The organic extract was washed with brine, dried over anhydrous magnesium sulfate, filtered and the filtrate was evaporated in vacuo. The residue was purified by flash column chromatography on silica gel, eluting with ethyl acetate : dichloromethane 2.5 : 97.5, to give N-(4-chloro-3- methylisothiazol-5-yl)-2-(4-methoxyphenyl)propionamide (12.5g) as a colourless solid.
1H ΝMR (CDC13) δ: 1.63(d,3H); 2.35(s,3H); 3.83(s,3H); 3.83(q,lH); 6.95(m,2H); 7.28(m,2H); 7.98(b,lH)ppm. Step 4
Preparation of N-(4-chloro-3-methylisothiazol-5-yl)-2-(4-hydroxyphenyl)propionamide
Boron tribromide (1.0 M solution in dichloromethane, 110ml, O.l lmol) was added dropwise to a stirred solution of N-(4-chloro-3-methylisothiazol-5-yl)-2-(4-methoxyphenyl)- propionamide (12.5 g, 0.040 moi) in dichloromethane (200 ml) at -70°C. Once the addition was complete the cooling bath was removed and the mixture was allowed to warm to room temperature overnight. The mixture was cooled to 0°C and excess methanol added cautiously. The solvent was evaporated in vacuo, and the residue was partitioned between ethyl acetate and brine. The organic layer was dried over anhydrous magnesium sulfate, filtered and the filtrate was evaporated in vacuo to give N-(4-chloro-3-methylisothiazol-5-yl)- 2-(4-hydroxyphenyl)propionamide (11.8g), which was used without further purification in the next step. 1H NMR (CDCI3) δ: 1.62(d,3H); 2.38(s,3H); 3.83(q,lH); 5.51(b,lH); 6.90(m,2H);
7.23(m,2H); 7.98(b,lH)ppm.
Step 5
Preparation of N-(4-chloro-3-methylisothiazol-5-yl)-2-(4-hydroxy-3-nitrophenyl)- propionamide
Ferric nitrate nonahydrate (16.16g, 0.04mol) was added to a solution of N-(4-chloro-
3-methylisothiazol-5-yl)-2-(4-hydroxyphenyl)propionamide (11.8 g, 0.04 moi) in ethanol
(100 ml) and the mixture was stirred and warmed at 50 °C for 2V2hours. The mixture was cooled to room temperature and the solvent removed in vacuo. The residue was partitioned between 2M aqueous hydrochloric acid and ethyl acetate and the organic phase was dried over anhydrous magnesium sulfate, filtered and the filtrate was evaporated in vacuo.
Purification by flash column chromatography on silica gel, eluting with ethyl acetate : dichloromethane 5 : 95, gave N-(4-chloro-3-methylisothiazol-5-yl)-2-(4-hydroxy-3- nitrophenyl)propionamide (l l.lg) as a yellow solid. 1H ΝMR (CDCI3) δ: 1.66(d,3H); 2.38(s,3H); 3.93(q,lH); 7.21(d,lH); 7.65(dd,lH);
8.10(d,lH); 8.41(b,lH); 10.55(s,lH)ppm.
Step 6
Preparation of N-(4-chloro-3-methylisothiazol-5-yl)-2-(3-amino-4-hydroxyphenyl)- propionamide A mixture of N-(4-chloro-3-methylisothiazol-5-yl)-2-(4-hydroxy-3- nitrophenyl)propionamide (11.0 g, 0.0322 moi) and 3% platinum on carbon in
NN-dimethylformamide (100 ml) was hydrogenated at 15bar (15xl05Νm~2) for 6 hours at room temperature. The catalyst was removed by filtration and the filtrate evaporated in vacuo to give N-(4-chloro-3-methylisothiazol-5-yl)-2-(3-amino-4- hydroxyphenyl)propionamide (9.0g) as an off-white solid, m.p.222-223°C.
1H ΝMR ( -DMSO / CDCI3) δ: 1.08(d,3H); 1.96(s,3H); 2.90(b,2H); 3.62(q,lH);
6.14(dd,lH); 6.30(m,2H); 8.33(b,lH); 10.1(b,lH)ppm.
Step 7
Preparation of N-(4-chloro-3-methylisothiazol-5-yl)-2-[4-hydroxy-3-(3,3,3- trifluoropropionamido)phenyl]propionamide
A mixture of N-(4-chloro-3-methylisothiazol-5-yl)-2-(3-amino-4-hydroxyphenyl)- propionamide (0.65g, 0.002mol), 3,3,3-trifluoropropionic acid (0.267g, 0.002mol) and l-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.40g, 0.002mol) was stirred in NN-dimethylacetamide (8ml) at room temperature for 7hours and was then allowed to stand at room temperature overnight. The reaction was quenched with water and extracted with ethyl acetate. The organic extract was washed with water, dried over anhydrous magnesium sulfate, filtered and the filtrate was evaporated in vacuo. The residue was purified by flash column chromatography on silica gel, eluting with ethyl acetate : hexane 1:1, to give N-(4-chloro-3-methylisothiazol-5-yl)-2-[4-hydroxy-3-(3,3,3- trifluoropropionamido)phenyl]propionamide ( 0.62g) as a white solid.
1H ΝMR (CDC13) δ: 1.54(d,3H); 2.37(d,3H); 3.36(q,2H); 3.96 (q,lH); 6.98(d,lH); 7.04(dd,lH); 7.86(d,lH)ppm. Step 8
A mixture of N-(4-chloro-3-methylisothiazol-5-yl)-2-[4-hydroxy-3-(3,3,3- trifluoropropionamido)phenyl]propionamide (0.58 g, 0.0014 moi) and pαra-toluenesulfonic acid (0.02 g) in 1,1,2,2-tetrachloroethane was heated at reflux for 26 hours. The mixture was cooled to room temperature and the solvent evaporated in vacuo. The residue was purified by flash column chromatography on silica gel, eluting with ethyl acetate : hexane 35 : 65, to give the desired product (0.255 g) as a pale yellow solid.
EXAMPLE 10 This Example illustrates the preparation of Compound No. 78 of Table No. 1. A solution of N,O-bis(trimethylsilyl)acetamide (0.141g, 0.0007mol) in dichloromethane (1ml) was added to a solution of N-(4-chloro-3-methylisothiazol-5-yl)-2-[2- (2,2,2-trifluoroethyl)benzoxazol-5-yl]propionamide (0.236g, O.OOOόmol) in dichloromethane (4ml) and the mixture was stirred at room temperature for 15minutes. Chloromethylethyl ether (0.1 lg, O.OOlmol) was added and stirring was continued for 24hours. Further quantities of N,O-bis(trimethylsilyl)acetamide (0.141g, 0.0007mol) and chloromethylethyl ether (0.1 lg, O.OOlmol) were added and stirring was continued for 6hours. The reaction was quenched with saturated aqueous sodium bicarbonate solution and extracted with ethyl acetate. The organic extract was washed with brine, dried over anhydrous magnesium sulfate, filtered and the filtrate was evaporated in vacuo. Purification by flash column chromatography on silica gel, eluting initially with ethyl acetate : hexane 1 : 4 and then with ethyl acetate : hexane 45 : 55, gave the desired product (0.04 g) as an oil. EX AMPLE 11 This Example illustrates the preparation of Compound No. 10 of Table No. 1. Step l Preparation of methyl (3-heptafluorobutyramido-4-hydroxyphenyl)acetate Sodium bicarbonate (51g, 0.607mol) was suspended in 1,2-dimethoxyethane (180ml), and methyl (3-amino-4-hydroxyphenyl)acetate (58.26g, 0.32mol) was added, followed by a further quantity of 1,2-dimethoxyethane (75ml). To this mixture was added, dropwise, a solution of heptafluorobutyryl chloride (112.5g, 0.48mol) in 1,2-dimethoxyethane (140ml), at such a rate that the reaction temperature was maintained at 19-20°C. Once the addition was complete, the mixture was stirred at room temperature for lVihours. The reaction mixture was filtered and the solid was taken up in ethyl acetate and washed with saturated aqueous bicarbonate solution and brine. The organic phase was dried over anhydrous magnesium sulfate, filtered and the filtrate was evaporated in vacuo. The residue was taken up in acetone (450ml) and water (450ml) was added. The mixture was stirred for lV-ihours, during which time an oil separated. The aqueous acetone was decanted and a further quantity (250ml) of water was added to the oil. The mixture was stirred for lhour, during which time the desired product crystallised; it was collected by filtration, washed with water and dried to give methyl (3-heptafluorobutyramido-4-hydroxyphenyl)acetate (87. Og).
1H NMR ( -DMSO / CDC13) δ: 3.56(s,2H); 3.69(s,3H); 6.95(m,2H); 8.1(d,lH); 8.83(b,lH); 9.51(s,lH)ppm. Step 2 Preparation of methyl (2-heptafluoropropylbenzoxazol-5-yl)acetate
A mixture of methyl (3-heptafluorobutyramido-4-hydroxyphenyl)acetate (20.0g, 0.053mol) and pαr -toluenesulfonic acid (1.71g) in toluene (150ml) was heated at reflux (a Dean & Stark™ assembly was fitted to remove water) for 24hours. The mixture was cooled to room temperature and the mixture was diluted with ethyl acetate (150ml). The mixture was washed with saturated aqueous sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate, filtered and the filtrate was evaporated in vacuo. The residue was purified by column chromatography on silica gel, eluting with dichloromethane to give methyl (2-heptafluoropropylbenzoxazol-5-yl)acetate (12.9g) as an off-white solid.
Η NMR (CDC13) δ: 3.71(s,3H); 3.8(s,2H); 7.48(dd,lH); 7.63(d,lH); 7.8(d,lH)ppm. Step 3
Preparation of methyl 2-(2-heptafluoropropylbenzoxazol-5-yl)propionate
A solution of lithium diisopropylamide (2.0M solution in tetrahydrofuran /ethyl benzene / heptane, 15.32ml, 0.0306mol) was added dropwise to a solution of methyl (2-heptafluoropropylbenzoxazol-5-yl)acetate (11.Og, 0.0306mol) in tetrahydrofuran (175ml) at -70°C under a nitrogen atmosphere and the mixture was stirred at -70°C for lhour. A solution of methyl iodide (39. lg, 0.275mol) in tetrahydrofuran (25ml) was added dropwise and the mixture was stirred at -70°C for a further lhour. The cooling bath was removed and the mixture was allowed to warm to room temperature over a period of 3hours. The reaction was quenched with water, acidified with dilute aqueous hydrochloric acid and extracted with ethyl acetate. The organic extract was washed with brine, dried over anhydrous magnesium sulfate, filtered and the filtrate was evaporated in vacuo to give methyl 2-(2-heptafluoropropylbenzoxazol-5-yl)propionate (11.6g) as a reddish oil, which was used without further purification in the next step. 1H NMR (CDC13) δ: 1.56(d,3H); 3.67(s,3H); 3.9(q,lH); 7.5(dd,lH); 7.62(d,lH);
7.82(d,lH)ppm. Step 4 Preparation of 2-(2-heptafluoropropylbenzoxazol-5-yl)propionic acid
A mixture of methyl 2-(2-heptafluoropropylbenzoxazol-5-yl)propionate (11.6g, 0.031 lmol), hexamethyldisilane (6.81g, 0.047mol) and iodine (11.85g, 0.047mol) was stirred in refluxing toluene (110ml) for 6 hours. The mixture was cooled to room temperature, diluted with ethyl acetate and washed sequentially with water, saturated aqueous sodium thiosulfate solution and brine. The organic phase was dried over anhydrous magnesium sulfate, filtered and the filtrate was evaporated in vacuo. The residue was purified by column chromatography on silica gel, eluting initially with dichloromethane and then with ethyl acetate : dichloromethane 1: 4, to give 2-(2-heptafluoropropylbenzoxazol-5-yl)propionic acid (6.3g).
1H NMR (CDCI3) δ: 1.6(d,3H); 3.9(q,lH); 7.52(dd,lH); 7.64(d,lH); 7.87(d,lH)ppm. Step 5 Oxalyl chloride (4.46g, 0.035mol) was added dropwise to a solution of
2-(2-heptafluoropropylbenzoxazol-5-yl)propionic acid (6.3g, 0.0176mol) in dichloromethane (60ml) and the mixture was stirred at room temperature overnight. The solvent was evaporated in vacuo and the residue was dissolved in 1,2-dichloroethane (70ml) and warmed to reflux. A solution of 5-amino-4-chloro-3-methylisothiazole (3.12g, 0.021mol) in 1,2-dichloroethane (30ml) was added dropwise over 30minutes to the refluxing mixture and the mixture was heated at reflux for a further 5hours. The mixture was cooled to room temperature and the solid was collected by filtration, washed with 1 ,2-dichloroethane and diethyl ether and dried to give the desired product (6.4 g). Resolution of enantiomers of Compound 10 of Table 1.
Racemic N-(4-chloro-3-methylisothiazol-5-yl)-2-[(2-heptafluoropropyl)benzoxazol- 5-yl]propionamide (0.05 g) was dissolved in 60ml of 2-methylpentane : propan-2-ol 90:10 and loaded onto a Chiralcel OT™ column (0.46cm x 25cm) in aliquots of cα.0.008ml. The chromatographic system was equilibrated and run using a mobile phase of 2-methylpentane : propan-2-ol (95:5) at 2ml min and fractions were collected and assesed by analytical HPLC under the conditions described immediately above.
Enantiomer A (0.029g) eluted first; enantiomer B (0.016g) eluted second. Fractions containing mixtures of enantiomers were discarded.
EXAMPLE 12 This Example illustrates the preparation of Compound No. 80 of Table No. 1. A solution of N,0-bis(trimethylsilyl)acetamide (0.50 g, 0.00245 moi) was added to a solution of N-(4-chloro-3-methylisothiazol-5-yl)-2-[2-heptafluoropropylbenzoxazol-5- yl]propionamide (l.OOg, 0.002mol) in dichloromethane (10ml) and the mixture was stirred at room temperature for 15minutes. Chloromethylethyl ether (0.386g, 0.004mol) was added and stirring was continued for 48hours. The reaction mixture was diluted with dichloromethane and poured into water. The organic phase was washed with brine, dried over anhydrous magnesium sulfate, filtered and the filtrate was evaporated in vacuo. The residue was purified by flash column chromatography on silica gel, eluting initially with ethyl acetate : hexane 4 : 1 and subsequently with a gradient elution to ethyl acetate : hexane 1 : 1, to give the desired product (0.057 g).
EXAMPLE 13 This Example illustrates the preparation of Compound No. 7 of Table No. 82. Step 1
Preparation of N-(2-hydroxy-5-bromophenyl)-3,3-dimethylbutyramide A solution of tert-butylacetyl chloride (2.7g, 0.020mol) in diethyl ether (20ml) was added dropwise to a solution of 2-amino-4-bromophenol (3.8g, 0.020mol) and triethylamine (2.1g, 0.020mol) in diethyl ether (160ml) and the mixture was stirred at room temperature for 3hours. The mixture was filtered and the filtrate was evaporated in vacuo. Purification by flash column chromatography on silica gel, eluting initially with ethyl acetate : dichloromethane 1.5 : 98.5 and then with ethyl acetate : dichloromethane 2.5 : 97.5, gave N-(2-hydroxy-5-bromophenyl)-3,3-dimethylbutyramide (1.8g).
1H ΝMR (CDC13) δ: 1.12(s,9H); 2.32(s,2H); 6.90(d,lH); 7.17(d,lH); 7.22(dd,lH); 7.32(b,lH); 8.69(s,lH)ppm. Step 2
Preparation of 2-(2,2-dimethylpropyl)-5-bromobenzoxazole
A mixture of N-(2-hydroxy-5-bromophenyl)-3,3-dimethylbutyramide (1.75g, O.OOόmol) and pαrα-toluenesulfonic acid (0.05g) was heated in refluxing 1,1,2,2-tetrachloroethane (40ml) for 24hours. The mixture was cooled to room temperature, the solvent removed in vacuo and the residue purified by flash column chromatography on silica gel, eluting with ethyl acetate : hexane 5 : 95, to give 2-(2,2-dimethylpropyl)-5- bromobenzoxazole (1.38g).
1H ΝMR (CDC13) δ: 1.08(s,9H); 2.22(s,2H); 7.38(d,lH); 7.41(dd,lH); 7.82(d,lH)ppm. Step 3
Preparation of ethyl 3-[2-(2,2-dimethylpropyl)benzoxazol-5-yl]propenoate
A mixture of 2-(2,2-dimethylpropyl)-5-bromobenzoxazole (0.60g, 0.00225mol), ethyl acrylate (1.08g, 0.0108mol), palladium acetate (0.051g, 0.00023mol), tri-o-tolylphosphine (0.135 g,0.0045mol) and NN-diisopropylethylamine (0.585g, 0.0045mol) was heated at 100°C for όhours. The mixture was cooled to room temperature, diluted with water and extracted with ethyl acetate. The organic extracts were dried over anhydrous magnesium sulfate, filtered and the filtrate was evaporated in vacuo. The residue was purified by flash column chromatography on silica gel, eluting with ethyl acetate : dichloromethane 3 : 97, to give ethyl 3-[2-(2,2-dimethylpropyl)benzoxazol-5-yl]propenoate (0.634g). 1H ΝMR (CDCI3) δ: 1.10(s,9H); 1.35(t,3H); 2.83(s,2H); 4.29(q,2H); 6.45(d,lH);
7.50(s,2H); 7.80(d,lH); 7.85(s,lH)ppm. Step 4
Preparation of ethyl 3-[2-(2,2-dimethylpropyl)benzoxazol-5-yl]propanoate
A solution of ethyl 3-[2-(2,2-dimethylpropyl)benzoxazol-5-yl]propenoate (0.500g, 0.00174mol) in ethanol (30ml) was hydrogenated at 4.0bar (4xl05Nm~2) over 5% Pd on C for 4hours at room temperature and then at 5.5bar (5.5xl05Nπ 2) for όhours. The catalyst was removed by filtration and the filtrate was evaporated in vacuo. The residue was purified by flash column chromatography on silica gel, eluting with ethyl acetate : dichloromethane 3:97, to give ethyl 3-[2-(2,2-dimethylpropyl)benzoxazol-5-yl]propanoate (0.465g).
1H NMR (CDC13) δ: 1.08(s,9H); 1.24(t,3H); 2.67(t,2H); 2.80(s,2H); 3.06(t,2H); 4.14(q,2H); 7.14(dd,lH); 7.40(d,lH); 7.51(d,lH)ppm. Step 5
5-Amino-4-chloro-3-methylisothiazole (0.225g, 0.00152mol) was added to a suspension of sodium methoxide (0197g, 0.00365mol) in tetrahydrofuran (8ml) and the mixture was stirred at room temperature for 20minutes. A solution of ethyl 3-[2-(2,2-dimethylpropyl)benzoxazol-5-yl]propanoate (0.400g, 0.00138mol) in tetrahydrofuran (2ml) was added dropwise and the mixture was then stirred at room temperature for 20hours. The mixture was diluted with water, acidified with saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The organic extracts were combined, washed with brine, dried over anhydrous magnesium sulfate, filtered and the filtrate was evaporated in vacuo. The residue was purified by flash column chromatography on silica gel, eluting with ethyl acetate : dichloromethane 15 : 85, to give the desired product (0.49g).
By similar procedures, Compound No. 83 of Table No. 7 and Compound No. 86 of Table No. 7 were each made individually. EXAMPLE 14
This Example illustrates the preparation of Compound No. 86 of Table No. 39. Step l Preparation of methyl 4-fluoro-3-nitrophenylacetate
4-Fluoro-3-nitrophenylacetic acid (31.0g, 0.156mol) was added to a mixture of concentrated sulfuric acid (1 .6ml) and methanol (160ml) and the mixture was stirred for 3days at room temperature. Most of the solvent was removed in vacuo and the residue was partitioned between diethyl ether and water. The organic phase was washed with saturated aqueous sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate, filtered and the filtrate was evaporated in vacuo to give methyl 4-fluoro-3 -nitrophenylacetate (27.2 g) as a yellow oil.
1H NMR (CDC13) δ 3.72(s,2H); 3.75(s,3H); 7.27(dd,lH); 7.58(m,lH); 8.01(dd,lH)ppm. Step 2 Preparation of methyl 3-amino-4-fluorophenylacetate
Iron powder (8.1g) was added to a solution of methyl 4-fluoro-3-nitrophenylacetate (27.24g, 0.128mol) in a mixture of concentrated hydrochloric acid (1.5ml), isopropanol (265ml) and water (26.5ml) and the mixture was stirred at room temperature for lhour. A second portion of iron powder (8.1g) was added and the mixture was heated to reflux for lhour. A further quantity of concentrated hydrochloric acid was added and the mixture was refluxed for a further lhour. The mixture was cooled to room temperature, filtered through a plug of Hyflo® diatomaceous earth and the filtrate was evaporated in vacuo to give methyl 3-amino-4-fluorophenylacetate (22.98g) which was used without further purification in the next step. Step 3 Preparation of methyl 4-fluoro-3-(3-methylbutyramido)phenylacetate
Isovaleryll chloride (2.93ml, 2.90g, 0.024mol) was added, dropwise, to a chilled (ice-bath) solution of methyl 3-amino-4-fluorophenylacetate (4.00g, 0.022mol) in pyridine (16ml) and, once the addition was complete, the cooling bath was removed and the reaction mixture was stirred at room temperature for 30minutes. The mixture was diluted with water and extracted with ethyl acetate. The organic extract was washed with water, dried over anhydrous magnesium sulfate, filtered and the filtrate was evaporated in vacuo. Trituration with dichloromethane / hexane gave methyl 4-fluoro-3-(3-methylbutyramido)phenylacetate (4.88g) as a pale brown solid.
1H NMR (CDCI3) δ: 1.03(d,6H); 2.22(m,lH); 2.26(s,2H); 3.6(s,2H); 3.69(s,3H); 6.98(m,lH); 7.03(dd,lH); 7.33(b,lH); 8.39(d,lH)ppm. Step 4 Preparation of methyl [2-(2-methylpropyl)benzothiazol-5-yl]acetate
2,4-bw(4-Methoxyphenyl)- 1 ,3-dithia-2,4-diphosphetane-2,4-disulfide (7.39g, 0.018mol) was added, portionwise, to a solution of methyl 4-fluoro-3-(3- methylbutyramido)phenylacetate (4.88g, 0.018mol) in refluxing 1,2-dimethoxyethane (70ml) and, once the addition was complete, the mixture was refluxed for 3hours. The mixture was cooled to room temperature, poured into water and extracted with dichloromethane. The organic phase was dried over anhydrous magnesium sulfate, filtered and the filtrate was evaporated in vacuo. The residue was passed through a plug of silica gel, eluting with ethyl acetate : hexane 1 : 1, and fractions containing the desired product were combined and evaporated in vacuo. The residue (5.92g) was taken up in N,N-dimethylacetamide (48ml) and potassium carbonate (5.776g, 0.042mol) was added and then the mixture was heated to 110°C for 2hours. The mixture was cooled to room temperature, poured into water and extracted with dichloromethane. The organic extract was washed with brine, dried over anhydrous magnesium sulfate, filtered and the filtrate was evaporated in vacuo. The residue was further purified by flash column chromatography on silica gel, eluting with ethyl acetate : hexane 1 : 4, to give methyl [2-(2-methylpropyl)benzothiazol-5-yl]acetate (2.0 lg).
1H ΝMR (CDC13) δ 1.07(d,6H); 2.23(m,lH); 3.00(d,2H); 3.71(s,3H); 3.78(s,2H); 7.29(dd,lH); 7.79(d,lH); 7.88(d,lH)ppm. Step 5 Preparation of methyl 2-[2-(2-methylpropyl)benzothiazol-5-yl]propionate
A solution of lithium diisopropylamide (2.0M solution in tetrahydrofuran /ethyl benzene / heptane, 2.09ml, 0.0042mol) was added, dropwise, to a solution of methyl [2-(2-methylpropyl)benzothiazol-5-yl]acetate (1. lg, 0.0042mol) in tetrahydrofuran (27ml) at -78°C under a nitrogen atmosphere and the mixture was stirred at below -60°C for lhour. Methyl iodide (2.29ml, 0.037mol) was added, dropwise, and the mixture was stirred at below -60°C for a further lhour. The cooling bath was removed and the mixture was allowed to warm to room temperature over a period of lhour. The mixture was diluted with water, acidified with 2M aqueous hydrochloric acid and extracted with ethyl acetate. The organic extract was dried over anhydrous magnesium sulfate, filtered and the filtrate evaporated in vacuo to give methyl 2-[2-(2-methylpropyl)benzothiazol-5-yl]propionate (1.15g) which was used without further purification in the next step.
1H ΝMR (CDCI3) δ: 1.04(d,6H); 1.58(d,3H); 2.22(m,lH); 2.98(d,2H); 3.67 (s,3H); 3.87(q,lH); 7.31(dd,lH); 7.79(d,lH); 7.91(d,lH)ppm. Step 6 Preparation of N-(4-chloro-3-ethylisothiazol-5-yl)-2-[2-(2-methylpropyl)benzothiazol- 5-yl]propionamide
5-Amino-4-chloro-3-ethylisothiazole (0.81 g, 0.005 moi) was added to a suspension of sodium methoxide (0.56 g, 0.010 moi) in tetrahydrofuran (5 ml) and the mixture stirred at room temperature for 25 minutes. A solution of methyl 2-[2-(2-methylpropyl)benzothiazol-5- yl]propionate (1.15 g, 0.004 moi) in tetrahydrofuran (4 ml) was added dropwise and the mixture stirred at room temperature for 1 Vi hours. The mixture was diluted with saturated aqueous ammonium chloride solution and extracted with dichloromethane. The organic extract was dried over anhydrous magnesium sulfate, filtered and the filtrate evaporated in vacuo. Trituration with diethyl ether gave the desired product (1.06g).
EXAMPLE 15 This Example illustrates the preparation of Compound No. 156 of Table No. 39. A mixture of N,O-bis(trimethylsilyl)acetamide (0.533ml, 0.439g, 0.0022mol), N-(4-chloro-3-ethylisothiazol-5-yl)-2-[2-(2-methylpropyl)benzothiazol-5-yl]propionamide (0.800g, 0.002mol) and chloromethylethyl ether (0.365ml, 0.358g, 0.0038mol) in dichloromethane (10ml) was stirred at room temperature for 5V2hours. The reaction mixture was diluted with dichloromethane and washed with saturated aqueous sodium bicarbonate solution. The organic phase was dried over anhydrous magnesium sulfate, filtered and the filtrate was evaporated in vacuo. The residue was purified by column chromatography on silica gel, eluting with ethyl acetate : hexane 1 : 4, to give the desired product (0.278g).
EXAMPLE 16 This Example illustrates the preparation of Compound No. 7 of Table No. 6. Step l
Preparation of methyl 2-[2-(2,2-dimethylpropyl)benzoxazol-5-yl]-2-fluoropropionate A solution of lithium diisopropylamide (2.0M solution in tetrahydrofuran /ethyl benzene / heptane, 4.55ml, 0.009mol) was added, dropwise, to a solution of methyl 2-[2-(2,2- dimethylpropyl)benzoxazol-5-yl]propionate (2.5g, 0.009mol) in tetrahydrofuran (65ml) at -70°C under a nitrogen atmosphere and the mixture was stirred at -70°C for lhour. A solution of N-fluorobenzensulfonimide (2.9g. 0.009mol) in tetrahydrofuran (15ml) was added and the mixture was stirred at -70°C for a further lhour. The cooling bath was removed and the reaction mixture was allowed to warm to room temperature, with stirring over IVihours. The mixture was quenched with water, acidified with dilute aqueous hydrochloric acid and extracted with ethyl acetate. The organic extract was washed with brine, dried over anhydrous magnesium sulfate, filtered and the filtrate was evaporated in vacuo. The residue was purified by flash column chromatography on silica gel, eluting with ethyl acetate : dichloromethane 1 : 99, to give methyl 2-[2-(2,2-dimethylpropyl)benzoxazol- 5-yl]-2-fluoropropionate (2.06g).
1H NMR (CDC13) δ: 1.08(s,9H); 2.00(d,3H); 2.82(s,2H); 3.78(s,3H); 7.48(m,2H); 7.74(d,lH)ppm. Step 2
Preparation of N-(4-chloro-3-methylisothiazol-5-yl)-2-[2-(2,2-dimethylpropyl)- benzoxazol-5-yI]-2-fluoropropionamide
5-Amino-4-chloro-3-methylisothiazole (0.28g, 0.00188mol) was added to a suspension of sodium methoxide (0.24g, 0.004mol) in tetrahydrofuran (6ml) and the mixture was stirred at room temperature for 20minutes. A solution of methyl 2-[2-(2,2- dimethylpropyl)benzoxazol-5-yl]-2-fluoropropionate (0.50g, 0.00171mol) in tetrahydrofuran (2ml) was added, dropwise, and the mixture was stirred at room temperature for 3hours. The mixture was diluted with water, acidified with saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The organic extract was dried over anhydrous magnesium sulfate, filtered and the filtrate was evaporated in vacuo. The residue was purified by flash column chromatography on silica gel, eluting with ethyl acetate : hexane 12:88, to give the desired product (0.575g) as a pale yellow gum.
EXAMPLE 17 This Example illustrates the pesticidal insecticidal properties of compounds of formula (I). The activities of individual compounds of formula (I) were determined using a variety of pests. The pests were treated with a liquid composition containing 500 parts per million (ppm) by weight of a compound of formula (I). Each composition was made by dissolving the compound in an acetone and ethanol (50:50 by volume) mixture and diluting the solution with water containing 0.05% by volume of a wetting agent, SYNPERONIC NP8, until the liquid composition contained the required concentration of the compound. SYNPERONIC is a registered trade mark. The test procedure adopted with regard to each pest was essentially the same and comprised supporting a number of the pests on a medium, which was usually a substrate, a host plant or a foodstuff on which the pests feed, and treating either or both the medium and the pests with a composition. Pest mortality was assessed usually between two and five days after treatment.
In each test against peach potato aphids (Myzus persicae), Chinese cabbage leaves were infested with aphids, the infested leaves were sprayed with a test composition and pest mortality was assessed after three days.
Similar tests were conducted against, independently, two-spotted spider mites (Tetranychus urticae), fruit flies (Drosophila melanogaster), tobacco budworms (Heliothis virescens), diamond back moth (Plutella xylostella) and com root worm (Diabrotica balteata). Tests were also conducted against root knot nematodes (Meloidogyne incognita) using an in vitro test in which nematodes were suspended in a liquid composition which had been prepared as described above except that it contained a concentration of 12.5ppm by weight of a compound of formula (I) and it contained no SYNPERONIC NP8.
Results from these tests are displayed in Table 104, in which each mortality (score) is designated as 9, 5 or 0 wherein 9 indicates 80-100% mortality, 5 indicates 40-79% mortality and 0 indicates less than 40% mortality; and Dm represents Drosophila melanogaster; Mp represents Myzus persicae; Hv represents Heliothis virescens; Px represents Plutella xylostella; Tu represents Tetranychus urticae; Db represents Diabrotica balteata; and Mi represents Meloidogyne incognita. Table 104
Table Compound Dm Mp Hv Px Tu Db Mi
Number Number
6 0 0 9 9 0
7 5
8 0 5 9 9 9 0
10 0 0 9 5 0
76 9 9 5 9 9 5
77 0 9 9 9 9 0
78 9 9 9 9 9 0
80 0 5 9 9 9 0
81 9 9 9 9 0
86 9 9 9 9 0
87 9 9 9 9 0
88 0 9 9 9 0
90 0 0 9 9 0
156 9 0
157 0 9 9 9 9 0
159 9 9 9 9 0 Table Compound Dm Mp Hv Px Tu Db Mi
Number Number
1 160 9 9 9 9 0
2 10 0 5 9 9 0
2 90 0 0 9 0 0
4 7 5
5 6 9 9 9 9 9
5 7 9 9
5 10 9 9 9 9 9 0
5 77 0 9 5 9 9 0
5 86 9 9 9 9
5 87 9 9 9 9
5 90 9 9 9 9 0
5 157 9 9 9 9 9 55
5 160 0 9 9 9 0
6 7 5 9 9 9 0
7 7 9 0 9 9 9
9 86 5 9 9 9 9 5
10 7 9 9 0 0
12 7 0 0 9 9 9 0
13 7 0 9 0
14 7 9 9
15 7 9 9
16 7 (Z isomer) 9 9
16 7 (E isomer) 5 9
17 7 9 0
19 7 5 9
19 7 9 9
20 7 0 5 0 9 9 0 0
22 7 0 9
28 7 0 5 9 0 0
30 7 9
39 86 0 5 9 9 9
39 87 0 0 9 9 9 0
39 156 0 9 9 9
39 157 0 9 9 9 9
40 87 0 0 0 0 5 0
42 7 9 9 9 5 9 0
42 87 9 9 9 9 9 0
81 77 0 0 0 0 0 9 0
82 77 0 9 0 0 0
EXAMPLE 18 This Example illustrates the fungicidal properties of compounds of formula (I). The compounds were tested against a variety of foliar fungal diseases of plants. The technique employed was as follows. Plants were grown in John Innes Potting Compost (No.l or 2) in 4cm diameter, 3.5cm depth minipots. The test compounds were individually formulated as a solution either in acetone or acetone/ethanol (1:1 by volume) which was diluted in deionised water to a concentration of lOOppm (that is, lmg of compound in a final volume of 10ml) immediately before use. When foliar sprays were applied to monocotyledonous crops, TWEEN 20 (0.1% by volume) was added. TWEEN is a registered trade mark.
Individual compounds of formula (I) were applied as a foliar (Folr) application (where the chemical solution was applied to the foliage of the test plants by spraying the plant to maximum droplet retention.) These tests were carried out against Uncinula necator (UNCINE), on vines; Venturia inaequalis (VENTIN) on apples; Phytophthora infestans lycopersici (PHYTIN) on tomatoes; Puccinia recondita (PUCCRT), on wheat; and Pyricularia oryzae (PYRIOR) on rice. Each treatment was applied to two or more replicate plants for Phytophthora infestans lycopersici and Uncinula necator. For tests on Puccinia recondita and Pyricularia oryzae two replicate pots each containing 6 to 10 plants were used for each treatment. The plants were inoculated one day before (Erad) or one day after (Prot) chemical application. The Phytophthora infestans lycopersici, Puccinia recondita and Pyricularia oryzae plants were inoculated with a calibrated fungal spore suspension. The Uncinula necator plants were inoculated using a 'blowing' inoculation technique. After chemical application and inoculation, the plants were incubated under high humidity conditions and then put into an appropriate environment to allow infection to proceed, until the disease was ready for assessment. The time period between chemical application and assessment varied from five to fourteen days according to the disease and environment. However, each individual disease was assessed after the same time period for all compounds.
Assessments were performed on each of two leaves on each of the replicate plants for Phytophthora infestans lycopersici. Assessments were performed on a single leaf of each of the replicate plants for Uncinula necator. For Puccinia recondita and Pyricularia recondita assessments were carried out collectively on the plants in each replicate pot. The disease level present (that is, the percentage leaf area covered by actively sporulating disease) was assessed visually. For each treatment, the assessed values for all its replicates were meaned to provide mean disease values. Untreated control plants were assessed in the same manner. The data were then processed by the method, described hereinafter, to provide PRCO (Percentage Reduction from Control) values. An example of a typical calculation is as follows: Mean disease level for treatment A = 25% Mean disease level on untreated controls = 85%
PRCO = 100 - { Mean disease level for treatment A } x 100 {Mean disease level on untreated controls}
= 100 - (25 x 100) = 70.6
85
The PRCO is then rounded to the nearest whole number; therefore, in this particular example, the PRCO result is 71. It is possible for negative PRCO values to be obtained.
Results are displayed in Table 105.
TABLE 105
Figure imgf000104_0001
Key to Table 105:
VENTIN = Venturia inaequalis
PHYTIN = Phytophthora infestans lycopersici
PUCCRT = Puccinia recondita
PYRIOR = Pyricularia oryzae
UNCINE = Uncinula necator
EXAMPLE 19
This Example illustrates the fungicidal properties of compounds of formula (I). The compounds were tested against a variety of foliar fungal diseases of plants. The techniques employed were as follows.
Plants were grown either in John Innes Potting Compost (No.l or 2) in 4cm diameter, 3.5cm depth minipots or on an artificial, cellulose based growing medium. The test compounds were individually formulated as a solution either in acetone or acetone/ethanol (1:1 by volume) which was diluted in reverse osmosis water to a concentration of lOOppm (that is, lmg of compound in a final volume of 10ml) immediately before use. When foliar sprays were applied to monocotyledonous crops, TWEEN 20 (0.1% by volume) was added. TWEEN is a registered trade mark.
Individual compounds of formula (I) were applied as a foliar (Prot) application (where the chemical solution was applied to the foliage of the test plants by spraying the foliage to maximum droplet retention) or as a systemic (Syst) application (where the chemical was added to a small beaker in which the test plant pots were standing).
These tests were carried out against Plasmopara viticola (PLASVI) on vines; Phytophthora infestans lycopersici (PHYTIN) on tomatoes; and Blumeria graminis f.sp. tritici (ERYSGT), Stagonospora nodorum (LEPTNO) and Puccinia triticina (PUCCRT) on wheat. Each treatment was applied to two or more replicate plants for Plasmopara viticola and Phytophthora infestans lycopersici and in all tests where the cellulose growing medium was employed. In minipot tests on Blumeria graminis f.sp. tritici, Stagonospora nodorum and Puccinia triticina, two replicate pots each containing 6 to 10 plants were used for each treatment. The plants were inoculated with a calibrated fungal spore either 6hours or one day after chemical application.
After chemical application and inoculation, the plants were incubated under high humidity conditions and then put into an appropriate environment to allow infection to proceed, until the disease was ready for assessment. The Blumeria graminis f.sp. tritici plants were inoculated using a 'shake' inoculation technique. For Plasmopara viticola, the plants were reincubated under high humidity conditions for 24hours prior to assessment. The time period between chemical application and assessment varied from five to nine days according to the disease and environment. However, each individual disease was assessed after the same time period for all the compounds tested against that particular disease.
Assessments were performed on a single leaf of each of the two replicate plants for Plasmopara viticola and on each of two leaves on each of the replicate plants for Phytophthora infestans lycopersici. For Blumeria graminis f.sp. tritici, Stagonospora nodorum and Puccinia triticina, assessments were carried out collectively on the plants in each replicate minipot or cellulose medium.
The disease level present (that is, the percentage leaf area covered by actively sporulating disease) was assessed visually. For each treatment, the assessed values for all its replicates were meaned to provide mean disease values. Untreated control plants were assessed in the same manner. The data were then processed by either of two alternative methods, described below, each providing its own PRCO (Percentage Reduction from Control) value. All assessments on plants grown on cellulose media (and some grown in soil) used method 1. METHOD 1 This method uses banded assessment values.
The mean disease values are banded in the manner shown below. If the disease level value falls exactly mid-way between two of the points, the result will be the lower of the two points.
0 = 0% disease present 10 = 5.1-10% disease present
1 = 0.1-1% disease present 20 = 10.1-20% disease present 3 = 1.1-3% disease present 30 = 20.1-30% disease present 5 = 3.1-5% disease present 60 = 30.1-60% disease present
90 = 60.1-100% disease present
An example of a typical banded calculation is as follows:
Mean disease level for treatment A = 25% Therefore banded mean disease level for treatment A = 30 Mean disease level on untreated controls = 85% Therefore banded mean disease level on untreated controls = 90 PRCO = 100 - { Banded mean disease level for treatment A } x 100
{Banded mean disease level on untreated controls}
= 100 - (30 x 100) = 66.7 90
The PRCO is then rounded to the nearest whole number; therefore, in this particular example, the PRCO result is 67. METHOD 2 This method uses unhanded assessment values (that is, the mean disease values are used in the PRCO calculation without a banding step).
An example of a typical unhanded calculation is as follows:
Mean disease level for treatment A = 25% Mean disease level on untreated controls = 85%
PRCO = 100 - { Mean disease level for treatment A } x 100 {Mean disease level on untreated controls}
= 100 - (25 x 100) = 70.6 85
The PRCO is then rounded to the nearest whole number; therefore, in this particular example, the PRCO result is 71.
It is possible for negative PRCO values to be obtained. Results are displayed in Table 106.
TABLE 106
Figure imgf000108_0002
Figure imgf000108_0001
Key to Table 106:
ERYSGT = Blumeria graminis f.sp. tritici PLASVI = Plasmopara viticola PHYTIN = Phytophthora infestans lycopersici PUCCRT = Puccinia recondita

Claims

A compound of formula (I):
Figure imgf000109_0001
where A is optionally substituted Q-6 alkylene, optionally substituted C2-6 alkenylene, optionally substituted C2- alkynylene, optionally substituted cycloalkylene, optionally substituted Q-6 alkylenoxy, optionally substituted oxy(Q-6)alkylene, optionally substituted Q-6 alkylenethio, optionally substituted thio(C1-6)alkylene, optionally substituted Ci-6 alkylenamino, optionally substituted amino(Q-6)alkylene, optionally substituted [Q-6 alkyleneoxy(Q-6)alkylene], optionally substituted [Q-6 alkylenethio(Q-6)alkylene], optionally substituted [Q-6 alkylenesulfinyl(Q- 6)alkylene], optionally substituted [Ci-6 alkylenesulfonyl(Q-6)alkylene] or optionally substituted [Ci-6 alkyleneamino(Q-6)alkylene]; provided that A is not CH2 or CH2O; B is N, N-oxide or CR8; Y is O, S or NR9; Z is O, S or NR10; R1 is hydrogen, halogen, optionally substituted Q-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, optionally substituted Q-6 alkoxy, optionally substituted Q-6 alkylthio, optionally substituted Q-7 cycloalkyl, cyano, nitro or SF5; R2 is hydrogen, halogen, optionally substituted Q-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, optionally substituted Q-6 alkoxy, optionally substituted Q-6 alkylthio, optionally substituted Q- alkylsulfinyl, optionally substituted Q-6 alkylsulfonyl, cyano, nitro, formyl, optionally substituted Ci-6 alkylcarbonyl, optionally substituted Q-6 alkoxycarbonyl, SF5 or RuON=C(R12); or R1 and R2 together with the atoms to which they are attached may be joined to form a five, six or seven-membered saturated or unsaturated, carbocylic or heterocyclic ring which may contain one or two heteroatoms selected from O, N or S and which is optionally substituted by Q-6 alkyl, Q-6 haloalkyl or halogen; R3 is hydrogen, optionally substituted Q-io alkyl, optionally substituted [C2-6 alkenyl(Q-6)alkyl], optionally substituted [C _6 alkynyl(Q-6)alkyl], optionally substituted Q-7 cycloalkyl, optionally substituted Cno alkylcarbonyl, optionally substituted Q-10 alkoxycarbonyl, formyl, optionally substituted Q-io alkylaminocarbonyl, optionally substituted di(Q-10)alkylaminocarbonyl, optionally substituted phenoxycarbonyl, optionally substituted Ci-6 alkylthio, optionally substituted Q-6 alkylsulfinyl, optionally substituted Ci-6 alkylsulfonyl, optionally substituted Q-6 arylthio, optionally substituted Q-6 arylsulfinyl, optionally substituted Ci-6 arylsulfonyl or R13R14NS(O)p; p is 0, 1 or 2; R4, R5 and R6 are, independently, hydrogen, halogen, optionally substituted Ci-6 alkyl, optionally substituted Ci-6 alkoxy, optionally substituted Q-6 alkylthio, optionally substituted Q-6 alkylsulfinyl, optionally substituted Ci-6 alkylsulfonyl, cyano, nitro, optionally substituted Ci-6 alkylcarbonyl, optionally substituted Q-6 alkoxycarbonyl or SF5; R7 is hydrogen, halogen, cyano, optionally substituted Q- o alkyl, optionally substituted C2-20 alkenyl, optionally substituted C2-20 alkynyl, optionally substituted C3-7 cycloalkyl, optionally substituted C5-6 cycloalkenyl, formyl, optionally substituted Q-20 alkoxycarbonyl, optionally substituted Q-2o alkylcarbonyl, aminocarbonyl, optionally substituted Q-2o alkylaminocarbonyl, optionally substituted di(Q-2o)alkylaminocarbonyl, optionally substituted aryloxycarbonyl, optionally substituted arylcarbonyl, optionally substituted arylaminocarbonyl, optionally substituted N-(Q-6)alkyl- N-arylaminocarbonyl, optionally substituted diarylaminocarbonyl, optionally substituted heteroaryloxycarbonyl, optionally substituted heteroarylcarbonyl, optionally substituted heteroarylaminocarbonyl, optionally substituted N-(Q-6)alkyl- N-heteroarylaminocarbonyl, optionally substituted diheteroarylaminocarbonyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted heterocyclyl, SH, optionally substituted Q-2o alkylthio, optionally substituted Q-20 alkylsulfinyl, optionally substituted Q-2o alkylsulfonyl, optionally substituted arylthio, optionally substituted arylsulfinyl, optionally substituted arylsulfonyl, R15O, R16R17N or R18ON=C(R19); R8 is hydrogen, halogen, nitro, cyano, optionally substituted Q-8 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C -6 alkynyl, optionally substituted C3-7 cycloalkyl, optionally substituted Q-6 alkoxycarbonyl, optionally substituted Q-6 alkylcarbonyl, optionally substituted Q-6 alkylaminocarbonyl, optionally substituted di(Q-6)alkylaminocarbonyl, optionally substituted phenyl or optionally substituted heteroaryl; R9 is hydrogen, cyano, nitro, optionally substituted Q-6 alkyl, optionally substituted C3-7 cycloalkyl, optionally substituted (C2-6)alkenyl(Ci-6)alkyl, optionally substituted (C2-6)alkynyl(Q-6)alkyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted Ci-6 alkylcarbonyl, optionally substituted Q-6 alkoxycarbonyl, optionally substituted Q-6 alkylamino, optionally substituted di(Q-6)alkylamino, optionally substituted Ci-6 alkylcarbonylamino, optionally substituted Ci-6 alkoxycarbonylamino, optionally substituted Ci-6 alkoxy, optionally substituted Ci-6 alkylthio, optionally substituted Q-6 alkylsulfinyl, optionally substituted Ci-6 alkylsulfonyl, optionally substituted arylthio, optionally substituted arylsulfinyl, optionally substituted arylsulfonyl or Ci-6 alkylcarbonyloxy; R10 is hydrogen, cyano, optionally substituted Q-8 alkyl, optionally substituted [C2-6 alkenyl(Q-6)alkyl], optionally substituted [C2-6 alkynyl(Q-6)alkyl], optionally substituted C3-7 cycloalkyl, optionally substituted [Q-7 cycloalkyl(Q-6)alkyl], Q-6 alkoxy(Q-6)alkyl, optionally substituted Q-6 alkoxycarbonyl, optionally substituted Q-6 alkylcarbonyl, optionally substituted Q-6 alkylaminocarbonyl, optionally substituted di(Q-6)alkylaminocarbonyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted alkylsulfonyl or optionally substituted arylsulfonyl; R11 and R18 are, independently, hydrogen, optionally substituted phenyl (Q-2)alkyl or optionally substituted Q-2o alkyl; R12 and R19 are, independently, hydrogen, optionally substituted phenyl or optionally substituted Ci-6 alkyl; R13 and R14 are, independently, optionally substituted Ci- alkyl; or R13 and R14 together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one or two further heteroatoms selected from O, N and S and which is optionally substituted by one or two independently selected Q-6 alkyl groups; R15 is hydrogen, optionally substituted Q-2o alkyl, optionally substituted [C2-20 alkenyl(Q-6)alkyl], optionally substituted [C2-2o alkynyl(Q-6) alkyl], optionally substituted Q-7 cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, (Q-6)alkylCH=N, optionally substituted arylCH=N, optionally substituted [aryl(Q-6)alkyl]CH=N, optionally substituted heteroarylCH=N, optionally substituted [heterocyclyl(Q-6)alkyl]CH=N, optionally substituted arylC(CH3)=N, optionally substituted heteroarylC(CH3)=N or optionally substituted di(Q-6)alkylC=N; and R16 and R17 are, independently, hydrogen, optionally substituted Q.2o alkyl, optionally substituted C3.7 cycloalkyl, optionally substituted [C -2o alkenyl(Ci-6)alkyl], optionally substituted [C2-2o alkynyl(Q-6)alkyl], optionally substituted Q-2o alkoxycarbonyl, optionally substituted phenoxycarbonyl, formyl, optionally substituted Q.2o alkylcarbonyl, optionally substituted Cι-2o alkylsulfonyl or optionally substituted phenylsulfonyl.
2. A compound of formula (I) according to claim 1 which is a compound of formula
(IA):
wherein A, B, Y, Z, R1, R2 , R3, R4, R5, R6 and R7 are as claimed in claim 1.
3. A compound of formula (I) as claimed in claim 1 or 2 where A is Ci-6 alkylene, Ci-6 alkenylene, Ci-6 alkylenoxy, oxy(Q-6)alkylene or Q-6 alkylenamino, each of which is optionally substituted by Q-3 alkyl, Q-3 haloalkyl, Q-3 cyanoalkyl, halogen, Q-3 alkoxy, Q-6 alkoxycarbonyl, cyano, =O, =NR20 or =CR21R22; where R20 is Q-6 alkyl,
OR23 or NR24R25; R23 is Q-6 alkyl or phenyl(Q-2)alkyl (where the phenyl group is optionally substituted by halo, nitro, cyano, Q-6 alkyl, Ci-6 haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy); R24 and R25 are, independently, hydrogen, Q-8 alkyl or phenyl (which may be optionally substituted by halo, nitro, cyano, Ci-6 alkyl, Q-6 haloalkyl, Ci-6 alkoxy or Q-6 haloalkoxy); R21 is hydrogen, Ci-6 alkyl or Q-6 haloalkyl; R22 is hydrogen, Ci-6 alkyl, Ci-6 haloalkyl, Q-6 alkoxy, cyano, Ci-6 alkoxycarbonyl, Q-6 alkylcarbonyl or NR R ; and R and R are, independently, hydrogen, Q-8 alkyl, Q-7 cycloalkyl, C3-6 alkenyl, C3-6 alkynyl, - haloalkyl, Q-6 alkoxy(Q-6)alkyl, Q-6 alkoxycarbonyl(Q-6)alkyl, carboxy(Q-6)alkyl or phenyl(Q- )alkyl; or R26 and R27 together with the N atom to which they are attached form a five, six or seven- membered heterocyclic ring which may contain one or two further heteroatoms selected from O, N or S and which may be optionally substituted by one or two Q-6 alkyl groups; provided that A is not CH2 or CH2O. - I l l -
4. A compound of formula (I) as claimed in any preceding claim where Y is O or S.
5. A compound of formula (I) as claimed in any preceding claim where R1 is hydrogen, halogen, Q-6 alkyl, Ci-6 cyanoalkyl, Q-6 haloalkyl, Q-7 cycloalkyl(Q- )alkyl, Q-6 alkoxy(Q-6)alkyl, C2-6 alkenyl, -6 alkynyl, Q-6 alkoxy, Ci-6 haloalkoxy, Q-6 alkylthio, Ci-6 haloalkylthio, -6 cycloalkyl, cyano, nitro or SF5.
6. A compound of formula (I) as claimed in any preceding claim where R2 is hydrogen, halogen, Q-6 alkyl, Q-6 haloalkyl, Q-6 alkoxy(Q-6)alkyl, C2-6 alkenyl, Q-6 alkynyl,
Ci-6 alkoxy, Q-6 haloalkoxy, Ci-6 alkylthio, Q-6 haloalkylthio, Ci-6 alkylsulfinyl, Q-6 haloalkylsulfinyl, Ci-6 alkylsulfonyl, Q-6 haloalkylsulfonyl, cyano, nitro, formyl, Q-6 alkylcarbonyl, Ci-6 alkoxycarbonyl or CH=NORn; or R1 and R2 together with the atoms to which they are attached may be joined to form a five, six or seven- membered saturated or unsaturated, carbocylic or heterocyclic ring which may contain one or two heteroatoms selected from O, N or S and which is optionally substituted by Q-6 alkyl, Ci-6 haloalkyl or halogen; where R11 is phenyl(Q-2)alkyl (wherein the phenyl group is optionally substituted by halo, nitro, cyano, Q-6 alkyl, Ci-6 haloalkyl, Ci-6 alkoxy or Ci-6 haloalkoxy) or Q-6 alkyl.
7. A compound of formula (I) as claimed in any preceding claim where R3 is hydrogen, Q-io alkyl, Ci-6 alkylcarbonyloxy(Q-6)alkyl, benzoyloxymethyl (where the phenyl ring is optionally substituted with halogen or ^ alkyl), Ci-6 alkoxy(Q-6)alkyl (where the alkyl group is optionally substituted by aryl or Q--t alkoxycarbonyl), Q-6 alkenyloxy(Q-4)alkyl, -6 alkynyloxy(Q-4)alkyl, benzyloxy(Q- )alkyl (where the phenyl ring is optionally substituted with halogen or Q-4 alkyl), Q-7 cycloalkyl- (Q.4)alkyl, heteroaryl(Ci-3)alkyl (where the heteroaryl group is optionally substituted with halogen), tri(Q- )alkylsilyl(Q-6)alkyl, -6 alkenyl(Q-6)alkyl (especially allyl), -6 haloalkenyl(Q-6)alkyl, Q-4 alkoxycarbonyl(Q-6)alkenyl- (Q.6)alkyl, Q-6 alkynyl(Q-6)alkyl, tri(Q-4)alkylsilyl(C2-6)alkynyl(Q-6)alkyl or Q-10 alkylcarbonyl.
8. A compound of formula (I) as claimed in any preceding claim where R4, R5 and R6 are, independently, hydrogen, halogen, Q-6 alkyl, Q-6 haloalkyl, Ci-6 alkoxy, Ci-6 haloalkoxy, Ci-6 alkylthio, Q-6 haloalkylthio, Q-6 alkylsulfinyl, Q-6 haloalkylsulfinyl, Q-6 alkylsulfonyl, Ci-6 haloalkylsulfonyl, cyano, nitro, Ci-6 alkylcarbonyl or Q-6 alkoxycarbonyl.
9. A compound of formula (I) as claimed in any preceding claim where R7 is cyano, Q-8 alkyl, Q-8 haloalkyl, Q-8 cyanoalkyl, Q-7 cycloalkyl(Q-6)alkyl, -6 cycloalkenyl- (Q-6)alkyl, Ci-6 alkoxy(Q-6)alkyl, Q-6 alkenyloxy(Q-6)alkyl, Q-6 alkynyloxy- (Q-6)alkyl, aryloxy(C1-6)alkyl, Ci-6 carboxyalkyl, Q-6 alkylcarbonyl(Q-6)alkyl, C2-6 alkenylcarbonyl(Ci-6)alkyl, -6 alkynylcarbonyl(Q-6)alkyl, Q-6 alkoxycarbonyl- (Ci-6)alkyl, -6 alkenyloxycarbonyl(Q-6)alkyl, C3-6 alkynyloxycarbonyl(Ci-6)alkyl, aryloxycarbonyl(Ci-6)alkyl, Ci-6 alkylthio(Q-6)alkyl, Ci-6 alkylsulfinyl(Ci-6)alkyl, Ci-6 alkylsulfonyl(Q-6)alkyl, aminocarbonyl(Q-6)alkyl, Q-6 alkylaminocarbonyl- (Q-6)alkyl, di(Ci-6)alkylaminocarbonyl(C1-6)alkyl, phenyl(Ci-4)alkyl (wherein the phenyl group is optionally substituted by halo, nitro, cyano, Q-6 alkyl, Ci-6 haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy), heteroaryl(Q-4)alkyl (where the heteroaryl group is optionally substituted by halo, nitro, cyano, Ci-6 alkyl, Ci-6 haloalkyl, Ci-6 alkoxy or Q-6 haloalkoxy), heterocyclyl(C1-4)alkyl (where the heterocyclyl group is optionally substituted by halo, cyano, Ci- alkyl, Q-6 haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy), -6 alkenyl, C2-6 haloalkenyl, Q-6 cyanoalkenyl, -6 cycloalkenyl, aminocarbonyl- (C2-6)alkenyl, Ci- alkylaminocarbonyl(Q-6)alkenyl, di(Q-6)alkylaminocarbonyl- (Q-6)alkenyl, phenyl(Q-4)alkenyl (wherein the phenyl group is optionally substituted by halo, nitro, cyano, Ci-6 alkyl, Q-6 haloalkyl, Ci-6 alkoxy or Ci-6 haloalkoxy), -6 alkynyl, aminocarbonyl(C2-6)alkynyl, alkylaminocarbonyl(Q-6)alkynyl, di(Q-6) alkylaminocarbonyl(Q-6)alkynyl, Q-7 cycloalkyl, Q-7 halocycloalkyl, Q-7 cyanocycloalkyl, Q-3 alkyl(Q-7)cycloalkyl, Q-3 alkyl(C3- )halocycloalkyl, -6 cycloalkenyl, formyl, Ci-6 alkoxycarbonyl, Q-6 alkylcarbonyl, aminocarbonyl, Ci-6 alkylaminocarbonyl, di(Q-6)alkylaminocarbonyl, phenyl (optionally substituted by halo, nitro, cyano, Q-6 alkyl, Q-6 haloalkyl, Q-6 alkoxy or Ci-6 haloalkoxy), heteroaryl (optionally substituted by halo, nitro, cyano, Q-6 alkyl, Q- haloalkyl, Q_6 alkoxy or Ci-6 haloalkoxy), heterocyclyl (optionally substituted by halo, nitro, cyano, Q-6 alkyl, Q.6 haloalkyl, Ci-6 alkoxy or Ci-6 haloalkoxy), Q-8 alkylthio, R15O, R16R17N or R18ON=C(R19); where R15 is hydrogen, Q-8 alkyl, Q-6 haloalkyl, Q-6 cyanoalkyl, Ci-6 alkoxy(C!-6)alkyl, phenyl(Q- )alkyl, (wherein the phenyl group is optionally substituted by halo, nitro, cyano, Ci-6 alkyl, Ci-6 haloalkyl, Q-6 alkoxy or Ci-6 haloalkoxy), heteroaryl(Q-4)alkyl (wherein the heteroaryl group is optionally substituted by halo, nitro, cyano, Ci- alkyl, Q-6 haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy), heterocyclyl(Q-4)alkyl (wherein the heterocyclyl group is optionally substituted by halo, nitro, cyano, Ci-6 alkyl, Q-6 haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy), Ci-6 alkoxycarbonyl(Q-6)alkyl, -6 alkenyl, -6 alkynyl or N=C(CH3)2; R19 is phenyl (optionally substituted by halo, nitro, cyano, Q-6 alkyl, Q-6 haloalkyl,
Q-6 alkoxy or Ci-6 haloalkoxy), Ci-6 alkyl or Ci-6 haloalkyl; R16 and R17 are, independently, hydrogen, Q-8 alkyl, Q-7cycloalkyl(Q-4)alkyl, Q-6 haloalkyl, Q-6 alkoxy(Q-6)alkyl, Q-7 cycloalkyl, C3-6 alkenyl, -6 alkynyl or Q-6 alkoxycarbonyl; and R18 is phenyl(Q-2)alkyl (wherein the phenyl group is optionally substituted by halo, nitro, cyano, Q-6 alkyl, Q-6 haloalkyl, Q-6 alkoxy or Q-6 haloalkoxy) or Q-6 alkyl.
10. A fungicidal, insecticidal, acaricidal, molluscicidal or nematicidal composition comprising a fungicidally, insecticidally, acaricidally, molluscicidally or nematicidally effective amount of a compound of formula (I) as claimed in claim 1 and a carrier or diluent therefor.
11. A method of combating and controlling fungi comprising applying to a plant, to a seed of a plant, to the locus of the plant or seed or to the soil a fungicidally effective amount of either a compound of formula (I) as claimed in claim 1 or a composition as claimed in claim 10.
12. A method of combating and controlling insects, acarines, nematodes or molluscs which comprises applying to a pest, to a locus of a pest, or to a plant susceptible to attack by a pest an insecticidally, acaricidally, nematicidally or molluscicidally effective amount of either a compound of formula (I) as claimed in claim 1 or a composition as claimed in claim 10.
PCT/GB2001/000338 2000-01-28 2001-01-26 Isothiazole derivatives and their use as pesticides WO2001055144A1 (en)

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DE60116732T DE60116732T2 (en) 2000-01-28 2001-01-26 ISOTHIAZOL DERIVATIVES AND THEIR USE AS PESTICIDES
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WO2007020437A1 (en) * 2005-08-19 2007-02-22 Syngenta Limited Chemical process for the preparation of benzoxazole derivatives used as pesticides
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BR102013021210B1 (en) 2013-01-25 2015-12-01 Fundação Universidade Fed De São Carlos process of obtaining biopolymeric nanoparticles containing oil and azadirachta extracts indicates a. juss (neem), biopolymer nanoparticles and powder microparticles
CN107207490A (en) * 2014-12-02 2017-09-26 拜耳作物科学股份公司 It is used as the dicyclic compound of pest control agent

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CN103288771A (en) * 2012-02-29 2013-09-11 中国中化股份有限公司 Isothiazole compound and use thereof as fungicide
CN103288771B (en) * 2012-02-29 2014-12-03 中国中化股份有限公司 Isothiazole compound and use thereof as fungicide
US11641858B2 (en) 2016-04-13 2023-05-09 Redag Crop Protection Ltd. Agricultural chemicals

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US6703347B2 (en) 2004-03-09
DK1265892T3 (en) 2006-05-29
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PE20010830A1 (en) 2001-09-06
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US20030207926A1 (en) 2003-11-06
AR029439A1 (en) 2003-06-25
AR077486A2 (en) 2011-08-31
SV2002000296A (en) 2002-07-16
AU2001230358A1 (en) 2001-08-07
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JP2003523355A (en) 2003-08-05
DE60116732T2 (en) 2006-10-26

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