WO1996015672A1 - Fungicidal composition - Google Patents

Fungicidal composition Download PDF

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Publication number
WO1996015672A1
WO1996015672A1 PCT/GB1995/002576 GB9502576W WO9615672A1 WO 1996015672 A1 WO1996015672 A1 WO 1996015672A1 GB 9502576 W GB9502576 W GB 9502576W WO 9615672 A1 WO9615672 A1 WO 9615672A1
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WO
WIPO (PCT)
Prior art keywords
alkyl
alkenyl
phenyl
hydrogen
optionally substituted
Prior art date
Application number
PCT/GB1995/002576
Other languages
French (fr)
Inventor
Michael Drysdale Turnbull
Patrick Jelf Crowley
Ewan James Turner Chrystal
John Martin Clough
David Youle
Kevin Beautement
Susan Patricia Barnett
Roger John Ponsford
Dennis James Outred
Patrick Mamalis
Glenn Hatter
Peter Duncan Smith
Peter Bellini
Original Assignee
Zeneca Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Zeneca Limited filed Critical Zeneca Limited
Priority to AU38107/95A priority Critical patent/AU3810795A/en
Publication of WO1996015672A1 publication Critical patent/WO1996015672A1/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 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
    • A01N43/64—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with three nitrogen atoms as the only ring hetero atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
    • C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
    • C07D251/10—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
    • C07D251/72—Heterocyclic compounds containing 1,3,5-triazine rings condensed with carbocyclic rings or ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6515—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having three nitrogen atoms as the only ring hetero atoms
    • C07F9/6521—Six-membered rings

Definitions

  • the present invention provides a fungicidal composition comprising a 1,3,5-triazine derivative, a method of using said composition to combat fungal infections of plants, certain novel 1,3,5-triazines and processes for their preparation.
  • 1,3,5-triazines are known from, for example, GB831252 and GB1270831, as bactericide or anti-malarial agents.
  • Certain 1,3,5-triazine derivatives are disclosed in US5300503 as having insecticidal activity (especially against the larvae of Lepidoptera and Coleoptera insects).
  • the present invention provides a fungicidal composition
  • a fungicidal composition comprising, as an active ingredient, a compound of formula (Ia) or (Ib), or a tautomer thereof, wherein R 1 and R 2 are, independently, hydrogen; C 1 -C 6 alkyl, optionally substituted with OH or halo; C 2 -C R alkenyl, optionally
  • R 1 and R 2 together form a 3 to 8 membered cycloalkyl or cycloalkenyl ring either of which is optionally substituted with C 1 -C 6 alkyl, C 2 -C 6 alkenyl, OH or halo;
  • R 3 is hydrogen, C 1 -C 20 alkyl, C 2 -C 20 alkenyl or C 2 -C 20 alkynyl group, any of which is optionally substituted with one or more substituents independently selected from: halo, OR 6 , COR 6 , COOR 6 , CONR 6 R 7 , NHCOR 6 , NR 6 R 7 , SR 6 , SOR 6 , SO 2 R 6 ( OCOR 6 , N 3 , NO-, cyano, SO 2 NR 6 R 7 , CR 6 :NOR 7 , CS.NR 6 R 7 , NR 6 .CONR 7 R 7' , O.CO 2 R 6 ,
  • X is benzyl, phenyl, a 3 to 8 membered cycloalkyl, cycloalkenyl or saturated or unsaturated heterocyclic ring, or a fused ring system containing up to four 3 to 8 membered rings; the rings of the fused ring system are cycloalkyl, cycloalkenyl, phenyl or saturated or unsaturated heterocyclic rings or a combination of any these;
  • R 3 may also be a group Z-Q, wherein Z is R 10 , R 10 -Y-Y-R 10 , R 10 -Y-O-Y-R 10 ,
  • R 10 -Y-SO 2 -R 10 R 10 -NHCO-Y-CONH-R 10 , R 10 -Y-R 10 , R 10 -O-R 10 , R 10 -O-R 10 -O-R 10 ,
  • R 10 -S-R 10 or R 10 -NR 11 -R 10 are each C 1 -C 20 alkyl or C 2 -C 8 alkenyl
  • Y is a linking group derived from benzyl, phenyl, a 3 to 8 membered cycloalkyl, cycloalkenyl or saturated or unsaturated heterocyclic ring, or a fused ring system containing up to four 3 to 8 membered rings; the rings of the fused ring system are cycloalkyl, cycloalkenyl, phenyl or saturated or unsaturated heterocyclic rings or a combination of any these; the groups X and Y are, independently, optionally substituted with cyano, halo, SO 2 NR 8 R 8' , NO 2 , C 1 -C 8 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 1 -C 8 haloalkyl,
  • the compounds of formula (Ia) can exist in different tautomeric forms.
  • the compound of formula (Ib) is a tautomeric form of formula (Ia).
  • Compositions comprising such tautomers, and mixtures thereof in all proportions, and methods of using such tautomers, and mixtures thereof, in all proportions, for combating fungal infections of plants constitute a part of the present invention.
  • Alkyl groups are straight or branched chain.
  • Alkyl is, for example, methyl, ethyl, n-propyl, iso-propyl, tert-butyl or hexyl.
  • Alkenyl groups are straight or branched chain and have at least one double bond.
  • Alkenyl is, for example, ethenyl, 1-propenyl or hexenyl.
  • Alkynyl groups are straight or branched chain and have at least one triple bond.
  • Alkynyl is, for example, ethynyl or propargyl.
  • Cycloalkyl preferably comprises 3-7 carbon atoms and is, for example, cyclopropyl, cyclopentyl, cyclohexyl or cycloheptyl.
  • Cycloalkenyl preferably comprises 3-7 carbon atoms and is, for example, cyclohexenyl.
  • halo and halogen include fluorine, chlorine, bromine and iodine.
  • Heterocyclic rings are preferably 5- or 6-membered rings containing one or more of the same or different heteroatoms (especially nitrogen, oxygen or sulphur).
  • heterocyclic rings are furan, pyrrole, thiophene or pyridine and their partially and fully saturated derivatives (such as piperidine, pyrrolidine or tetrahydrofuran) or pyrimidine, imidazole, triazole, imidazoline, triazine, oxazole or oxazoline.
  • R 6 and R 7 , R 7 and R 7 ', R 8 and R 8 ' or R 9 and R 9 ' join to form a fused heterocyclic ring it is preferred that the ring is a 5- or 6-membered ring containing one or two nitrogen or oxygen atoms.
  • a ring is, for example, piperidine, pyrrolidine, morpholine or piperazine.
  • fused ring systems include aromatic ring systems such as naphthalene, anthracene and phenanthrene as well as partially saturated systems such benzocyclohexane and fully saturated systems such as
  • fused ring systems which comprise a heterocyclic ring or a carbocyclic ring fused to a heterocyclic ring are benzimidazole, benzofuran, indole, quinoline and indolinone.
  • Salts include salts of a mineral acid [for example, a salt of a haloacid (such as a hydrochloride, hydrobromide or hydroiodide) or of phosphoric, nitric, sulphuric, tetrafluoroboric, hexafluorophosphoric or carbonic acid] or an organic acid [for example acetic, butyric,
  • a metal complex is a complex with a metal salt, such as complexes with a transition metal salt (for example a salt having a cation of copper, silver, iron (II), iron (III), zinc or nickel, and an anion of a halide (such as chloride or bromide) or nitrate).
  • a transition metal salt for example a salt having a cation of copper, silver, iron (II), iron (III), zinc or nickel, and an anion of a halide (such as chloride or bromide) or nitrate).
  • the present invention provides a fungicidal composition
  • a compound of formula (Ia), or a tautomer thereof wherein R 1 and R 2 are, independently, hydrogen; C 1 -C 6 alkyl, optionally substituted with OH or halo; C 2 -C 6 alkenyl, optionally substituted with OH or halo; or R 1 and R 2 together form a 3 to 8 membered cycloalkyl or cycloalkenyl ring either of which is optionally substituted with C 1 -C 6 alkyl, C 2 -C 6 alkenyl, OH or halo; R 3 is hydrogen or C 1 -C 20 alkyl or C 2 -C 20 alkenyl group, any of which is
  • R 6 and R 7 are each independently selected from hydrogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 1 -C 6 alkyl-X, C 2 -C 6 alkenyl-X, any of which is optionally substituted by OH or halo, or a group X;
  • X is benzyl, phenyl, a
  • cycloalkyl 3 to 8 membered cycloalkyl, cycloalkenyl or saturated or unsaturated heterocyclic ring, or a fused ring system containing up to four 3 to 8 membered rings; the rings of the fused ring system are cycloalkyl, cycloalkenyl, phenyl or saturated or unsaturated heterocyclic rings or a combination of any these; the group X is optionally substituted with CN, halo, SO 2 NH 2 , NO 2 , oxo (where possible), imino (where possible), phenyl
  • R 8 is hydrogen, C 1 -C 8 alkyl
  • R 3 may also be a group Z-Q, wherein Z is R 10 , R 10 -Y-Y-R 10 R 10 -Y-O-Y-R 10 , R 10 -Y-SO 2 -R 10 , R 10 -NHCO-Y-CONH-R 10 , R 10 -Y-R 10 , R 10 -O-R 10 ,
  • R 10 and R 11 are each C 1 -C 20 alkyl or C 2 -C 8 alkenyl, Y is as defined above for X except that it is a
  • R and R are as defined below; alternatively, R is a group R 10 -W(R 10 Q) 2 wherein W is as defined above for X except that it
  • R and R may be the same or different and are hydrogen, CO 2 R 9 , COR 9 , CONR 9 , OCOR 9 , CO 2 X, COX, SO 2 X or CONX, wherein X is as defined above; and, R 9 is hydrogen, C 1 -C 8 alkyl, C 2 -C 8 alkenyl, C 1 -C 8 haloalkyl or C 2 -C 8 haloalkenyl; or a salt thereof; and a fungicidally acceptable carrier or diluent.
  • the present invention provides a fungicidal
  • composition comprising, as an active ingredient, a compound of formula
  • R and R are, independently, C 1 -C 6 alkyl; or R 1 and R 2 together form a 3 to 8 membered cycloalkyl ring which is optionally substituted with C 1 -C 6 alkyl;
  • R 3 is C 1 -C 20 alkyl or C 2 -C 20 alkenyl, either of which is optionally substituted with one or more substituents independently selected from: OR 6 , NR 6 R 7 , SR , OCOR 6 or a group
  • X; R 6 and R 7 are each independently selected from hydrogen or a group X;
  • X is phenyl, a 3 to 8 membered cycloalkyl, cycloalkenyl or an unsaturated heterocyclic ring, or a fused ring system containing up to four 3 to 8 membered rings; the rings of the fused ring system are phenyl or
  • the group X is optionally substituted with CN, halo, NO 2 , phenyl, C 1 -C 8 alkyl, C 2 -C 8 alkenyl, C 1 -C 8 haloalkyl, C 3-6 cycloalkyl, C 2 -C 8 haloalkenyl, OR 8 , COR 8 , COOR 8 , NHR , C 1-8 alkyl-R 8 or phenyl(C 2-6 )alkenyl; R 8 is hydrogen, C 1 -C 8 alkyl, phenyl or phenoxy(C 1-4 )alkyl; R 3 may also be a group Z-Q, wherein Z is R 10 , R 10 -[C 3-6 cycloalkyl] -R 10 or R 10 -S-R 10 ; R 10 and R 11 are each C 1 -C 20 alkyl, and Q is a group of formula (II), where
  • R and R are as defined below; R and R may be the same or different and are hydrogen or COR 9 ; and, R 9 is hydrogen, C 1 -C 8 alkyl or C 1 -C 8 haloalkyl; or a salt thereof; and a fungicidally acceptable carrier or diluent.
  • the present invention provides a fungicidal composition
  • a compound of formula (Ia), or a tautomer thereof wherein R 3 is (CH 2 ) n OX wherein n is an integer from 2-12; and X is hydrogen or phenyl (optionally substituted with C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, C 1 -C 4 alkoxy, C 2 -C 4 alkenyl, hydroxy, C 2 -C 4 alkylcarbonyl, halogen, NH 2 , CO 2 R 21 , cyano or nitro); OR (CH 2 ) n X wherein n is an integer from 1-12; X is (CHR 22 )R 23 ; R 22 is hydrogen or C 1 -C 4 alkyl; R 23 is phenoxy, phenyl or naphthyl, these groups being optionally substituted with C
  • the present invention provides a fungicidal composition
  • a fungicidal composition comprising, as an active ingredient, a compound of formula (Ia), or a tautomer thereof, wherein R 3 is: (CH 2 ) n OX wherein n is an integer from 2-12 (especially 3-10); and X is hydrogen or phenyl
  • R 21 is C 1 -C 4 alkyl, (X is especially 3,4,5-trimethoxyphenyl); OR (CH 2 ) n X wherein n is an integer from 1-12 (especially 1-10); X is (CHR 22 )R 23 ; R 22 is hydrogen or C 1 -C 4 alkyl; R 23 is phenoxy, phenyl (optionally substituted with halogen) or naphthyl
  • R 4 and R 5 are the same and are hydrogen or C 1 -C 4 alkylcarbonyl; or a hydrochloride or hydrobromide salt thereof; and a fungicidally acceptable carrier or diluent.
  • the present invention provides a fungicidal composition
  • a fungicidal composition comprising, as an active ingredient, a compound of formula
  • R 1 and R 2 are both methyl; R 4 and R 5 . are both hydrogen; and R 3 is phenoxy(C 1-12 )alkyl wherein the alkyl group is straight or branched chain and is, for example, (CH 2 ) n wherein n is an integer from 1 to 12 (such as 3, 4, 6, 8 or 10); and the phenoxy is unsubstituted or substituted by one or more, or a mixture of, halogen (such as bromine or chlorine atoms), nitro, C 1-4 alkyl (such as methyl or n-propyl), C 1-4 alkoxy (such as methoxy), C 2 -C 4 alkenyl (especially
  • propen-2-yl or C 1 -C 4 alkylcarbonyl (such as acetyl); and a fungicidally acceptable carrier or diluent.
  • the present invention provides a fungicidal composition
  • a fungicidal composition comprising, as an active ingredient, a compound of formula (Ia), or a tautomer thereof, wherein R 1 and R 2 are both methyl; R 4 and R 5 are both hydrogen; and R 3 is:
  • phenyl (C 1-4 )alkyl wherein the phenyl is optionally substituted by halogen (especially one or two chlorine atoms), nitro or C 2-4 alkenyl (especially propen-2-yl), and the alkyl group, which is straight or branched chain is, for example, CH 2 , CH(CH 3 ) or (CH 2 ) 3 ;
  • phenoxy(C 1-12 ) alkyl wherein the alkyl group is straight or branched chain and is, for example, (CH 2 ) n wherein n is an integer from 1 to 12 (such as 3, 4, 6, 8 or 10); and the phenoxy is unsubstituted or substituted by one or more, or a mixture of, halogen (such as bromine or chlorine atoms), nitro, C 1-4 alkyl (such as methyl or n-propyl) or C 1-4 alkoxy (such as methoxy);
  • the present invention provides a fungicidal composition
  • a compound of formula (Ia), or a tautomer thereof wherein R 1 and R 2 are C 1 -C 4 alkyl (especially methyl) or C 1 -C 4 haloalkyl (such as CH 2 Cl) or R 1 and R together form a cyclohexyl ring optionally substituted with C 1 -C 4 alkyl (especially methyl); R 4 and R 5 are the same and are hydrogen or C 1 -C 4 alkylcarbonyl (especially acetyl); R 3 is (CH 2 ) n R 20 ; n is 0 or an integer from 1 to 14; R 20 is hydrogen, hydroxy, cyano, C 1 -C 10 alkyl (optionally substituted with hydroxy or phenyl), C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 2 -C 4 alkenyl (optionally substituted
  • the present invention provides a fungicidal
  • composition comprising, as an active ingredient, a compound of formula (III), or a tautomer thereof, wherein R 1 and R 2 are C 1 -C 4 alkyl (especially methyl) or R 1 and R 2 together form a cyclohexyl ring optionally substituted with C 1 -C 4 alkyl (especially methyl); R 4 and R 5 are the same and are hydrogen or C 1 -C 4 alkylcarbonyl (especially acetyl); L 1 is hydrogen or C 1 -C 4 alkyl; L 2 , L 3 , L 4 , L 5 and L are, independently, hydrogen, C 1 -C 12 alkyl, C 1 -C 4
  • C 1 -C 4 alkyl especially methyl
  • C 1 -C 4 alkoxy especially methoxy, ethoxy, iso-propoxv or n-butoxy
  • C 1 -C 4 haloalkoxy such as OCF,
  • L 2 and L 3 , or L 3 and L 4 , or L 4 and L 5 , or L and L 6 join to form a fused aromatic ring optionally substituted as for phenyl; or a salt thereof (especially a hydrochloride or hydrobromide salt); and a fungicidally acceptable carrier or diluent.
  • the present invention provides a fungicidal composition
  • a compound of formula (IV), or a tautomer thereof wherein R 1 and R 2 are C 1 -C 4 alkyl (especially methyl); R 4 and R 5 are the same and are hydrogen, C 1 -C 4 alkylcarbonyl (especially acetyl) or C 1 -C 4 haloalkylcarbonyl (especially CF 3 CO); n is an integer from 1 to 11 (especially 1-6); Link is CH 2 or CHR 33 ; Z 1 is oxygen or sulphur; and L 1 , L 2 , L 3 , L 4 and L 5 are, independently, hydrogen, C 1 -C 12 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, C 2 -C 4 alkenyl (optionally substituted with phenyl or halogen), C 2 -C 4 alky
  • fungicidally acceptable carrier or diluent such as OCF 3 ; or a salt thereof (especially a hydrochloride or hydrobromide salt); and a fungicidally acceptable carrier or diluent.
  • Tables V-VIII give melting point, selected proton nuclear magnetic resonance (NMR), melting point (Mpt) or mass spectral (MS) data for certain compounds described in Tables I-IV. Chemical shifts were measured at room temperature and are in parts per million (ppm) from tetramethylsilane. Where shown, NMR data are selective, no attempt has been made to list every absorption in all cases. The following abbreviations are used:
  • R 21 is C 1 -C 4 alkyl; OR (CH 2 ) n X wherein n is an integer from 1-12; X is (CHR 22 )R 23 ;
  • R 22 is hydrogen or C 1 -C 4 alkyl
  • R 23 is phenoxy, phenyl (optionally
  • R 24 is hydrogen or C 1 -C 4 alkyl and R 25 is C 3 -C 7 cycloalkyl, phenyl (optionally substituted with halogen) or C 2 -C 4 alkenyl; R 4 and R 5 are the same and are hydrogen or C 1 -C 4 alkylcarbonyl; or a
  • the compounds of formula (Ia) and (Ib) can be made by using or adapting literature methods, such as methods described in any of the following documents: GB831252, US3105074, GB945159, DE1813243, DE1934120, DE1963759,
  • the compounds of formula (Ia) and (Ib), or their tautomers, wherein R 4 and R 5 are other than hydrogen can be prepared by treating a compound of formula (VI), or a tautomer thereof, wherein R 1 , R 2 and R 3 are as defined above, with an acylating agent of formula R 9 C(O)L, wherein R 9 is as defined above and L is a leaving group (such as a halogen atom, C 1 -C 4 alkoxy or a mesylate group).
  • Compounds of formulae (Ia) or (Ib) in which R 4 and R 5 are both hydrogen may be prepared by the reaction of a compound of formula (VII), wherein R 1 and R 2 are as defined above, or a salt thereof with an alkylating agent of formula R 3 -L, wherein R 3 is as defined above and L is as defined above.
  • the reaction is typically carried out in a polar solvent (such as methanol or ethanol) .
  • Alkyl ating agents of formula R 3 -L are readily available or may be prepared by methods known to those skilled in the art.
  • the solvent used which is preferably an alcoholic solvent (such as methanol or ethanol).
  • Carbonyl compounds of formula (X) are readily available or may be synthesised by methods known to those skilled in the art.
  • the compound of formula (IX) may be prepared by the reaction of
  • a hydroxy1amine of formula R 3 -ONH 2 may be used in place of Q-benzylhydroxy1amine in the reaction with dicyandiamide to produce a compound of formula (XI).
  • a compound of formula (Ia) or (Ib), wherein R 4 and R 5 are both hydrogen can be prepared by reacting a compound of formula (XI) with a compound of formula
  • a metal complex of a compound of formula (Ia) or (Ib) can be prepared by treating the free base of a compound of formula (Ia) or (Ib) with a metal salt in a suitable solvent (such as aqueous ethanol).
  • a suitable solvent such as aqueous ethanol
  • a salt of a compound of formula (Ia) or (Ib) can be prepared by treating the free base of a compound of formula (Ia) or (Ib) with the desired acid in a suitable solvent (such as water or ethanol) at room temperature.
  • a suitable solvent such as water or ethanol
  • the free base of a compound of formula (Ia) or (Ib) can be purified using standard techniques known in the literature (such as crystalisation, reverse phase chromatography or by the use of ion exchange resins).
  • the present invention provides processes for preparing the compounds of formula (Ia) and (Ib).
  • the present invention provides a fungicidal
  • composition comprising, as an active ingredient, a compound obtainable by treating a compound of formula (VI), or a tautomer thereof, wherein R 1 , R 2 and R 3 are as defined above, with an acylating agent of formula R 9 C(O)L, wherein R 9 is as defined above and L is a leaving group (such as a halogen atom, C 1 -C 4 alkoxy or a mesylate group).
  • the compounds of formula (Ia) and (Ib) are active fungicides and may be used to control one or more of the following pathogens: Pyricularia oryzae 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 e.g. turf, rye, coffee, pears, apples, peanuts, sugar beet, vegetables and ornamental plants; Erysiphe graminis (powdery mildew) on barley, wheat, rye and turf and other powdery mildews on various hosts such as Sphaerotheca macularis on hops, Sphaerotheca fuliginea on cucurbits (e.g. cucumber), Podosphaera leucotricha on apple and Uncinula necator on vines; Cochliobolus spp.,
  • arachidicola and Cercosporidium personatum on peanuts and other Cercospora species 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 (e.g. cucumber), oil-seed rape, apples, tomatoes, cereals (e.g. 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 (e.g.
  • Plasmopara viticola on vines other downy mildews such as Bremia lactucae on lettuce, Peronospora spp. on soybeans, tobacco, onions and other hosts,
  • 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,
  • compositions show a broad range of activities against fungi in vitro.
  • compositions may be active as seed dressings against pathogens including Fusarium spp., Septoria spp., Tilletia spp., (e.g. bunt, a seed-borne disease of wheat), Ustilago spp. and
  • compositions of the present invention are used to combat fungal diseases of cereal crops.
  • the compounds of formula (Ia) and (Ib) may move acropetally/locally in plant tissue.
  • formulations comprise 0.0001 to 95%, more preferably 1 to 85%, for example 1 to 25% or 25 to 60%, of a compound of formula (Ia) and (Ib).
  • the compounds of formula (Ia) and (Ib) are applied at rates of 0.1g to 10Kg, preferably 1g to 8Kg, more preferably 10g to 4Kg, of active ingredient per hectare.
  • the compounds of formula (Ia) and (Ib) are used at rates of 0.0001g (for example 0.001g or 0.05g) to 10g, preferably 0.005g to 8g, more preferably 0.005g to 4g, of active ingredient per kilogram of seed.
  • compositions of the invention can be applied in a number of ways. For example, they can be applied, formulated or unformulated, directly to the foliage of a plant, to seeds or to other medium in which plants are growing or are to be planted, or they can be sprayed on, dusted on or applied as a cream or paste formulation, or they can be applied as a vapour or as slow release granules.
  • compositions may also be injected into plants or sprayed onto vegetation using electrodynamic spraying techniques or other low volume methods.
  • plant as used herein includes seedlings, bushes and trees. Furthermore, the fungicidal method of the invention includes preventative, protectant, prophylactic, systemic and eradicant treatments.
  • composition used in any instance will depend upon the particular purpose envisaged.
  • compositions may be in the form of dustable powders or granules comprising the active ingredient and a solid diluent or carrier, for example, fillers such as kaolin, bentonite, kieselguhr, dolomite, calcium carbonate, talc, powdered magnesia, fuller's earth, gypsum, diatomaceous earth and china clay.
  • a solid diluent or carrier for example, fillers such as kaolin, bentonite, kieselguhr, dolomite, calcium carbonate, talc, powdered magnesia, fuller's earth, gypsum, diatomaceous earth and china clay.
  • Such granules can be preformed granules suitable for application to the soil without further treatment.
  • These granules can be made either by impregnating pellets of filler with the active ingredient or by pelleting a mixture of the active ingredient and powdered filler.
  • compositions for dressing seed may include an agent (for example, a mineral oil) for assisting the adhesion of the composition to the seed; alternatively the active ingredient can be formulated for seed dressing purposes using an organic solvent (for example, N-methylpyrrolidone, propylene glycol or
  • compositions may also be in the form of wettable powders or water dispersible granules comprising wetting or dispersing agents to facilitate the dispersion in liquids.
  • the powders and granules may also contain fillers and suspending agents.
  • the compositions may also be in the form of soluble powders or granules, or in the form of solutions in polar solvents.
  • Soluble powders may be prepared by mixing the active ingredient with a water-soluble salt such as sodium bicarbonate, sodium carbonate, magnesium sulphate or a polysaccharide, and a wetting or dispersing agent to improve water dispersibility/solubility. The mixture may then be ground to a fine powder. Similar compositions may also be granulated to form water-soluble granules. Solutions may be prepared by dissolving the active ingredient in polar solvents such as ketones, alcohols and glycol ethers. These solutions may contain surface active agents to improve water dilution and prevent crystallisation in a spray tank.
  • polar solvents such as ketones, alcohols and glycol ethers.
  • Emulsifiable concentrates or emulsions may be prepared by dissolving the active ingredient in an organic solvent optionally containing a wetting or emulsifying agent and then adding the mixture to water which may also contain a wetting or emulsifying agent.
  • organic solvents are aromatic solvents such as alkylbenzenes and alkylnaphthalenes, ketones such as cyclohexanone and methyleyelohexanone, chlorinated hydrocarbons such as chlorobenzene and trichlorethane, and alcohols such as benzyl alcohol, furfuryl alcohol, butanol and glycol ethers.
  • Suspension concentrates of largely insoluble solids may be prepared by ball or bead milling with a dispersing agent with a suspending agent included to stop the solid settling.
  • compositions to be used as sprays may be in the form of aerosols wherein the formulation is held in a container under pressure of a propellant, e.g. fluorotrichloromethane or dichlorodifluoromethane.
  • a propellant e.g. fluorotrichloromethane or dichlorodifluoromethane.
  • the compounds of formula (Ia) and (Ib) can be mixed in the dry state with a pyrotechnic mixture to form a composition suitable for generating in enclosed spaces a smoke containing the compounds.
  • compositions of the invention may be used in micro-encapsulated form. They may also be formulated in biodegradable polymeric formulations to obtain a slow, controlled release of the active substance.
  • additives for improving the uptake, distribution, adhesive power and resistance to rain on treated surfaces the different compositions can be better adapted for various utilities.
  • Other additives may be included to improve the biological efficacy of the various formulations.
  • Such additives can be surface active materials to improve the wetting and retention on surfaces treated with the formulation and also the uptake and mobility of the active material, or additionally can include oil based spray additives, for example, certain mineral oil and natural plant oil (such as soya bean and rape seed oil) additives, or blends of them with other adjuvants.
  • the compounds of formula (Ia) and (Ib) can be used as mixtures with fertilisers (e.g. nitrogen-, potassium- or phosphorus-containing
  • compositions comprising only granules of fertiliser
  • Such granules suitably contain up to 25% by weight of the compound.
  • Wettable powders, emulsifiable concentrates and suspension concentrates will normally contain surfactants, e.g. a wetting agent, dispersing agent, emulsifying agent or suspending agent. These agents can be cationic, anionic or non-ionic agents.
  • Suitable cationic agents are quaternary ammonium compounds, for example, cetyltrimethyl ammonium bromide.
  • Suitable anionic agents are soaps, salts of aliphatic monoesters of sulphuric acid (for example, sodium lauryl sulphate), and salts of sulphonated aromatic compounds (for example, sodium
  • dodecylbenzenesulphonate sodium, calcium or ammonium lignosulphonate, butylnaphthalene sulphonate, and a mixture of sodium diisopropyl- and triisopropylnaphthalene sulphonates).
  • Suitable non-ionic agents are the condensation products of ethylene oxide with fatty alcohols such as oleyl or cetyl alcohol, or with alkyl phenols such as octyl- or nonylphenol and octylcresol.
  • Other non-ionic agents are the partial esters derived from long chain fatty acids and hexitol anhydrides, the condensation products of the said partial esters with ethylene oxide, and the lecithins.
  • Suitable suspending agents are
  • hydrophilic colloids for example, polyvinylpyrrolidone and sodium carboxymethylcellulose
  • swelling clays such as bentonite or attapulgite
  • compositions for use as aqueous dispersions or emulsions are generally supplied in the form of a concentrate containing a high proportion of the active ingredient, the concentrate being diluted with water before use.
  • concentrates should preferably be able to withstand storage for prolonged periods and after such storage be capable of dilution with water in order to form aqueous preparations which remain homogeneous for a sufficient time to enable them to be applied by conventional spray equipment.
  • the concentrates may conveniently contain up to 95%, suitably 1-85%, for example 1-25% or 25-60%, by weight of the active ingredient.
  • aqueous preparations may contain varying amounts of the active ingredient depending upon the intended purpose, but an aqueous preparation containing 0.0001 to 10%, for example 0.005 to 10%, by weight of active ingredient may be used.
  • compositions may contain other compounds having biological activity, e.g. compounds having similar or complementary fungicidal activity or which possess plant growth regulating, herbicidal or insecticidal activity.
  • An additional fungicidal compound may be present in the composition.
  • the resulting composition can have a broader spectrum of activity or a greater level of intrinsic activity than the compound of formula (Ia) or (Ib) alone. Further the other fungicide can have a synergistic effect on the fungicidal activity of the compound of formula (Ia) or (Ib).
  • fungicidal compounds which may be included in the composition are (RS)-1-aminopropylphosphonic acid, (RS)-4-(4-chlorophenyl)-2-phenyl-2-(1H-1,2,4-triazol-1-ylmethyl)butyronitrile, (Z)-N-but-2-enyloxymethyl-2-chloro-2',6'-diethylacetanilide, 1-(2-cyano-2-methoxy-iminoacetyl)-3-ethyl urea, 4-(2,2-difluoro-1,3-benzodioxol-4-yl)-pyrrole-3-carbonitrile, 4-bromo-2-cyano-N,N-dimethyl-6-trifluoromethyl-benzimidazole-1-sulphonamide, 5-ethyl-5,8-dihydro-8-oxo(1,3)-dioxol(4,5-q)quinoline-7-carboxylic acid,
  • carboxamide alanycarb, aldimorph, ampropylfos, anilazine, azaconazole, BAS 490F, benalaxyl, benomyl, biloxazol, binapacryl, bitertanol, blasticidin S, bromuconazole, bupirimate, butenachlor, buthiobate, captafol, captan, carbendazim, carbendazim chlorhydrate, carboxin, chinomethionate, chlorbenzthiazone, chloroneb, chlorothalonil, chlorozolinate, clozylacon, copper containing compounds such as copper oxychloride, copper oxyquinolate, copper sulphate, copper tallate, and Bordeaux mixture, cycloheximide, cymoxanil, cyproconazole, cyprofuram, debacarb, di-2-pyridyl disulphide 1,1'-dioxide, dichlo
  • O,O-di-iso-propvl-S-benzvl thiophosphate dimefluazole, dimetconazole, dimethomorph, dimethirimol, diniconazole, dinocap, dipyrithione, ditalimfos, dithianon, dodemorph, dodine, doguadine, edifenphos, epiconazole,
  • etaconazole ethirimol, ethoxyquin, ethyl (Z)-N-benzyl-N-([methyl(methylthioethylideneamino-oxycarbonyl)amino]thio)- ⁇ -alaninate, etridiazole, fenaminosulph, fenapanil, fenarimol, fenbuconazole, fenfuram, fenpiclonil, fenpropidin, fenpropimorph, fentin acetate, fentin hydroxide, ferbam, ferimzone, fluazinam, fludioxonil, fluoroimide, fluquinconazole, flusilazole, flutolanil, flutriafol, folpet, fuberidazole, furalaxyl, furconazole-cis, guazatine, hexaconazole, hydroxy-isoxazole
  • organomercury compounds oxadixyl, oxolinic acid, oxycarboxin, pefurazoate, penconazole, pencycuron, phenazin oxide, phosetyl-AI, phosphorus acids, phthalide, polyoxin D, polyram, probenazole, prochloraz, procymidone, propamocarb, propamocarb hydrochloride, propiconazole, propineb, propionic acid, prothiocarb, pyracarbolid, pyrazophos, pyrifenox, pyrimethanil, pyroquilon, pyroxyfur, pyrrolnitrin, quaternary ammonium compounds,
  • This Example illustrates the preparation of 1-(6-(3,4,5-trimethoxyphenoxy)hex-1-yloxy)-2,2-dimethyl-4,6-diamino-1,2-dihydro-1,3,5-triazine hydrobromide.
  • Aminooxymethylbenzene hydrochloride (25.0g) and dicyandiamide (13.17g) were dissolved in industrial methylated spirits (85ml) with warming and stirring and the resulting solution was heated at reflux for 3 hours. The mixture was then concentrated under reduced pressure to leave an oily residue. The residue was mixed with water (500ml) and basified with 6N sodium hydroxide solution. A benzyloxydiguanide base separated. This solidified on cooling as a crystalline white solid. The solid was filtered from the reaction mixture and washed with water.
  • This Example illustrates the preparation of 1-(10-hydroxydec-1-yloxy)-2,2-dimethyl-4,6-diamino-1,2-dihydro-1,3,5-triazine hydrobromide.
  • This Example illustrates the preparation of the butyric acid salt of 1-(10-hydroxydec-1-yloxy)-2,2-dimethyl-4,6-diamino-1,2-dihydro-1,3,5-triazine.
  • This Example illustrates the preparation of 1-[3-(4-bromophenoxy)-prop-1-oxy-]-2,2-dimethyl-4,6-diamino-1,2-dihydro-1,3,5-triazine hydrobromide.
  • This Example illustrates the preparation of 1-[3-(2,4,5-trichlorophenoxy)-prop-1-oxy-]-2,2-dimethyl-4,6-diamino-1,2-dihydro-1,3,5-triazine.
  • the crude product was purified by reverse phase chromatography.
  • a Varian Mega Bond ELUT C18 reverse phase column was washed with water, and then the crude product (0.05g) in water (1ml) was applied to the column.
  • the column was then washed with water containing 1% acetic acid (50ml), followed by water containing 70% acetonitrile and 1% acetic acid (100ml).
  • the pure product was isolated by freeze drying the appropriate fractions, as a white solid (0.34g).
  • This Example illustrates the preparation of 1-[6-(3,4,5-trimethoxyphenoxy)hex-1-yloxy]-2,2-dimethyl-4,6-bis-(acetamido)-1,2-dihydro-1,3,5-triazine.
  • This Example illustrates the preparation of 1-(12-hydroxydodec-1-yloxy)-2,2-dimethyl-4,6-diamino-1,2-dihydro-1,3,5-triazine hydrobromide.
  • Tetrabutylammonium hydrogen sulfate (31.23g) was added to a stirred solution of sodium hydroxide (7.36g) in water (92ml) (slight exotherm).
  • N-1-(2,6-Dichlorophenyl)ethoxyphthalimide was treated successively with hydrazine hydrate and concentrated hydrochloric acid in the same way as described for a related compound in Example 8 to give
  • Triethylamine (1.93g) was added to a solution of 1-[1-(2,6-dichlorophenyl)ethoxy]-2,2-dimethyl-4,6-diamino-1,2-dihydro-1,3,5-triazine hydrochloride (1.00g) in water (250ml). The resulting mixture was stirred for an hour (white solid began to appear) and then allowed to stand overnight. The precipitated solid was filtered off and dried to
  • the compounds were tested against a variety of foliar fungal diseases of plants.
  • the technique employed was as follows.
  • the plants were grown in John Innes Potting Compost (No 1 or 2) in 4cm diameter minipots.
  • the test compounds were formulated either by bead milling with aqueous DISPERSOL T, or as a solution in acetone, ethanol or acetone/ethanol which was diluted to the required concentration (300 or 100 ppm active ingredient) immediately before use.
  • the formulations were sprayed on to the foliage to maximum retention using a hand held Devilbiss spray gun.
  • TWEEN 20 was added to give a final concentration of 0.05% when the sprays were applied to cereals.
  • the plants were inoculated with the pathogens using spore suspensions sprayed onto the leaves of test plants 6hours, 1 day or 2 days after treatment, depending on disease. After inoculation, the plants were put into an appropriate environment to allow infection to proceed and then incubated until the disease was ready for assessment. The period between inoculation and assessment varied from four to fourteen days according to the disease and environment.
  • Plasvi Plasmopara viticola

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Abstract

A fungicidal composition comprising, as an active ingredient, a compound of formula (Ia) or (Ib) or a tautomer thereof, wherein R?1 and R2¿ are, independently, hydrogen; C¿1?-C6 alkyl, optionally substituted with OH or halo; C2-C6 alkenyl, optionally substituted with OH or halo; or R?1 and R2¿ together form a 3 to 8 membered cycloalkyl or cycloalkenyl ring either of which is optionally substituted with C¿1?-C6 alkyl, C2-C6 alkenyl, OH or halo; R?3¿ is hydrogen, C¿1?-C20 alkyl, C2-C20 alkenyl or C2-C20 alkynyl group, any of which is optionally substituted; R?4 and R5¿ are, independently, hydrogen, CO¿2?R?9, COR9, CONR9R9', OCOR9, CO¿2X, COX, SO2X or CONHX, wherein X is benzyl, phenyl, a 3 to 8 membered cycloalkyl, cycloalkenyl or saturated or unsaturated heterocyclic ring, or a fused ring system; R?9 and R9'¿ are, independently, hydrogen, C¿1?-C8 alkyl, C2-C8 alkenyl, C1-C8 haloalkyl or C2-C8 haloalkenyl; or a salt or metal complex thereof; and a fungicidally acceptable carrier or diluent.

Description

FUNGICIDAL COMPOSITION
The present invention provides a fungicidal composition comprising a 1,3,5-triazine derivative, a method of using said composition to combat fungal infections of plants, certain novel 1,3,5-triazines and processes for their preparation.
Certain 1,3,5-triazines are known from, for example, GB831252 and GB1270831, as bactericide or anti-malarial agents. Certain 1,3,5-triazine derivatives are disclosed in US5300503 as having insecticidal activity (especially against the larvae of Lepidoptera and Coleoptera insects).
The present invention provides a fungicidal composition comprising, as an active ingredient, a compound of formula (Ia) or (Ib), or a tautomer thereof, wherein R1 and R2 are, independently, hydrogen; C1-C6 alkyl, optionally substituted with OH or halo; C2-CR alkenyl, optionally
substituted with OH or halo; or R1 and R2 together form a 3 to 8 membered cycloalkyl or cycloalkenyl ring either of which is optionally substituted with C1-C6 alkyl, C2-C6 alkenyl, OH or halo; R3 is hydrogen, C1-C20 alkyl, C2-C20 alkenyl or C2-C20 alkynyl group, any of which is optionally substituted with one or more substituents independently selected from: halo, OR6, COR6, COOR6, CONR6R7, NHCOR6, NR6R7, SR6, SOR6, SO2R6 ( OCOR6, N3, NO-, cyano, SO2NR6R7, CR6:NOR7, CS.NR6R7, NR6.CONR7R7' , O.CO2R6,
O.CONR6R7, NR6.CO2R7, CONR6.NR7R7', CONR6OR7, NR6SO2R7, P+X3 (with an associated halide anion) or a group X; R6, R7 and R7' are each
independently selected from hydrogen, a group X, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkyl-X, C2-C6 alkenyl-X, any of which is optionally substituted by OH or halo; X is benzyl, phenyl, a 3 to 8 membered cycloalkyl, cycloalkenyl or saturated or unsaturated heterocyclic ring, or a fused ring system containing up to four 3 to 8 membered rings; the rings of the fused ring system are cycloalkyl, cycloalkenyl, phenyl or saturated or unsaturated heterocyclic rings or a combination of any these;
R3 may also be a group Z-Q, wherein Z is R10, R10-Y-Y-R10, R10-Y-O-Y-R10,
R10-Y-SO2-R10, R10-NHCO-Y-CONH-R10, R10-Y-R10, R10-O-R10, R10-O-R10-O-R10,
R10-S-R10 or R10-NR11-R10; R10 and R11 are each C1-C20 alkyl or C2-C8 alkenyl; Y is a linking group derived from benzyl, phenyl, a 3 to 8 membered cycloalkyl, cycloalkenyl or saturated or unsaturated heterocyclic ring, or a fused ring system containing up to four 3 to 8 membered rings; the rings of the fused ring system are cycloalkyl, cycloalkenyl, phenyl or saturated or unsaturated heterocyclic rings or a combination of any these; the groups X and Y are, independently, optionally substituted with cyano, halo, SO2NR8R8', NO2, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C1-C8 haloalkyl, C3-6 cycloalkyl, C2-C8 haloalkenyl, OR8, COR8, COOR8, CONR8R8', NR8R8', SR8, SOR8, SO2R8, phenyl, phenyl (C1-6)alkyl, phenyl (C2-6) alkenyl, (the phenyl groups of the last three groups may themselves be substituted with halo, C1-C6 alkyl, C1-C6 alkoxy or cyano), C1-C8 alkyl-OR8 or C2-C8 alkenyl -OR8, or, where possible, oxo or imino; R8 and R8' are,
independently, hydrogen, C1-C8 alkyl, C1-C8 haloalkyl, C3-C8 cycloalkyl, C2-C8 alkenyl, C2-C8 alkynyl, phenyl, benzyl or phenoxy(C1-4)alkyl, which are optionally substituted with cyano, halo, SO2NH2, NO2, NH2, C1-C8 alkyl, C2-C8 alkenyl, C1-C8 haloalkyl or C2-C8 haloalkenyl, or, where possible oxo or imino; Q is a group of formula (II), wherein R1 and R2 are as defined above and R4 and R5 are as defined below; alternatively, R3 is a group R10-W(R10Q)2 wherein W is as defined above for Y except that it is a trivalent linking group; R4 and R5 are, independently, hydrogen, CO2R9,
COR9 , CONR9R9 ' , OCOR9 , CO7X, COX, SO2X or CONHX, wherein X i s as defined above; and, R9 and R9' are, independently, hydrogen, C1-C8 alkyl, C2-C8 alkenyl, C1-C8 haloalkyl or C2-C8 haloalkenyl; when any of the foregoing groups comprise NR6R7, NR7R7' , NR8R8' or NR9R9' the substituents R6 and R7, R7 and R7' , R8 and R8' or R9 and R9' may join to form a fused heterocyclic ring optionally substituted with cyano, halo, SO2NR12R12', NO2. C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C1-C8 haloalkyl, C3-6 cycloalkyl,
C2-C8 haloalkenyl, OR12, COR12, COOR12, CONR12R12', NR12R12 ' , SR12, SOR12,
SO2R12, phenyl, phenyl(C1-6)alkyl, phenyl(C2-6)alkenyl, (the phenyl groups of the last three groups may themselves be substituted with halo, C1-C6 alkyl, C1-C6 alkoxy or cyano), or, where possible, oxo or imino; wherein R12 and R12 are, independently, hydrogen, C1-C8 alkyl, C3-C8 cycloalkyl,
C2-C8 alkenyl, C2-C8 alkynyl, phenyl, benzyl or phenoxy(C1-4)alkyl, which are optionally substituted with cyano, halo, SO2NH2, NO2, NH2, C1-C8 alkyl,
C2-C8 alkenyl, C1-C8 haloalkyl or C2-C8 haloalkenyl, or, where possible, oxo or imino; or a salt or metal complex thereof; and a fungicidally acceptable carrier or diluent.
The compounds of formula (Ia) can exist in different tautomeric forms.
For example when R4 and R5 are both hydrogen, the compound of formula (Ib) is a tautomeric form of formula (Ia). Compositions comprising such tautomers, and mixtures thereof in all proportions, and methods of using such tautomers, and mixtures thereof, in all proportions, for combating fungal infections of plants constitute a part of the present invention.
Alkyl groups are straight or branched chain. Alkyl is, for example, methyl, ethyl, n-propyl, iso-propyl, tert-butyl or hexyl.
Alkenyl groups are straight or branched chain and have at least one double bond. Alkenyl is, for example, ethenyl, 1-propenyl or hexenyl.
Alkynyl groups are straight or branched chain and have at least one triple bond. Alkynyl is, for example, ethynyl or propargyl.
Cycloalkyl preferably comprises 3-7 carbon atoms and is, for example, cyclopropyl, cyclopentyl, cyclohexyl or cycloheptyl.
Cycloalkenyl preferably comprises 3-7 carbon atoms and is, for example, cyclohexenyl.
As used herein the terms "halo" and halogen include fluorine, chlorine, bromine and iodine.
Heterocyclic rings are preferably 5- or 6-membered rings containing one or more of the same or different heteroatoms (especially nitrogen, oxygen or sulphur). Examples of heterocyclic rings are furan, pyrrole, thiophene or pyridine and their partially and fully saturated derivatives (such as piperidine, pyrrolidine or tetrahydrofuran) or pyrimidine, imidazole, triazole, imidazoline, triazine, oxazole or oxazoline.
When R6 and R7, R7 and R7', R8 and R8' or R9 and R9' join to form a fused heterocyclic ring it is preferred that the ring is a 5- or 6-membered ring containing one or two nitrogen or oxygen atoms. Such a ring is, for example, piperidine, pyrrolidine, morpholine or piperazine.
Examples of fused ring systems include aromatic ring systems such as naphthalene, anthracene and phenanthrene as well as partially saturated systems such benzocyclohexane and fully saturated systems such as
dicyclohexane, tricyclohexane, norbornane and adamantane. Examples of fused ring systems which comprise a heterocyclic ring or a carbocyclic ring fused to a heterocyclic ring are benzimidazole, benzofuran, indole, quinoline and indolinone.
Salts include salts of a mineral acid [for example, a salt of a haloacid (such as a hydrochloride, hydrobromide or hydroiodide) or of phosphoric, nitric, sulphuric, tetrafluoroboric, hexafluorophosphoric or carbonic acid] or an organic acid [for example acetic, butyric,
trifluoracetic, maleic, malonic, oxalic, gluconic, succinic, fumaric, tartaric, citric, salicylic, sorbic, lactic, DL-mandelic, saccharinic or sulphonic (such as p-toluenesulphonic, 1,5-naphthylidenesulphonic or camphorsulphonic) acid].
A metal complex is a complex with a metal salt, such as complexes with a transition metal salt (for example a salt having a cation of copper, silver, iron (II), iron (III), zinc or nickel, and an anion of a halide (such as chloride or bromide) or nitrate).
In one particular aspect the present invention provides a fungicidal composition comprising, as an active ingredient, a compound of formula (Ia), or a tautomer thereof, wherein R1 and R2 are, independently, hydrogen; C1-C6 alkyl, optionally substituted with OH or halo; C2-C6 alkenyl, optionally substituted with OH or halo; or R1 and R2 together form a 3 to 8 membered cycloalkyl or cycloalkenyl ring either of which is optionally substituted with C1-C6 alkyl, C2-C6 alkenyl, OH or halo; R3 is hydrogen or C1-C20 alkyl or C2-C20 alkenyl group, any of which is
optionally substituted with one or more substituents independently selected from: halo, OR6, COR6, COOR6, CONR6R7, NHCOR6, NR6R7, SR6, SO2R6, OCOR6 or a group X; R6 and R7 are each independently selected from hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkyl-X, C2-C6 alkenyl-X, any of which is optionally substituted by OH or halo, or a group X; X is benzyl, phenyl, a
3 to 8 membered cycloalkyl, cycloalkenyl or saturated or unsaturated heterocyclic ring, or a fused ring system containing up to four 3 to 8 membered rings; the rings of the fused ring system are cycloalkyl, cycloalkenyl, phenyl or saturated or unsaturated heterocyclic rings or a combination of any these; the group X is optionally substituted with CN, halo, SO2NH2, NO2, oxo (where possible), imino (where possible), phenyl
(itself optionally substituted by halogen), C1-C8 alkyl, C2-C8 alkenyl, C1-C8 haloalkyl, C3-6 cycloalkyl, C2-C8 haloalkenyl, OR8, COR , COOR8,
CONHR8, NHR8, SR8, SO2R8, phenyl(C1-6)alkyl, C1-C8 alkyl -OR8,
phenyl(C2-6)alkenyl or C2-C8 alkenyl-OR8; R8 is hydrogen, C1-C8 alkyl,
C2-C8 alkenyl, phenyl, benzyl or phenoxy(C1-4)alkyl, which are optionally substituted with CN, halo, SO2NH2, NO2, NH2, oxo (where possible), imino
(where possible), C1-C8 alkyl, C2-C8 alkenyl, C1-C8 haloalkyl or C2-C8 haloalkenyl; R3 may also be a group Z-Q, wherein Z is R10, R10-Y-Y-R10 R10-Y-O-Y-R10, R10-Y-SO2-R10, R10-NHCO-Y-CONH-R10, R10-Y-R10, R10-O-R10,
R10-O-R10-O-R10, R10-S-R10 or R10-NR11-R10; R10 and R11 are each C1-C20 alkyl or C2-C8 alkenyl, Y is as defined above for X except that it is a
1 2 divalent linking group and Q is a group of formula (II), wherein R and R
4 5 3 are as defined above and R and R are as defined below; alternatively, R is a group R10-W(R10Q)2 wherein W is as defined above for X except that it
4 5
is a trivalent linking group; R and R may be the same or different and are hydrogen, CO2R9, COR9, CONR9, OCOR9, CO2X, COX, SO2X or CONX, wherein X is as defined above; and, R9 is hydrogen, C1-C8 alkyl, C2-C8 alkenyl, C1-C8 haloalkyl or C2-C8 haloalkenyl; or a salt thereof; and a fungicidally acceptable carrier or diluent.
In another aspect the present invention provides a fungicidal
composition comprising, as an active ingredient, a compound of formula
1 2
(Ia), or a tautomer thereof, wherein R and R are, independently, C1-C6 alkyl; or R1 and R2 together form a 3 to 8 membered cycloalkyl ring which is optionally substituted with C1-C6 alkyl; R3 is C1-C20 alkyl or C2-C20 alkenyl, either of which is optionally substituted with one or more substituents independently selected from: OR6 , NR6R7, SR , OCOR6 or a group
X; R6 and R7 are each independently selected from hydrogen or a group X; X is phenyl, a 3 to 8 membered cycloalkyl, cycloalkenyl or an unsaturated heterocyclic ring, or a fused ring system containing up to four 3 to 8 membered rings; the rings of the fused ring system are phenyl or
unsaturated heterocyclic rings or a combination of any these; the group X is optionally substituted with CN, halo, NO2, phenyl, C1-C8 alkyl, C2-C8 alkenyl, C1-C8 haloalkyl, C3-6 cycloalkyl, C2-C8 haloalkenyl, OR8, COR8, COOR8, NHR , C1-8 alkyl-R8 or phenyl(C2-6)alkenyl; R8 is hydrogen, C1-C8 alkyl, phenyl or phenoxy(C1-4)alkyl; R3 may also be a group Z-Q, wherein Z is R10, R10-[C3-6 cycloalkyl] -R10 or R10-S-R10; R10 and R11 are each C1-C20 alkyl, and Q is a group of formula (II), wherein R1 and R2 are as defined
4 5 4 5
above and R and R are as defined below; R and R may be the same or different and are hydrogen or COR9; and, R9 is hydrogen, C1-C8 alkyl or C1-C8 haloalkyl; or a salt thereof; and a fungicidally acceptable carrier or diluent.
In a further aspect the present invention provides a fungicidal composition comprising, as an active ingredient, a compound of formula (Ia), or a tautomer thereof, wherein R3 is (CH2)nOX wherein n is an integer from 2-12; and X is hydrogen or phenyl (optionally substituted with C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C2-C4 alkenyl, hydroxy, C2-C4 alkylcarbonyl, halogen, NH2, CO2R21, cyano or nitro); OR (CH2)nX wherein n is an integer from 1-12; X is (CHR22)R23; R22 is hydrogen or C1-C4 alkyl; R23 is phenoxy, phenyl or naphthyl, these groups being optionally substituted with C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C2-C4 alkenyl, hydroxy, C2-C4 alkylcarbonyl, halogen, NH2, CO2R21, cyano or nitro; OR CHR24R25 wherein R24 is hydrogen or C1-C4 alkyl and R25 is C3-C7 cycloalkyl, phenyl (optionally substituted with C1-C4 alkyl, C1-C4 haloalkyl, C1-C, haloalkoxy, C1-C4 alkoxy, C2-C4 alkenyl, hydroxy, halogen, NH2, CO2R21, cyano or nitro) or C2-C4 alkenyl; R4 and R5 are the same and are hydrogen or C1-C4 alkylcarbonyl; R21 is C1-C4 alkyl; or a hydrochloride or hydrobromide salt thereof; and a fungicidally acceptable carrier or diluent.
In a still further aspect the present invention provides a fungicidal composition comprising, as an active ingredient, a compound of formula (Ia), or a tautomer thereof, wherein R3 is: (CH2)nOX wherein n is an integer from 2-12 (especially 3-10); and X is hydrogen or phenyl
(optionally substituted with C1-C4 alkyl, C1-C4 alkoxy, C2-C4 alkenyl, hydroxy, halogen, NH2 or CO2R21); R21 is C1-C4 alkyl, (X is especially 3,4,5-trimethoxyphenyl); OR (CH2)nX wherein n is an integer from 1-12 (especially 1-10); X is (CHR22)R23; R22 is hydrogen or C1-C4 alkyl; R23 is phenoxy, phenyl (optionally substituted with halogen) or naphthyl
(optionally substituted with C1-C4 alkyl); OR CHR24R25 wherein R24 is hydrogen or C1-C4 alkyl and R25 is C3-C7 cycloalkyl (especially
cyclohexyl), phenyl (optionally substituted with halogen) or C2-C4 alkenyl; R4 and R5 are the same and are hydrogen or C1-C4 alkylcarbonyl; or a hydrochloride or hydrobromide salt thereof; and a fungicidally acceptable carrier or diluent.
In another aspect the present invention provides a fungicidal composition comprising, as an active ingredient, a compound of formula
(Ia), or a tautomer thereof, wherein R1 and R2 are both methyl; R4 and R5. are both hydrogen; and R3 is phenoxy(C1-12)alkyl wherein the alkyl group is straight or branched chain and is, for example, (CH2)n wherein n is an integer from 1 to 12 (such as 3, 4, 6, 8 or 10); and the phenoxy is unsubstituted or substituted by one or more, or a mixture of, halogen (such as bromine or chlorine atoms), nitro, C1-4 alkyl (such as methyl or n-propyl), C1-4 alkoxy (such as methoxy), C2-C4 alkenyl (especially
propen-2-yl) or C1-C4 alkylcarbonyl (such as acetyl); and a fungicidally acceptable carrier or diluent.
In a further aspect the present invention provides a fungicidal composition comprising, as an active ingredient, a compound of formula (Ia), or a tautomer thereof, wherein R1 and R2 are both methyl; R4 and R5 are both hydrogen; and R3 is:
a) phenyl (C1-4)alkyl wherein the phenyl is optionally substituted by halogen (especially one or two chlorine atoms), nitro or C2-4 alkenyl (especially propen-2-yl), and the alkyl group, which is straight or branched chain is, for example, CH2, CH(CH3) or (CH2)3; b) phenoxy(C1-12) alkyl wherein the alkyl group is straight or branched chain and is, for example, (CH2)n wherein n is an integer from 1 to 12 (such as 3, 4, 6, 8 or 10); and the phenoxy is unsubstituted or substituted by one or more, or a mixture of, halogen (such as bromine or chlorine atoms), nitro, C1-4 alkyl (such as methyl or n-propyl) or C1-4 alkoxy (such as methoxy);
c) C3-7 cycloalkyl (C1-10)alkyl wherein the cycloalkyl is especially cyclohexyl and the alkyl group is especially (CH2)n wherein n is an integer from 1 to 10 (especially 1 or 6);
d) hydroxy(C1-12) alkyl wherein the alkyl group is especially (CH2)n wherein n is an integer from 1 to 12 (especially 10); or
e) C6 cycloalkenylmethyl such as cyclohex-3-en-1-yl methyl;
and a fungicidally acceptable carrier or diluent.
In a still further aspect the present invention provides a fungicidal composition comprising, as an active ingredient, a compound of formula (Ia), or a tautomer thereof, wherein R1 and R2 are C1-C4 alkyl (especially methyl) or C1-C4 haloalkyl (such as CH2Cl) or R1 and R together form a cyclohexyl ring optionally substituted with C1-C4 alkyl (especially methyl); R4 and R5 are the same and are hydrogen or C1-C4 alkylcarbonyl (especially acetyl); R3 is (CH2)nR20; n is 0 or an integer from 1 to 14; R20 is hydrogen, hydroxy, cyano, C1-C10 alkyl (optionally substituted with hydroxy or phenyl), C1-C4 haloalkyl, C1-C4 alkoxy, C2-C4 alkenyl (optionally substituted with halogen or phenyl), C2-C4 alkenyloxy, C2-C4 alkynyl, C3-C6 cycloalkyl (optionally substituted with C1-4 alkyl, halogen), C3-C6 cycloalkenyl, phenyl, naphthyl, O(CO)R30, CO2R30, CONR30R31, NR30R31, NHCOR30, NHCO2R30, COR30, O(CONHR30) , O(CO2R30), N(SO2R30)R31 or CH=NOH; R30 and R31 are, independently, hydrogen, C1-4 alkyl, C3-C4 alkenyl, C3-C4 alkynyl, phenyl, phenyl(C1-C4)alkyl, COR32, C3-C6 cycloalkyl or C3-C8 cycloalkenyl; R32 is C1-4 alkyl, C3-C4 alkenyl, phenyl or phenyl (C1-C4)alkyl; wherein any of the foregoing phenyl or naphthyl moieties are optionally substituted with halogen (especially chlorine or fluorine), C1-C4 alkyl (especially methyl), C4-C4 alkoxy (especially methoxy, ethoxy, iso-propoxy or n-butoxy) or C1-C4 haloalkoxy (such as OCF3); or a salt thereof (especially a hydrochloride or hydrobromide salt); and a fungicidally acceptable carrier or diluent.
In another aspect the present invention provides a fungicidal
composition comprising, as an active ingredient, a compound of formula (III), or a tautomer thereof, wherein R1 and R2 are C1-C4 alkyl (especially methyl) or R1 and R2 together form a cyclohexyl ring optionally substituted with C1-C4 alkyl (especially methyl); R4 and R5 are the same and are hydrogen or C1-C4 alkylcarbonyl (especially acetyl); L1 is hydrogen or C1-C4 alkyl; L2, L3, L4, L5 and L are, independently, hydrogen, C1-C12 alkyl, C1-C4
haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C2-C4 alkenyl (optionally
substituted with phenyl or halogen), C2-C4 alkynyl (optionally substituted with phenyl), phenyl, phenoxy, phenyl(C1-C4)alkyl, phenoxy(C1-C4)alkyl, phenyl(C1-C4)alkoxy, COR35, CO-R35, phenoxy(C1-C4)alkoxy, nitro, halogen, cyano, C3-C6 cycloalkyl, NR35R36, SR35, S(O)R35 or SO2R35; R35 and R36 are, independently, hydrogen, C1-C4 alkyl, C1-C4 haloalkyl or phenyl; wherein any of the foregoing phenyl moieties are optionally substituted with halogen
(especially chlorine or fluorine), C1-C4 alkyl (especially methyl), C1-C4 alkoxy (especially methoxy, ethoxy, iso-propoxv or n-butoxy) or C1-C4 haloalkoxy (such as OCF,); or L2 and L3, or L3 and L4, or L4 and L5, or L and L6 join to form a fused aromatic ring optionally substituted as for phenyl; or a salt thereof (especially a hydrochloride or hydrobromide salt); and a fungicidally acceptable carrier or diluent.
In yet another aspect the present invention provides a fungicidal composition comprising, as an active ingredient, a compound of formula (IV), or a tautomer thereof, wherein R1 and R2 are C1-C4 alkyl (especially methyl); R4 and R5 are the same and are hydrogen, C1-C4 alkylcarbonyl (especially acetyl) or C1-C4 haloalkylcarbonyl (especially CF3CO); n is an integer from 1 to 11 (especially 1-6); Link is CH2 or CHR33; Z1 is oxygen or sulphur; and L1, L2, L3, L4 and L5 are, independently, hydrogen, C1-C12 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C2-C4 alkenyl (optionally substituted with phenyl or halogen), C2-C4 alkynyl (optionally substituted with phenyl), phenyl, phenoxy, phenyl(C1-C4)alkyl, phenoxy(C1-C4)alkyl, phenyl(C1-C4)alkoxy, COR34, CO2R34, phenoxy(C1-C4) alkoxy, nitro, halogen, cyano, C3-C6 cycloalkyl, NH2, SR34, S(O)R34 or SO2R34; R33 and R34 are, independently, C1-C4 alkyl, C1-C4 haloalkyl or phenyl; wherein any of the foregoing phenyl moieties are optionally substituted with halogen (especially chlorine or fluorine), C1-C4 alkyl (especially methyl), C1-C4 alkoxy
(especially methoxy, ethoxy, iso-propoxy or n-butoxy) or C1-C4 haloalkoxy
(such as OCF3); or a salt thereof (especially a hydrochloride or hydrobromide salt); and a fungicidally acceptable carrier or diluent.
Examples of compounds of formula (Ia) that can be used as an active ingredient in a composition of the invention follow in TABLES I-IV.
TABLE I is directed to compounds of formula (Ia) wherein R3 is (CH2)nR20.
TABLE II is directed to compounds of formula (III).
TABLE III is directed to compounds of formula (IV).
TABLE IV is directed to compounds of formula (V).
Note that when there is no entry in the 'Salt' column of Tables I-IV the compound is in the form of a free base. The chemical structure of Compound Nos. II.23 and III.162 is to be found with the chemical structures at the end of the description. The following abbreviations are used in these Tables:
Me = methyl Et = ethyl
n-Pr = n-propyl i-Pr = iso-propyl
s-Bu = sec-butyl n-Bu = n-butyl
Figure imgf000012_0001
Figure imgf000013_0001
Figure imgf000014_0001
Figure imgf000015_0001
Figure imgf000016_0001
Figure imgf000017_0001
Figure imgf000018_0001
Figure imgf000019_0001
Figure imgf000020_0001
Figure imgf000021_0001
Figure imgf000022_0001
Figure imgf000023_0001
Figure imgf000024_0001
Figure imgf000025_0001
Figure imgf000026_0001
Figure imgf000027_0001
Figure imgf000028_0001
Figure imgf000029_0001
Figure imgf000030_0001
Figure imgf000031_0001
Figure imgf000033_0001
Figure imgf000034_0001
Figure imgf000035_0001
Tables V-VIII give melting point, selected proton nuclear magnetic resonance (NMR), melting point (Mpt) or mass spectral (MS) data for certain compounds described in Tables I-IV. Chemical shifts were measured at room temperature and are in parts per million (ppm) from tetramethylsilane. Where shown, NMR data are selective, no attempt has been made to list every absorption in all cases. The following abbreviations are used:
s = singlet d = doublet
t = triplet q = quartet
m = multiplet dd = doublet of doublets
bs & br s = broad singlet br d = broad doublet
br m = broad multiplet FAB = fast atom bombardment
CI = chemical ionisation EI = electron ionisation
dec & decomp = decomposition
Figure imgf000037_0001
Figure imgf000038_0001
Figure imgf000039_0001
Figure imgf000040_0001
Figure imgf000041_0001
Figure imgf000042_0001
Figure imgf000043_0001
Figure imgf000044_0001
Figure imgf000045_0001
Certain compounds of formula (Ia) or (Ib) are novel. The present invention provides therefore a compound of formula (Ia), or a tautomer thereof, wherein R3 is: (CH2)nOX wherein n is an integer from 2-12; and X is hydrogen or phenyl (optionally substituted with C1-C4 alkyl, C1-C4 alkoxy,
71 21 C2-C4 alkenyl, hydroxy, C2-C4 alkylcarbonyl, halogen, NH2 or CO2R21); R21 is C1-C4 alkyl; OR (CH2)nX wherein n is an integer from 1-12; X is (CHR22)R23;
R22 is hydrogen or C1-C4 alkyl; R23 is phenoxy, phenyl (optionally
substituted with halogen) or naphthyl (optionally substituted with C1-C4 alkyl); OR CHR24R25 wherein R24 is hydrogen or C1-C4 alkyl and R25 is C3-C7 cycloalkyl, phenyl (optionally substituted with halogen) or C2-C4 alkenyl; R4 and R5 are the same and are hydrogen or C1-C4 alkylcarbonyl; or a
hydrochloride or hydrobromide salt thereof.
The compounds of formula (Ia) and (Ib) can be made by using or adapting literature methods, such as methods described in any of the following documents: GB831252, US3105074, GB945159, DE1813243, DE1934120, DE1963759,
DE1965941, DE1965925, DE1965711, DE1957769, GB1250531, DE2107905, DE2116252,
US3660394, US3682912 or US4496549.
Alternatively, the compounds of formula (Ia) and (Ib), or their tautomers, wherein R4 and R5 are other than hydrogen, can be prepared by treating a compound of formula (VI), or a tautomer thereof, wherein R1, R2 and R3 are as defined above, with an acylating agent of formula R9C(O)L, wherein R9 is as defined above and L is a leaving group (such as a halogen atom, C1-C4 alkoxy or a mesylate group).
Compounds of formulae (Ia) or (Ib) in which R4 and R5 are both hydrogen may be prepared by the reaction of a compound of formula (VII), wherein R1 and R2 are as defined above, or a salt thereof with an alkylating agent of formula R3-L, wherein R3 is as defined above and L is as defined above. The reaction is typically carried out in a polar solvent (such as methanol or ethanol) .
Alkyl ating agents of formula R3-L are readily available or may be prepared by methods known to those skilled in the art.
Compounds of formula (VII) can be prepared from compounds of formula (VIII), wherein R1 and R2 are as defined above, by catalytic hydrogenolysis using a catalyst (such as palladium or platinum). The catalytic
hydrogenolysis is preferably conducted at room temperature, atmospheric pressure and in an alcoholic solvent (such as methanol or ethanol). Compounds of formula (VIII) can be prepared by reacting a compound of formula (IX), or one of its tautomers, with a carbonyl compound of formula (X), wherein R1 and R2 are as defined above. The reaction proceeds
favourably under acidic conditions at the reflux temperature of the solvent used, which is preferably an alcoholic solvent (such as methanol or ethanol).
Carbonyl compounds of formula (X) are readily available or may be synthesised by methods known to those skilled in the art.
The compound of formula (IX) may be prepared by the reaction of
O-benzylhydroxylamine with dicyandiamide, both of which are readily
available.
In an alternative approach, a hydroxy1amine of formula R3-ONH2, wherein R3 is as defined above, may be used in place of Q-benzylhydroxy1amine in the reaction with dicyandiamide to produce a compound of formula (XI). A compound of formula (Ia) or (Ib), wherein R4 and R5 are both hydrogen can be prepared by reacting a compound of formula (XI) with a compound of formula
(X) under the conditions described above.
A metal complex of a compound of formula (Ia) or (Ib) can be prepared by treating the free base of a compound of formula (Ia) or (Ib) with a metal salt in a suitable solvent (such as aqueous ethanol).
A salt of a compound of formula (Ia) or (Ib) can be prepared by treating the free base of a compound of formula (Ia) or (Ib) with the desired acid in a suitable solvent (such as water or ethanol) at room temperature.
The free base of a compound of formula (Ia) or (Ib) can be purified using standard techniques known in the literature (such as crystalisation, reverse phase chromatography or by the use of ion exchange resins).
In a still further aspect the present invention provides processes for preparing the compounds of formula (Ia) and (Ib).
In another aspect the present invention provides a fungicidal
composition comprising, as an active ingredient, a compound obtainable by treating a compound of formula (VI), or a tautomer thereof, wherein R1, R2 and R3 are as defined above, with an acylating agent of formula R9C(O)L, wherein R9 is as defined above and L is a leaving group (such as a halogen atom, C1-C4 alkoxy or a mesylate group).
The compounds of formula (Ia) and (Ib) (which is an active ingredient in the compositions of the invention) are active fungicides and may be used to control one or more of the following pathogens: Pyricularia oryzae 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 e.g. turf, rye, coffee, pears, apples, peanuts, sugar beet, vegetables and ornamental plants; Erysiphe graminis (powdery mildew) on barley, wheat, rye and turf and other powdery mildews on various hosts such as Sphaerotheca macularis on hops, Sphaerotheca fuliginea on cucurbits (e.g. cucumber), Podosphaera leucotricha on apple and Uncinula necator on vines; Cochliobolus spp.,
Helminthosporium spp., Drechslera spp. (Pyrenophora spp.), Rhynchosporium spp., Septoria spp. (including Mycosphaerella graminicola and Leptosphaeria nodorum), Pseudocercosporella herpotrichoides and Gaeumannomyces graminis on cereals (e.g. wheat, barley, rye), turf and other hosts; Cercospora
arachidicola and Cercosporidium personatum on peanuts and other Cercospora species 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 (e.g. cucumber), oil-seed rape, apples, tomatoes, cereals (e.g. 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 (e.g. wheat); Monilinia spp. on stone fruit, tree nuts and other hosts; Didymella spp. on tomatoes, turf, wheat 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;
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. 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 Rhizoctoni a species on various hosts such as wheat and barley, vegetables, cotton and turf; Sclerotinia spp. on turf, peanuts, oil-seed rape and other hosts; Sclerotium spp. on turf, peanuts and other hosts; Colletotrichum spp. on a range of hosts including turf, coffee and vegetables; Laetisaria fuciformis on turf; Mycosphaerella spp. on banana, peanut, citrus, pecan, papaya and other hosts; Diaporthe spp. on citrus, soybean, melon, pear, lupin and other hosts; Elsinoe spp. on citrus, vines, olives, pecans, roses and other hosts; 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 and other hosts; post-harvest diseases particularly of fruit (e.g. Pencillium digitatum and P. 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, Pseudopezicula tracheiphila and
Stereum hirsutum; other pathogens on 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 e.g. Polymyxa graminis on cereals as the vector of barley yellow mosaic virus (BYMV).
Some of the compositions show a broad range of activities against fungi in vitro.
Further, some of the compositions may be active as seed dressings against pathogens including Fusarium spp., Septoria spp., Tilletia spp., (e.g. bunt, a seed-borne disease of wheat), Ustilago spp. and
Helminthosporium spp. on cereals, Rhizoctonia solani on cotton and
Pyricularia oryzae on rice.
It is preferred that the compositions of the present invention are used to combat fungal diseases of cereal crops.
The compounds of formula (Ia) and (Ib) may move acropetally/locally in plant tissue.
It is preferred that all compositions, both solid and liquid
formulations, comprise 0.0001 to 95%, more preferably 1 to 85%, for example 1 to 25% or 25 to 60%, of a compound of formula (Ia) and (Ib).
When applied the foliage of plants, the compounds of formula (Ia) and (Ib) are applied at rates of 0.1g to 10Kg, preferably 1g to 8Kg, more preferably 10g to 4Kg, of active ingredient per hectare.
When used as seed dressings, the compounds of formula (Ia) and (Ib) are used at rates of 0.0001g (for example 0.001g or 0.05g) to 10g, preferably 0.005g to 8g, more preferably 0.005g to 4g, of active ingredient per kilogram of seed.
The compositions of the invention can be applied in a number of ways. For example, they can be applied, formulated or unformulated, directly to the foliage of a plant, to seeds or to other medium in which plants are growing or are to be planted, or they can be sprayed on, dusted on or applied as a cream or paste formulation, or they can be applied as a vapour or as slow release granules.
Application can be to any part of the plant including the foliage, stems, branches or roots, or to soil surrounding the roots, or to the seed before it is planted, or to the soil generally, to paddy water or to hydroponic culture systems. The compositions may also be injected into plants or sprayed onto vegetation using electrodynamic spraying techniques or other low volume methods.
The term "plant" as used herein includes seedlings, bushes and trees. Furthermore, the fungicidal method of the invention includes preventative, protectant, prophylactic, systemic and eradicant treatments.
The type of composition used in any instance will depend upon the particular purpose envisaged.
The compositions may be in the form of dustable powders or granules comprising the active ingredient and a solid diluent or carrier, for example, fillers such as kaolin, bentonite, kieselguhr, dolomite, calcium carbonate, talc, powdered magnesia, fuller's earth, gypsum, diatomaceous earth and china clay. Such granules can be preformed granules suitable for application to the soil without further treatment. These granules can be made either by impregnating pellets of filler with the active ingredient or by pelleting a mixture of the active ingredient and powdered filler. Compositions for dressing seed may include an agent (for example, a mineral oil) for assisting the adhesion of the composition to the seed; alternatively the active ingredient can be formulated for seed dressing purposes using an organic solvent (for example, N-methylpyrrolidone, propylene glycol or
N,N-dimethylformamide). The compositions may also be in the form of wettable powders or water dispersible granules comprising wetting or dispersing agents to facilitate the dispersion in liquids. The powders and granules may also contain fillers and suspending agents. The compositions may also be in the form of soluble powders or granules, or in the form of solutions in polar solvents.
Soluble powders may be prepared by mixing the active ingredient with a water-soluble salt such as sodium bicarbonate, sodium carbonate, magnesium sulphate or a polysaccharide, and a wetting or dispersing agent to improve water dispersibility/solubility. The mixture may then be ground to a fine powder. Similar compositions may also be granulated to form water-soluble granules. Solutions may be prepared by dissolving the active ingredient in polar solvents such as ketones, alcohols and glycol ethers. These solutions may contain surface active agents to improve water dilution and prevent crystallisation in a spray tank.
Emulsifiable concentrates or emulsions may be prepared by dissolving the active ingredient in an organic solvent optionally containing a wetting or emulsifying agent and then adding the mixture to water which may also contain a wetting or emulsifying agent. Suitable organic solvents are aromatic solvents such as alkylbenzenes and alkylnaphthalenes, ketones such as cyclohexanone and methyleyelohexanone, chlorinated hydrocarbons such as chlorobenzene and trichlorethane, and alcohols such as benzyl alcohol, furfuryl alcohol, butanol and glycol ethers.
Suspension concentrates of largely insoluble solids may be prepared by ball or bead milling with a dispersing agent with a suspending agent included to stop the solid settling.
Compositions to be used as sprays may be in the form of aerosols wherein the formulation is held in a container under pressure of a propellant, e.g. fluorotrichloromethane or dichlorodifluoromethane.
The compounds of formula (Ia) and (Ib) can be mixed in the dry state with a pyrotechnic mixture to form a composition suitable for generating in enclosed spaces a smoke containing the compounds.
Alternatively, the compositions of the invention may be used in micro-encapsulated form. They may also be formulated in biodegradable polymeric formulations to obtain a slow, controlled release of the active substance.
By including suitable additives, for example additives for improving the uptake, distribution, adhesive power and resistance to rain on treated surfaces, the different compositions can be better adapted for various utilities. Other additives may be included to improve the biological efficacy of the various formulations. Such additives can be surface active materials to improve the wetting and retention on surfaces treated with the formulation and also the uptake and mobility of the active material, or additionally can include oil based spray additives, for example, certain mineral oil and natural plant oil (such as soya bean and rape seed oil) additives, or blends of them with other adjuvants.
The compounds of formula (Ia) and (Ib) can be used as mixtures with fertilisers (e.g. nitrogen-, potassium- or phosphorus-containing
fertilisers). Compositions comprising only granules of fertiliser
incorporating, for example coated with, a compound of formula (Ia) or (Ib) are preferred. Such granules suitably contain up to 25% by weight of the compound.
Wettable powders, emulsifiable concentrates and suspension concentrates will normally contain surfactants, e.g. a wetting agent, dispersing agent, emulsifying agent or suspending agent. These agents can be cationic, anionic or non-ionic agents.
Suitable cationic agents are quaternary ammonium compounds, for example, cetyltrimethyl ammonium bromide. Suitable anionic agents are soaps, salts of aliphatic monoesters of sulphuric acid (for example, sodium lauryl sulphate), and salts of sulphonated aromatic compounds (for example, sodium
dodecylbenzenesulphonate, sodium, calcium or ammonium lignosulphonate, butylnaphthalene sulphonate, and a mixture of sodium diisopropyl- and triisopropylnaphthalene sulphonates).
Suitable non-ionic agents are the condensation products of ethylene oxide with fatty alcohols such as oleyl or cetyl alcohol, or with alkyl phenols such as octyl- or nonylphenol and octylcresol. Other non-ionic agents are the partial esters derived from long chain fatty acids and hexitol anhydrides, the condensation products of the said partial esters with ethylene oxide, and the lecithins. Suitable suspending agents are
hydrophilic colloids (for example, polyvinylpyrrolidone and sodium carboxymethylcellulose), and swelling clays such as bentonite or attapulgite.
Compositions for use as aqueous dispersions or emulsions are generally supplied in the form of a concentrate containing a high proportion of the active ingredient, the concentrate being diluted with water before use.
These concentrates should preferably be able to withstand storage for prolonged periods and after such storage be capable of dilution with water in order to form aqueous preparations which remain homogeneous for a sufficient time to enable them to be applied by conventional spray equipment. The concentrates may conveniently contain up to 95%, suitably 1-85%, for example 1-25% or 25-60%, by weight of the active ingredient. After dilution to form aqueous preparations, such preparations may contain varying amounts of the active ingredient depending upon the intended purpose, but an aqueous preparation containing 0.0001 to 10%, for example 0.005 to 10%, by weight of active ingredient may be used.
The compositions may contain other compounds having biological activity, e.g. compounds having similar or complementary fungicidal activity or which possess plant growth regulating, herbicidal or insecticidal activity.
An additional fungicidal compound may be present in the composition. By including another fungicide, the resulting composition can have a broader spectrum of activity or a greater level of intrinsic activity than the compound of formula (Ia) or (Ib) alone. Further the other fungicide can have a synergistic effect on the fungicidal activity of the compound of formula (Ia) or (Ib). Examples of fungicidal compounds which may be included in the composition are (RS)-1-aminopropylphosphonic acid, (RS)-4-(4-chlorophenyl)-2-phenyl-2-(1H-1,2,4-triazol-1-ylmethyl)butyronitrile, (Z)-N-but-2-enyloxymethyl-2-chloro-2',6'-diethylacetanilide, 1-(2-cyano-2-methoxy-iminoacetyl)-3-ethyl urea, 4-(2,2-difluoro-1,3-benzodioxol-4-yl)-pyrrole-3-carbonitrile, 4-bromo-2-cyano-N,N-dimethyl-6-trifluoromethyl-benzimidazole-1-sulphonamide, 5-ethyl-5,8-dihydro-8-oxo(1,3)-dioxol(4,5-q)quinoline-7-carboxylic acid, α-[N-(3-chloro-2,6-xylyl)-2-methoxy-acetamido]-g-butyrol actone, N-(2-methoxy-5-pyridyl)-cyclopropane
carboxamide, alanycarb, aldimorph, ampropylfos, anilazine, azaconazole, BAS 490F, benalaxyl, benomyl, biloxazol, binapacryl, bitertanol, blasticidin S, bromuconazole, bupirimate, butenachlor, buthiobate, captafol, captan, carbendazim, carbendazim chlorhydrate, carboxin, chinomethionate, chlorbenzthiazone, chloroneb, chlorothalonil, chlorozolinate, clozylacon, copper containing compounds such as copper oxychloride, copper oxyquinolate, copper sulphate, copper tallate, and Bordeaux mixture, cycloheximide, cymoxanil, cyproconazole, cyprofuram, debacarb, di-2-pyridyl disulphide 1,1'-dioxide, dichlofluanid, dichlone, diclobutrazol, diclomezine, dicloran, didecyl dimethyl ammonium chloride, diethofencarb, difenoconazole,
O,O-di-iso-propvl-S-benzvl thiophosphate, dimefluazole, dimetconazole, dimethomorph, dimethirimol, diniconazole, dinocap, dipyrithione, ditalimfos, dithianon, dodemorph, dodine, doguadine, edifenphos, epiconazole,
etaconazole, ethirimol, ethoxyquin, ethyl (Z)-N-benzyl-N-([methyl(methylthioethylideneamino-oxycarbonyl)amino]thio)-β-alaninate, etridiazole, fenaminosulph, fenapanil, fenarimol, fenbuconazole, fenfuram, fenpiclonil, fenpropidin, fenpropimorph, fentin acetate, fentin hydroxide, ferbam, ferimzone, fluazinam, fludioxonil, fluoroimide, fluquinconazole, flusilazole, flutolanil, flutriafol, folpet, fuberidazole, furalaxyl, furconazole-cis, guazatine, hexaconazole, hydroxy-isoxazole, hymexazole, ICIA5504, imazalil, imibenconazole, ipconazole, iprobenfos, iprodione, isopropanyl butyl carbamate, isoprothiolane, kasugamycin, mancozeb, maneb, mepanipyrim, mepronil, metalaxyl, metconazole, methfuroxam, metiram, metiram-zinc, metsulfovax, myclobutanil, NTN0301, neoasozin, nickel
dimethyldithiocarbamate, nitrothal-isopropyl, nuarimol, ofurace,
organomercury compounds, oxadixyl, oxolinic acid, oxycarboxin, pefurazoate, penconazole, pencycuron, phenazin oxide, phosetyl-AI, phosphorus acids, phthalide, polyoxin D, polyram, probenazole, prochloraz, procymidone, propamocarb, propamocarb hydrochloride, propiconazole, propineb, propionic acid, prothiocarb, pyracarbolid, pyrazophos, pyrifenox, pyrimethanil, pyroquilon, pyroxyfur, pyrrolnitrin, quaternary ammonium compounds,
quinconazole, quinomethionate, quintozene, rabenazole, sodium
pentachlorophenate, streptomycin, sulphur, tebuconazole, techlofthalam, tecnazene, tetraconazole, thiabendazole, thicyofen, thifluzamide,
2-(thiocyanomethylthio)benzothiazole, thiophanate-methyl, thiram,
timibenconazole, tolclofos-methyl, tolylfluanid, triacetate salt of
1,1'-iminodi(octamethylene)diguanidine, triadimefon, triadimenol, triazbutyl, triazoxide, tricyclazole, tridemorph, triforine, triflumizole, triticonazole, validamycin A, vapam, vinclozolin, XRD-563, zineb and ziram. The compounds of formula (Ia) and (Ib) can be mixed with soil, peat or other rooting media for the protection of plants against seed-borne, soil-borne or foliar fungal diseases.
The following Examples illustrate methods by which compounds of formula (Ia) and (Ib) can be prepared. Where used in the following Examples, HYFLO, DOWEX and DISPERSOL are Trade Names or Trade Marks.
Where shown, NMR data are selective, no attempt has been made to list every absorption in all cases. The following abbreviations are used throughout:
d = doublet s = singlet
NMR = nuclear magnetic resonance m = multiplet
DMSO - Dimethylsulphoxide br = broad
ppm = parts per million DMF = O-dimethylformamide t = triplet q = quartet
dd = doublet of doublets bs & br s = broad singlet br d = broad doublet br m = broad multiplet
FAB = fast atom bombardment CI = chemical ionisation
EI = electron ionisation
EXAMPLE 1
This Example illustrates the preparation of 1-(6-(3,4,5-trimethoxyphenoxy)hex-1-yloxy)-2,2-dimethyl-4,6-diamino-1,2-dihydro-1,3,5-triazine hydrobromide.
Aminooxymethylbenzene hydrochloride (25.0g) and dicyandiamide (13.17g) were dissolved in industrial methylated spirits (85ml) with warming and stirring and the resulting solution was heated at reflux for 3 hours. The mixture was then concentrated under reduced pressure to leave an oily residue. The residue was mixed with water (500ml) and basified with 6N sodium hydroxide solution. A benzyloxydiguanide base separated. This solidified on cooling as a crystalline white solid. The solid was filtered from the reaction mixture and washed with water.
To a solution of benzyloxydiguanide (21.3g) in industrial methylated spirits (81.3ml) was added concentrated hydrochloric acid (17.62ml) followed by acetone (81.3ml). The resulting mixture was heated at reflux for 3 hours and then concentrated under reduced pressure to leave a solid. The solid was triturated with acetone to leave 1-benzyloxy-2,2-dimethyl-4,6-diamino-1,2-dihydro-1,3,5-triazine hydrochloride.
1-Benzyloxy-2,2-dimethyl-4,6-diamine-1,2-dihydro-1,3,5-triazine hydrochloride (16.0g) was dissolved in a mixture of ethanol (250ml) and water (150ml). 10% Palladium on charcoal (384mg) was added and the resulting mixture was hydrogenated at room temperature and atmospheric pressure. After filtering the reaction mixture through "HYFLO" the filtrate was concentrated under reduced pressure to leave a solid. The solid was recrystallised from ethanol to leave 1-hydroxy-2,2-dimethyl-4,6-diamino-1,2-dihydro-1,3,5-triazine hydrochloride (3.2g) as a white solid.
To a solution of 3,4,5-trimethoxyphenol (3.71g) in N,N-dimethylformamide (30ml) was added potassium carbonate (2.8g). The resulting suspension was stirred under nitrogen for 30 minutes. 6-Bromohexan-1-ol (3.65g) was added to the suspension and the resulting mixture was heated at 100°C for 1 hour. Most of the N,N-dimethylformamide was removed under vacuum. The residue was partitioned between diethyl ether and water, the aqueous layer separated and washed with further diethyl ether. The combined diethyl ether fractions were washed with brine, dried over magnesium sulphate and the solvent evaporated to give a brown oil. This was purified by chromatography on silica, eluting with ethyl acetate:hexane 2:1, to yield 6-(3,4,5-trimethoxyphenoxy)hexan-1-ol (3.7g).
To a cooled solution of 6-(3,4,5-trimethoxyphenoxy)hexan-1-ol (3.7g) in diethyl ether (30ml) at 5°C was added phosphorus tribromide (1.76g) dropwise. The resulting mixture was stirred with cooling for 1.5 hours after which it was neutralised with sodium bicarbonate solution. The organic layer was separated and the aqueous layer was extracted with diethyl ether (2×30ml). The combined extracts were dried (magnesium sulphate) and filtered. The filtrate was concentrated under reduced pressure to leave 1-bromo-6-(3,4,5-trimethoxyphenoxy)hexane (2.2g) as an oil.
To a warm solution of 1-hydroxy-2,2-dimethyl-4,6-diamino-1,2-dihydro-1,3,5-triazine hydrochloride (1.22g) in ethanol (50ml) was added a solution of sodium hydroxide (0.24g) in ethanol (20ml). The solid which precipitated was filtered off and the filtrate was evaporated under reduced pressure to leave a solid. This solid was suspended in
N,N-dimethylformamide (40ml) and 1-bromo-6-(3,4,5-trimethoxyphenoxy)hexane (2.2g) added. Mild heating resulted in the formation of a yellow solution. The solution was heated for 30 minutes after which it was concentrated under reduced pressure to leave the title compound (3.056g) as a brown gum.
1H NMR (d6 DMSO): 1.2-1.8(14H,m); 3.5(3H,s); 3.7(6H,s); 3.8-3.9(4H,m); 6.15(2H,s)ppm.
EXAMPLE 2
This Example illustrates the preparation of 1-(10-hydroxydec-1-yloxy)-2,2-dimethyl-4,6-diamino-1,2-dihydro-1,3,5-triazine hydrobromide.
To a warmed solution of 1-hydroxy-2,2-dimethyl-4,6-diamino-1,2- -dihydro-1,3,5-triazine hydrochloride (3.34g, prepared as in EXAMPLE 1) in ethanol (100ml) was added a solution of sodium hydroxide (0.655g) in ethanol (50ml). The solid which precipitated was filtered off and the filtrate was evaporated under reduced pressure to leave a solid. This solid was suspended in N,N-dimethylformamide (50ml) and 10-bromodecan-1-ol (4.1g) added. The mixture was warmed gently and the reaction mixture turned yellow. The mixture was then heated at 80°C for 30 minutes after which it was concentrated under reduced pressure to leave the title compound as yellow gum (4.28g).
1H NMR (d6 DMSO): 1.1-1.7(22H,m); 3.7-3.9(2H,br s); 4.3(2H,m);
7.9(1H,d); 8.5(1H,d); 8.7(1H,br s)ppm.
EXAMPLE 3
This Example illustrates the preparation of the butyric acid salt of 1-(10-hydroxydec-1-yloxy)-2,2-dimethyl-4,6-diamino-1,2-dihydro-1,3,5-triazine.
1-(10-Hydroxydec-1-yloxy)-2,2-dimethyl-4,6-diamino-1,2-dihydro-1,3,5-triazine hydrobromide (4.0g) in deionised water (50ml) was added to a column of ion exchange resin (D0WEX 1-8X, 70 ml, prewashed with sodium hydroxide until basic, and then water until neutral). The column was eluted with water (750ml) until the fractions were neutral. The aqueous solution obtained was freeze dried to give the free base as a white powder (2.17g; mpt 105-108°C; mass spectrum: MH+ = 313 (FAB)).
The free base (0.2g) was suspended in water and butyric acid (0.056g) added. The mixture was stirred at room temperature for 1 hour and then concentrated under reduced pressure. Excess water was removed by drying over P2O5 in vacuo to give the salt (0.035g).
1H NMR (d6 DMSO): 1.15-1.70 (m,22H); 3.30 (m,2H), 3.80 (bs,2H) ppm.
EXAMPLE 4
This Example illustrates the preparation of 1-[3-(4-bromophenoxy)-prop-1-oxy-]-2,2-dimethyl-4,6-diamino-1,2-dihydro-1,3,5-triazine hydrobromide.
1-Hydroxy-2,2-dimethyl-4,6-diamino-1,2-dihydro-1,3,5-triazine free base (0.485g) was suspended in dry DMF (10ml) and 3-(4-bromophenoxy)-prop-1-yl bromide (1.0g) was added. The mixture was heated to
approximately 80°C for 2 hours, during which time a yellow solution was obtained. The DMF was removed in vacuo to leave the crude product as an orange solid. This was triturated with ethyl acetate to remove excess bromide, and then recrystallised from water to remove unreacted
1-hydroxy-2,2-dimethyl-4,6-diamino-1,2-dihydro-1,3,5-triazine, giving the pure product as a cream solid (0.48g).
1H NMR (d6 DMSO): 1.20-1.60 (bs,6H); 2.0-2.20 (m,2H); 4.0 (m,4H); 6.90
(d,2H); 7.40 (d,2H), 8.00 (s,1H); 8.60 (s,1H); 8.70 (s,1H) ppm.
Mass spectrum: MH+ = 369 (FAB)
EXAMPLE 5
This Example illustrates the preparation of 1-[3-(2,4,5-trichlorophenoxy)-prop-1-oxy-]-2,2-dimethyl-4,6-diamino-1,2-dihydro-1,3,5-triazine.
1-Hydroxy-2,2-dimethyl-4,6-diamino-1,2-dihydro-1,3,5-triazine free base (1.34g) was suspended in dry DMF (25ml) and 3-(2,4,5-trichlorophenoxy)prop-1-yl bromide (3.0g) was added. The mixture was heated to approximately 80°C for 2 hours, during which time a yellow solution was obtained. The DMF was removed in vacuo to leave the crude product, contaminated with 1-hydroxy-2,2-dimethyl-4,6-diamino-1,2-dihydro-1,3,5-triazine, as a white solid.
The crude product was purified by reverse phase chromatography. A Varian Mega Bond ELUT C18 reverse phase column was washed with water, and then the crude product (0.05g) in water (1ml) was applied to the column. The column was then washed with water containing 1% acetic acid (50ml), followed by water containing 70% acetonitrile and 1% acetic acid (100ml). The pure product was isolated by freeze drying the appropriate fractions, as a white solid (0.34g).
1H NMR (d6 DMSO): 1.30 (bs,6H); 2.10 (bs,2H); 4.00 (t,2H); 4.18 (t,2H); 7.45 (s,1H); 7.78 (s,1H) ppm.
EXAMPLE 6
This Example illustrates the preparation of 1-[6-(3,4,5-trimethoxyphenoxy)hex-1-yloxy]-2,2-dimethyl-4,6-bis-(acetamido)-1,2-dihydro-1,3,5-triazine.
1-[6-(3,4,5-Trimethoxyphenoxy)hex-1-yloxy]-2,2-dimethyl-4,6-diamino-1,2-dihydro-1,3,5-triazine (0.2g) was heated with acetic anhydride (6ml) on a steam bath, with stirring, for approximately 30 minutes. The solvent was then removed in vacuo and the crude product purified by vacuum filtration through silica gel, eluting with ethyl acetate to give the product as a colourless gum (0.150g). 1H NMR (d6 DMSO): 1.40-1.60 (bs,4H); 1.70 (s,6H); 1.70-1.84 (m,4H); 2.15 (s,3H); [2.25 (s) + 2.35 (s)](3H); 3.75 (s,3H); 3.85 (s,6H); 3.90-4.00 (m,4H); 6.15 (s,2H) ppm.
Mass spectrum MH+ = 508 (FAB)
EXAMPLE 7
This Example illustrates the preparation of 1-(12-hydroxydodec-1-yloxy)-2,2-dimethyl-4,6-diamino-1,2-dihydro-1,3,5-triazine hydrobromide.
1-Hydroxy-2,2-dimethyl-4,6-diamino-1,2-dihydro-1,3,5-triazine free base (liberated from 1.72g of the hydrochloride, as in Example 2), was suspended in dry DMF (50ml) and 12-bromododecan-1-ol (2.35g) was added. The mixture was heated and stirred at 80°C for 3 hours. The DMF was removed in vacuo and the resultant gum was triturated with acetone. The grey solid, 1-hydroxy-2,2-dimethyl-4,6-diamino-1,2-dihydro-1,3,5-triazine, was filtered. The filtrate was concentrated under reduced pressure to leave a yellow liquid, which was then washed with chloroform and then acetone to remove unreacted bromide, to give the product as a
whitish-yellow solid. This was shown by NMR to contain 45% of the starting 1-hydroxy-2,2-dimethyl-4,6-diamino-1,2-dihydro-1,3,5-triazine, and was used directly for testing.
1H NMR (d6 DMSO): 1.20-1.40 (m,26H); 3.40 (t,2H); 3.80 (bs,2H); 4.30 (t,1H) ppm.
EXAMPLE 8
Preparation of 1-[2-(2,4-dichlorophenyl)prop-1-yloxy]-2,2-dimethyl¬
-4,6-diamino-1,2-dihydro-1,3,5-triazine hydrochloride.
Tetrabutylammonium hydrogen sulfate (31.23g) was added to a stirred solution of sodium hydroxide (7.36g) in water (92ml) (slight exotherm). A mixture of methyl 2,4-dichlorophenylacetate (10.06g) and methyl iodide (26.13g) in dichloromethane (92ml) was added with vigorous stirring to the resulting solution. After 4 hours, the dichloromethane and aqueous layers were separated, and the former was concentrated in vacuo until almost all of the solvent had been removed. Diethyl ether (150ml) was added, the resulting precipitate was filtered off, and the filtrate was concentrated to give methyl 2-(2,4-dichlorophenyl)propanoate (8.97g, 84% yield) as an oil.
Methanol (28.4ml) was added dropwise over 70 minutes to a stirred mixture of methyl 2-(2,4-dichlorophenyl)propanoate (8.97g) and sodium borohydride (3.61g) in refluxing tetrahydrofuran (100ml) (90-95°C bath temperature). Vigorous effervescence was observed. After a further 40 minutes heating, the reaction mixture was allowed to cool then dilute hydrochloric acid was added, whereupon a white precipitate formed. The supernatant was decanted off, concentrated under reduced pressure, and re-combined with the precipitate. Water was added to the resulting material and it was extracted with tert-butyl methyl ether. The extracts were combined, washed with water, dried over magnesium sulfate and concentrated in vacuo to give 2-(2,4-dichlorophenyl)propan-1-ol (7.56g, 97% yield) as an oil.
Diethyl azodicarboxylate (6.61g) was added to a stirred solution of 2-(2,4-dichlorophenyl)propan-1-ol (7.00g), triphenylphosphine (9.96g) and N-hydroxyphthalimide (5.54g) in tetrahydrofuran (150ml). The solution quickly went dark red and then faded to a yellow colour (see E Grochowski and J Jurczak, Synthesis, 1976, 682). After about 20 minutes the volatiles were evaporated off under reduced pressure. The resulting yellow solid was triturated with a 1:1 mixture of hexane:tert-butyl methyl ether (150ml) and filtered off, and the filtrate was concentrated to give a yellow oil
(15.23g). This yellow oil was twice chromatographed on columns of silica gel using a 1:1 mixture of hexane:tert-butyl methyl ether as eluent to give N-2-(2,4-dichlorophenyl)prop-1-yloxyphthalimide as a white solid (9.925g, 83% yield). 1H NMR (CDCl3, 270MHz) δ 1.46(3H,d), 3.76(1H, sextet),
4.22(1H,dd), 4.41(1H,dd), 7.24(1H,m), 7.38(2H,m), 7.74(2H,m), 7.81(2H,m) ppm.
Ethanol (30ml) and hydrazine hydrate (0.609g) were added successively to N-2-(2,4-dichlorophenyl)prop-1-yloxyphthalimide (4.260g) and the resulting mixture was stirred and heated under reflux. After about 45 minutes, the reaction mixture was allowed to cool and concentrated hydrochloric acid (3.05ml) was added, and the mixture was again heated briefly to reflux and allowed to cool. A solid appeared, and this was filtered off and washed with ethanol. The filtrate was concentrated in vacuo, the further quantities of solid which formed during concentration again being filtered off and discarded. Diethyl ether (100ml) was added to the resulting oil and, on standing, a white solid crystallised. This was filtered off and dried to give O-2-(2,4-dichlorophenyl)prop-1-yl
hydroxylamine hydrochloride (2.672g, 86% yield) as a white crystalline solid. 1H NMR (CDCl3, 270MHz) δ 1.14(3H,d), 3.43(m), 4.06(1H,dd),
4.13(1H,dd), 7.40(2H,m), 7.56(1H,d), 10.80(2H,s) ppm.
A mixture of O-2-(2,4-dichlorophenyl)prop-1-yl hydroxyl amine
hydrochloride (2.672g) and dicyandiamide (0.962g) in ethanol (30ml) was heated with stirring under an atmosphere of nitrogen for 3 hours, then allowed to cool. Gaseous hydrogen chloride was bubbled through the resulting mixture for 3 minutes, then diethyl ether (100ml) was added and hydrogen chloride was passed through the solution for a further 2 minutes. A white solid precipitated and was filtered off and dried. It was dissolved in water and treated with a solution of potassium carbonate (2.8g) in water (10ml) until the mixture reached pH11, and was then extracted with chloroform. The chloroform solution was dried over magnesium sulfate and concentrated in vacuo to give
1-[2-(2,4-dichlorophenyl)prop-1-yloxy]biguanide as a clear gum (1.735g, 55% yield). 1H NMR (CDCl3, 270 MHz) δ 1.25(3H,d), 3.18(1H,sextet),
3.87(1H,dd), 3.98(1H,dd), 7.20(2H,d), 7.35(1H,d) ppm, and 2 broad peaks centred at 4.48 and 5.25 ppm.
Acetone (100ml) and concentrated hydrochloric acid (0.47ml) were added successively to 1-[2-(2,4-dichlorophenyl)prop-1-yloxy]biguanide (1.735g) (precipitate forms) and the resulting mixture was heated at 80°C with stirring for 5 hours under a nitrogen atmosphere. On cooling, white crystals formed and these were filtered off and dried to give the title compound (1.065g, 49% yield) as a white crystalline solid.
EXAMPLE 9
Preparation of 1-[1-(2,6-dichlorophenyl)ethoxy]-2,2-dimethyl-4,6-diamino-1,2-dihydro-1,3,5-triazine hydrochloride.
l-(2,6-Dichlorophenyl)ethanol (prepared by treatment of
2,6-dichlorobenzaldehyde with methylmagnesium chloride) was converted into N-1-(2,6-dichlorophenyl)ethoxyphthalimide using N-hydroxyphthalimide, triphenylphosphine and diethyl azodicarboxylate under the conditions described for the preparation of a related compound in Example 8. The product was a white crystalline solid, melting point 133-4°C. 1H NMR (CDCl3, 270MHz) δ 1.95(3H,d), 6.10(1H,q), 7.17(1H,t), 7.30(2H,d),
7.75(4H,m) ppm.
N-1-(2,6-Dichlorophenyl)ethoxyphthalimide was treated successively with hydrazine hydrate and concentrated hydrochloric acid in the same way as described for a related compound in Example 8 to give
O-2-(2,6-dichlorophenyl)prop-1-yl hydroxylamine hydrochloride as a white crystalline solid. 1H NMR (d6-DMSO, 270MHz) δ 1.63(3H,d), 5.90(1H,q), 7.40(1H,dd), 7.50(2H,m) ppm.
A mixture of O-2-(2,6-dichlorophenyl)prop-1-yl hydroxylamine
hydrochloride (6.0g) and dicyandiamide (2.5g) in ethanol (25ml) was heated under reflux for 2 hours and allowed to cool. Water and a solution of potassium carbonate (3.5g) in water were added successively, and the resulting mixture was extracted with ethyl acetate. The extracts were combined and washed with water and brine, dried over magnesium sulfate and concentrated to give a viscous yellow oil (6.2g). This oil was taken up in acetone (400ml) and concentrated hydrochloric acid (1.9ml) was added. The resulting clear solution was heated under reflux for 9 hours, during which time a white solid precipitated. The reaction mixture was allowed to cool and the solid was filtered off, washed with acetone and dried to give the title compound (4.63g, 51% yield) as a white solid.
EXAMPLE 10
Preparation of 1-[2-chloro-3,6-difluorobenzyloxy]-2,2-dimethyl-4,6-diamino-1,2-dihydro-1,3,5-triazine hydrobromide.
Dowex 1-X8 (Cl) standard grade ion exchange resin, particle size 0.300-0.850mm, (20ml) was loaded into a glass column and washed with a 4% aqueous solution of sodium hydroxide (100ml) and then with deionised water until the eluent was neutral. A solution of 1-hydroxy-2,2-dimethyl-4,6-diamino-1,2-dihydro-1,3,5-triazine hydrochloride (1.60g) in deionised water was applied to the column and eluted through with deionised water (100ml). The aqueous solution collected was freeze-dried to give
1-hydroxy-2,2-dimethyl-4,6-diamino-1,2-dihydro-1,3,5-triazine as the free base, a white powder (1.20g, 92% yield), melting point 205°C
(decomposition). A solution of this dihydrotriazine (0.157g) in methanol (2.5ml) was added to 2-chloro-3,6-difluorobenzyl bromide (0.266g) in a glass tube and the resulting mixture was shaken thoroughly. DMF (4ml) was added, and the mixture was heated at 90-100°C for 3 hours, during which time methanol was allowed to evaporate off. The mixture was left to cool and the volatiles were stripped off under reduced pressure. Deionised water (5ml) was added and a solid precipitated. The mixture was washed with ethyl acetate, leaving the solid in the aqueous layer. The aqueous layer and solid were concentrated to give the title compound (0.366g, 92% yield) as a white powder.
EXAMPLE 11
Preparation of 1-[1-(2,6-dichlorophenyl)ethoxy]-2,2-dimethyl-4,6-diamino-1,2-dihydro-1,3,5-triazine, acetic acid salt.
Triethylamine (1.93g) was added to a solution of 1-[1-(2,6-dichlorophenyl)ethoxy]-2,2-dimethyl-4,6-diamino-1,2-dihydro-1,3,5-triazine hydrochloride (1.00g) in water (250ml). The resulting mixture was stirred for an hour (white solid began to appear) and then allowed to stand overnight. The precipitated solid was filtered off and dried to
givel-[1-(2,6-di-chlorophenyl)ethoxy]-2,2-dimethyl-4,6-diamino-1,2-dihydro-1,3,5-triazine as the free base (0.741g), a white solid. Glacial acetic acid (0.10g) was added to a stirred solution of the free base
(O.55lg) in tetrahydrofuran (10ml). The resulting mixture was stirred for an hour, allowed to stand overnight, then filtered to remove a small quantity of precipitate. The filtrate was concentrated in vacuo to give a sticky solid which, on trituration with diethyl ether, became granular. This was filtered off and dried to give the title compound as a white solid.
EXAMPLE 12
The compounds were tested against a variety of foliar fungal diseases of plants. The technique employed was as follows.
The plants were grown in John Innes Potting Compost (No 1 or 2) in 4cm diameter minipots. The test compounds were formulated either by bead milling with aqueous DISPERSOL T, or as a solution in acetone, ethanol or acetone/ethanol which was diluted to the required concentration (300 or 100 ppm active ingredient) immediately before use. The formulations were sprayed on to the foliage to maximum retention using a hand held Devilbiss spray gun. TWEEN 20 was added to give a final concentration of 0.05% when the sprays were applied to cereals.
The plants were inoculated with the pathogens using spore suspensions sprayed onto the leaves of test plants 6hours, 1 day or 2 days after treatment, depending on disease. After inoculation, the plants were put into an appropriate environment to allow infection to proceed and then incubated until the disease was ready for assessment. The period between inoculation and assessment varied from four to fourteen days according to the disease and environment.
The disease control was assessed by visual assessment of the percentage leaf area covered by actively sporulating disease. In Tables IX-XII a compound showing more than 70% control of a specific disease at 100ppm is marked with an asterisk ("*") while a compound showing more than 70% control of a specific disease at 300ppm is marked with a dollar sign ("$"). Throughout Tables IX-XII the following abbreviations are used:
Erysgt = Erysiphe graminis tritici
Leptno = Septoria nodorum
Phytin = Phytophthora infestans lycopersici
Plasvi = Plasmopara viticola
Puccrt = Puccinia recondita
Pyrior = Pyricularia oryzae
Ventin = Venturia inaequalis
Figure imgf000065_0001
Figure imgf000066_0001
Figure imgf000067_0001
Figure imgf000068_0001
Figure imgf000069_0001
Figure imgf000070_0001
Figure imgf000071_0001
Figure imgf000072_0001
Figure imgf000073_0001
Figure imgf000074_0001
Figure imgf000075_0001
Figure imgf000076_0001
Figure imgf000077_0001
Figure imgf000078_0001
Figure imgf000079_0001
Figure imgf000080_0001

Claims

1. A fungicidal composition comprising, as an active ingredient, a
compound of formula (Ia) or (Ib):
Figure imgf000081_0001
Figure imgf000081_0002
or a tautomer thereof, wherein R1 and R2 are, independently, hydrogen; C1-C6 alkyl, optionally substituted with OH or halo; C2-C6 alkenyl, optionally substituted with OH or halo; or R1 and R2 together form a 3 to 8 membered cycloalkyl or cycloalkenyl ring either of which is optionally substituted with C1-C6 alkyl, C2-C6 alkenyl, OH or halo;
R3 is hydrogen, C1-C20 alkyl, C2-C20 alkenyl or C2-C20 alkynyl group, any of which is optionally substituted with one or more substituents independently selected from: halo, OR6, COR6, COOR6, CONR6R7, NHCOR6,
NR6R7, SR6, SOR6, SO-R6, OCOR6, N3, NO2, cyano, SO2NR6R7, CR6:NOR7,
CS.NR6R7, NR6.CONR7R7', O.CO2R6, O.CONR6R7, NR6.CO2R7, CONR6.NR7R7' , CONR6OR7, NR6SO2R7, P+X7 (with an associated halide anion) or a group X; R6, R7 and R7' are each independently selected from hydrogen, a group X, C1-C6 alkyl, C2-C6 alkenyl, C2-C8 alkynyl, C1-C6 alkyl-X,
C2-C6 alkenyl-X, any of which is optionally substituted by OH or halo;
X is benzyl, phenyl, a 3 to 8 membered cycloalkyl, cycloalkenyl or saturated or unsaturated heterocyclic ring, or a fused ring system containing up to four 3 to 8 membered rings; the rings of the fused ring system are cycloalkyl, cycloalkenyl, phenyl or saturated or unsaturated heterocyclic rings or a combination of any these;
R3 may also be a group Z-Q, wherein Z is R10, R10-Y-Y-R10,
R10-Y-O-Y-R10, R10-Y-SO2-R10, R10-NHCO-Y-CONH-R10, R10-Y-R10,
R10-O-R10, R10-O-R10-O-R10, R10-S-R10 or R10-NR11-R10;
R10 and R11 are each C1-C20 alkyl or C2-C8 alkenyl; Y is a linking group derived from benzyl, phenyl, a 3 to 8 membered cycloalkyl, cycloalkenyl or saturated or unsaturated heterocyclic ring, or a fused ring system containing up to four 3 to 8 membered rings; the rings of the fused ring system are cycloalkyl, cycloalkenyl, phenyl or saturated or unsaturated heterocyclic rings or a combination of any these; the groups X and Y are, independently, optionally substituted with cyano, halo, SO2NR8R8' , N02, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C1-C8 haloalkyl, C3-6 cycloalkyl, C2-C8 haloalkenyl, OR8, COR8, COOR8, CONR8R8', NR8R8 , SR8, SOR8, SO2R8, phenyl,
phenyl(C1-6)alkyl, phenyl(C2-6)alkenyl, (the phenyl groups of the last three groups may themselves be substituted with halo, C1-C6 alkyl, C1-C6 alkoxy or cyano), C1-C8 alkyl-OR8 or C2-C8 alkenyl-OR8, or, where possible, oxo or imino; R8 and R8' are, independently, hydrogen, C1-C8 alkyl, C1-C8 haloalkyl, C3-C8 cycloalkyl, C2-C8 alkenyl, C2-C8 alkynyl, phenyl, benzyl or phenoxy(C1-4)alkyl, which are optionally substituted with cyano, halo, SO2NH2, NO2, NH2, C1-C8 alkyl, C2-C8 alkenyl, C1-C8 haloalkyl or C2-C8 haloalkenyl, or, where possible, oxo or imino; Q is a group of formula (II):
Figure imgf000082_0001
wherein R1 and R2 are as defined above and R4 and R5 are as defined below; alternatively, R3 is a group R10-W(R10Q)2 wherein W is as defined above for Y except that it is a trivalent linking group;
R4 and R5 are, independently, hydrogen, CO2R9, COR9, CONR9R9', OCOR9, CO2X, COX, SO7X or CONHX, wherein X is as defined above; and,
R9 and R9' are, independently, hydrogen, C1-C8 alkyl, C2-C8 alkenyl, C1-C8 haloalkyl or C2-C8 haloalkenyl; when any of the foregoing groups comprise NR6R7, NR7R7', NR8R8' or NR9R9' the substituents R6 and R7, R7 and R7', R8 and R8 or R9 and R9' may join to form a fused heterocyclic ring optionally substituted with cyano, halo, SO2NR12R12', NO2, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C1-C8 haloalkyl, C3-6 cycloalkyl, C2-C8 haloalkenyl, OR1 , COR12, COOR12, CONR12R12', NR12R12', SR12, SOR12, SO2R12, phenyl, phenyl(C1-6)alkyl, phenyl(C2-6)alkenyl, (the phenyl groups of the last three groups may themselves be substituted with halo, C1-C6 alkyl, C1-C6 alkoxy or cyano), or, where possible, oxo or imino; wherein R12 and R12' are, independently, hydrogen, C1-C8 alkyl, C3-C8 cycloalkyl, C2-C8 alkenyl,
C2-C8 alkynyl, phenyl, benzyl or phenoxy(C1-4)alkyl, which are optionally substituted with cyano, halo, SO2NH2, NO2, NH2, C1-C8 alkyl, C2-C8 alkenyl, C1-C8 haloalkyl or C2-C8 haloalkenyl or, where possible, oxo or imino; or a salt or metal complex thereof; and a fungicidally acceptable carrier or diluent.
2. A fungicidal composition as claimed in claim 1 comprising, as an
active ingredient, a compound of formula (Ia), or a tautomer
thereof, wherein R1 and R2 are, independently, hydrogen; C1-C6 alkyl, optionally substituted with OH or halo; C2-C6 alkenyl, optionally substituted with OH or halo; or R1 and R2 together form a 3 to 8 membered cycloalkyl or cycloalkenyl ring either of which is optionally substituted with C1-C6 alkyl, C2-C6 alkenyl, OH or halo; R3 is hydrogen or C1-C20 alkyl or C2-C20 alkenyl group, any of which is optionally substituted with one or more substituents independently selected from: halo, OR6, COR6, COOR6, CONR6R7, NHCOR6, NR6R7, SR6,
SO2R6, OCOR6 or a group X; R6 and R7 are each independently selected from hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkyl-X, C2-C6 alkenyl-X, any of which is optionally substituted by OH or halo, or a group X; X is benzyl, phenyl, a 3 to 8 membered cycloalkyl,
cycloalkenyl or saturated or unsaturated heterocyclic ring, or a fused ring system containing up to four 3 to 8 membered rings; the rings of the fused ring system are cycloalkyl, cycloalkenyl, phenyl or saturated or unsaturated heterocyclic rings or a combination of any these; the group X is optionally substituted with CN, halo, SO2NH2,
NO2, oxo (where possible), imino (where possible), phenyl (itself optionally substituted by halogen), C1-C8 alkyl, C2-C8 alkenyl, C1-C8 haloalkyl, C3-6 cycloalkyl, C2-C8 haloalkenyl, OR8, COR8, COOR8, CONHR8, NHR8, SR8, S02R8, phenyl(C1-6)alkyl, C1-C8 alkyl-OR8, phenyl(C2-6)alkenyl or C2-C8 alkenyl-OR8; R8 is hydrogen, C1-C8 alkyl, C2-C8 alkenyl, phenyl, benzyl or phenoxy(C1-4)alkyl, which are optionally substituted with CN, halo, SO2NH2, NO2, NH2, oxo (where possible), imino (where possible), C1-C8 alkyl, C2-C8 alkenyl, C1-C8 haloalkyl or C2-C8 haloalkenyl; R3 may also be a group Z-Q, wherein Z is R10, R10-Y-Y-R10, R10-Y-O-Y-R10, R10-Y-SO2-R10,
R10-NHCO-Y-CONH-R10, R10-Y-R10, R10-O-R10, R10-O-R10-O-R10, R10-S-R10 or R10-NR11-R10; R10 and R11 are each C1-C20 alkyl or C2-C8 alkenyl, Y is as defined above for X except that it is a divalent linking group and Q is a group of formula (II):
Figure imgf000084_0001
whereirr R1 and R2 are as defined above and R4 and R5 are as defined below; alternatively, R3 is a group R10-W(R10Q)2 wherein W is as defined above for X except that it is a trivalent linking group; R4 and R5 may be the same or different and are hydrogen, CO2R9, COR9,
CONR9, OCOR9, CO2X, COX, SO2X or CONX, wherein X is as defined above; and, R9 is hydrogen, C1-C8 alkyl, C2-C8 alkenyl, C1-C8 haloalkyl or
C2-C8 haloalkenyl; or a salt thereof; and a fungicidally acceptable carrier or diluent.
3. A fungicidal composition as claimed in claim 1 or 2 comprising, as an active ingredient, a compound of formula (Ia), or a tautomer thereof, wherein R1 and R2 are, independently, C1-C6 alkyl; or R1 and R2 together form a 3 to 8 membered cycloalkyl ring which is optionally substituted with C1-C6 alkyl; R3 is C1-C20 alkyl or C2-C20 alkenyl, either of which is optionally substituted with one or more
substituents independently selected from: OR6, NR6R7, SR6, OCOR6 or a group X; R6 and R7 are each independently selected from hydrogen or a group X; X is phenyl, a 3 to 8 membered cycloalkyl, cycloalkenyl or an unsaturated heterocyclic ring, or a fused ring system containing up to four 3 to 8 membered rings; the rings of the fused ring system are phenyl or unsaturated heterocyclic rings or a combination of any these; the group X is optionally substituted with CN, halo, NO2, phenyl, C1-C8 alkyl, C2-C8 alkenyl, C1-C8 haloalkyl, C3-6 cycloalkyl, C2-C8 haloalkenyl, OR8, COR8, COOR8, NHR8, C1-8 alkyl-R8 or
phenyl(C2-6)alkenyl; R8 is hydrogen, C1-C8 alkyl, phenyl or
phenoxy(C1-4)alkyl; R3 may also be a group Z-Q, wherein Z is R10, R10-[C3-6 cycloalkyl]-R10 or R10-S-R10; R10 and R11 are each C1-C20 alkyl, and Q is a group of formula (II):
Figure imgf000085_0001
wherein R1 and R2 are as defined above and R4 and R5 are as defined below; R4 and R5 may be the same or different and are hydrogen or
COR9; and, R9 is hydrogen, C1-C8 alkyl or C1-C8 haloalkyl; or a salt thereof; and a fungicidally acceptable carrier or diluent.
4. A fungicidal composition as claimed in claim 1 or 2 comprising, as an active ingredient, a compound of formula (Ia):
Figure imgf000085_0002
or a tautomer thereof, wherein R3 is:
(CH2)nOX wherein n is an integer from 2-12; and X is hydrogen or
phenyl (optionally substituted with C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C2-C4 alkenyl, hydroxy, C2-C4 alkylcarbonyl, halogen, NH2, CO2R21, cyano or nitro);
OR
(CH2)nX wherein n is an integer from 1-12; X is (CHR22)R23; R22 is hydrogen or C1-C4 alkyl; R23 is phenoxy, phenyl or naphthyl, these groups being optionally substituted with C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C2-C4 alkenyl, C2-C4 alkylcarbonyl, hydroxy, halogen, NH2, CO2R21, cyano or nitro;
OR
CHR24R25 wherein R24 is hydrogen or C1-C4 alkyl and R25 is C3-C7
cycloalkyl, phenyl (optionally substituted with C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C2-C4 alkenyl, hydroxy, halogen, NH2, CO2R21, cyano or nitro) or C2-C4 alkenyl;
R4 and R5 are the same and are hydrogen or C1-C4 alkylcarbonyl;
R21 is C1-C4 alkyl;
or a hydrochloride or hydrobromide salt thereof; and a fungicidally acceptable carrier or diluent.
5. A fungicidal composition as claimed in claim 1, 2, 3 or 4 comprising, as an active ingredient, a compound of formula (Ia):
Figure imgf000086_0001
or a tautomer thereof, wherein R3 is:
(CH2)nOX wherein n is an integer from 2-12; and X is hydrogen or phenyl (optionally substituted with C1-C4 alkyl, C1-C4 alkoxy, C2-C4 alkenyl, hydroxy, halogen, NH2 or CO2R21); R21 is C1-C4 alkyl;
OR
(CH2)nX wherein n is an integer from 1-12; X is (CHR22)R23; R22 is hydrogen or C1-C4 alkyl; R23 is phenoxy, phenyl (optionally substituted with halogen) or naphthyl (optionally substituted with C1-C4 alkyl);
OR
CHR24R25 wherein R24 is hydrogen or C1-C4 alkyl and R25 is C3-C7
cycloalkyl, phenyl (optionally substituted with halogen) or C2-C4 alkenyl;
R4 and R5 are the same and are hydrogen or C1-C4 alkylcarbonyl;
or a hydrochloride or hydrobromide salt thereof; and a fungicidally acceptable carrier or diluent.
6. A fungicidal composition comprising, as an active ingredient, a
compound obtainable by treating a compound of formula (VI):
Figure imgf000087_0001
wherein R1, R2 and R3 are as defined in claim 1, with an acylating agent of formula R9C(O)L, wherein R9 is as defined in claim 1 and L is a leaving group.
7. A method of combating fungi which comprises applying to plants, to the seeds of plants or to the locus of seeds or plants a composition as defined in claim 1.
8. A compound of formula (Ia):
Figure imgf000088_0001
or a tautomer thereof, wherein R3 is:
(CH2)nOX wherein n is an integer from 2-12; and X is hydrogen or
phenyl (optionally substituted with C1-C4 alkyl, C1-C4 alkoxy, C2-C4 alkenyl, hydroxy, C2-C4 alkylcarbonyl, halogen, NH2 or CO2R21); R21 is C1-C4 alkyl;
OR
(CH2)nX wherein n is an integer from 1-12; X is (CHR22)R23; R22 is
23
hydrogen or C1-C4 alkyl; R is phenoxy, phenyl (optionally substituted with halogen) or naphthyl (optionally substituted with C1-C4 alkyl);
OR
CHR24R25 wherein R24 is hydrogen or C1-C4 alkyl and R25 is C3-C7
cycloalkyl, phenyl (optionally substituted with halogen) or C2-C4 alkenyl;
4 5 9
R and R are the same and are hydrogen or R CO;
R9 is C1-C4 alkyl;
or a hydrochloride or hydrobromide salt thereof.
9. Compound No. I.3, I.6-13, I.21, I.28-41, I.67-I.270, II.8-9, II.11, II.25-26 II.32-35, II.59-II.124, III.1-40, III.43-44, III.55-56, III.58-75, III.78, III.80-87, III .88-III.162, IV.2, IV.7, IV.8 or IV.9.
10. A process for preparing a compound as claimed in claim 8 the process comprising:
4 5 to prepare a compound of formula (Ia) or (Ib) wherein R and R are both hydrogen :
a) reacting a compound of formul a (VI I) :
Figure imgf000089_0001
with an alkyl ating agent of formula R3-L;
OR
b) reacting a compound of formula (XI):
Figure imgf000089_0002
with a compound of formula (X)
Figure imgf000089_0003
to prepare a compound of formula (Ia) or (Ib) wherein R4 and R5 are not hydrogen, reacting a compound of formula (VI):
Figure imgf000090_0001
with an acyl ating agent of formula R9C(O)L;
wherein R1, R2, R3 and R9 are as defined in claim 8 and L is a leaving group.
PCT/GB1995/002576 1994-11-22 1995-11-02 Fungicidal composition WO1996015672A1 (en)

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1963759A1 (en) * 1968-12-20 1970-07-09 Beecham Group Ltd 1,2-Dihydro-1,3,5-triazine derivatives, processes for their production and their use for the production of medicinal preparations
DE1965711A1 (en) * 1969-01-01 1970-09-03 Beecham Group Ltd 1,2-Dihydro-1,3,5-triazine derivatives, processes for their production and their use for the production of medicinal preparations
DE1957769A1 (en) * 1968-11-22 1970-09-17 Beecham Group Ltd 1,2-Dihydro-1,3,5-triazine derivatives, processes for their production and their use for the production of medicinal preparations
DE2116252A1 (en) * 1970-04-04 1971-10-21 Beecham Group Ltd Brentford, Middlesex (Großbritannien) Dihydrotnazines, their acid addition salts and N-acyldenvates, processes for their preparation and pharmaceuticals which keep these compounds as active ingredients
US5300503A (en) * 1991-11-01 1994-04-05 Fmc Corporation Insecticidal 4,6-diamino-1,2-dihydro-1,3,5-triazine derivatives

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1957769A1 (en) * 1968-11-22 1970-09-17 Beecham Group Ltd 1,2-Dihydro-1,3,5-triazine derivatives, processes for their production and their use for the production of medicinal preparations
DE1963759A1 (en) * 1968-12-20 1970-07-09 Beecham Group Ltd 1,2-Dihydro-1,3,5-triazine derivatives, processes for their production and their use for the production of medicinal preparations
DE1965711A1 (en) * 1969-01-01 1970-09-03 Beecham Group Ltd 1,2-Dihydro-1,3,5-triazine derivatives, processes for their production and their use for the production of medicinal preparations
DE2116252A1 (en) * 1970-04-04 1971-10-21 Beecham Group Ltd Brentford, Middlesex (Großbritannien) Dihydrotnazines, their acid addition salts and N-acyldenvates, processes for their preparation and pharmaceuticals which keep these compounds as active ingredients
US5300503A (en) * 1991-11-01 1994-04-05 Fmc Corporation Insecticidal 4,6-diamino-1,2-dihydro-1,3,5-triazine derivatives

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