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GB2189485A - Heterocyclic acrylic acid derivatives useful as fungicides - Google Patents

Heterocyclic acrylic acid derivatives useful as fungicides Download PDF

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Publication number
GB2189485A
GB2189485A GB08707642A GB8707642A GB2189485A GB 2189485 A GB2189485 A GB 2189485A GB 08707642 A GB08707642 A GB 08707642A GB 8707642 A GB8707642 A GB 8707642A GB 2189485 A GB2189485 A GB 2189485A
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GB
United Kingdom
Prior art keywords
optionally substituted
formula
compound
methyl
hydrogen
Prior art date
Legal status (The legal status 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 status listed.)
Granted
Application number
GB08707642A
Other versions
GB2189485B (en
GB8707642D0 (en
Inventor
Vivienne Margaret Anthony
John Martin Clough
Paul Defraine
Christopher Richard Ay Godfrey
Ian Ferguson
Patrick Jelf Crowley
Michael Gordon Hutchings
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Imperial Chemical Industries Ltd
Original Assignee
Imperial Chemical Industries Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from GB868609454A external-priority patent/GB8609454D0/en
Priority claimed from GB868630825A external-priority patent/GB8630825D0/en
Priority to GB8707642A priority Critical patent/GB2189485B/en
Application filed by Imperial Chemical Industries Ltd filed Critical Imperial Chemical Industries Ltd
Priority to MYPI87000510A priority patent/MY101728A/en
Priority to BR8701892A priority patent/BR8701892A/en
Publication of GB8707642D0 publication Critical patent/GB8707642D0/en
Publication of GB2189485A publication Critical patent/GB2189485A/en
Priority to GB8922842A priority patent/GB2223016B/en
Priority to GB8922843A priority patent/GB2223017B/en
Priority to GB9001442A priority patent/GB2226817B/en
Publication of GB2189485B publication Critical patent/GB2189485B/en
Application granted granted Critical
Priority to HK102/92A priority patent/HK10292A/en
Anticipated expiration legal-status Critical
Revoked legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/63—One oxygen atom
    • C07D213/64—One oxygen atom attached in position 2 or 6
    • C07D213/643—2-Phenoxypyridines; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
    • 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
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/54—1,3-Diazines; Hydrogenated 1,3-diazines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/63—One oxygen atom
    • C07D213/65—One oxygen atom attached in position 3 or 5
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/63—One oxygen atom
    • C07D213/65—One oxygen atom attached in position 3 or 5
    • C07D213/66—One oxygen atom attached in position 3 or 5 having in position 3 an oxygen atom and in each of the positions 4 and 5 a carbon atom bound to an oxygen, sulphur, or nitrogen atom, e.g. pyridoxal
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/63—One oxygen atom
    • C07D213/68—One oxygen atom attached in position 4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/69—Two or more oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/70—Sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/70—Sulfur atoms
    • C07D213/71—Sulfur atoms to which a second hetero atom is attached
    • C—CHEMISTRY; METALLURGY
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
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    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/79—Acids; Esters
    • C07D213/80—Acids; Esters in position 3
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/84—Nitriles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/84—Nitriles
    • C07D213/85—Nitriles in position 3
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D215/20—Oxygen atoms
    • C07D215/22—Oxygen atoms attached in position 2 or 4
    • C07D215/227—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/32—One oxygen, sulfur or nitrogen atom
    • C07D239/34—One oxygen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/32—One oxygen, sulfur or nitrogen atom
    • C07D239/38—One sulfur atom
    • C—CHEMISTRY; METALLURGY
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    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/52—Two oxygen atoms
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    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/56—One oxygen atom and one sulfur atom
    • C—CHEMISTRY; METALLURGY
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    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/58—Two sulfur atoms
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

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  • Chemical & Material Sciences (AREA)
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  • Life Sciences & Earth Sciences (AREA)
  • Agronomy & Crop Science (AREA)
  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Dentistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Environmental Sciences (AREA)
  • Pyridine Compounds (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Plural Heterocyclic Compounds (AREA)

Description

GB 2 189 485 A
SPECIFICATION
Fungicides This invention relates to derivatives of acrylic acid useful in agriculture (especially as fungicides but also as 5 plant growth regulators, insecticides and nematocides), to processes for preparing them, to agricultural (especially fungicidal) compositions containing them, and to methods of using them to combat fungi, especially fungal infections in plants, to regulate plant growth and to kill or control insect or nematode pests.
The invention provides a compound having the formula (I):
10 W CO R 2 A X c Y CH z 2 OR 20 and stereoisomers thereof, wherein W is a substituted pyridinyl orsubstituted pyrimidinyl group linkedtoA by any of its ring carbon atoms; A is either an oxygen atom or S(O),, wherein n is 0, 1 or 2; X, Y and Z, which are the same or different, are hydrogen or halogen atoms, or hydroxy, optionally substituted alkyl (including haloalkyl), optionally substituted alkenyi, optionally substituted alkynyi, optionally substituted alkoxy, 25 (including haloalkoxy), optionally substituted alkylthio, optionally substituted aryloxy, optionally substituted arylalkoxy, optionally substituted acyloxy, optionally substituted amino, optionally substituted acylamino, 3 4 7 -CONR R5,COR'or-S(O)mR (wherein m isO, 1 or2) groups, oranytwo of the groups nitro, cyano, C02R X, Y and Z, when they are in adjacent positions on the phenyl ring, may join to form a fused ring, either 2 aromatic or aliphatic, optionally containing one or more heteroatoms; R' and R, which are the same or 30 different, are optionally substituted alkyl (including fluoroalkyl) groups provided that when W is 5 trifl u oro methyl pyridin-2-yI, A is oxygen, X is hydrogen, and R' and R 2 are both methyl, Y and Z are not both hydrogen, Y is not F, Cl, methyl, nitro, 5-CF3,5-SCH3 or 4-(CH3)2N if Z is hydrogen and Y and Z together are not 3 4 6 7 3-nitro-5-chloro, 3,5-dinitro, 4,5-dimethoxy or 4,5-methylenedioxy; and R, R, R5, R and R, which are the same or different, are hydrogen atoms or optionally substituted alkyl, optionally substituted cycloalky], 35 optionally substituted cycloalkylalkyl, optionally substituted alkenyi, optionally substituted alkynyl, optionally substituted aryl or optionally substituted aralkyl groups; and metal complexes thereof.
The compounds of the invention contain at least one carbon-carbon double bond, and are sometimes obtained in the form of mixtures of geometric isomers. However, these mixtures can be separated into individual isomers, and this invention embraces such isomers and mixtures thereof in all proportions 40 including those which consist substantially of the (2)-isomer and those which consist substantially of the (E)-Isomer.
The individual isomers which result from the unsymmetrically substituted double bond of the acrylate group are identified by the commonly used terms -E- and -Z-. These terms are defined according to the Cahn-Ingold-Prelog system which is fully described in the literature (see, for example, J March, "Advanced 45 Organic Chemistry," 3rd edition, Wiley-Interscience, page 109 et seq).
Usually one isomer is more fungicidally active then the other; the more active isomer being the one in which the group OR 2 is on the same side of the double bond as the phenyl ring. In the case of the compounds of the present invention this is the (E)-isomer. The (E)-isomers form a preferred embodiment of the invention.
The formula: 50 CO R 2 c 55 CH OR 2 60 used hereinafter signifies a separable mixture of both geometric isomers about the acrylate d ouble bond, i.e.
2 GB 2 189 485 A 2 C02R1 C02R1 1 1 C-H and C-OR2 5 OR2 10 Alkyl groups, wherever present as a group or moiety in, for example, "alkoxy", "alkyithio" and "aralkyi", can be in the form of straight or branched chains, and contain preferably 1 to 6, more preferably 1 to 4, carbon atoms; examples are methyl, ethyl, propyl, (n- or iso-propyl) and butyl (n-, sec-, iso- or t-butyl).
2 R' and R, which are optionally substituted alkyl groups, are preferably optionally substituted C,-4, 15 - particularly C,-2, alkyl groups. A preferred substituent is fluorine of which one or more atoms may be present.
It is particularly preferred that R' and R' are both methyl, either one or both methyl groups being optionally substituted by one, two or three fluorine atoms.
Halogen atoms, wherever referred to are particularly fluorine, chlorine or bromine atoms and especially f Worine or chlorine atoms. 20 Cycloalkyl is preferably C3-6 cycloalkyl, for example cyclohexyl, and cycloalkylaikyl is preferably C3-6 cycloalkyl(C1-4)alkyi, for example, cyclopro pyl ethyl. Alkenyl and alkynyl groups preferably contain 2 to 6, more preferably 2 to 4, carbon atoms in the form of straight or branch chains. Examples are ethenyi, allyl and propargyl. Aryl is preferably phenyl and aralkyl is preferably benzyl, phenylethyl or phenyl n-propy].
Optionally substituted alkyl includes in particular, haloalkyl, hydroxyalkyl, alkoxyalkyi, optionally substituted 25 aralkyl, especially optionally substituted phenylalkyl, and optionally substituted phenoxyalkyl; optionally substituted alkenyl includes optionally substituted phenylaikenyl, especially optionally substituted pheny lethenyl; optionally substituted aryloxy includes optionally substituted phenyloxy; and optionally substituted arylalkoxy includes optionally substituted benzyloxy. Optional substitutents for "alkoxy- and "alkyithio" include those described above for "alkyl-. 30 Substituents which may be present in any optionally substituted aryl or heteroaryl moiety include one or more of the following; halogen, hydroxy, C1-4 alkyl (especially methyl and ethyl), C1-4 alkoxy (especially methoxy), haio(C14)alkyi(especially trifl uo ro methyl), halo (C,- 4)aikoxy (especially trifluoromethoxy), C1-4 alkylthio (especially methylthio), (C,--4)aikoxy(C1-4)aikyi, C3_6 cycloalkyl, C3-6 cycloalkyi(C1-4)alkyi, aryl (espe cially phenyl), aryloxy (especially phenyloxy), aryl(C1-4)aikyl (especially benzyi, phenylethyl and phenyl 35 n-propyl), aryl Cl4 alkoxy (especially benzyloxy), aryloxy(C1-4)aikyl (especially phenyloxymethyl), acyloxy (especially acetyloxy and benzoyloxy), cyano, thiocyanato, nitro,-NR'R", - NHCOW,-NHCONIRW' ' -CONR'R- ' -COOR', -OSO2R, -S02R', -COR', -OCOR', -CR'=NR" or-N=CIRW' in which Wand W' are independently hydrogen, C,_4alkyl, C,_4alkoxy, C1-4 alkylthio, C3-6 cycloalkyl, C3_6 cycloalkyl(C1-4)aikyl, phenyl or benzyi, the phenyl and benzyl groups being optionally substituted with halogen, C1-4 alkyl or C1-4 alkoxy. 40 Optionally substituted amino, acylamino and acyloxy groups include the groups -NIRW,-NHCOR'and -OCOR'in which Wand W' are as defined above.
The substituents on the substituted pyridinyl or substituted pyrimidinyl ring W, which are the same or different, include any of the values given for X, Y and Z. In particular, they include halogen atoms, or hydroxy, optionally substituted alkyl (including haloalkyl), especially C1-4 alkyl, optionally substituted alkenyl, especial- 45 ly C3-C4 alkenyl, optionally substituted aryl, optionally substituted alkynyl, especially C3-C4 alkynyi, optionally substituted alkoxy (including haloalkoxy), especially C1-4 alkoxy, optionally substituted aryioxy, optionally substituted heterocyclyloxy, (especially heteroaryloxy), optionally substituted aryi, optionally substituted heterocyclyl, (especially 5- and 6-membered carbon-nitrogen rings eg.
50 N N 1 55 H nitro,cyano,-NR'R",-NHCOR',-CONR'R" ' -OCORI, -C02RI, -COR', -CH= NOW, - CH2NR'R", -CH20R',-CH2NHCOR',-CH20COR',ors(O)mR'(wheein misM or2) groups oranytwo of the substituents on the pyridinyl or pyrimidinyl rings, when they are in adjacent positions on the ring may join to 60 form an optionally substituted fused ring, either aromatic or aliphatic, optionally containing one or more heteroatoms; and R', W, R 3, R 4, R5, R 6 and R 7 are as defined above.
Pyridines and pyrimidines with hydroxy substituents in appropriate positions may also exist in the corresponding tautomeric oxo-forms, ie. as the corresponding pyridones and pyrimidones, respectively. It is intended that when there is a hydroxy substituent on the pyridinyl or pyrimidinyl ring W the present invention 65 3 GB 2 189 485 A 3 should include all such tautomeric forms and mixturesthereof (see, for example, G R Newkorne and W W Paudler, Contemporary Heterocyclic Chemistr), WileyInterscience pp236241).
Preferred substituent haloalkyl and haloalkoxy groups are halo Cl-4 alkyl and halo (Cl-4)alkoxy groups. Haloalkyl includes particularly trihalomethyl and especially trifluoromethyl (except where otherwise indicated). 5 Preferred aryl groups, or moieties, [e.g. as in aryfoxyl are phenyl whilst substituents on a substituted amino group, or moiety are preferably Cl-4 alkyl.
Preferred heterocyclic groups, or moieties (e.g. as in heterocyclyl or heterocyclyfoxy) are, for example, 2-,3-, or 4-optionally substituted pyridines or 2-,4- or 5- optionally substituted pyrimidines.
In one particular aspect, the invention provides compounds having the formula (1): 10 CO,) R W 15 A C CH Y OR 2 20 z and stereoisomers thereof, wherein W is a substituted pyridinyl or a substituted pyrimidinyl group linked to A by any one of its carbon atoms and bearing substituents as defined above; A is either an oxygen atom or S(O)n 25 wherein n is 0, 1 or 2; X, Y and Z, which are the same or different, are hydrogen, fluorine, chlorine or bromine atoms, or hydroxy, Cl-4 alkyl, C2-5 alkenyl, C2-r, alkynyl, phenyl, Cl-4 haloalkyl, Cl-4 alkoxy, phenoxy, benzyloxy or monoor dialkylamino groups, or any two ofthe groups X, Y and Z, when they are in adjacent positions on the phenyl ring, join to form a fused aromatic ring; wherein the afiphatic moieties of any ofthe foregoing are optionally substituted with one or more Cl-4 alkoxy groups, fluorine, chlorine or bromine atoms, phenyl rings 30 which themselves are optionally substituted, heteracyclic rings which are either aromatic or non-aromatic and are themselves optionally substituted, nitro, amino, cyano, hydroxyl or carboxyl groups, and wherein the phenyl moieties of any ofthe foregoing are optionally substituted with one or more fluorine, chlorine or bromine atoms, phenyl rings, Cl-4 alkyl, Cl-4 alkoxy, cyano, amino, nitrile, hydroxyl or carboxyl groups; and 2 R' and R ' which are the same or different, are Cl-4 alkyl (especially both methyl), each optionally substituted 35 with one, two or three halogen (especially fluorine), atoms provided that when W is 5-trifluoromethylpyridin 2-yI, A is oxygen, X is hydrogen, and R' and R 2 are both methyl, Y and Z are not both hydrogen, Y is not F, Cl, methyl, nitro, 5-CF3,5-SCH3 or 4-(CHA2N ifZ is hydrogen and Y and Z together are not 3-nitro-5-chloro, 3,5-dinitro, 4,5-dimethoxy or 4,5-methylenedioxy.
When one or more of X, Y and Z are otherthan hydrogen it is preferred that they are single atoms or 40 sterically small groups such as fluorine, chlorine, bromine, hydroxy, methyl, methoxy, trifluoromethyl, methylamino and dimethylamino. It is further preferred that one of such substituents occupies the 5-position of the phenyl ring (the acrylate group being attached to the 1-position) as this may offer advantages with respect to phytotaxicity especially where there is present only a single substituent such as chlorine.
In another aspect the invention provides compounds having the formula (fa): 45 CO CH 2 3 A C Ia) 50 CH OCH 3 55 and stereoisomers thereof, wherein A is S(O),, wherein n is 0, 1 or 2, or preferably, an oxygen atom; W is a substituted pyridinyl or a substituted pyrimidinyl group linked to A by any one of its carbon atoms, the substituents on the pyridinyl or pyrimidinyl rings, which are the same or different, being one or more halogen atoms, or hydroxy, optionally substituted alkyl (including haloalkyl), optionally substituted alkenyl, optionally 60 substituted aryl, optionally substituted alkynyf, optionally substituted alkoxy, (including haloalkoxy), optional ly substituted aryloxy, optionally substituted heterocyclyfoxy, optionally substituted aryl, optionally substi tuted heterocyclyl, optionally substituted acyloxy, optionally substituted amino, optionally substituted acylamino, nitro, cyano, -C02R, -CONR 4 Rs, -COR6 or S(O),,,R' (wherein m=O, 1 or 2) groups; provided that when W is 5-trifluoromethylpyridin-2-yl, A is oxygen, X is hydrogen, and R' and R2 are both methyl, Y and Z 65 4 GB 2189 485 A 4 are not both hydrogen, Y is not F, Cl, methyl, nitro, 5-CF3,5-CF3,5-SCH3 or4-(C1-13)2N if Z is hydrogen and Y and Z together are not 3-nitro-5-chloro, 3,5-dinitro, 4,5-dimethoxy or 4,5- methylenedioxy; and R 3, R 4 1 R5, R 6 and 7 are as defined above.
Preferred substituents on the pyridinyl or pyrimidinyl ring are chlorine, fluorine, bromine, methyl, trifluoromethyl (except where otherwise indicated), trichloromethyl and methoxy. 5 In a still further aspect the invention provides compounds having the formula (ib):
Q 1 Q 10 0 c OCH3 Ib) CH 02C c 3 1 15 H where Q is methyl, trifluoromethyl (but not 5-triff uoro methyl), methoxy, bromine, fluorine or, especially, chlorine.
Q is preferably in the 4-,5- or 6- position ofthe pyridine ring, and more preferably in the 4- position when it 20 is methyl, for instance.
The invention is illustrated bythe compounds presented in Tables 1 to Ill below.
GB 2 189 485 A 5 TABLE 1
W 0 CO CH 2 3 5 X C.
3 Y 10 OCH3 Compound Melting NO. W X Y Z Point X) Olefinic Isomert 15 1 X-Fluoropyridin-2'-yl H H H E 2 X-Chloropyridin-2'-yl H H H E 3 X-Bromopyridin-2'-yl H H H E 4 3:-Methylpyridin-2'-yi H H H E 20 3 _(Trifluoromethyi)pyridin-2'-yi H H H E 6 3'-Methoxypyridin-2'-yl H H H E 7 4'-Fluoropyridin-2'-yi H H H E 8 4'-Chloropyridin-2'-yl H H H E 9 4'-Bromopyridin-2'-yi H H H E 25 4'-Methylpyridin-2'-yi H H H gum 7.37 E 11 4'-(Trifl uo rom ethyl) pyridin-2'-y] H H H gum 7.44 E 12 4'-Methoxypyridin-2'-yi H H H E 13 W-Fluoropyridin-2'-yl H H H E 14 5'-Chloropyridin-2'-yl H H H 77-8 7.41 E 30 5'-Bromopyridin-2'-yl H H H 104.6-105.4 7.43 E 16 W-Methylpyridin-2'-y] H H H gum 7.42 E 17 5'-Methoxypyridin-2'-yi H H H E 18 W-Ruoropyridin-2'-yl H H H E 19 6'-Chloropyridin-2'-yi H H H E 35 W-Bromopyridin-2'-yl H H H E 21 W-Methylpyridin-2'-yl H H H gum 7.40 E 22 W-(Trifl uoro methyl) pyridin-2'-yl H H H gum 7.42 E 23 W-Methoxypyridin-2'-yl H H H E 24 2'-Fluoropyridin-3'-yi H H H E 40 2'-Chloropyridin-3'-yi H H H E 26 2'-Bromopyridin-3'-yi H H H E 27 2'-Methylpyridin-3'-yl H H H E 28 2'-(Trifluoromethyl)pyridin-3'-yl H H H E 29 2'-Methoxypyridin-3'-yl H H H E 45 4'-Fluoropyridin-3'-yi H H H E 31 4'-Chloropyridin-3'-yi H H H E 32 4'-Bromopyridin-3'-yl H H H E 33 4'-Methylpyridin-3'-yi H H H E 34 4'-(Trifl uo ro methyl) pyridin-X-yl H H H E 50 4'-Methoxypyridin-3'-yi H H H E 36 5'-Fluoropyridin-3'-yf H H H E 37 5'-Chloropyridin-3'-yl H H H E 38 W-Bromopyridin-X-yl H H H E 39 W-Methylpyridin-X-yl H H H E 55 5'-(Trifluoromethyl)pyridin-3'-yl H H H E 41 5'-Methoxypyridin-3'-yi H H H E 42 6'-Fluoropyridin-3'-yi H H H E 43 6'-Chloropyridin-3'-yl H H H E 44 W-Bromopyridin-X-V1 H H H E 60 W-Methylpyridin-X-yl H H H Oil 7.51 E Chemical shift of singlet from olefinic proton on beta-methoxyacrylate group (ppm from tetramethyisilane).
Solvent CDC13.
t Geometry of beta-methoxyacrylate group. 65 6 GB2189485A 6 TABLE 1 (cont) Compound Melting No. W X Y Z Point (C) Olefinic Isomert 5 46 6'-(Trifluoromethyl)pyridin-3'-yf H H H E 47 W-Methoxypyridin-X-yl H H H E 48 2'-Fluoropyridin-4'-yi H H H E 49 2'-Chforopyridin-4'-yi H H H E 50 2'-Bromopyridin-4'-yi H H H E 10 51 2'-M ethyl pyridi n-4'-yl H H H E 52 2'-(Trifluoromethyi)pyridin-4'-yl H H H E 53 2'-Methoxypyridin-4'-yi H H H E 54 X-Fluoropyridin-4'-yl H H H E 55 X-Chloropyridin-4'-y] H H H E 15 56 X-Bromopyridin-4'-yl H H H E 57 X-Methylpyridin-4'-y] H H H E 58 3'-(Trifluoromethyi)pyridin-4'-yl H H H E 59 X-Methoxypyridin-4'-yl H H H E 60 4'-Fluoropyrimidin-2'-yi H H H E 20 61 4'-Chloropyrimidin-2'-yl H H H 120-121.5 7.40 E 62 4'-Bromopyrimidin-2'-yl H H H E 63 4'-M ethyl pyrim i d in-2'-y] H H H E 64 4'-(Trifl u o rom ethyl) pyri mid in-2'-yl H H H E 65 4'-Methoxypyrimidin-2'-yi H H H E 25 66 5'-Fluoropyrimidin-2'-yl H H H E 67 W-Chloropyrimidin-2'-yl - H H H gum 7.40 E 68 W-Bromopyrimidin-2'-yr H H H E 69 W-M ethyl pyrim idin-2'-yl H H H E 70 5-(Trifluoromethyl)pyrimidin-2'-yl H H H E 30 71 W-Methoxypyrimidin-2'-y] H H H E 72 2'-Fluoropyrimidin-4'-yl H H H E 73 2'-Chloropyrimidin-4'-yl H H H E 74 2'-Bromopyrimidin-4'-yl H H H E 75 2'-Methylpyrimidin-4'-yi H H H E 35 76 2'-(Trifluoromethyf)pyrimidin-4'-yf H H H E 77 2'-Methoxypyrimidin-4'-yl H H H E 78 5'-Fluoropyrimidin-4'-yi H H H E 79 5'-Chloropyrimidin-4'-yf H H H E 80 5'-Bromopyrimidin-4'-yl H H H E 40 81 5'-Methylpyrimidin-4-yl H H H E 82 5'-(Trifluo rom ethyl) pyrim idin-4'-yl H H H E 83 W-Methoxypyrimidin-4'-yl H H H E 84 W-Fluoropyrimidin-4'-yl H H H E 85 6'-Chforopyrimidin-4'-yi H H H E 45 86 W-Bromopyrimidin-4'-y] H H H E 87 6'-Methylpyrimidin-4'-yi H H H E 88 W-(Trifluorom ethyl) pyrim idin-4'-yl H H H E 89 W-Methoxypyrimidin-4'-yl H H H E so 90 2'-Fluoropyrimidin-5'-yi H H H E 50 91 2'-Chloropyrimidin-5'-yi H H H E 92 2'-Bromopyrimidin-5'-yl H H H E 93 2'-M ethyl pyrim idin-5'-yi H H H E 94 2'-(Trifluoromethyl)pyrimidin-5'-yl H H H E 95 2'-Methoxypyrimidin-5'-yi H H H E 55 96 4'-Fluoropyrimidin-5'-yi H H H E 97 4'-Chloropyrimidin-5'-yi H H H E 98 4'-Bromopyrimidin-5'-yi H H H E 99 4'-M ethyl pyrim idin-5'-yl H H H E 60100 4'-(Trifl uo rom ethyl) pyrim idin-5'-yl H H H E 60 101 4'-Methoxypyrimidin-5'-yi H H H E 102 5'-(Trifluoromethyi)pyridin-2'-yl 3-F 5-F H E 103 X-Fluoro-5' (trif 1 uo rom ethyl) pyridin-2'-yl H H H E 7 GB 2 189 485 A 7 TABLE 1 (cont) Compound Melting No. W X Y Z Point (-C) Ofetinic Isomert 5 104 5'-(Trifluoromethyl)pyridin-3'-yl 4-17 H H E X,W-Dichloro-W (trifluoromethyf)pyridin-2'-yi H H H E 106 5',6'-Dichloro-3'- H H H E (trifluoromethyi)pyridin-2'-yi 107 W-Chloro-YH H H E (trifluoromethyl)pyridin-2'-yi T 108 X-Chloro-W- H H H E (trifluoromethyi)pyridin-2'-yi 1.5 109 6'-Chforo-4'-cyanopyridin-2'-yi H H H E 15 3'-Cyano-5'-nitropyridin-2'-yl H H H E 2'-Chloro-6'-fluoropyridin-4'-yl H H H E 112 6'-Chloro-4'-fluoropyridin-2'-yl H H H E 113 4',6'-Difiuoropyridin-2'-yl H H H E 114 3',5'-Dichloro-6'-fluoropyridin- 20 2'-yi H H H E 6'-Methoxy-3'-nitropyridin-2'-yl H H H E 116 4'-Cyano-6'-fluoropyridin-2'-yl H H H E 117 6'-Chloro-5'-cyanopyridin-2'-yi H H H E 118 6'-Chforo-3'-cyanopyridin-2'-yi H H H E 25 119 4'-Cyano-3',5',6'-trifluaropyridin- H H H E 2'-yl 4'-Cyano-2',5',6'-trifluoropyridin- H H H E Y-Y1 121 6'-Chforo-5'-nitropyridin-2'-yl H H H E 30 122 6'-Chloro-3'-nitropyridin-2'-yl H H H E 123 5'-Cyano-6'-fluoropyridin-2'-yi H H H E 124 3'-Cyano-6'-fluoropyridin-2'-yl H H H E 4',6'-Dicyanopyridin-2'-yi H H H E 126 5'-(Trichforomethyi)pyridin-2'-yl H H H E 35 127 5'-Cyanopyridin-2'-yi H H H 108.5-109.5 7.45 E 128 W-Brorno-4'- H H H E (trifluoromethyi)pyridin-2'-yl 129 3'-Nitro-5'-(trifluoromethyl)- H H H 113-114 7.41 E pyridin-2'-yl 40 5'-Formamidopyridin-2'-yl H H H gum obscured E 131 W-Aminopyridin-2'-yl H H H gum 7.40 E 132 2',3',5',6'-Tetrafluoropyridin-4'-yl H H H gum 7.55 E 133 W-Nitropyridin-2'-yl H H H 107109 7.45 E 134 4'-Methyi-5'-nitropyridin-2'-yi H H H E 45 5'-(Difluoromethyi)pyridin-2'-yl H H H E 136 5'-(Fluoromethyi)pyridin-2'-yi H H H E 137 4',6'-Difluoropyridin-2'-yi H H H gum 7.44 E 138 2',6'-Difluoropyridin-4'-yl H H H 79-80 7.46 E 139 2'-Chloro-W- H H H 113-114 7.50 E so (trichloromethyl)pyridin-4'-yi 2',6'-Dichloropyridin-4'-yi H H H 93-94 7.46 E 141 5'-(Methoxycarbonyl)pyridin-2'-yl H H H Oil 7.32 E 142 5'-Chloro-6'-fluoropyridin-2'-yl H H H E 143 5'-Chforo-6'-hydroxypyridin-2'-y1 H H H E 55 144 5'-Chloro-6'-methoxypyridin-2'-y1 H H H E 5'-Chforo-6'-cyanopyridin-2'-yi H H H E 146 5',6'-Dichloropyridin-2'-yl H H H E 147 6'-Bromo-5'-chforopyridin-2'-yi H H H E 148 5'-Chloro-6'-acetoxypyridin-2'-yl H H H E 60 149 5'-Bromo-6'-fluoropyridin-2'-yi H H H E 5'-Bromo-6'-chloropyridin-2'-yi H H H E 151 5'-Bromo-6'-cyanopyridin-2'-yl H H H E 152 5'-Bromo-6'-hydroxypyridin-2'-yl H H H E 153 5'-Bromo-6'-methoxypyridin-2'-yl H H H E 65 8 GB 2 189 485 A 8 TABLE 1 (cont) Compound Melting No. W X Y Z Point C0 Otefinic Isomert 5 154 5',6'-Dibromopyridin-2'-yi H H H E 4'-Cyanopyridin-2'-yl H H H E 156 W-Cyanopyridin-2'-yl H H H E 157 5-Chloropyridin-2'-yi 5-F H H E 158 5'-Chforopyridin-2'-yi 3-F 5-F H E 10 159 5'-Chloropyridin-2'-yi 4-F 6-F H E 5'-Chloropyridin-2'-yi 4-F 5-F 6-F E 161 5'-Chloropyridin-2'-yi 5-Cl H H E 161 5'-Chloropyridin-2'-yf 5-CH3 H H E 1.5 162 5'-Chloropyridin-2'-yi 5-CH30 H H E is 163 5'-Fluoropyridin-2'-yi 5-cl H H E 164 5'-Fluoropyridin-2'-yi 5-Cl 3-F H E 165;11. 20 C nM-1 H H H Oil 7.43 E 166 4'-Ch 1 o ro-W-m ethyl pyri mid in-2'-y] H H H 115-130 7.44 E 167 2'-Chloro-6'-fluoropyrimidin-4'-yl H H H Oil 7.46 E 168 5'-Bromo-4'- H H H E (trifl uo rom ethyl) pyrid in-2'-yl 25 169 4',5'-Dichloropyridin-2'-yi H H H E 4',5'-Dibromopyridin-2'-yi H H H E 171 5',6'-Dichloropyridin-2'-yi H H H E 172 4',6'-Dichloropyridin-2'-yi H H H E 173 4',6'-Dibromopyridin-2'-yi H H H E 30 174 5',6-Dibromopyridin-2'-yi H H H E 4'-Bro mo-5'-ch lo ropyridin-2'-yl H H H E 176 W-B ro mo-5'-ch lo ro pyridi n-2'-yl H H H E 177 W-Bro mo-4'-ch io ropyrid in-2'-y] H H H E 178 5'-Bromo-6-chforopyridin-2-yl H H. H E 35 179 W-Bromo-4'-chloropyridin-2'-yl H H H E 4'-B romo-6'-ch io ropyridin-2-yl H H H E 181 6'-Chloro-4'-methoxypyridin-2'-yi H H H E 182 6'-Bromo-4-methoxypyridin-2'-yl H H H E 183 cl 40 N H H H E 184 W-(Benzyloxycarbonyl)pyridin- H H H Gum 7.39 E 45 2'-yl 4'-Formylpyridin-2'-yl H H H Oil 7.40 E 186 W-Formylpyridin-2'-yl H H H E 187 W-Formylpyridin-2'-yl H H H E 50188 4'-Cyanopyridin-2'-yl H H H E 50 189 W-Cyanopyridin-2'-yl H H H E W-Hydroxymethylpyridin-2'-yl H H H E 191 W-Woro-4'- H H H E trifluoromethylpyridin-2'-yl 55192 W-Ch loro-4'-trifl uo ro methyl pyrid- H H H E 55 2'-yl 193 W-Ch loro-4'-m ethyl pyrid in-2'-yl H H H E 194 2',5-Dichloro-6'-cyanopyridin- H H H E 2'-yl 60195 2',5'-Dichloro-6'-carboxypyridin- H H H E 60 2'-yl 196 2',5'-Dichloro-6'H H H E methoxycarbonylpyridin-2'-yi 197 6'-Trifluoromethylpyridin-2'-yi H H H E 198 6'-Methoxycarbonylpyridin-2'-yi H H H E 65 GB 2 189 485 A 9 TABLE 1 (cont) Compound Melting No. W X Y Z Point (-C) Otefinic lsomert 5 199 6'-Carboxypyridin-2'-yf H H H E 4'-Phenoxypyridin-2'-yi H H H E 201 5'-Phenoxypyridin-2'-yl H H H E 202 6'-Phenoxypyridin-2'-yi H H H E 203 6'-Chloropyridin-3'-yi H H H z 10 15 20 25 30 35 40 45 50 55 60 65 GB 2 189 485 A TABLE 11
W ---- S co-)CHI 5 Y xn, c CH 10 z OCH3 Compound Melting No. W X Y Z Point (OC) Olefinic Isomert 15 1 X-Fluoropyridin-2'-yl H H H E 2 3'-Chforopyridin-2'-yi H H H E 3 3'-Bromopyridin-2'-yi H H H E - 4 X-Methylpyridin-2'-yl H H H E 20 X-Rrif 1 u o rom ethyl) pyridi n-2'-yl H H H E 6 3'-Methoxypyridin-2'-yi H H H E 7 4'-Fluoropyridin-2'-yl H H H E 8 4'-Chforopyridin-2'-yi H H H E 9 4'-Bromopyridin-2'-yi H H H E 25 4'-M ethyl pyrid i n-2'-yl H H H E 11 4'-(Trifi uo ro m ethyl) pyridin-2'-y] H H H E 12 4'-Methoxypyridin-2'-yi H H H E 13 W-Ruoropyridin-2'-yl H H H E 14 5'-Chloropyridin-2'-yi H H H Oil 7.47 E 30 W-Bromopyriclin-2'-yl H H H Oil 7.47 E 16 W-Methylpyridin-2'-yl H H H E 17 W-Methoxypyridin-2'-yl H H H E 18 W-Ruoroypyridin-2'-y] H H H E 19 6'-Chloropyridin-2'-yi H H H E 35 W-Bromopyridin-2'-yl H H H E 21 W-Methylpyridin-2'-y] H H H E 22 6-(Trifluoromethyi)pyridin-2'-yl H H H E 23 W-Methoxypyridin-2'-yl H H H E 24 2'-Fluoroypyridin-3'-yl H H H E 40 2'-Chloropyridin-3'-yi H H H E 26 2'-Bromopyridin-31-yi H H H E 27 2'-M ethyl pyridin-3'-yi H H H E 28 2'-(Trifluoromethyi)pyridin-3'-yl H H H E 29 2'-Methoxypyridin-31-yl H H H E 45 4'-Fluoropyridin-3'-yi H H H E 31 4'-Chloropyridin-X-yl H H H E 32 4'-Bromopyridin-3'-yl H H H E 33 4'-M ethyl pyridin-3'-yi H H H E 34 4'-(Trifl u o ro methyl) pyridin-X-yl H H H E 50 4'-Methoxypyridin-3'-yi H H H E 36 5'-Fluoropyridin-3'-yl H H H E 37 5'-Chloropyridin-3'-yi H H H E 38 W-Bromopyridin-X-yl H H H E 39 5'-Methylpyridin-3'-yi H H H E 55 5'-(Trifi uo ro methyl) pyridi n-X-yl H H H E 41 W-Methoxypyridin-X-yl H H H E 42 6'-Fluoropyridin-3'-yi H H H E 43 6-Chloropyridin-3'-yi H H H E 44 W-Bromopyridin-X-yl H H H E 60 W-Methylpyridin-3'-yl H H H E Chemical shift of singlet from olefinic proton on beta-methoxyacrylate group (ppm from tetramethylsilane).
Solvent CDC13 (unless otherwise stated).
t Geometry of beta-methoxyacrylate group. 65 GB 2 189 485 A TABLE 11 (cont) Compound Melting No.
W X Y Z Point (OC) Olefinic lsomert 46 6'-(Trifluoromethyi)pyridin-3'-yl H H H E 47 6'-Methoxypyridin-3'-yt H H H E 48 2'-Fluoropyridin-41-yi H H H E 49 2'-Chforopyridin-4'-yi H H H E 50 2'-Bromopyridin-4'-yi H H H E 10 51 2'-Methylpyridin-4'-yi H H H E 52 2'-(Trifluoromethyi)pyridin-4'-yl H H H E 53 2'-Methoxypyridin-4'-yi H H H E 54 X-Fluoropyridin-4'-y] H H H E 55 3'-Chloropyridin-4'-yi H H H E 56 X-Bromopyridin-4'-yl H H H E - 57 X-Methylpyridin-4'-yl H H H E 58 3'-(Trifluoromethyl)pyridin-4y-yl H H H E 59 X-Methoxypyridin-4'-yl H H H E 60 4'-Fluoropyrimidin-2'-yi H H H E 20 61 4'-Chloropyrimidin-2'-yl H H H E 62 4'-Bromopyrimidin-2'-yi H H H E 63 4'-Methylpyrimidin-2'-yl H H H E 64 4'-(Trifluoromethyl)pyrimidin-2'-yl H H H E 65 4'-Methoxypyrimidin-2'-yl H H H E 25 66 5'-Fluoropyrimidin-2'-yl H H H E 67 5'-Chloropyrimidin-2'-yi H H H E 68 5'-Bromopyrimidin-2'-yi H H H E 69 5'-Methylpyrimidin-2'-yl H H H E 70 5'-(Trifluoromethyi)pyrimidin-2'-yl H H H E 30 71 W-Methoxypyrimidin-2'-yl H H H E 72 2'-Fluoropyrimidin-4'-yl H H H E 73 2'-Chforopyrimidin-4'-yi H H H E 74 2'-Bromopyrimidin-4'-yl H H H E 75 2'-Methylpyrimidin-4'-yl H H H E 35 76 2'-(Trifluoromethyl)pyrimidin-4'-yl H H H E 77 2'-Methoxypyrimidin-4'-yl H H H E 78 5'-Fluoropyrimidin-4'-yl H H H E 79 5'-Chloropyrimidin-4'-yi H H H E 80 5'-Bromopyrimidin-4'-yl H H H E 40 81 W-Methoxypyrimidin-4'-yl H H H E 82 5'-(Trifluoromethyl)pyrimidin-4'-yl H H H E 83 W-Methoxypyrimidin-4'-yl H H H E 84 W-Fluoropyrimidin-4'-y] H H H E 85 6'-Chloropyrimidin-4'-yi H H H E 45 86 W-Bromopyrimidin-4'-yl H H H E 87 6'-Methylpyrimidin-4'-yl H H H E 88 6'(Trifluoromethyi)pyrimidin-4'-yi H H H E 89 6'-Methoxypyrimidin-4'-yl H H H E 90 2'-Fluoropyrimidin-5'-yl H H H E 50 91 2'-Chforopyrimidin-5'-yi H H H E 92 2'-Bromopyrimidin-5'-yi H H H E 93 2'-Methylpyrimidin-5'-yi H H H E 94 2'-(Trifluoromethyl)pyrimidin-5'-yl H H H E 95 2'-Methoxypyrimidin-5'-yl H H H E 96 4'-Fluoropyrimidin-5'-yi H H H E 97 4'-Chforopyrimidin-5'-yi H H H E 98 4'-Bromopyrimidin-5'-yi H H H E 99 4'-Methylpyrimidin-5'-yl H H H E 60loo 4'-(Trifluoromethyl)pyrimidin-5'-yl H H H E 60 101 4'-Methoxypyrimidin-5'-yi H H H E 102 5'-(Trifluoromethyl)pyridin-2'-yl 4-F H H E 103 5'(Trifluoromethyi)pyridin-2'-yl H H H Oil 7.47 E 104 5'-Chloropyridin-2'-yi 5-F H H E 65105 5'-Chforopyridin-2'-yi 3-17 5-F H E 65 12 GB 2 189 485 A 12 TABLE 11 (cont) Compound Melting No. W X Y Z Point (OC) Olefinic Isomert 106 5'-Chloropyridin-2'-yi 4-F 5-F 6-F E 107 5'-Chloropyridin-2'-yl 5-Cl H H E 108 5'-Chioropyridin-2'-yi 5-CH30 H H E 109 5'-Chloropyridiri-2'-yi 5-CH3 H H E 110 W-Ruoropyridin-2'-yl 5-Cl H H E 10 ill W-Ruoropyridin-2'-yl 5-Cl 3-F H E TABLE Ill is is W CO,)CH, (0)n S 20 CH CCH 3 Y z 25 Compound Melting No. W n X Y Z Point (OC) Olefinic lsomert 30 1 5'-Bromopyridin-2'-yl 1 H H H gum 7.60 E 2 W-Bromopyridin-2'-yl 2 H H H gum 7.24 E 3 5'-Chloropyridin-2'-yf 1 H H H E 4 5-Chloropyridin-2'-yi 2 H H H E 5 5'-(Trifluoromethyi)- 1 5-F H H E 35 pyridin-2'-yl Chemfcal shift of singlet from oiefinic proton on beta-methoxyacrylate group (ppm from tetra m ethylsila ne).
Solvent CDC13 (unless otherwise stated).
t Geometry of beta-methoxyacrylate group. 40 13 GB 2 189 485 A 13 TABLE IV
TABLE 1V. Selected proton NMR data Table IVshows selected proton NMR data for certain compounds described in Tables 1, 11 and 111 and 5 characterised therein as oils or gums. Chemical shifts are measured in ppm from tetramethyisilane, and deuterochloroform was used as solvent throughout. The following abbreviations are used.
br = broad t = triplet ppm =parts per million s =singlet q = quartet d =doublet m multiplet 10 Compound No.
is 15 2.28 (3H,s); 3.52 (3H,s); 3.69 (3H,s); 6.77-7.98 (Table 1) (7H,m); 7.37 (1 H,s) ppm.
11 3.57 (3H,s); 3.72 (3H,s); 7.0-7.4 (m); 7.44 (Table 1) (1 HM; 8.34 (H,d)ppm. 20 16 2.26 (3H,s); 3.56 (3H,s); 3.72 (3H,s); 6.65-7.98 (Table 1) (7H,m); 7.42 (1H,s) ppm.
21 2.40 (3H,s); 3.51 (3H,s); 3.67 (3H,s); 6.41-7.55 25 (Table 1) (7H,m); 7.4 (1 H,s) ppm.
22 3.54 (3H,s); 3.74 (3H,s); 7.42 (1 H,s); ppm.
(Table 1)
67 3.60 (3H,s); 3.75 (3H,s); 7.20-7.4 (m); 7.40 30 (Table 1) (1 HM; 8.40 (2H,s) ppm.
3.85 (3H,s); 3.95 (3H,s); 7.44-7.84 (9H,m) ppm.
(Table 1)
35 131 3.50 (3H,s); 3.60 (3H,s); 3.50 (21-1 br.s.); 7.40 (Table 1) (1 HM; 7.60 (1 H,d) plam.
132 (Table 1) 3.70 (3H,s); 3.80 (3H,s); 7.55 (1 H,s) ppm. 40 133 3.60 (3H,s); 3.75 (3H,s); 6.95 (1 H,d); 7.45 (Table 1) (1 HM; 8.45 (1 H,dd); 9.05 (1 H,dd) ppm.
45 137 3.62 (3H,s); 3.76 (3H,s); 6.22 (1 HM; 7.20-7.50 (Table 1) (4H,m); 7.44 (1 H,s) ppm.
3.52 (3H,s); 3.72 (3H,s); 7.14-7.38 (6H,m); 7.40 (Tablet) (1 HM; 8.36-8.38 (1 H,m); 10.00 (1 HM. so 14 3.60 (3H,s); 3.74 (3H,s); 6.68-6.72 (1 H,d); 72-7.4 (Table 11) (4H,m); 7.47 (1 H,s); 7.62-7.65 (11-14; 8.34 (1 H,s) ppm.
15 3.60 (3H,s); 3.74 (3H,s); 6.62-6.65 (1 H,d); 72-7.5 55 (Table 11) MM; 7.47 (1 HM; 7.62-7.64 (1 H,d); 8.42 (1 H,s) ppm.
103 3.60 (3H,s); 3.73 (3H,s); 6.78-6.82 (11-14; 7.35-7.55 (Table 11) (4H,m); 7.47 (1 H,s); 7.65-7.68 (11-14; 8.6 (1 H,s) ppm.
60 3.51 (3H,s); 3.69 (3H,s); 7.01 (1 H,d); 7.23-7.46 (Table 1) (5H,m); 7.43 (1 H,s); 7.62 (1 HM; 7.76 (1 H4; 7.85 (1 H,d); 8.11 (1 H,d) ppm.
14 GB 2 189 485 A 14 TABLE IV (cont) Compound No.
5 167 3.64 (3H,s); 3.76 (3H,s); 6.31 (1 H,d); 6.70 (Table 1) (1 HM; 7.11 (1 H,d); 7.2-7.5 (4H,m) including 7.46 (1 H s) ppm.
112 3.60 (3H,s); 3.73 (3H,s); 6.78-6.82 (1 H,d); 10 (Table 11) 7.36-7.56 (4H,m); 7.47 (1 H,s); 7.65-7.68 (1 H,d); 8.60 (1 H,s) ppm.
1 3.68 (3H,s); 3.87 (3H,s); 7.16-7.20 (1 Km); (Table 111) 7.42-7.45 (2H,m); 7.60 (1 H,s); 7.76-7.79 15 - (1 H,d); 7.86-7.93 (2H,m); 8.47 (1 H,s); ppm.
2 3.50 (3H,s); 3.55 (3H,s); 7.16-7.18 (1 H,d); (Table 111) 7.24 (1 H,s); 7.54-7.65 (2H,m); 8.00 (2H,s); 8.36-8.41 (1 H,d); 8.63 (1 H,s) ppm. 20 The compounds of the invention having the general formula (1) can be prepared from substituted phenols or thiophenols of general formula (V11) by the steps shown in Scheme L Throughout Scheme /the terms W, R 2, A, X, Y, Z and Ware as defined above, L is a halogen atom or another good leaving group which can sometimes 25 be a nitro group and R8 is hydrogen or a metal atom (such as a sodium atom).
Thus, compounds of general formula (1), which exist as geometric isomers which may be separated by chromatography, fractional crystallisation or distillation, can be prepared by treatment of phenylacetates of formula OV) with a base (such as sodium hydride or sodium methoxide) and a formic ester such as methyl formate in a suitable solvent such as N,N-dimethyiformamide and at a suitable temperature (step (b) of 30 Scheme n. If a species of formula R2L, wherein L is as defined above, is then added to the reaction mixture, compounds of formula (1) may be obtained (step (a) of Scheme 1). If a protic acid is added to the reaction mixture, compounds of formula (111) wherein R' is hydrogen are obtained. Alternatively, the species of formula (111) wherein R8 is a metal atom (especially an alkali metal atom such as sodium atom) may themselves be isolated from the reaction mixture. 35 Compounds of formula (111) wherein R' is a metal atom can be converted into compounds of formula (1) by treatment with a species of formula R'-L, wherein L is as defined above, in a suitable solvent. Compounds of formula (111) wherein R' is hydrogen can be converted into compounds of formula (1) by successive treatments with a base (such as potassium carbonate) and a species of general formula R 2 -L, in a suitable solvent.
Alternatively, compounds of general formula (1) can be prepared from acetals of general formula (X111) by 40 elimination of the appropriate alkanol under either acidic or basic conditions, at a suitable temperature and often in a suitable solvent (step (c) of Scheme 1). Examples of reagents or reagent mixtures which can be used for this transformation are lithium di-isopropylamide; potassium hydrogen sulphate (see, for example, T Yamada, H Hagiawa and H Uda, J. Chem. Soc., Chemical Communications, 1980, 838, and references therein); and triethylamine, often in the presence of a Lewis acid such as titanium tetrachloride (see, for example, K 45 Nsunda and L Heresi, J. Chem. Soc., Chemical Communications, 1985, 1000).
Acetals of general formula (X111) can be prepared by treatment of alkyl silyl ketene acetals of general formula (XIV), wherein R is an alkyl group, with a trialkyl orthoformate of formula (WO)3CH in the presence of a Lewis acid such as titanium tetrachloride, at a suitable temperature and in a suitable solvent (see, for example, K Saigo, M Osaki and T Mukaiyama, Chemistry Letters, 1976,769). so Alkyl silyl ketene acetals of general formula (M) can be prepared from esters of general formula (IV) by treatmentwith a base and a trialkylsilyl halide of general formula R3SiCI or R3SiBr, such as trimethylsilyl chloride, or a base and a trialkylsilyl triflate of general formula R3Si- OSO2CF3, in a suitable solvent and at a suitable temperature (see, for example, C Ainswor-th, F Chen and Y Kuo, J. Organometallic Chemistry, 1972, 5546,59). 55 It is not always necessary to isolate the intermediates (XlIl) and (XIV); under appropriate conditions, compounds of general formula (1) may be prepared from esters of general formula (N) in a "one pot" sequence by the successive addition of suitable reagents listed above.
Compounds of general formula (IV) can be prepared by esterification of compounds of general formula (V) by standard methods described in the chemical literature (Step (d) of Scheme 1). 60 Compounds of general formula (V) can be prepared by the reaction of compounds of general formula (V11) with compounds of formula (V[) in the presence of a base (such as potassium carbonate) and, if necessary, a transition metal ortransition metal salt catalyst (such as copper-bronze) in a convenient solvent (such as N,N-dimethyiformamide) (Step (e) of Scheme 1).
Alternatively, compounds of general formula (IV) can be prepared from esters of general formula (V111) by 65 GB 2 189 485 A 15 reaction with compounds of general formula (V1) in the presence of a base (such as potassium carbonate) and, if necessary, a transition metal or transition metal salt catalyst (such as copper-bronze) in a convenient solvent (such as NN-dimethyiformamide) (Step (f) of Scheme n.
Esters of general formula (VII0 can be prepared by esterification of compounds of general formula (VII) by standard methods described in the chemical literature (Step (g) of Scheme 1). 5 Compounds of general formula (V11) can be prepared by standard methods described in the chemical literature. (For example, see, A. Clesse, W. Haeffiger, D. Hauser, H. U. Gubler, B. Dewald and M. Baggiolini, J.Med.Chern., 1981,24,1465) and P D Clark and D M McKinnon, Can. J. Chem., 1982,60,243 and references therein).
Compounds of general formula (1) wherein A is sulphur may be converted into compounds of formula (1) 10 wherein A is S(O) or SM2 by standard methods of oxidation as described in the chemical literature, using, for example, a peracid such as meta-chloroperbenzoic acid, in a suitable solvent and at a suitable temperature.
Alternatively, compounds of the invention having the general formula (1) can be prepared from phenylace tates of general formula (Xli) by the steps shown in Scheme 11. Throughout Scheme lithe terms W, R2 R', A, 1.5 W, X, Y, Z and L are as defined above, and M is a protecting group for a phenol or thiophenol group. 15 Thus compounds of general formula (1) can be prepared by reaction of compounds of general formula (IX) - with compounds of general formula (V1) in the presence of a base (such as potassium carbonate) and, if necessary, a transition metal ortransition metal salt catalyst in a convenient solvent (such as NN dimethylformamide) (step (h) of Schemeffi.
Compounds of general formula (IX) can be prepared from protected phenol orthiophenol derivatives of 20 general formula (X) by standard deprotection procedures as set out in the chemical literature (step (i) of Scheme 11). For example, phenols of general formula (IX, A is 0) can be prepared from benzyl ethers of general formula (X, A is 0, M is CH2Ph) by hydrogenolysis in the presence of a suitable catalyst (such as palladium supported on carbon).
Compounds of general formula (X), in which the group M is a standard phenol or thiophenol protecting 25 group (such as benzyl), can be prepared bytreatment of phenylacetates of formula (Xli) with a base (such as sodium hydride or sodium methoxide) and a formic ester (such as methyl formate) in a suitable solvent such as NN-dimethylformamide and at a suitable temperature (step (k) of Scheme 11). If a species of formula R2-L, wherein L is as defined above, is then added to the reaction mixture, compounds of formula (X) may be obtained (step (j) of Scheme 11). If a protic acid is added to the reaction mixture, compounds of formula (X0 30 wherein R8 is hydrogen are obtained. Alternatively, the species of formula (Xl) wherein R' is a metal atom (especially an alkali metal atom such as a sodium atom) may themselves be isolated from the reaction mixture.
Compounds of formula (X0 wherein R8 is a metal atom can be converted into compounds of formula (X) by treatment with a species of formula R2-L, in a suitable solvent. Compounds of formula (Xl) wherein R' is 35 hydrogen can be converted into compounds of formula (X) by successive treatment with a base (such as potassium carbonate) and a species of formula R'-L.
Compounds of general formula (X11) can be prepared from compounds of general formula (VIII) by standard methods described in the chemical literature.
i 16 GB2189485A 16 Scheme 1 W co 2R1 i 5 A c C H ster) (c) X 2 10 y z OR W 02R A CH CH(OR 2)2 R 2_L (II) X step \(a) y z (XIII) W C02R 20 A c W CH (111) 25 -- c 8 A CH=C(OR1)(OSiR3) X OR (XIV) y X 30 T, 1 y W CO 2R step (b) z A H 2 35 X (IV) W-L y (VI) 40 step (d) step (f) H C02R1 (VI) step A 45 W A C02 H X -91"z (VIII) l CH 2 50 step (g) X W-L H 0 11 C, 2 55 y z (VI A CH2 (V) step (e) X 60 y z (VII) 17 GB 2 189 485 A 17 Scheme 11 W CO Ri 1 2 5 A c CH 2 X OR 10 y z W-L (VI) step (h) 15 - H 0 Ri C, 2 A c 20 CH 2 OR X y z (IX) 25 step m Co R 30 2 A c CH 2 X OR 35 y z (X) step (j) 40 M. CO R 2 A c:
45 CH X OR so (Xi) 50 step (k) m A CO R 2 H2 X 60 y z (XTI) 18 GB 2189485 A 18 Alternatively, compounds of the invention having the general formula (1) can be prepared from substituted benzenes of general formula (XIX) by the steps shown in Scheme fil. Throughout Scheme Ill the terms R', R 2, A, W, X, Y and Z are as defined above, D is hydrogen or halogen and E is a metal atom (such as a lithium atom) or a metal atom plus an associated halogen atom (such as MgI, MgBr or MgC1).
Thus, compounds of general formula (1) can be prepared by treatment of ketoesters of general formula (XV) 5 with phosphoranes of general formula (XVI) in a convenient solvent such as diethyl ether (see, for example, EP-A-0044448 and EP-A-0178826 (Step (c) of Scheme 111).
Ketoesters of general formula (XV) can be prepared by treatment of metallated species (XVII) with an oxalate (XVIII) in a suitable solvent such as diethyl ether or tetrahydrofuran. The preferred method often involves slow addition of a solution of the metallated species (XVII) to a stirred solution of an excess of the 10 oxalate (XVIII) (see, for example, L M Weinstock, R B Currie and A V Lovell, Synthetic Communications, 1981, 11, 943, and references therein) (step (m) of Scheme 111).
- The metallated species (XVII) in which E is MgI, MgBr or MgC] (Grignard reagents) can be prepared by standard methods from the corresponding aromatic halides (M) in which D is 1, Br or Cl respectively. With certain substituents X Y and Z, the metallated species (XVII) in which E is Li can be prepared by direct 15 - lithiation of compounds (M) in which D is H using a strong lithium base such as n-butyl-lithium or lithium di-isopropylamide (see, for example, H W Gschwend and H R Rodriguez, Organic Reactions, 1979,26, 1) (step (n) of Scheme 111).
Compounds of general formula (M) can be prepared by standard methods described in the chemical - literature. 20 19 GB 2 189 485 A 19 Scheme Ill W A CO R 2 X C- CH y OR2 z + 2 15 + 2 Ph 3 P. CHIOR ((X XVI W S t 20 A step (1) X CO R 2 c y 0 25 (XVIII) z R 0 C. CO R 2 2 (XV) 30 W step (m) A 35 X E y 40 z W (XVII) 45 X step (n) 50 y z 55 (XIX) GB 2 189 485 A 20 Alternative methods for the preparation of ketoesters of general formula (XV) are described in the chemical literature (see, for example, D C Atkinson, K E Godfrey, B Meek, J F Saville and M R Stillings, J. Med. Chern., 1983,26,1353; D Horne, J Gaudino and W J Thompson, Tetrahedron Lett., 1984,25,3529; and G P Axiotis, Tetrahedron Lett., 1981,22,1509).
Methods for preparing compounds of the invention having the general formula (1), as described in Schemes 5 1 and 11 are generally applicable where W in general formula (1) is a substituted 2-pyridinyl, or a 2- or 4pyrimidinyl group, and where W is a 4-pyridinyl group containing strong electron withdrawing substituents such as nitro, trifluoromethyl or fluoro. Howeverfor compounds of general formula (1) where W is a substituted 3- or 4-pyridinyl group the methods shown in Scheme 11 may not be generally applicable.
Also, although compounds of the invention having the general formula (1) where W is a substituted 3- or 10 4-pyridinyl group may be prepared from compounds of general formula (N) by steps (a), (b) and (c) as shown in Scheme 1, the preparation of compounds of general formula (IV) where W is a substituted 3- or 4- pyridinyl group may not be generally prepared by the steps (e) and (f) in Scheme L Therefore an alternative method of preparation of compounds of general formula (R) may need to be used.
In general, compounds of formula (IV) where W is a substituted 3- or 4pyridinyl group, may preferably be 15 prepared by the route shown in Scheme IV.
Thus, in Scheme Wcompounds of formula (R) where W is a substituted 3- or 4-pyridinyl group can be prepared from compounds of formula (XX) where) W is a substituted 3- or 4-pyridinyl group.
i 21 GB 2 189 485 A 21 Scheme IV W CO R 2 5 A H X 10 y z W A is is (IV) T z 20 y (XX) p A 25 T W-AH X (XXV) 30 /H (XXI 1 z W-L 35 P-L (XXIV) (VI) L AH 40 T T X (XXIII) 45 y z y z (XXI 50 so 22 GB2189485A 22 Throughout Scheme 1V, A, X, Y, Z and L areas defined above for Schemes I- fil and T is any group that can be converted by standard methods in the literature, in one or more steps, into an acetic ester side chain of structure CH2COOR' as shown in formula OV). For example, T may be a formyl group or any group that is capable of being transformed into a formyl group, such as a formyl acetal which may be hydrolysed by aqueous acid to the formyl group or such as a nitrile which may be reduced to the formyl group by metal 5 hydride reduction (see, for example, A E G Miller, J W Bliss and L H Schwartzmann, J. Org. Chem., 1959,24, 627) or by Raney Alloy in formic acid (see, for example, van Es and Staskun, J. Chem. Soc. 1965,5775). When T is a formy] group, it may then be converted into the acetic ester residue CH2COOR' by reaction with methyl methyisulphinyimethyisulphide (CH3SOCH2SCH3) (see, for example, K Ogura and G Tsuchihashi, Tetrahedron Lett., 1972, 1383-6), followed by hydrolysis with an alcohol R'OH in the presence of an acid such as hydrogen 10 chloride. For example T may also be a group such as a methyl group which can be halogenated, for example by bromine or N-bromosuccinimide, to give a halomethyl group which can then be treated with cyanide ion to give a cyano methyl group, which in turn can be hydrolysed to the acetic ester residue CH2COOR' by methods well known in the literature. T may also be for example a carboxylic acid or ester group which may be reduced to a hydroxymethyl group, which in turn can be converted to a cyanomethyl group by methods well known in 15 the literature.
Compounds of formula (XX), where W is a substituted 3-pyridinyl group, can be prepared from compounds of formula (XXI), where L is defined as for Scheme 1, by reaction with compounds of formula (XXII), where W is a substituted 3-pyridinyi group, under conditions generally used forthe well known Ullmann synthesis. For example the compounds of formula (XXI) can be treated with the metal salt (preferably the sodium or 20 potassium salt) of the compounds of formula (XXII), either neat or in a suitable solvent such as N,N dimethylformamide or dimethyisulphoxide at 50-250'C, but preferably at 1 OG1 80'C, in the presence of a transition metal catalyst such as copper bronze or copper halides. - Compounds of general formula (XXI) can be prepared by standard methods in the chemical literature.
Compounds of formula (XX), where W is a substituted 4-pyridinyl group, can be prepared by reaction of the 25 metal salt (preferably the sodium or potassium salt) of compounds of formula (XXIII) with compounds of formula (V1), where X is a substituted 4-pyridinyl group, in a suitable solvent such as NN-climethylformarnicle or dimethyisulphoxide at 20-200'C, bui preferably at 50-150'C, and optionally in the presence of transition metal catalysts such as copper bronze or copper halides.
Compounds of formula WX) may also be prepared from compounds of formula (XXV), where P is defined as 30 a pyridine N-oxide linked to A through the 4-position. P may or may not be substituted by substituents as def ined for W in compounds of formula (1). If P in compounds of formula (XXV) is substituted, then deoxygenation of the N-oxide by standard methods, for example with phosphorus trichloride, will give compounds of formula (XX) where W is substituted 4-pyridiny]. If P in compounds of formula (XXV) is substituted or unsubstituted, then the well known reaction of pyridine Noxides with phosphory] or thionyl 35 haHdes can be used to give the compounds of formula (XX) containing an additional halogen atom in the 2or 6-position, with concurrent loss of the N-oxide function, (see, for example, "The chemistry of the Heterocyclic Compounds: Pyridine and Its Derivatives% Ed. E Klingsberg, Part Two, p 121).
Compounds of formula (XXV) can be prepared bythe reaction of the metal salt (preferably the sodium or potassium salt) of the compounds of formula (XXIII), with the compounds of formula (XXIV), wherein P and L 40 are as defined above, in a suitable solvent such as NN-dimethylformamide or dimethyisulphoxide, at W-200'C but preferably at 5G-1 500C, optionally in the presence of a transition metal catalyst such as copper bronze or copper halides. Compounds of formula 0M11) can be prepared by standard methods in the chemical literature.
In further aspects, the invention provides processes as herein described for preparing the compounds of the 45 invention and the intermediate chemicals of formulae (111)-(V), (IX)-(XV), (XVII), (XIX), (XX), and (XXV) used therein.
The compounds are active fungicides, and may be used to control one or more of the following pathogens:
Pyricularia oryzae on rice Puccinia recondita, Puccinia strYformis and other rusts on wheat, Puccinia hordei, Puccinia strifflormls and 50 other rusts on barley, and rusts on other hosts e.g. coffee, pears, apples, peanuts, vegetables and ornamental plants. Erysiphe graminis (powdery mildew) on barley and wheat and other powdery mildews on various hosts such as Sphaerotheca macularis on hops Sphaerotheca fuliginea on cucurbits (e.g. cucumber), Podosphaera leucotricha on apples and Uncinula 55 necator on vines.
Helminthosporium spp., Rhynchosporium spp., Septoria spp., Pseudocercosporella herpotricholdes and Gaeumannomyces graminis on cereals.
Cercospora arachidicola and Cercosporidium personata on peanuts and other Cercospora species on other hosts for example sugar beet, bananas, soya beans and rice. 60 Botrytis cinerea (grey mould) on tomatoes, strawberries, vegetables, vines and other hosts.
Alternaria species on vegetables (e.g. cucumber), oil seed rape, apples, tomatoes and other hosts.
Venturia inaequalis (scab) on apples Plasmopara viticola on vines.
Other downy mildews such as Bremia lactucae on lettuce, Peronospora spp. on soybeans, tobacco, onions 65 23 GB 2 189 485 A 23 and other hosts and Pseudoperonospora humuflon hops and Pseudoperonospora cubensis on cucurbits Phytophthora intestans on potatoes and tomatoes and other Phytophthora spp. on vegetables, strawberries, avocado, pepper, ornamentals, tobacco, cocoa and other hosts.
Thanatephorus cucumeris on rice and other Rhizoctonia species on various host such as wheat and barley, vegetables, cotton and turf. 5 Some of the compounds have also shown a broad range of activities gainst fungi in vitro. They may have activity against various post-harvest diseases of fruit (e.g. Penicillium digitatum and italicum and Trichoderma viride on oranges and Gloesporium musarum on bananas).
Further some of the compounds may be active as seed dressings against Fusarium spp., Septoria spp., Tilletia spp., (bunt, a seed borne disease of wheat), Ustilago spp., Heiminthosporium spp. on cereals, 10 Rhizoctonia solani on cotton and Pyricularia oryzae on rice.
The compounds can move acropetally in the plant tissue. Moreover, they may be volatile enough to be active in the vapour phase against fungi on the plant.
Therefore in another aspect of the invention there is provided a method of combating fungi, which comprises applying to a plant, to seed of a plant, or to the locus of the plant or seed, an effective amount of a 15 fungicidal compound of formula (1).
The compounds may also be useful as industrial (as opposed to agricultural) fungicides, e.g. in the prevention of fungal attack on wood, hides, leather and especially paint films.
Some of the compounds of the invention exhibit insecticidal and nematocidal activity.
Therefore in a further aspect of the invention there is provided a method of killing or controlling insect or 20 nematode pests which comprises administering to the pest or to the locus thereof an effective amount of an ins3cticidailnematocidal compound of formula (1).
A preferred group of compounds for use in this aspect of the invention are compounds of formula (1) where X is substituted pyridinyl wherein the substituents are preferably selected from halogen or haloalkyl.
Particularly preferred compounds for use in this method are compounds 14 and 15 in Table 1. 25 Similarly, some compounds exhibit plant growth regulating activity and may be deployed for this purpose at appropriate rates of application. Therefore in yet a further aspect of the invention there is provided a method of regulating plant growth which comprises applying to a plant an effective amount of a plant growth regulating compound of formula (1).
The compounds may be used directly for agricultural purposes but are more conveniently formulated into 30 compositions using a carrier or diluent. Therefore in yet a further aspect of the invention there are provided fungicidal, insecticidallnematocidal and plant growth regulator compositions comprising a compound of general formula (1) as hereinbefore defined, and an acceptable carrier or diluent therefor.
As fungicides the compounds 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 orto other medium in which plants are 35 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, orto soil surrounding the roots, orto the seed before it is planted; or to the soil generally, to paddy water or to hydroponic culture systems. The invention compounds may also be injected into plants or sprayed onto vegetation using electrodynamic spraying techniques or 40 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 and eradicant treatment.
The compounds are preferably used for agricultural and horticultural purposes in the form of a composition.
The type of composition used in any instance will depend upon the particular purpose envisaged. 45 The compositions may be in the form of dustable powders or granules comprising the active ingredient (invention compound) 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 reformed 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 50 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 methyl pyrro 1 idone, propylene glycol or dimethylformamide). The compositions may also be in the form of wettable powders or water dispersible granules comprising wetting or dispersing agents to facilitate the 55 dispersion in liquids. The powders and granules may also contain fillers and suspending agents.
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 alkyl naphtha lenes, ketones such as isophorone, cyclohexanone, and methylcyclohex- 60 anone, chlorinated hydrocarbons such as benzyi alcohol, chlorobenzene and trichlorethane, and alcohols such as furfuryl alcohol, butanol and glycol ethers.
Suspension concentrates of largely insoluble solids may be prepared by ball or bead milling with a dispersing agent and including a suspending agent 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 65 24 GB2189485A 24 container under pressure in the presence of a propellant, eg. fluorotrichloromethane or dichlor odifluoromethane.
The invention compounds 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 compounds may be used in a micro-encapsulated form. They may also be formulated in 5 biodegradable polymeric formulations to obtain a slow, controlled release of the active substance.
By including suitable additives, for example additives for improving the distribution, adhesive power and resistance to rain on treated surfaces, the different compositions can be better adapted for various utilities.
The invention compounds can be used as mixtures with fertilisers (eg. nitrogen-, potassium- or phosphor- us-containing fertilisers). Compositions comprising only granules of fertiliser incorporating, for example 10 coated with, the compound are preferred. Such granules suitably contain up to 25% by weight of the compound. The invention therefore also provides a fertiliser composition comprising a fertiliser and the compound of general formula (1) or a salt or metal complex thereof.
Wettable powders, emulsifiable concentrates and suspension concentrates will normally contain surfac tants eg. a wetting agent, dispersing agent, emulsifying agent or suspending agent. These agents can be 15 cationic, anionic or non-ionic agents.
Suitable cationic agents are quaternary ammonium compounds, for example cetyltrimethylammonium bromide. Suitable anionic agents are soaps, saltsof aiiphatic monoesters of sulphuric acid (for example sodium lauryi sulphate), and salts of sulphonated aromatic compounds (for example sodium dodecylben zenesulphonate, sodium, calcium or ammonium Pg nosul phonate, butyinaphthaiene sulphonate, and a 20 mixture of sodium diisopropyi- and triisopropyl-naphthaiene sulphonates).
Suitable non-ionic agents are the condensation products of ethylene oxide with fatty alcohols such as oieyl or cetyl alcohol, or with alkyl phenols such as octyl- or nonyl-phenol 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 25 colloids (for example polyvinyl pyrrof idone and sodium ca rboxymethylcel lu lose), 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 30 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 10-85%, for example 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 35 containing 0.0005% or 0.01 % to 10% by weight of active ingredient may be used.
The compositions of this invention may contain other compounds having biological activity, eq. com pounds having similar or complementary fungicidal activity or which plant possess plant growth regulating, herbicidal or insecticidal activity.
Afungicidal compound which may be present in the composition of the invention may be one which is 40 capable of combating ear diseases of cereals (eg. wheat) such as Septoria, Gibberella and Helminthosporium spp., seed and soil borne diseases and downy and powdery mildews on grapes and powdery mildew and scab on apple etc. By including another fungicide, the composition can have a broader spectrum of activity than the compound of general formula (1) alone. Furtherthe other fungicide can have a synergistic effect on the fungicidal activity of the compound of general formula (1). Examples of fungicidal compounds which may be 45 included in the composition of the invention are carbendazim, benomyi, thiophanate-methyl, thiabendazole, fuberidazole, etridazole, dichlofluanid, cymoxanil, oxadixyl, ofurace, metalaxyl, furalaxyi, 4-chforo-N-(1 cyano-l-ethoxymethyi)benzamide, benalaxy], fosetyfaluminium, fenarimol, iprodione, prothiocarb, procymi done, vinclozolin, penconazole, myclobutanil, propamocarb, R01 51297, diconazole, pyrazophos, ethirimol, ditalimfos, buthiobate, tridemorph, triforine, nuarimol, triazbutyl, guazatine, triacetate salt of 1,V- 50 iminodi(octamethylene)diguanidine, propiconazole, prochloraz, flutriafol, hexaconazole, (2 RS, 3 RS)-2-(4 chlorophenyi)-3-cyclopropyi-l-(1'-1,2,4-triazol-l-yi)butan-2-ol, (RS)-1(4-chioro-phenyi)-4,4-dimethyi-3-(1 H 1,2,4-triazol-1 -yimethyi)pentan-3-ol, flusilazole, triadimefon, triadimenoi, diclobutrazol, fenpropimorph, pyrifenox, fenpropidin, chlorozolinate, imazalil, fenfuram, carboxin, oxycarboxin, methfuroxam, dodemorph, BAS 454, blasticidin S, kasugamycin, edifenphos, Kitazin P, cycloheximide, phthalide, probenazole, iso- 55 prothiolane, tricyclazole, pyroquilon, chlorbenzthiazone, neoasozin, polyoxin D, vaUdamycin A, mepronil, flutolanil, pencycuron, diclomezine, phenazin oxide, nickel dimethyidithiocarbamate, techlofthalam, biterta no], bupirimate, etaconazole, hydroxyisoxazole, streptomycin, cyprofuram, biloxazol, quinomethionate, dimethirimol, 1-(2-cyano-2-methoxyiminoacetyl)-3-ethyl urea, fenapanil, tolclofos-methyl, pyroxyfur, poly ram, maneb, mancozeb, captafol, chlorothalonil, anilazine, thiram, captan, folpet, zineb, propineb, sulphur, 60 dinocap, dichlone, chloroneb, binapacryl, nitrothal-isopropyl, dodine, dithianon, fentin hydroxide, fentin acetate, tecnazene, quintozene, dicloran, copper containing compounds such as copper oxychloride, copper sulphate and Bordeaux mixture, and organomercury compounds.
The compounds of general formula (1) can be mixed with soil, peat or other rooting media forthe protection of plants against seed-borne, soil-borne or foliar fungal diseases. 65 GB 2 189 485 A 25 Suitable insecticides which may be incorporated in the composition of the invention include pirimicarb, dimethoate, demeton-s-methyl, formothion, carbaryl, isoprocarb, XMC, BPMC, carbofuran, carbosulfan, diazinon, fenthion, fenitrothion, phenthoate, chlorpyrifos, isoxathion, propaphos, monocrotophas, bup rofezin, ethroproxyfen and cycloprothrin.
Plant growth regulating compounds are compounds which control weeds or seedhead formation, or 5 selectively control the growth of less desirable plants (eg. grasses).
Examples of suitable plant growth regulating compounds for use with the invention compounds are the gibberellins (eg. GA3, GA4 or GA7), the auxins (eg. indoleacetic acid, indolebutyric acid, naphthoxyacetic acid or naphthylacetic acid), the cytokinins (eg. kinetin, diphenylurea, benzimidazole, benzyladenine or benzylami nopurine), phenoxyacetic acids (eg. 2,4-D or MCPA), substituted benzoic acid (eg. triiodobenzoic acid), 10 morphactins (eg. chlorfluoroecol), maleic hydrazide, glyphosate, glyphosine, long chain fatty alcohols and acids, dikegulac, paclobutrazol, fluoridamid, mefluidide, substituted quaternary ammonium and phospho nium compounds (eg. chloromequat chlorphonium or mepiquatchloride), ethephon, carbetamide, methyl-3,6 dich lo roan isate, daminozicle, asulam, abscisic acid, isopyrimol, 1-(4- chlorophenyl)-4,6-dimethyi-2-oxo-1,2dihydropyridine-3-carboxylic acid, hydroxybenzonitriles (eg. bromoxynil), difenzoquat, benzoylprop-ethyl 15 3,6-dichloropicolinic acid, fenpentezol, inabenfide, triapenthenol and tecriazene.
The following Examples illustrate the invention. Throughout these Examples, the term 'ether'refers to diethyl ether; chromatography was carried out using silica gel as the solid phase; magnesium sulphate was used to dry solutions; and reactions involving water- or air-sensitive intermediates were performed under nitrogen and in dried solvents. Where shown, infrared and NMR data are selective; no attempt is made to list 20 every absorption. Unless otherwise stated, NMR spectra were recorded using deuterochloroform solutions.
The following abbreviations are used throughout:
9 = grammes(s) delta = chemical shift mmol = micromole(s) CDC13 = deuterochloroform 25 mi = millilitre(s) s = singlet mmHg = Millimetres pressure cl = doublet of mercury t = triplet br = broad 30 DIVIF = NN-Dimethylformamide max. = maximum or maxima HPLC = High performance liquid chromatography mp. = Melting point ppm. = parts per million 35 NMR = Nuclear magnetic resonance Example 1
This Example illustrates the preparation of (E)-methyl 2-[2'-(5'chforopyridin-2"-yioxy)phenyll-3- methoxyacrylate (Compound No. 14 of Table 1). 40 Asolution of 2,5-dichloropyridine (7.709, 52.03mmol), potassium carbonate (14.01g, 101.37mmol) andthe disodium saltderivedfrom o-hydroxyphenylacetic acid (10.209,52.58mol) in dimethyisulphoxide (50mi) was stirred overnight at 1600C under an atmosphere of nitrogen. The dark reaction mixture was poured into water (1 00mi), and extracted with ether (3 x 75mi). The aqueous phase was acidified to pH 6 with concentrated hydrochloric acid and then extracted with ethyl acetate (3x100mi). The combined organic layers were washed 45 with brine (2 x 100mi), dried and then evaporated under reduced pressure to give [2-(5'-chloropyridin-2' yloxy)phenyllacetic acid (5.30g) as a dark brown liquid (infrared max. 3500-2700,1700,1370,1440,750 cm-1) which was used without further purification. 2-(5'-Chforopyridin-2'- yioxy)phenylacetic acid (5.20g, 19.73mmol), potassium carbonate (5.53g, 40mmol) and dimethyl sulphate (2. 91 g, 23.07mmol) were stirred together overnight at room temperature in DIVIF (50mi). The reaction mixture was poured into water (1 00mi) 50 and extracted with ethyl acetate (2 X 75mi) and ether (1 x 100ml). The combined organic layers were washed with water (3 x 75mi) and brine (2 X 1 00mi), and then dried and evaporated under reduced pressure to give methyl 2-(5'-chloropyridin-2'-yioxy)phenylacetate (4.189) as a dark brown liquid which was distilled at 152'C/O.lmmHg.
To a stirred suspension of sodium hydride (0.78g, 50% dispersion in oil) in DMF (40mi) at -25'C was added 55 dropwise a solution of methyl 2-5'-chloropyridin-2'-yioxy)phenylacetate (2.909,10.45mmol) and methyl formate (14.889, excess) in DIVIR The reaction mixture was partitioned between saturated sodium carbonate solution and ether. The aqueous layerwas acidified with concentrated hydrochloric acid to pH 4-5 (yellow precipitate) and then extracted with ethyl acetate (3 x 100mi). The organic extracts were combined, dried and evaporated under reduced pressure to give methyl 2-[2'-(5"-chloropyridin2"-yioxy)phenyll-3-hydroxyacrylate 60 as an orange-red solid (2.36g). The solid (2.30g, 7.54mmol) was stirred overnight in DMF (50mi) at room temperature with dimethyl sulphate (1.21 g, 9.59mmol) and potassium carbonate (2.44g, 17.6mmol). The reaction mixture was poured into water (1 00mi) and then extracted with ethyl acetate (3 X 1 00mi). The combined organic layers were washed with water (3 x 75mi) and brine (2 X 1 00mi), and then dried and evaporated under reduced pressure to give a brown viscous liquid. HPLC (eluent ether- petroleum ether 65 26 GB2189485A 26 50:50) gave a pale yellow liquid which crystallised on standing (2.14g). Recrystallisation from methanol gave (E)-methyl 2-[2'-(5"-chloropyridin-2"-yioxy)phenyll-3-methoxyacrylate, m. p. 77-WC; infrared max. 1700,1625, 1260,1200 cm-l; 'H NMR delta (CDC13) 3.57 (3H,s), 3.74 (3H,s), 6.75 (1 H, d), 7.41 (1H,s), 8.10 (1 H,brs), 7.1-7.6 (m) ppm.
5 Example 2
This Example illustrates the preparation of (E)-methyi-2-[2',5"cyanopyridin-2"-yloxy)phenyll-3- methoxyacrylate (Compound No. 127 of Table 1).
0 rtho-hyd roxyph enyl acetic acid (3.089; 0.02 mol) was added to a stirred solution of potassium hydroxide (2.26g, 0.04 mol) in methanol (40 mi). After 15 minutes the solution was evaporated to dryness under reduced 10 pressure and the solid residue slurred in DIVIF (50 mi). 6Chloronicotinonitrile (3.08g; 0.022 mol) and copper bronze (0.1 g) was added and the mixture stirred at 80-90'C for 1 hour, then cooled and drowned into water (200 mi). The mixture was filtered and the pH ofthe filtrate was adjusted to 2-3 by addition of hydrochloric acid. The mixture was extracted with ether (x3). The combined ether extracts were extracted with saturated sodium bicarbonate solution. The aqueous phase was acidified with hydrochloric acid (pH 2-3) to produce a 15 tarry solid. Trituration with a little methanol gave a white solid (1.27g, 25% yield). Recrystallisation from water afforded 2-[2'-W-cya n opyridin-2"-yi oxy) phenyl]acetic acid as a white solid mp. 12WC. Infrared max. 1672 cm-1; 1 H NMR W6 DIVISO; 60MHz) delta 3.45 (2H,s); 7.05-7.45 (5H,m); 8.25- 8.35 (mA W; 8.6 (1 H,d); 6.3 (brs.1 H) ppm.
The acid (3.09, 0.0118 mol) was stirred at reflux in methanol (50 mi) containing concentrated sulphuric acid 20 (0.1 mi) for 3 hours. The mixture was cooled, water (200 mi) was added and the mixture was extracted with ether (3 x 50 mi). The combined ether extracts were washed with saturated sodium bicarbonate solution (30 ml), water (3 x 30 mi) and saturated brine (1 x 30 mi). After drying and filtration the ether solution was evaporated to yield methyl 2-[2'-(5"-cya no pyrid in-2"-yl oxy) phenyl] acetate as an amber oil (2.77g, 87.5% yield); infrared max. (thin film) 2200,1700 cm-l; 'H NMR (CDC13) 3.5 (5H, s); 6.8-7.3 (5H,m); 7.8 (1 H,q); 8.3 25 (1 H,d) ppm.
Trimethylsilyl trifluoromethyisu 1 phonate (1.42g; 0.0064 mol) was added dropwise to a solution oftriethyia mine (0.65g; 0.0064 mol) in diethyl ether (10 mi) at room temperature. The mixture was allowed to stand for 20 minutes then added dropwise over 15 minutes to a stirred solution of methyl 2-[2'-(5" cyanopyridyloxy)phenyllacetate (1.1 5g; 0.0043 moles) in ether (10 mi) at 0-50C. The mixture was allowed to 30 warm to room temperature and stirred for an hour to yield a two phase mixture. The upper layer (solution A) was retained.
Meanwhile, titanium tetrachloride (1.22g, 0.0064 mol) was added dropwise to a stirred solution oftrimethyl orthoformate (0.71g; 0.0064 mol) in dichloromethane (10mi) at -70'C. The resulting yellow precipitate was stirred for 15 minutes and solution A was added dropwise over 20 minutes maintaining the temperature at 35 -70'C. The mixture was stirred at -70'c for 1 hour then allowed to warm to room temperature and stirred for 1 hour. Saturated sodium carbonate solution (50 mi) was added and the mixture was filtered. The filtrate was extracted-with ether (3 x 20 mi). The combined organic extracts were washed with water (3 x 15 mi), saturated brine (15 mi) and after drying and filtration the ether solution was evaporated to dryness under reduced pressure. Chromatography ofthe residue (hexanelether) gave the title compound as a glass which on 40 trituration with methanol gave white crystals (40 mg, 3% yield) mp. 108.5- 109.5'C; 'H NMR delta 3.58 (3H,s); 3.75 (3H,s); 6.9 (1 H,d); 7.1 (1 H4; 7.28-7.4 (4HM; 7.45 (1 HM; 7.85 (1 H, q); 8.45 (1 H,d) ppm.
Example 3
This Example illustrates the preparation of (E)-methyl 2-[2'-(5"nitropyridin-2"-yloxy) phenyl]-3- 45 methoxyacrylate (Compound No. 133 ofTable 1).
2-(Hydroxyphenyi)acetic acid (50g) was added to a solution of hydrogen chloride in methanol [prepared from acetyl chloride (25 mi) and methanol (250 m01. The solution was stirred at room temperature for three hours and then allowed to stand overnight (fifteen hours). The resulting mixture was concentrated under reduced pressure, and the residue was taken up in ether (250mi) and washed with an aqueous solution of 50 sodium bicarbonate until effervescence ceased. The ethereal solution was dried and then concentrated under reduced pressure and the resulting solid was recrystallized from etherlpetrol to afford methyl (2 hydroxyphenyl)acetate (50g; 92% yield) as white, powdery crystals, mp. 7G- 72'C; infrared max. (nujol mull):
3420,1715 cm-l; 'H nmr (90 MHz): delta 3.70 (2H,s), 3.75 (3H,s), 6.80-6. 95 (2H,m), 7.05-7.10 (1 HM, 7.15-7.25 (1 HM, 7.40 (1 H,s) ppm. 55 Methyl (2-hydroxyphenyi)acetate (21.0g) was dissolved in DMF (200mi), and potassium carbonate (1 9.35g) was added in one portion. Benzyl bromide (23.94g) in DIVIF (50mi) was added dropwise to this mixture, with stirring, at room temperature. After eighteen hours the mixture was poured into water (500mi) and extracted with ether (2 x 400mi). The extracts were washed with water (3 x 150mi) and brine (1 00mi), dried and filtered through silica gel (50g; Merck 60), then concentrated under reduced pressure to afford a yellow oil. Distillation 60 at 16WC and 0.05 mmHg afforded methyl 2-benzyl oxyph enyl acetate as a clear, colourless oil (26.999; 83% yield), infrared max. (film): 1730 cm-'; 'H rimr (90 MHz): delta 3.60 (3H, s), 3.75 (2H,s), 4.10 (2H,s), 6.80-7.40 (9H,m) ppm.
A mixture of methyl 2-be nzy] oxyp h enyl acetate (26.99g) and methyl formate (126.62g) in dry DIVIF (300mi) was added dropwise to a stirred suspension of sodium hydride (50% disp. in oil, 10.139) in DIVIF (300 m)) at 65 27 GB 2 189 485 A 27 o,C. After stirring at OOC for two hours the mixture was poured into water (1000mi) and washed with ether (2 x-150mi). The aqueous layerwas acidified to pH4 with 6M hydrochloric acid then extracted with ether (2 x 350mi). The extracts were dried and concentrated under reduced pressure to afford crude methyl 2-[2'-benzyloxyphenyll-3-hydroxyacrylate as a yellow oil, infrared max. (film): 1720,1660 cm-1.
The crude methyl 2-(2'-benzyloxyphenyi)-3-hydroxyacrylate was dissolved in dry DIVIF (1 00mi) and 5 potassium carbonate (29.0g) was added in one portion. Dimethyl sulphate (1 6.00g) in dry DIVIF (1 Omi) was then added dropwise with stirring. After ninety minutes, water (300mi) was added and the solution was extracted with ether (2 x 300mi). After washing with water (3 x 150mi) and brine, the extracts were dried and concentrated under reduced pressure, and the resulting yellow oil solidified on trituration with etherlpetrol.
Recrystal 1 ization from dry methanol afforded (E)-m ethyl 2-(2'benzyloxyphenyl)-3-m eth oxyacrylate as a white, 10 crystalline solid (5.44g, 17% yield from methyl 2-benzyioxyphenylacetate), mp. 7677'C; infrared max. (nujol mull): 1710,1640 cm-l; 'H nmr (90 MHz): delta 3.63 (3H,s), 3.75 (3H,s), 5. 05 (2H,s), 6.80-7.40 (9H,m), 7.50 (1 H,s) ppm.
(E)-Methyl 2-(2'-benzyfoxyphenyl)-3-methoxyaerylate (5.44g) was dissolved in ethyl acetate (50m1) and 5% palladium on carbon (0.259) was added. The stirred mixture was hydrogenated atthree atmospheres 15 pressure, with stirring, until no more hydrogen was taken up, then filtered through celite and silica gel (50g, Merck 60). Concentration of the filtrate under reduced pressure afforded (E)-methyl 2-(-2'-hydroxyphenyi)-3 methoxyacrylate as a white crystalline solid (3.76g; 99% yield), mp. 125126'C; infrared max. (nujol mull):
3400,1670 cm-l; 'H NMR (270 MHz): delta 3.80 (3H,s), 3.90 MHM, 6.20 (1 HM, 6.80-7.00 (2H,m), 7.10-7.30 (2HM, 7.60 (1 H,s) ppm. 20 (E)-Methyl 2-(2'-hydroxyphenyi)-3-methoxyacrylate (0.30g, 1.44 mmol), 2chloro-5-nitropyridine (0.46g, 2.88 mmol) and potassium carbonate (0.40g, 2.88 mmol) were stirred together in DIVIF (20 mi) at room temperature under an atmosphere of nitrogen. After 18 hours, the reaction mixture was poured into water and then extracted twice with ether. The combined ether layers were washed twice with water and brine, and then dried. The resultant solution was filtered through a plug of silica gel and then concentrated to afford a pink 25 solid. Chromatography (eluent-ether) afforded (E)-methyl 2-[2'-(5"- nitropyridin-2"-yioxy)phenyll-3methoxyacrylate (240 mg) as a yellow gum which crystallised on standing, m.p. 1071 09-C; H NMR: As Table 1V.
Example 4 30
This Example illustrates the preparation of (E)-methyl 2-[2'-(4"chloropyrimidin-2"-yloxy)phenyll-3- methoxyacrylate (Compound No. 61 of Table 1).
E-Methyl 2-(2'-hydroxyphenyi)-3-methoxyacrylate(O.63g),2,4dichforopyrimidine (0.75g) and potassium carbonate (0.69g) were stirred together in DIVIF at room temperature. After 2 hours the reaction mixture was poured into water (50 mi) and extracted twice with ether. The combined ether layers were washed with water 35 (x3) and brine (X 1) and then dried. Filtration and evaporation of the solvent under reduced pressure afforded a clear oil. Chromatography (eluent-ether) gave (E)-methA 2-[2'-(4"- chloropyrimidin-2"-yioxy)phenyll-3- methoxyacrylate (0.35g) as an oil which crystallised on trituration with ether, m.p. 120-121.5'C; 'H NMR delta 3.60 (3H,s); 3.80 (3H,s); 6.60 (1 HAJ=4H4; 7.40 (1 H,s); 8.40 (1 H,d, J=4Hz) ppm.
40 Example 5
This Example illustrates the preparation of (E)-methyl 2-[2'(5"chforopyridin-2"-yithio)phenyll-3- methoxyacrylate (Compound No. 14 of Table 11).
To a mixture of the disodium salt of o-mercaptophenytacetic acid (formed by treatment of 0 mercaptophenylacetic acid (1.68g) with sodium hydroxide (0.8g) in methanol (10 m]) followed by evaporation 45 of half of the resultant solution to dryness and re-dissolution in 10 mi of DMF).and copper-bronze was added a solution of 2,5-dichloropyridine in DIVIF (5 mi). The reaction mixture was heated to 11 0-120'C for 90 minutes, added to water, acidified, and then extracted (x 3) with ether. The combined ether layers were extracted with 2N sodium hydroxide (x 1) and the resultant orange aqueous phase was acidified with dilute hydrochloric acid. The resulting suspension was filtered, and the solid was thoroughly washed with water and dried to give 50 [2'-(5'-chforopyridin-2"-yithio)phenyll-acetic acid (0.88g) as a fawncoloured solid, m.p. 141-4'C.
[2'-(5'-Chloropyridin-2"-ylthio)phenyllacetic acid (0.65g) was heated to reflux in methanol (15 mi) containing two drops of concentrated sulphuric acid. After 90 minutes, the solution was cooled to room temperature, poured into water and then extracted (x 2) with ether. The combined organic phases were washed with 1 M sodium hydroxide solution and water (X 3) and then dried. Concentration under reduced pressure afforded 55 methyl [2'-(5"-chloropyridin-2'-ylthio)phenyll-acetate (610 mg) as a brown oil which was used without further purification.
To a stirred suspension of hexane-washed sodium hydride (0.1 44g, 50% dispersion in oil) in DMF cooled to 20C (icelsalt bath) was added a solution containing methyl [2'- (5"chloropyridin-2'-ylthio)phenyllacetate (0.44g) and methyl formate (1.8g) in DIVIF (10 mi). The resultant reaction mixture was allowed to warm to room 60 temperature. After 41 hours, the reaction was quenched by careful addition of water, acidified with dilute hydrochloric acid, and then extracted (x 3) with ether. The orange organic layers were combined, washed with water and then dried. Concentration under reduced pressure gave a crude mixture containing methyl 2-[2'-(5"chloropyridin-2"-ylthio)phenyll-3-hydroxyacrylate (0.40g) as an orange gum (infrared max. 1665 cm-') which was used directly in the next stage. The orange gum was dissolved in DMF (10 m[) and potassium 65 28 GB 2189485 A 28 carbonate was added. The resulting suspension was cooled to OOC and then a solution of dimethyl sulphate in DIVIF (2 mi) was added dropwise over 5 minutes. After stirring at O'C for 1 hour, the reaction mixture was warmed to room temperature, poured into water and then extracted (X 4) with ethyl acetate. The combined organic phases were washed with water (x 2) and then dried. Concentration under reduced pressure afforded a red oil (0.469) which was chromatographed (eiuent-ether-hexane 1:1) to give the title compound (0.085g) as 5 a thick gum, infrared max. 1700,1630 cm-1, 'H NMR: As Table 1V.
Example 6
This Example illustrates the preparation of (E)-methyl 2-[2'-(5"bromopyridin-2"-yithio)phenyll-3- methoxyacrylate (Compound No. 15 of Table 11), (E)-methyi 2-(2'-(5"- bromopyridin-2"-yisulphinyi)phenyi]-3methoxyacrylate (compound No. 1 of Table 111) and (E)-methyl 2-[2'-(5"bromopyridin-2"-yisulphonyi)phenyll- 3-methoxyacrylate (compound No. 2 of Table 111).
- (E)-Methyl 2-[2'-(5"-bromopyridin-2"-yithio)phenyll-3-methoxyacrylate (200 mg) prepared from 2,5 dibromopyridine following the procedure outlined in Example 5) was treated with meta-chloroperbenzoic acid (113 mg) in dry dichloromethane (10 mi) at OoC. The orange solution became colourless within 15 minutes. 15 - After stirring for 30 minutes, the reaction mixture was partitioned with aqueous sodium hydrogen carbonate solution. The organic layer was washed with a second portion of aqueous sodium hydrogen carbonate solution and then with water and dried. The solvent was removed under reduced pressure to give a yellow gum (0.149) which was chromatographed (eluent ether) to afford (E)-methyl 2-[2'-(5"-bromopyrid-2'- yisulphinyi)phenyll-3-methoxyacrylate as a gum (30 mg); 'H NMR as Table W; and (E)-methyl 2-[2'-(5"bromopyrid-2"-ylsulphonyl)phenyll-3-methoxyacrylate as an amorphous solid (30 mg); 'H NMR as Table 1V.
Example 7
This Example illustrates the preparation of (E)-methyl 2-[2'-5"methoxycarbonylpyridin-2'-yloxy)phenyll-3- methoxyacrylate (Compound No. 141 of Table 1). 25 Methyl 2-[2'-5"-cyanopyridin-2"-yloxy)phenyllacetic (2.03g 0.008 mol; prepared as described in Example 2) was heated at reflux in a solution of potassium hydroxide (1.0g; 0.017 mol) in water (30 m]) for 16 hours. The solution was cooled to room temperattire and the pH was adjusted to 2-3 bythe addition of hydrochloric acid.
The resulting precipitate was filtered, washed with a little ice-cold water and dried at WC (1.83g).
Recrystallisation from aqueous methanol afforded 2-[2'-(5'-carboxypyridin2"-yioxy)phenyllacetic acid (1.83g) 30 as white crystals; mp. 187-188'C; infrared max3400,2556,1710,1686 cm-l; 'H NMR (d6 DIVISO) delta 3.42 (2H,s); 6.32 (1 H,Brs); 6.95-7.44 (5H,m); 8.1 (1 H,brs); 8.27 (1 H'q); 8. 62 (1 H,d) ppm.
A mixture of 2-[2'("-carboxypyrid-2"-yioxy)phenyl1 acetic acid (1.46g; 0. 0053 mol), methyl iodide (1.52g, 0.00107 mol), potassium carbonate (2.95g; 0.021 moll and DIVIF was stirred at room temperature for 3 hours.
The mixture was drowned into water (100 mi) and extracted with ether (2 X 40 mi). The combined organic 35 extract was washed with water (3 X 20 mi), and saturated brine (20 mi). After drying the filtration, evaporation of the ether solution gave methyl 2-[2'-(5'-methoxycarbonylpyridin-2"yioxy)phenyl1 acetate as ain oil (0.73g) H NMR delta 3.45 (3H,s); 3.47 (2H,s); 3.79 (3H,s); 6.73-7.3 (5H,m); 8.2 (1 H'q); 8.7 (1 H,d) ppm.
Trimethylsilyl trifluoromethanesulphonate (0.81 g; 0.0036 molar) was added dropwise to a solution of triethylamine (0.379, 0.0036 mol) in ether (10 mi) at room temperature. After standing for 20 minutes the 40 resulting solution was added dropwise to a solution of methyl 2-[2'-(5methoxycarbonyi)pyridin-2'- yl oxy) phenyl] acetic in ether (10 mf) at 0-5'C over 20 minutes. The mixture was allowed to stir and warm to room temperature over 3 hours. The upper clear layer from this mixture was retained (solution A).
Meanwhile in a separate flask a solution of titanium tetrachloride (0.69g, 0.0036 mol) in dichloromethane (5 mi) was added to a solution of trimethylorthoformate (0.4g; 0.0036 moll in dichloromethane (10 mO at -700C. 45 The resulting yellow precipitate was stirred at -70'C for 15 minutes. Solution A was added to the mixture dropwise over 10 minutes, maintaining the temperature at -70'C. The mixture was stirred for 1 hour, left to stand for 16 hours. Saturated sodium carbonate solution (50 mi) was added and the mixture was filtered. The filtrate was extracted with ether (3 x 20 mi) and the combined organic extracts were washed with water (3 x 15 mi) and saturated brine (15 mi). After drying and filtration the ether solution was evaporated to leave a tarry 50 residue. The title compound was isolated as an oil from the residue by chromatography (eluent-hexane) (20 mg).
H NMR delta 3.47 (3H,s); 3.62 (3H,s); 3.82 (3H,s); 6.75-7.3 (5H,m); 7.32 (1 H,s); 8.15 (1 H,q); 8.72 (1 H,d) ppm.
55 Example 8
This Example illustrates the preparation of (E)-methyl 2-[2-(5"benzyioxycarbonylpyridin-2"-yioxy)phenyll- 3-methoxyacrylate (Compound No. 184 of Table 1).
2-[2'-(W-Ca rboxypyrid-2"-yf oxy) phenyl] acetic acid (1.5g; 0.005 molar; prepared as described in Example 7) was heated with methanol (50 mO and sulphuric acid (0.1 ml) under reflux for 8 hours. The mixture was 60 reduced to half bulk by evaporation, cooled, drowned into water (100 mi) and then extracted with ether (2 x 30 mi). The combined organic extracts were extracted with saturated sodium bicarbonate solution. The alkaline extract was acidified with hydrochloric acid to pH 2.3, cooled in icewater and the resulting white precipitate was filtered, washed with water and dried at WC to afford methyl 2-[2'- (5'-ca rb oxypyridi n-T-yl oxy) phenyl] acetate (0.63g); mp. 11 WC; 'H NMR delta 3.52 (3H,s); 3.57 (2H,s); 6.88-7. 4 (5H,m); 8.3 (1 H,q); 8.88 (1 H,d) ppm. 65 29 GB 2 189 485 A 29 A mixture of methyl (0.37g, 0.0021 moles), potassium carbonate (0.6g; 0.0043 moles) and DIVIF (30 mi) was stirred at room temperature for 1 hour. The mixture was drowned into water (100 mi) and extracted with ether (2 X 30 m]). The combined organic extract was washed with water (3 x 15 mi) and saturated brine (15 mi). After drying and filtration, the ether solution was evaporated to give methyl 2-[2'-(5"benzyioxycarbonylpyridin-2"- 5 yloxy)phenyllacetate as a colourless gumwhich was purified by chromatography (eluent/hexane) to give a colourless solid (0.69g); mp. WC; infrared max 1735,1722 cm-','H NMR delta 3.44 (3H,s); 3.5 (2H,s); 5.24 (2H,s); 6.76-7.4 (5H,m); 8.2 (1 H,q); 8.76 (1 H,d) ppm.
Trimethylsilyl trifluoromethyisulphonate (0.61 g, 0.0027 moles) was added dropwise at room temperature to a solution of triethylamine (0.277g; 0.0027 moles) in ether (5 mi). The mixture was allowed to stand for 20 10 minutes and the resulting solution was added to a stirred mixture of methyl 2-[2'-(5"a benzyioxycarbonylpyridin-2"yloxy)phenyllacetate in ether (5 m]) at O-WC over 15 minutes. The resulting mixture was allowed to stir and warm to room temperature over 3 hours then diluted with dichloromethane (5 mi) and retained (solution A).
Meanwhile a solution of titanium tetrachloride (0.52g, 0.0027 moles) in dichloromethane (2 m[) was added 15 dropwise to a solution of trimethylorthoformate (0.301g; 0.0077 moles) at -70'C. The resulting yellow precipitate was stirred at -70'C for 15 minutes and solution A was added dropwise over 30 minutes, maintaining the temperature at -70'C. The mixture was stirred, allowed to warm to room temperature over 1 hour then left to stand for 15 hours. Saturated sodium carbonate solution (30 m) was added and the mixture was stirred, then filtered. The filtrate was extracted with ether (3 X 15 m[). The combined ether extracts were '20 washed with water (3 x 10 m) and saturated brine (10 m]). After drying and filtration the ether solution was evaporated to give a gum. The title compound was isolated by chromatography (eluent-hexane) as a gum; 'H NMR delta 3.55 (3H,s); 3.60 (3H,s); 5.35 (2H,s); 6.82 (1 H,d); 7.18-7.48 (m, including a one proton singlet at 7.39); 8.25 (1 H,q); 8.25 (1 H,d) ppm.
25 Example 9
This Example illustrates the preparation of (E)-methyl 2-[2'-(6"m ethyl pyrid i n-3'-yi oxy) phenyij-3 methoxyacrylate (compound No. 45 of Table 1).
6-Methyi-3-hydroxypyridine (9.5g) was suspended in toluene (30 m[) and treated with aqueous potassium hydroxide [4.9g in water (8 m01. The mixture was stirred vigorously for 15 minutes then evaporated under 30 reduced pressure. Last traces of water were removed by repeated evaporation in the presence of toluene. The brown semi-solid formed was treated with a combination of 2-(2- bromophenyi)-1,3-dioxotane (1 0.0g), cuprous chloride (60 mg) and tris [2-(2-methoxyethoxy)ethyllamine (0. 1949) to solubilise the copper salt, in dry DIVIF (25 mi) and the mixture was heated to 155C with stirring under nitrogen for 30 hours. Further cuprous chloride (60 mg) was added and heating continued for 14 hours. 35 The mixture was cooled, poured into water and extracted with ethyl acetate. The extract was washed with 2N aqueous sodium hydroxide solution and water, followed by extraction with 2N hydrochloric acid. The acidic aqueous extract was treated with solid potassium carbonate until pH 8 and then extracted with ethyl acetate. This organic extract was dried and then evaporated under reduced pressure to give 2-(W- - 1 methyl pyridin-X-y] oxy)benzaldehyde (2.2g) as an oil; infrared maxima (film) 1697,1606,1480 cm-l; 'H NMR 40 delta 2.58 (3H,s); 6.86 (1 H,s); 7.28 (3H,m); 7.55 (1 H,t); 7.95 (1 H,m); 8.36 (1 H,m); 10.53 (1 H,s) ppm.
2-(6'-M ethyl pyridin-3'-ytoxy) benza Idehyde (2.089) and methyl methyisu 1 phi nyl methyl sulphide (1.21g) were dissolved in dry THF (15 mi) and Triton B (1.5 m() was added slowly dropwise with stirring at room temperature. The mixture was stood overnight, diluted with water and extracted with ethyl acetate. This extract was dried and then evaporated under reduced pressure, giving an orange-brown oil (3.2g). The oil was 45 treated with a methanol solution of hydrogen chloride (25 mi, 2.6N) and stood overnight at room temperature.
The solution was then diluted with water and broughtto pH 8 by the addition of sodium carbonate. The mixture was extracted with ethyl acetate and the extract dried and evaporated to give a brown oil (2.239) which was purified by HPLC (eluent 1A, ethyl acetate:hexane) to give methyl [2-(W-m ethyl pyridin-3' ytoxy)phenyllacetate, as a yellow oil (1.539) infrared maxima (film) 1747, 1488,1237 cm-l; 'H NMR delta 2.54 50 (3H,s); 3.63 (3H,s); 3.74 (2H,s); 6.84 (1 H,d); 7.24 (5H,m); 8.3 (1 H,d) ppm.
A mixture of methyl [2-W-methyl pyridin-3'-yfoxy) phenyl] acetate (1.39) and methyl formate (1.52g) in DIVIF (5 mf) was added dropwise to a suspension of sodium hydride (316 mg of 50% oil dispersion in DMF (5 mi), with stirring at WC) After stirring for 4 hours the mixture was diluted with water, made weakly acidic by addition of glacial acetic acid (pH 4-5) and extracted with ethyl acetate. This extract on drying and evaporation 55 under reduced pressure, gave methyl 2-[2'-(6"-methylpyridin-3"-yioxy)phenyll-3-hydroxyacrylate as a yellow oil (1.1 5g) 'H NMR delta 2.53 QHM; 3.63 (3H,s); 6.89 (1 HM; 7.2 (5H,m); 8.21 (1 H,d) ppm.
The oil (1.14g) was dissolved in DIVIF (15 mi), potassium carbonate (1. 1g) was added and the mixture stirred for 15 minutes. Dimethyl sulphate (0.53g) was dissolved in DIVIF (5 mi) and this solution added to the mixture.
The resulting mixture was stirred for 30 minutes then diluted with water and the resulting emulsion extracted 60 with ethyl acetate. This extract was dried and evaporated under reduced pressure to give a yellow oil (2. 06g), which was purified by HPLC (eluent ethyl acetate), to give (E)methyl 2-[2'-(6"-methylpyridin-3"-yioxy)phenyll3-methoxyacrylate as a pale yellow oil (0.739), infrared maxima (film) 1705,1642,1488 cm-l; 'H NMR delta 2.52 (3H,s); 3.63 (3H,s); 3.81 QHM; 6.88 (1 H,d); 7.04-7.32 (5H, m); 7.51 (1 H,s); 8.26 (1 H,d) ppm.
The following are examples of compositions suitable for agricultural and horticultural purposes which can 65 GB 2 189 485 A 30 be formulated from the compounds of the invention. Such compositions form another aspect of the invention.
Example 10
An emulsifiable concentrate is made up by mixing and stirring the ingredients until all are dissolved.
5 Compound No. 61 of Table 1 10% Benzy] alcohol 30% Calcium dodecyl benzenesu 1 phonate 5% Nonylphenolethoxylate (13 moles ethylene oxide) 10% 10 Alkyl benzenes 45% Example 11
The active ingredient is dissolved in methylene dichloride and the resultant liquid sprayed on to the granules of attapulgite clay. The solvent is then allowed to evaporate to produce a granular composition. 15 Compound No. 14 of Table 1 5% Attapulgite granules 95% Exam ole 12 20 A composition suitable for use as a seed dressing is prepared by grinding and mixing the three ingredients.
Compound No. 61 of Table 1 50% Mineral oil 2% China clay 48% 25 Exampie 13 A dustable powder is prepared by drinding and mixing the active ingredientwith talc.
Compound No. 61 of Table 1 5% 30 Talc 95% Example 14
A suspension concentrate is prepared by ball milling the ingredients to form an aqueous suspension of the ground mixture with water. 35 Compound No. 61 of Table 1 40% Sodium lignosulphonate 10% Bentonite clay 1 % Water 49% 40 This formulation can be used as a spray by diluting into water or applied directly to seed.
Example 15
A wettable powder formulation is made by mixing together and grinding the ingredients until all are 45 thoroughly mixed.
Compound No. 61 of Table 1 25% Sodium lauryl sulphate 2% Sodium lignosulphonate 5% 50 Silica 25% China clay 43% Example 16
The compounds were tested against a variety of foliar fungal diseases of plants. The technique employed 55 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 or acetonelethanol which was diluted to the required concentration immediately before use. For the foliage diseases, the formulations (100 ppm active ingredient) were sprayed onto the foliage and applied to the roots 60 of the plants in the soil. The sprays were applied to maximum retention and the root drenches to a final concentration equivalent to approximately 40 ppm a.i.ldry soil. Tween 20, to give a final concentration of 0.05%, was added when the sprays were applied to cereals.
For most of the tests the compound was applied to the soil (roots) and to the foliage (by spraying one or two days before the plant was inoculated with the disease. An exception was the test on Erysiphe graminis in 65 31 GB 2 189 485 A 31 which the plants were inoculated 24 hours before treatment. Foliar pathogens were applied by spray as spore suspensions onto the leaves of test plants. 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. 5 The disease control was recorded by the following grading:
4=no disease 3=trace -5% of disease on untreated plants 2=6-25% of disease on untreated plants 10 1 =26-59% of disease on untreated plants 0=60-100% of disease on untreated plants The results are shown in Table V.
i 1 A A cj W K) K) TABLEV
00 Erysiphe (0 Puccinia graminis Venturia Pyricularia Cercospora Plasmopara Phytophthora CO 01 Compound Table recondita hordei inaequalis oryzae arachidicola viticola infestans > no. no. (wheat) (barley) (apple) (rice) (peanut) (vine) (tomato) 1 4 4 4 4 3 4 4 11 3 4 4 2 0 4 4 14 4 4 2 4 4 4 4 4 - 3 3 4 16 2 4 4 4 4 4 4 21 3 4 4 4 4 4 3 22 4 4 4 4 4 4 3 61 3 4 4 0 4 1 0 67 3 2 0 0 4 4 0 129 1 0 4 4 0 0 0 0 1 3 0 0 0 4 0 0 131 1 3 0 0 0 0 0 0 133 1 4 4 4 4 - 4 0 137 1 2 0 4 0 0 0 0 138 1 4 0 3 0 0 4 0 139 1 4 0 0 2 4 4 0 1 2 0 0 0 0 4 0 1 2 4 4 2 4 4 3 166 1 4 4 4 1 4 3 3 167 1 4 4 4 3 0 4 14 11 4 4 4 3 4 4 0 11 2 3 0 0 1 4 0 1 Ill 0 0 3 0 0 0 0 2 Ill 3 0 3 0 0 0 0 ppm foliar spray only 40 ppm foliar spray only A W 33 GB 2 189 485 A 33 Example 17
This Example illustrates the plantgrowth regulating propertiesof compounds 14-16,22,61,132 and 138-140 of Table 1.
These compounds were tested on a whole plant screen for plant growth regulating activity against six species of plant. The plant species used in this screen are presented in Table V1 with the leaf stage at which 5 they were sprayed.
A formulation of each chemical was applied at 4000 ppm (4 kg/ha in a 1000 llha field volu me) using a tracksprayer and a SS8004E (Teejet) nozzle. Additional tests were done on tomatoes at 2000 and 500 ppm.
After spraying, the plants were grown in a glasshouse with 25C day/22'C night temperatures. The exceptions to this were the the temperate cereals, wheat and barley which were grown in 13-16'C 10 dayll 113'C night temperatures. Supplementary lighting was supplied when necessary to provide an average photoperiod of 16 hours (14 hours minimum).
After2-6 weeks in the glasshouse, depending on species and time of year, the plants were visually assessed for morphological characteristics against a control plant sprayed with a blank formulation. The results are presented in Table V11.
TABLE V1
* Plantmaterial used for whole plant screen Growth stage No. plants Compost Species Code Variety at treatment perXpot type Barley BR Atem 1-1.5 leaves 4 jlp Wheat ww Timmo 11.5 leaves 4 ilp 25 Maize MZ Earliking 211-21 leaves 1 PEAT Apple AP Red Delicious 4-5 leaves 1 JIP Rice RC Ishikari 2-21-leaves 4 ilp Tomato TO Ailsa Craig 2-21 leaves 1 PEAT 30 JIP John Innes Potting Compost TABLE V11
35 Compound no. Table BR WW RC AP MZ TO TO Tot 14 1 NT NT NT NT NT NT 2AT 2AT 40 1 1 2A NT 1AT 1AT 16 1 NT NT NT NT NT 3A NT NT 22 1 NT NT NT 1A NT NT NT 61 1 NT NT NT 1 NT NT 1 132 1 NT NT NT NT 1 1 45 138 1 3 NT NT 139 1 NT NT 1 G NT NT KEY 50 2000 ppm t500pprn Retardation 1-3 where 1 1 G-30% 2=2160% 55 3=61100% Greening effect= G Aplical damage= A Tillering or side shooting= T 60 Blank means less than 10% effect NT indicates thatthe compound was nottested againstthis species Example 18
This Example illustrates the insecticidal properties of certain of the compounds of formula (1). 65 34 GB2189485A 34 The activity of each compound was determined using a variety of insect mites and nematode pests. The compound was used in the form of liquid preparations containing from 100 to 500 parts per million (ppm) by weight of the compound. The preparations were made by dissolving the compound in the acetone and diluting the solutions with water containing 0.1 % by weight of a wetting agent sold under the trade name "SYNPERON1W NX until the liquid preparations contained the required concentration of the product. 5 "SYNIPERON1W is a Registered Trade Mark.
The test procedure adopted with regard to each pestwas basically the same and comprised supporting a number of the pests on a medium which was usually a host plant or a food stuff on which the pests feed, and treating either or both the pests and the medium with the preparations. The mortality of the pests was then assessed at periods usually varying from one to seven days after the treatment. 10 The results of the tests are given in Table IX for each of the products, at the rate in parts per million given in the second column as a grading of mortality designated as 9, 5 or 0 wherein 9 indicates 80-100% mortality (70-100% root-knot reduction as compared to untreated plants for Meloidogyne incognita, 5 indicates 50-79% mortality (50-69% root-knot reduction for Meloidogyne incognita) and 0 indicates less than 50% m o rta 1 ity (root-knot red uctio n fo r Meloidogyne incognita). 15 In Table IX the pest organism used is designated by a letter code and the pests species, the support medium or food, and the type and duration of test is given in Table VIII.
TABLE Vill
20 Code Support Type of letters Test species mediumIfood test Duration TUe Tetranychus uritcae French bean Contact 3 25 (spider mites and ova) leaf CP Chilo partellus Oil seed rape Residual 3 (maize stem borers) leaf 30 DB Diabrotica balteata Filter paper/ Residual 3 (rootworm larvae) maize seed MD Musca domestica Cotton wool/ Contact 1 (houseflies- adults) sugar 35 M1 Meloidogyne incognita Semi in-vitro residual 7 (tomato root knot eelworm larvae) 40 TABLE IX
Species (see Table V111) 45 Compound Rate of no. application Tue CP D8 MD m/ 14 500 0 9 - 5 9 15 500 0 9 0 50 250 - - - 9 GB 2 189 485 A 35

Claims (12)

1. A compound having the formula (I):
'0 R 5 W c A X Y CH 10 z OR 15 and stereoisomers thereof, wherein W is a substituted pyridinyi or substituted pyrimidinyl group linked to A by any one its ring carbon atoms; A is either an oxygen atom or S(O)n wherein n is 0, 1 or 2; X, Y and Z, which are the same or different, are hydrogen or halogen atoms, or hydroxy, optionally substituted alky], optionally substituted alkenyl, optionally substituted arVI, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted alkylthio, optionally substituted aryloxy, optionally substituted arylaikoxy, optionally 20 3 substituted acyloxy, optionally substituted amino, optionally substituted acylamino, nitro, cyano, C02R CONR4 R5, -COR6 or-S(O),R (wherein m is 0, 1 or 2) groups, or any two of the groups X, Y and Z, when they are in adjacent positions on the phenyl ring, join to form a fused ring, either aromatic or aliphatic, optionally 2 containing one or more heteroatoms; R' and R, which are the same or different, are optionally substituted alkyl groups; provided that when W is 5-trifluoromethylpyridin-2-yi, A is oxygen, X is hydrogen, and R' and R' 25 are both methyl, Y and Z are not both hydrogen, Y is not F, Cl, methyl, nitro, 5-CF3, 5-SCH3 or 4-(CH3)2N if Z is hydrogen and Y and Z together are not 3-nitro-5-chloro, 3,5- dinitro, 4,5-dimethoxy or 4,5-methylenedioxy; and R3 4 6 7 R Rs, R and R which are the same or different, are hydrogen atoms or optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl or optionally substituted aralkyl groups; and metal 30 complexes thereof.
2. A compound having the formula (I):
C02R W 35 A CH 40 Y R 2 X 0 z and stereoisomers thereof, wherein W is a substituted pyridinyl or a substituted pyrimidinyl group linked to A 45 by any one of its carbon atoms and bearing substituents as defined above; A is either an oxygen atom or S(O)n wherein n is 0, 1 or 2; X, Y and Z, which are the same or different, are hydrogen, fluorine, chlorine or bromine atoms, or Cl-4 alkyl, C25 alkenyl, C2_5 alkyny], phenyl, Cl-4 haloalkyl, Cl-4 alkoxy, phenoxy, benzyloxy or mono- or dialkylamino groups, or any two of the groups X, Y and Z, when they are in adjacent positions on the phenyl ring, join to form a fused aromatic ring; wherein the aliphatic moieties of any of the foregoing are 50 optionally substituted with one or more Cl-4 alkoxy groups, fluorine, chlorine or bromine atoms, phenyl rings which themselves are optionally substituted, heterocyclic rings which are either aromatic or non-aromatic and are themselves optionally substituted, nitro, amino, cyano, hydroxyl or carboxyl groups, and wherein the phenyl moieties of any of the foregoing are optionally substituted with one or more fluorine, chlorine or bromine atoms, phenyl rings, Cl-4 alkyl, Cl-4 alkoxy, nitro, amino, cyano, hydroxyl or carboxyl groups; and R' 55 and R', which are the same or different, are Cl-4 alkyl each optionally substituted with one, two or three halogen atoms provided that when W is 5-trifluoromethylpyridin-2-yl, A is oxygen, X is hydrogen, and R' and R 2 are both methyl, Y and Z are not both hydrogen, Y is not F, Cl, methyl, nitro, 5-CF3,5-SCH3 or 4-(C1-13)2N if Z is hydrogen and Y and Z together are not 3-nitro-5-chloro, 3,5-dinitro, 4, 5-dimethoxy or 4,5-methylenedioxy;
3. A compound having the formula (1a): 60 36 GB 2 189 485 A 36 C02CH3 W CH 5 )CH3 10 and stereoisomers thereof, wherein A is SOn Wherein n is 0, 1 or 2, or preferably, an oxygen atom; W is a substituted pyridinyl or a substituted pyrimidinyl group linked to A by any one of its carbon atoms, the substituents on the pyridyl or pyrimidinyl rings, which are the same or different, being one or more halogen 1.5 atoms, or hydroxy, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted aryl, 15 - optionally substituted alkyny], optionally substituted alkoxy, (including haloalkoxy), optionally substituted aryloxy, optionally substituted heterocyclyloxy, optionally substituted aryi, optionally substituted heterocyc ]yi, optionally substituted acyloxy, optionally substituted amino, optionally substituted acylamino, nitro, cyano,-C02R',-CONR 4 R5, -COR6 or S(O),Rl (wherein m is 0, 1 or 2) groups provided that when W is 5-trifluoromethylpyridin-2-yi, A is oxygen, X is hydrogen, and R' and R 2 are both methyl, Y and Z are not both 20 hydrogen, Y is not F, C], methyl, nitro, 5-CF3, 5-SCH3 or 4-(CH36N if Z is hydrogen and Y and Z together are not 3-nitro-5-chloro, 3,5-dinitro, 4,5-dimethoxy or 4,5-methylenedioxy; and R 3, R 4, R', R' and R' are as defined above.
4. A compound of the formula (1b):
25 Q 0 /? (Ib) 30 1-11 OCH3 CH c c 302 1 35 H wherein Q is methyl, trifluoromethyl, (but not 5-trifluorom ethyl), methoxy, fluorine, chlorine or bromine.
5. A process for preparing a compound of the formula (1) according to claim 1, which comprises (i) treating a compound of formula (111) 40 C02R1 W A 45 CH (III) so X R8 50 0 z where R8 is a metal atom, with a species of formula R 2 -L in a suitable solvent, or when R8 is hydrogen, successively with a base and a species of formula R 2 -L in a suitable solvent, or 55 (ii) eliminating the elements of the alkanol R 2 OH from an acetal of formula (Xlil):
37 GB 2 189 485 A 37 CO R 2 W.
A CH CH (OR2 )2 (XIII) Y X c j 10 z under acidic or basic conditions, or (iii) reacting a compound of formula ([X):
CO 2 R H 20 A CH (IX) Y 25 R2 X 0 z 30 with a compound of formula W-L in the presence of a base and optionally a transition metal ortransition metal salt catalyst in a convenient solvent, or (iv) treating a ketoester of formula (XV):
35 CO R1 2 W A C 40 0 (XV) Y X 45 z with a phosphorane of formula Ph3PCHOR' in a convenient solvent; so in which W, X Y, Z, R' and R 2 have the meanings given in claim 1, L is a halogen atom or another good leaving 50 group and Ph is phenyl.
6. The intermediate chemicals of formulae OW-(V), (IX)-(XV), (XVII), (M), (M) and (XXV) as defined herein. 55
7. A fungicidal composition comprising, as an active ingredient, a fungicidally effective amount of a compound according to claim land a fungicidally acceptable carrier or diluent therefor.
8. A method of combating fungi which comprises applying to plants or seeds, orto their locus, a compound according to claim 1 or a composition according to claim 7.
g. A plant growth regulating composition comprising, as an active ingredient, an effective amount of a 60 plant growth regulating of formula i as defined in claim land an acceptable carrier or diluent therefor.
10. A method of regulating plant growth which comprises applying to a plant an effective amount of a plant growth regulating compound of formula 1 according to claim 1.
11. An insecticidallnematocidal composition comprising an insecticidal ornematocidal compound of formula 1 as defined in claim 1 in combination with a carrier or diluent. 65 38 GB2189485A 38
12. A method of killing or controlling insect and nematode pests which comprises administering to the pest or to a locus thereof an effective amount of an insecticidal compound of formula 1 as defined in claim 1 or of a composition according to claim 11.
Printed for Her Majesty's Stationery Office by Croydon Printing Company (UK) Ltd,9187, D8991685. Published by The Patent Office, 25 Southampton Buildings, London WC2A lAY, from which copies may be obtained.
GB8707642A 1986-04-17 1987-03-31 Derivatives of acrylic acid useful in agriculture Revoked GB2189485B (en)

Priority Applications (7)

Application Number Priority Date Filing Date Title
GB8707642A GB2189485B (en) 1986-04-17 1987-03-31 Derivatives of acrylic acid useful in agriculture
MYPI87000510A MY101728A (en) 1986-04-17 1987-04-20 Fungicides
BR8701892A BR8701892A (en) 1986-04-17 1987-04-21 CHEMICAL COMPOUNDS, PROCESS FOR THEIR PREPARATION, FUNGICIDE COMPOSITION, PROCEDURE FOR COMBATING FUNGI, COMPOSITION AND PROCESS FOR REGULATING PLANT GROWTH, INSECTICIDE / NEMATOCID COMPOSITION AND PROCESS OF EXTERMINING OR CONTROLING INSECTS AND NESTLES
GB8922843A GB2223017B (en) 1986-04-17 1989-10-11 Pyridine and pyrimidine intermediates
GB8922842A GB2223016B (en) 1986-04-17 1989-10-11 2-phenyl-3,3-dialkoxy-propionate derivatives
GB9001442A GB2226817B (en) 1986-04-17 1990-01-22 Intermediates for agriculturally useful acrylic acid derivatives
HK102/92A HK10292A (en) 1986-04-17 1992-01-30 Intermediates for agriculturally useful acrylic acid derivatives

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GB868609454A GB8609454D0 (en) 1986-04-17 1986-04-17 Fungicides
GB868630825A GB8630825D0 (en) 1986-12-23 1986-12-23 Fungicides
GB8707642A GB2189485B (en) 1986-04-17 1987-03-31 Derivatives of acrylic acid useful in agriculture

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GB8707642D0 GB8707642D0 (en) 1987-05-07
GB2189485A true GB2189485A (en) 1987-10-28
GB2189485B GB2189485B (en) 1990-11-28

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Application Number Title Priority Date Filing Date
GB8707642A Revoked GB2189485B (en) 1986-04-17 1987-03-31 Derivatives of acrylic acid useful in agriculture
GB8922843A Expired - Fee Related GB2223017B (en) 1986-04-17 1989-10-11 Pyridine and pyrimidine intermediates
GB8922842A Revoked GB2223016B (en) 1986-04-17 1989-10-11 2-phenyl-3,3-dialkoxy-propionate derivatives
GB9001442A Expired - Fee Related GB2226817B (en) 1986-04-17 1990-01-22 Intermediates for agriculturally useful acrylic acid derivatives

Family Applications After (3)

Application Number Title Priority Date Filing Date
GB8922843A Expired - Fee Related GB2223017B (en) 1986-04-17 1989-10-11 Pyridine and pyrimidine intermediates
GB8922842A Revoked GB2223016B (en) 1986-04-17 1989-10-11 2-phenyl-3,3-dialkoxy-propionate derivatives
GB9001442A Expired - Fee Related GB2226817B (en) 1986-04-17 1990-01-22 Intermediates for agriculturally useful acrylic acid derivatives

Country Status (4)

Country Link
BR (1) BR8701892A (en)
GB (4) GB2189485B (en)
HK (1) HK10292A (en)
MY (1) MY101728A (en)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4876264A (en) * 1986-04-17 1989-10-24 Imperial Chemical Industries Plc Pyridine derivatives and their use as fungicides
GB2223017A (en) * 1986-04-17 1990-03-28 Ici Plc Pyridine and pyrimidine intermediates
GB2228480A (en) * 1986-08-06 1990-08-29 Ici Plc Alpha-dimethoxymethyl-phenylacetic acid intermediates for fungicides
GB2229720A (en) * 1986-08-20 1990-10-03 Ici Plc Fungicides
US5008275A (en) * 1989-02-17 1991-04-16 Bayer Aktiengesellschaft Pesticidal pyridyl-substituted acrylic ester compounds
GB2291874A (en) * 1994-07-28 1996-02-07 Zeneca Ltd Etherification process

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Publication number Priority date Publication date Assignee Title
DE4019307A1 (en) * 1990-06-16 1991-12-19 Bayer Ag 2-METHOXIMINOCARBONIC ACID ESTER
MY107955A (en) * 1990-07-27 1996-07-15 Ici Plc Fungicides.
GB9404375D0 (en) * 1994-03-07 1994-04-20 Zeneca Ltd Fungicides
ES2174256T3 (en) * 1996-05-22 2002-11-01 Basf Ag DERIVATIVES OF ACID 2- (O-PIRIMIDIN-4-IL) METHYLENEOXI) ACETIC PHENYL AND ITS EMPLOYMENT FOR THE COMBAT OF HARMFUL FUNGES AND ANIMAL PARASITES.
WO1998054139A1 (en) * 1997-05-30 1998-12-03 Basf Aktiengesellschaft Method for producing substituted thiopyridines
WO2000040537A1 (en) * 1998-12-29 2000-07-13 Nippon Soda Co., Ltd. Processes for producing acrylic acid derivative

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0391451A1 (en) * 1986-04-17 1990-10-10 Imperial Chemical Industries Plc Fungicides
GB2189485B (en) * 1986-04-17 1990-11-28 Ici Plc Derivatives of acrylic acid useful in agriculture

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4876264A (en) * 1986-04-17 1989-10-24 Imperial Chemical Industries Plc Pyridine derivatives and their use as fungicides
GB2223017A (en) * 1986-04-17 1990-03-28 Ici Plc Pyridine and pyrimidine intermediates
GB2223016A (en) * 1986-04-17 1990-03-28 Ici Plc Pyridine and pyrimidine intermediates
GB2223017B (en) * 1986-04-17 1991-01-09 Ici Plc Pyridine and pyrimidine intermediates
GB2223016B (en) * 1986-04-17 1991-01-02 Ici Plc 2-phenyl-3,3-dialkoxy-propionate derivatives
US4968688A (en) * 1986-04-17 1990-11-06 Imperial Chemical Industries Plc Pyrimidines and their use as fungicides
GB2228480B (en) * 1986-08-06 1990-12-05 Ici Plc Heterocyclic intermediates
GB2228480A (en) * 1986-08-06 1990-08-29 Ici Plc Alpha-dimethoxymethyl-phenylacetic acid intermediates for fungicides
GB2229720A (en) * 1986-08-20 1990-10-03 Ici Plc Fungicides
GB2229720B (en) * 1986-08-20 1991-02-13 Ici Plc Heterocyclic intermediates
US5008275A (en) * 1989-02-17 1991-04-16 Bayer Aktiengesellschaft Pesticidal pyridyl-substituted acrylic ester compounds
US5120734A (en) * 1989-02-17 1992-06-09 Bayer Aktiengesellschaft Fungicidal pyrid-2-yl-amino acetic acid esters
GB2291874A (en) * 1994-07-28 1996-02-07 Zeneca Ltd Etherification process
GB2291874B (en) * 1994-07-28 1996-09-25 Zeneca Ltd Etherification process
DE19525393B4 (en) * 1994-07-28 2006-04-13 Syngenta Ltd., Guildford Chemical process

Also Published As

Publication number Publication date
GB2223017A (en) 1990-03-28
BR8701892A (en) 1988-02-02
GB2223016B (en) 1991-01-02
GB9001442D0 (en) 1990-03-21
GB2223017B (en) 1991-01-09
GB8922842D0 (en) 1989-11-29
GB2226817A (en) 1990-07-11
GB2226817B (en) 1990-11-28
GB8922843D0 (en) 1989-11-29
GB2223016A (en) 1990-03-28
HK10292A (en) 1992-01-31
GB2189485B (en) 1990-11-28
GB8707642D0 (en) 1987-05-07
MY101728A (en) 1992-01-17

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732E Amendments to the register in respect of changes of name or changes affecting rights (sect. 32/1977)
773H Revocation action is not pursued (sect. 73(2)/1977)
773K Patent revoked under sect. 73(2)/1977