DK158947B - Tetrahydronaphthalin-,benzofuran- og benzothiophenderivater, fremstilling og anvendelse deraf samt rodenticid indeholdende saadanne derivater - Google Patents

Tetrahydronaphthalin-,benzofuran- og benzothiophenderivater, fremstilling og anvendelse deraf samt rodenticid indeholdende saadanne derivater Download PDF

Info

Publication number
DK158947B
DK158947B DK281883A DK281883A DK158947B DK 158947 B DK158947 B DK 158947B DK 281883 A DK281883 A DK 281883A DK 281883 A DK281883 A DK 281883A DK 158947 B DK158947 B DK 158947B
Authority
DK
Denmark
Prior art keywords
tetrahydro
compound
tetramethylbenzo
general formula
compound according
Prior art date
Application number
DK281883A
Other languages
English (en)
Other versions
DK158947C (da
DK281883A (da
DK281883D0 (da
Inventor
Michael Klaus
Peter Loeliger
Harald Weiser
Original Assignee
Hoffmann La Roche
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche
Publication of DK281883D0 publication Critical patent/DK281883D0/da
Publication of DK281883A publication Critical patent/DK281883A/da
Publication of DK158947B publication Critical patent/DK158947B/da
Application granted granted Critical
Publication of DK158947C publication Critical patent/DK158947C/da

Links

Classifications

    • 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
    • C07D213/79—Acids; Esters
    • C07D213/80—Acids; Esters in position 3
    • 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
    • A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
    • A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
    • A01N43/06—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings
    • A01N43/08—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings with oxygen as the ring hetero atom
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
    • A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
    • A01N43/06—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings
    • A01N43/10—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings with sulfur as the ring hetero atom
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
    • A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
    • A01N43/06—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings
    • A01N43/12—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings condensed with a carbocyclic ring
    • 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
    • A01N49/00—Biocides, pest repellants or attractants, or plant growth regulators, containing compounds containing the group, wherein m+n>=1, both X together may also mean —Y— or a direct carbon-to-carbon bond, and the carbon atoms marked with an asterisk are not part of any ring system other than that which may be formed by the atoms X, the carbon atoms in square brackets being part of any acyclic or cyclic structure, or the group, wherein A means a carbon atom or Y, n>=0, and not more than one of these carbon atoms being a member of the same ring system, e.g. juvenile insect hormones or mimics thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
    • C07C29/36—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring increasing the number of carbon atoms by reactions with formation of hydroxy groups, which may occur via intermediates being derivatives of hydroxy, e.g. O-metal
    • C07C29/38—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring increasing the number of carbon atoms by reactions with formation of hydroxy groups, which may occur via intermediates being derivatives of hydroxy, e.g. O-metal by reaction with aldehydes or ketones
    • C07C29/40—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring increasing the number of carbon atoms by reactions with formation of hydroxy groups, which may occur via intermediates being derivatives of hydroxy, e.g. O-metal by reaction with aldehydes or ketones with compounds containing carbon-to-metal bonds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C317/00—Sulfones; Sulfoxides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C35/00—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a ring other than a six-membered aromatic ring
    • C07C35/02—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a ring other than a six-membered aromatic ring monocyclic
    • C07C35/08—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a ring other than a six-membered aromatic ring monocyclic containing a six-membered rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/385—Saturated compounds containing a keto group being part of a ring
    • C07C49/403—Saturated compounds containing a keto group being part of a ring of a six-membered ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
    • C07C57/26—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing rings other than six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D307/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
    • C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur 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
    • C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
    • C07D333/54—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
    • C07D333/54—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
    • C07D333/56—Radicals substituted by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
    • C07D333/54—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
    • C07D333/60—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/655—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
    • C07F9/65515—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a five-membered ring
    • C07F9/65517—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a five-membered ring condensed with carbocyclic rings or carbocyclic ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having sulfur atoms, with or without selenium or tellurium atoms, as the only ring hetero atoms
    • C07F9/655345—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having sulfur atoms, with or without selenium or tellurium atoms, as the only ring hetero atoms the sulfur atom being part of a five-membered ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/14—The ring being saturated

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Zoology (AREA)
  • Agronomy & Crop Science (AREA)
  • Dentistry (AREA)
  • Pest Control & Pesticides (AREA)
  • Wood Science & Technology (AREA)
  • Plant Pathology (AREA)
  • Environmental Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Molecular Biology (AREA)
  • Insects & Arthropods (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Plural Heterocyclic Compounds (AREA)

Description

DK 158947 B
Den foreliggende opfindelse angår hidtil ukendte tetrahydronaphtha-lin-, benzofuran- og benzothiophenderivater med den almene formel I
/S__
Ti 5 h3C CH3 hvor X betegner -CH=CH-, -0- eller -S-; rA betegner en gruppe Ar-R^ eller -CH=CH-C(CH3)=CH-R^;
Ar betegner phenyl eller pyridyl; 10 betegner en gruppe -CX^R^; og R^ betegner hydrogen eller lavere alkyl; idet mindst én ring i molekylet er heterocyclisk, og, såfremt forbindelsen er en carboxylsyre, salte deraf med baser.
Opfindelsen angår endvidere en fremgangsmåde til fremstilling af 15 forbindelser med den almene formel I, rodenticider indeholdende en forbindelse med formlen I samt anvendelse af forbindelser med formlen I som rodenticid.
Det i nærværende beskrivelse anvendte udtryk "lavere alkyl" betegner fx ligekædede eller forgrenede alkylgrupper med 1-6, fortrinsvis 1-4, 20 carbonatomer, fx methyl, ethyl, propyl, isopropyl, butyl og sek.-butyl. Der foretrækkes især methyl og ethyl.
Forbindelserne med formlen I kan fremstilles ved fremgangsmåden ifølge opfindelsen, der er ejendommelig ved, at en forbindelse med den almene formel II
25 I I © © 11 S<^\x/^CH^(Ph)3 Y H3C CH3 ^ 2
DK 158947 B
omsættes med en forbindelse med den almene formel III
H
0 = C - R11 III
eller en forbindelse med den almene formel IV
H3C^CH3
X. /X IV
H3° CH3.X L°
omsættes med en forbindelse med den almene formel V
Q
• ^
10 (R0)2P - CH2R11 V
i hvilke ovenfor anførte formler II-V R betegner lavere alkoxy;
Ph betegner phenyl; og R^ betegner en gruppe -ArC02R^ eller -CH=CHC(CH3)=CHC02R^, og R^, Ar og X har den ovenfor anførte betydning, og Y betegner anionen af en uorganisk eller organisk syre, 15 og en vunden carboxylsyreester om ønsket hydrolyseres, eller en vunden carboxylsyre om ønsket omdannes til et salt deraf med en base.
Af de uorganiske syreanioner Y foretrækkes chlor- og bromionen eller hydrosulfationen, og af de organiske syreanioner foretrækkes tosyl-oxyionen.
20 Omsætningen mellem en formylforbindelse med formlen III og et phos-phoniumsalt med formlen II foretages på i og for sig kendt måde i nærværelse af et syrebindende middel, fx i nærværelse af en stærk base, fx butyllithium, natriumhydrid eller natriumsaltet af dimethyl-sulfoxid, eventuelt i et opløsningsmiddel, fx i en ether såsom di-25 ethylether eller tetrahydrofuran, eller i et aromatisk carbonhydrid, fx benzen, i et temperaturområde, der ligger mellem stuetemperatur og reaktionsblandingens kogetemperatur.
3
DK 158947 B
Omsætningen mellem et phosphonat med formlen V og en forbindelse med formlen IV foretages ligeledes på i og for sig kendt måde i nærværelse af en base, og fortrinsvis, i nærværelse af et inert organisk opløsningsmiddel, fx i nærværelse af natriumhydrid i benzen, toluen, 5 dimethylformamid, tetrahydrofuran, dioxan eller 1,2-dimethoxyethan, eller i nærværelse af et natriumalkoholat i en alkanol, fx natriumme-thylat i methanol, i et temperaturområde, der ligger mellem 0°C og reaktionsblandingens kogetemperatur.
En carboxylsyreester med formlen I kan hydrolyseres på i og for sig 10 kendt måde, fx ved behandling med baser, især ved behandling med vandig alkoholisk natrium-eller kaliumhydroxidopløsning, i et temperaturområde, der ligger mellem stuetemperatur og reaktionsblandingens kogetemperatur.
En carboxylsyre med formlen I danner saltje med baser, især med alka-15 limetalhydroxiderne, fortrinsvis med natrium- eller kaliumhydroxid, hvilke salte ligeledes er omfattet af opfindelsen.
Forbindelserne med formlen I kan forekontei som cis/trans-blandinger, som på i og for sig kendt måde om ønsket kan opspaltes i cis- og transkomponenterne eller isomeriseres til all trans-forbindelserne.
20 Forbindelserne med formlen I og salte deraf kan anvendes som roden-ticider. På rotter har de allerede i små doser en kraftig toxisk virkning, som imidlertid først kan erkendes nogle dage efter forgiftningen. Fx førte oral administration af ethyl p-[2-(4,5,6,7-tetrahydro-4,4,7,7-tetramethylbenzo[b]thien-2-yl)propenyl]benzoat i 25 doser på 1,25 mg/kg til rotter ved oral applikation i løbet af 8 dage til alle dyrenes død, idet ingen dyr døde de første 5 dage.
Anvendelsen af forbindelserne ifølge opfindelsen som rodenticid er baseret på vitamin A-hypervitaminose-virkning, dvs. den kroniske toxicitet. Symptomer på A-hypervitaminose er vægttab, håraffald, 30 hudlidelser og knoglefraktur i ekstremiteterne. Til bestemmelse af den dosis, som forårsagede en A-hypervitaminose, fik mus i løbet af 14 dage 10 intraperitoneale injektioner af teststoffet 1 olium ara- 4
DK 158947 B
chidum. Ved forsøgets afslutning blev dyrenes tilstand bedømt efter en subjektiv skala fra 0 til 4; en sådan dosis, ved hvilken der ved addition af samtlige symptomgrader mindst opnås 3 (Europ. J. Cancer 10, 731 (1974)), anses for at forårsage A-hypervitaminose. De neden-5 stående A-hypervitaminose-doser blev fundet på denne måde:
Forbindelse ifølge Dosis for A-hypervitaminose nedenstående Eksempel [mg/kg] 1 0,025 10 2 0,05 3 . 0,05 4 0,025 5 0,025 6 0,006 15 _- · _
Af særlig interesse er de forbindelser med formlen I, hvor X betegner -S- eller -0-, R-*- betegner en gruppe Ar-R^, hvor Ar betegner phenyl, eller pyridyl, og R^ betegner lavere alkoxycarbonyl, fx ethyl p-[2-(4,5,6,7-tetrahydro-4,4,7,7-tetramethylbenzo[b]thien-2-yl)propenyl]-20 benzoat og p-[2-(4,5,6,7-tetrahydro-4,4,7,7-tetramethyl-2-benzofu-ranyl)propenyl]benzoesyre-ethylester.
Forbindelserne med formlen I kan anvendes i flydende eller fast lokkemad. Til dette formål kan anvendes alle de i rodenticider sædvanlige bærestoffer. Eksempler på bærestoffer er næringsmidler såsom 25 sukker og sukkerholdige stoffer, stivelse, korn, gelatine og fedtstoffer; samt mineralske stoffer såsom calciumsilicat, calciumcarbo-nat, calciumphosphat og S1O2.
Forbindelserne med formlen I kan også foreligge i form af faste eller flydende koncentrater (Mastermix), som derefter kan forarbej des til 30 lokkemad med egnede fortyndingsmidler og/eller foderstoffer, fx hvede, majs, johannesbrødfrugter, bananer eller jordnødder. Lokkemaden indeholder hensigtsmæssigt forbindelserne med formlen I i 5
DK 158947 B
mængder på fra ca. 0,001 til 0,1 vægtprocent, fortrinsvis 0,005-0,01 vægtprocent.
Opfindelsen belyses nærmere i nedenstående eksempler: EKSEMPEL 1 5 30 g [l-(4,5,6,7-tetrahydro-4,4,7,7-tetramethylbenzo[b]thien-2-yl)- ethyljtriphenylphosphoniumbromid og 9,5 g 4-ethoxycarbonylbenzaldehyd suspenderes i 300 ml butylenoxid og opvarmes til kogning under tilbagesvaling i 4 timer. Den således vundne opløsning inddampes i vand-strålevakuum til 1/3 af det oprindelige volumen, hældes ud i 500 ml 10 af en methanol/vand-blanding i forholdet 6:4 og ekstraheres flere gange med hexan. Den organiske fase vaskes tre gange med vand, tørres over natriumsulfat og inddampes. Der fås en let brunlig olie, som ved filtrering over silicagel (elueringsmiddel: hexan/ether 19:1) renses yderligere. Efter omkrystallisation af hexan fås 11,3 g ethyl p-[2-15 (4,5,6,7-tetrahydro-4,4,7,7-tetramethylbenzo[b]thien-2-yl)propenyl]- benzoat i form af farveløse krystaller, smeltepunkt 118-120eC.
Det som udgangsprodukt anvendte [1-(4,5,6,7-tetrahydro-4,4,7,7-te-tramethylbenzo[b]thien-2-yl)ethyl]triphenylphosphoniumbromid kan fremstilles på følgende måde: 20 90 g 2,5-dimethyl-2,5-dichlorhexan og 195 ml thiophen opløses i 400 ml hexan. Under isafkøling tildryppes langsomt 54 ml titantetra-chlorid, der opvarmes til 40eC i 1 1/2 time og afkøles igen med is, og til den mørkerøde reaktionsblanding sættes forsigtigt isvand. Der ekstraheres tre gange med ether, vaskes med mættet natriumhydrogen-25 carbonatopløsning, tørres og inddampes. Den således vundne sorte olie filtreres først over silicagel (elueringsmiddel: hexan) og destilleres derefter i vandstrålevakuum. Der fås 18,5 g 4,5,6,7-tetrahydro- 4,4,7,7-tetramethylbenzo[b]thiophen i form af en farveløs væske, kogepunkt 95-96°C/10 mm Hg.
30 18,2 g 4,5,6,7-tetrahydro-4,4,7,7-tetramethylbenzo[b]thiophen og 7,4 g acetylchlorid opløses i 200 ml benzen og afkøles til 0°C. Ved denne
DK 158947B
6 temperatur dryppes langsomt 24,4 g tintetrachlorid. Efter 2 1/2 times omrøring ved stuetemperatur afkøles der igen til 0°C, og en blanding af 9,3 ml koncentreret saltsyre og 36,4 ml vand tildryppes. Reaktionsblandingen ekstraheres med ether, vaskes én gang med vand, 5 tørres, inddampes og destilleres i højvakuum. Der fås 21,7 g 2-ace-tyl-4,5,6,7-tetrahydro-4,4,7,7-tetramethylbenzo[b]thiophen i form af en farveløs væske, kogepunkt 108-115°C/0,05 mm Hg, som kan omkrystalliseres af hexan, smeltepunkt 53-55°C.
21,7 g 2-acetyl-4,5,6,7-tetrahydro-4,4,7,7-tetramethylbenzo[b]thio-10 phen opløses i 250 ml ethanol, og ved 0°C tilsættes der lidt efter lidt 5,5 g natriumborhydrid. Blandingen lades opvarme til stuetemperatur og omrøres i yderligere 2 timer. Reaktionsblandingen hældes ud på is, ekstraheres med ether, vaskes én gang med mættet kogsaltopløsning, tørres og inddampes. Råproduktet filtreres over silicagel 15 (elueringsmiddel:. hexan/ether 3:1) og omkrystalliseres af hexan. Der fås 20,2 g 4,5,6,7-tetrahydro-a,4,4,7,7-pentamethylbenzo[b]thiophen-methanol i form af farveløse krystaller, smeltepunkt 53-55°G.
20,2 g 4,5,6,7-tetrahydro-(i,4,4,7,7-pentamethylbenzo[b]thiophen-methanol opløses i 260 ml acetonitril og tilsættes 29,2 g triphenyl-20 phosphoniumbromid. Efter 3 timers omrøring ved 50°C inddampes der til tørhed, og remanensen optages i 80%'s vandigt ethanol og ekstraheres to gange med hexan. Ethanolfasen inddampes, opløses i methylen-chlorid, tørres over natriumsulfat og inddampes. Der fås 49,4 g [1-(4,5,6,7-tetrahydro-4,4,7,7-tetramethylbenzo[b]thien-2-yl)ethyl]-25 triphenylphosphoniumbromid i form af et amorft, hvidt pulver.
EKSEMPEL 2 4,50 g [1-(4,5,6,7-tetrahydro-4,4,7,7-tetramethylbenzo[b]thien-2-yl)-ethyl]triphenylphosphoniumbromid og 1,3 g 5-formyl-3-methylpenta-2,4-diensyreethylester opløses i 70 ml butylenoxid og opvarmes til kog-30 ning under tilbagesvaling i 2 timer. Den afkølede reaktionsblanding hældes ud i en methanol/vand-blanding (6:4) og ekstraheres flere gange med hexan. Hexanfasen vaskes tre gange med vand, tørres og inddampes. Efter filtrering af råproduktet over silicagel (eluerings- 7
DK 158947 B
middel: hexan/ether 9:1) fås 2,4 g 3-methyl-7-(4,5,6,7-tetrahydro- 4,4,7,7-tetramethylbenzo[b]thien-2-yl)-2,4,6 -octatriensyreethylester i form af en svagt gullig olie.
2,4 g af den således vundne ethylester opløses i 40 ml ethanol og 5 tilsættes en opløsning af 2,5 g kaliumhydroxid i 10 ml vand. Reaktionsblandingen opvarmes til 50°G i 3 timer, hældes ud på isvand, syrnes med 2N saltsyre og ekstraheres flere gange med ethylacetat.
Den organiske fase vaskes med vand, tørres og inddampes. Ved omkrystallisation af remanensen af ethylacetat fås 1,5 g 3-methyl-7-10 (4,5,6,7-tetrahydro-4,4,7,7-tetramethylbenzo[b]thien-2-yl)-2,4,6-oc- tatriensyre i form af svagt gullige krystaller, smeltepunkt 226-228°C.
EKSEMPEL 3 På samme måde fås ud fra 5,6 g triphenyl [1-(5,6,7,8-tetrahydro-15 5,5,8,8-tetramethyl-2-naphthyl)ethyl]phosphoniumbromid og 1,4 g 6- formylpyridin-3-carboxylsyre-ethylester efter chromatografi på sili-cagel (elueringsmiddel: hexan/ether 2:1) og krystallisation af hexan 0,6 g 6-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-propenyl]nicotinsyre-ethylester i form af farveløse krystaller, 20 smeltepunkt 114-115°C.
EKSEMPEL 4 På samme måde fås ud fra 4,6 g [l-(4,5,6,7-tetrahydro-4,4,7,7-tetra-methylbenzo[b]furan-2-yl)ethyl]triphenylphosphoniumbromid og 1,5 g 4-ethoxycarbonylbenzaldehyd efter chromatografi på silicagel (elue-25 ringsmiddel: hexan/ether 9:1) og krystallisation af hexan 2,2 g p-[2-(4,5,6,7-tetrahydro-4,4,7,7-tetrame thyl-2-benzofuranyl)propenyl]-benzoesyre-ethylester i form af farveløse krystaller, smeltepunkt 96-97°C.
8
DK 158947 B
Det som udgangsprodukt anvendte [l-(4,5,6,7-tetrahydro-4,4,7,7-tetra-methylbenzo [b ] furan-2-yl) ethyl] triphenylphosphoniumbromid kan fremstilles på følgende måde: 5,2 g magnesiumspåner suspenderes i 100 ml absolut ether og tilsættes 5 dråbevis 13,5 ml methyliodid. Efter tilsætning af 100 ml ether koges der under tilbagesvaling i yderligere 3 timer, indtil alt magnesium er opløst. Reaktionsblandingen afkøles til 0°C, og der tilsættes 20,7 g fintpulveriseret kobber(I)iodid. Efter 15 minutters omrøring ved 0°C tildryppes en opløsning af 10 g 3,6,6-trimethyl-2-cyclohexenon i 10 40 ml ether, og der omrøres i yderligere 4 timer ved 0°C. Derefter hældes den gule suspension ud på is/2N saltsyre, ekstraheres flere gange med ether, tørres og inddampes. Remanensen destilleres i vand-strålevakuum. Der fås 9 g 2,2,5,5-tetramethylcyclohexanon i form af en farveløs væske, kogepunkt 71-74eC/15 mm Hg.
15 En opløsning af 26,4 g 2,2,5,5-tetramethylcyclohexanon i 250 ml ether dryppes ved -20°C til 102,8 ml niethyllithium (2 molær i ether). Efter 2 1/2 times omrøring ved 0°C hældes blandingen ud på is/ΙΝ saltsyre og ekstraheres med ether. Den organiske fase vaskes med vand, tørres og inddampes. Remanensen destilleres i vandstrålevakuum. Der fås 22,6 20 g 1,2,2,5,5-pentamethylcyclohexanol i form af en farveløs væske, kogepunkt 81-87°C/17 mm Hg.
22,6 g 1,2,2,5,5-pentamethylcyclohexanol opløses i 280 ml benzen, og efter tilsætning af 100 mg p-toluensulfonsyre koges der i 7 timer med vandfraskiller. Efter afkøling af reaktionsopløsningen tilsættes 25 noget fast natriumcarbonat, og der filtreres og inddampes ved normaltryk. Remanensen destilleres i vandstrålevakuum. · Der fås 15,8 g 1,3,3,6,6-pentamethylcyclohexen i form af en farveløs væske, kogepunkt 56-57°C/17 mm Hg.
15 g 1,3,3,6,6-pentamethylcyclohexen opløses i 350 ml carbontetra-30 chlorid, og der tilsættes 19,3 g n-bromsuccinimid. Efter tilsætning af en spatelspids a,ce'-azoisobutyronitril koges der under tilbagesvaling i 1 1/2 time. Reaktionsblandingen afkøles, det resulterende succinimid frafiltreres, og filtratet inddampes. Der fås 23,8 g af en svagt gul olie, som straks videreforarbejdes. Olien opløses i 350 ml 9
DK 158947 B
dimethylformamid, og der tilsættes 21 g natrium-benzensulfinat. Efter 72 timers omrøring ved stuetemperatur tilsættes 600 ml ether, der omrøres i 15 minutter, det udfældede natriumbromid frafiltreres, og filtratet inddampes. Remanensen optages i vand og ekstraheres med 5 ethylacetat. Efter tørring, inddampning og omkrystallisation af ether/hexan fås 22,2 g phenyl (3,3,6,6-tetramethyl-l-cyclohexen-l-yl)methylsulfon i form af hvide krystaller, smeltepunkt 48-50eC.
21.6 g phenyl (3,3,6,6-tetramethyl-l-cyclohexen-l-yl)methylsulfon opløses i 600 ml tetrahydrofuran. Ved -40°C tildryppes 41,5 ml bu- 10 tyllithium (2 molær i hexan), og der omrøres i yderligere 40 minutter ved -40°C. Den orangefarvede opløsning hældes hurtigt ud på en blanding af fast carbondioxid og ether. Efter 30 minutters omrøring tilsættes vand, syrnes med IN svovlsyre og ekstraheres med ethylacetat.
Efter tørring, inddampning og omkrystallisation af ether/hexan fås 15 19,9 g 3,3,6,6-tetramethyl-a-(phenylsulfonyl)-l-cyclohexen-l-eddike- syre i form af farveløse krystaller, smeltepunkt 169-174°C.
20.6 g 3,3,6,6-tetramethyl-α-(phenylsulfonyl)-1-cyclohexen-l-eddikesyre opløses i 800 ml ethanol, og ved 0°C tilsættes 107,1 g natriumamalgam (5%). Der omrøres i 4 1/2 time ved stuetemperatur, kviksølvet 20 fradekanteres, der syrnes med 2N saltsyre og ekstraheres med ethylacetat. Den organiske fase vaskes med vand, tørres, inddampes og filtreres over silicagel (elueringsmiddel: hexan/ether 1:1). Efter omkrystallisation af héxan fås 10,2 g 3,3,6,6-tetramethyl-l-cyclo-hexen-1-eddikesyre i form af farveløse krystaller, smeltepunkt 50-25 54°C.
10,2 g 3,3,6,6-tetramethyl-1-cyclohexen-l-eddikesyre opløses i 140 ml methylenchlorid, og ved stuetemperatur tilsættes en opløsning af 14,2 g thallium(I)ethylat i 80 ml methylenchlorid. Den mælkehvide opløsning afkøles derefter til 0°C, og der tildryppes langsomt en opløs-30 ning af 2,7 ml brom i 70 ml methylenchlorid. Efter 4 timers omrøring ved stuetemperatur hældes der ud på is/vand og ekstraheres med methylenchlorid. Den organiske fase vaskes med vand, tørres og inddampes.
Det således vundne råprodukt filtreres over silicagel (elueringsmiddel: hexan/ether 4:1). Der fås 6,5 g af den tilsvarende lacton, 35 der straks videreforarbejdes. 6,5 g lacton opløses i 200 ml methylen- 10
DK 158947 B
chlorid, og ved -70eC tildryppes 40 ml diisobutylaluminiumhydrid (20% i toluen). Efter 3 1/2 times omrøring ved -70°C tildryppes 200 ml af en methanol/vand-blanding i forholdet 1:1, hvorefter blandingen lades antage 0°C, og der yderligere tildryppes 100 ml vand. Der syrnes med 5 IN saltsyre og ekstraheres med ether. Den organiske fase vaskes med vand, tørres og inddampes. Efter chromatografi af råproduktet på silicagel (elueringsmiddel: hexan/ether 9:1) fås 4,8 g 4,5,6,7-te-trahydro-4,4,7,7-tetramethylbenzo[b]furan i form af en farveløs væske.
10 1,6 g 4,5,6,7-tetrahydro-4,4,7,7-tetramethylbenzo[b]furan opløses i 40 ml tetrahydrofuran, og ved -30eC tildryppes 5,2 ml butyllithium (2 normal i hexan). Efter 3,5 timers omrøring ved -30“C tildryppes en opløsning af 550 mg acetaldehyd i 10 ml tetrahydrofuran. Blandingen lades antage stuetemperatur, der hældes ud på is, ekstraheres med 15 ether, tørres og inddampes. Den således vundne svagt gullige olie (2,2 g) opløses i 35 ml acetonitril, og der tilsættes 3,8 g tri-phenylphosphoniumbromid. Der opvarmes til 50°C i 3 timer, hvorefter der inddampes til tørhed. Den olieagtige remanens opløses i 80%'s vandigt ethanol og ekstraheres to gange med hexan, og ethanolfasen 20 inddampes til tørhed. Remanensen opløses i methylenchlorid, tørres over natriumsulfat og inddampes. Der fås 4,6 g [1-(4,5,6,7-tetrahy-dro-4,4,7,7-tetramethylbenzo[b]furan-2-yl)ethyl]triphenylphosphonium-bromid i form af et farveløst, amorft stof.
EKSEMPEL 5 25 3,0 g ethyl p-[2-(4,5,6,7-tetrahydro-4,4,7,7-tetramethylbenzo[b]thi- en-2-yl)propenyl]benzoat opløses i 100 ml ethanol, og der tilsættes en opløsning af 3,9 g kaliumhydroxid i 20 ml vand. Efter 3 timers omrøring ved 50°C afkøles der, hældes ud på isvand og syrnes med 2N svovlsyre. Reaktionsblandingen ekstraheres med ethylacetat, og den 30 organiske fase vaskes med vand, tørres over natriumsulfat og inddampes. Efter omkrystallisation af remanensen af ethylacetat fås 2,4 g p-[(E)-2-(4,5,6,7-tetrahydro-4,4,7,7-tetramethylbenzo[b]thien-2-yl)propenyl]benzoesyre i form af svagt gullige krystaller, smeltepunkt 236-238°C.
11
DK 158947 B
EKSEMPEL 6 10,2 g [1-(4,5,6,7-tetrahydro-4,4,7,7-tetramethylbenzo[b]thien-2-yl)-ethyl]triphenylphosphoniumbromid og 2,5 g 6-formylpyridin-3-carboxylsyre -ethyles ter suspenderes i 100 ml butylenoxid og opvarmes til 5 kogning under tilbagesvaling i 1 1/2 time. Ved den i eksempel 1 beskrevne oparbejdning fås 6,9 g af en gul olie, som chromatograferes over silicagel (elueringsmiddel: hexan/ether i forholdet 9:1) til fraskillelse af Z-isomeren. Den langsomst løbende E-isomer omkrystalliseres af hexan. Der fås 1,3 g 6-[(E)-2-(4,5,6,7-tetrahydro-4,4,7,7-10 tetramethylbenzo[b]thien-2-yl)propenyl]nicotinsyre-ethylester som gullige krystaller, smeltepunkt 83-84°C.
EKSEMPEL 7
Et rodenticidt middel kan have nedenstående sammensætning: A. Aktivstof, fx ethyl p-[2-(4,5,6,7-tetra- 15 hydro-4,4,7,7-tetramethylbenzo[b]thien- 2-yl)propenylJberi!zoat 0,005 %
Konserveringsmiddel (fx chlorerede phenoler) 0,500 %
Hydrofobiseringsmiddel (fx naturlige 20 og syntetiske voksarter) 5,000 Z
Farvestof (fx Berlinerblåt) 0,300 %
Lokkemiddel (fx æggehvidehydrolysat) 2,500 %
Fugtighedsbevarende midler (fx polyglycoler) 0,460 % 25 Neutralisationsmidler (fx alkylolaminer) 0,060 % Bærestof (uorganisk, fx kridt) 4,500 % Bærestof (organisk, fx hvedemel) 86,675 % 100,000 %

Claims (11)

1. Tetrahydronaphthalin-, benzofuran- og benzothiophenderivater med den almene formel I DK 158947 B i-1 ^ H3c CH3 ing hvor 5. betegner -CH=CH-, -O- eller -S-; r! betegner en gruppe Ar-R^ eller -CH=CH-C(CH3)=CH-R^; Ar betegner phenyl eller pyridyl; R^ betegner en gruppe -CO2R·*; og betegner hydrogen eller lavere alkyl; 10 idet mindst én ring i molekylet er heterocyclisk, og, såfremt forbindelsen er en carboxylsyre, salte deraf med baser.
2. Forbindelse ifølge krav 1, kendetegnet ved, at X betegner -S- eller -O-.
3. Forbindelse ifølge krav 2, 15 kendetegnet ved, at R^ betegner en gruppe Ar-R^, hvor Ar betegner phenyl eller pyridyl, og R^ har den i krav 1 anførte betydning .
4. Forbindelse ifølge et hvilket som helst af kravene 1-3, kendetegnet ved, at R^ betegner lavere alkoxycarbonyl.
5. Forbindelse ifølge krav 1, kendetegnet ved, at den er ethyl p-[2-(4,5,6,7-tetrahydro- 4,4,7,7-tetramethylbenzo[b]thien-2-yl)propenyl]benzoat.
5 Sukker, ad 100 % EKSEMPEL 8 Mastermixes kan have nedenstående sammensætning: A. Flydende Mastermix Aktivstof 0,25 %
10 Olie, fx plantefrøolie eller mineralolie 99,75 % 100,00 % B. Fast Mastermix
15 Aktivstof 0,1 % Støvhindrende middel, fx mineralolie 10,0 % Uorganisk bærestof, fx kaolin 89,9 % 20 100,0 % Disse Mastermixes blandes med forskellige lokkemidler (fx hvede, majs, johannesbrødfrugter, bananer, jordnødder, etc.) på en sådan måde, at aktivstofkoncentrationen fx bliver 0,005%.
6. Forbindelse ifølge krav 1, kendetegnet ved, at den er 6-[(E)-2-(4,5,6,7-tetrahydro-25 4,4,7,7-tetramethylbenzo[b]thien-2-yl)propenyl]nicotinsyre-ethyl- ester. DK 158947 B
7. Forbindelse ifølge krav 1, kendetegnet ved, at den er 3-methyl-7-(4,5,6,7-tetrahydro- 4,4,7,7-tetramethylbenzo[b]thien-2-yl)-2,4,6-octratriensyre, 6-[(E)- 2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]nico-5 tinsyre-ethylester, p-[2-(4,5,6,7-tetrahydro-4,4,7,7-tetramethyl-2- benzofuranyl)propenyljbenzoesyre-ethylester eller p-[(E)-2-(4,5,6,7-tetrahydro-4,4,7,7-tetramethylbenzo[b]thien-2-yl)propenyl]benzoesyre.
8. Rodenticid, kendetegnet ved, at det indeholder en forbindelse ifølge 10 krav 1 sammen med sædvanlige bærestoffer.
9. Anvendelse af forbindelser ifølge krav 1 som rodenticid.
10. Fremgangsmåde til fremstilling af forbindelser med den i krav 1 angivne almene formel I, kendetegnet ved, at en forbindelse med den almene formel 15 II H3C\^CH3 r>-—t II© Θ ’3 Y
11 H3C CH3 Ah3 omsættes med en forbindelse med den almene formel III 20 H
0. C - R11 III eller en forbindelse med den almene formel IV DK 158947 B COL, n3c ch3 IHs omsættes med en forbindelse med den almene formel V 5 0 t Λ , (RO)2P - CH2R11 V i hvilke almene formler II-V R betegner lavere alkoxy; Ph betegner 10 phenyl; og R^ betegner en gruppe -ArCX^R^, eller -CH=CH-C(CH3)=CHC02R^ og R^, Ar og X har den i krav 1 anførte betydning, og Y betegner anionen af en uorganisk eller organisk syre, og en vunden carboxylsyreester om ønsket hydrolyseres, eller en vunden carboxylsyre om ønsket omdannes til et salt deraf med en base.
DK281883A 1982-07-06 1983-06-17 Tetrahydronaphthalin-,benzofuran- og benzothiophenderivater, fremstilling og anvendelse deraf samt rodenticid indeholdende saadanne derivater DK158947C (da)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
CH411782 1982-07-06
CH411782 1982-07-06
CH272883 1983-05-19
CH272883 1983-05-19

Publications (4)

Publication Number Publication Date
DK281883D0 DK281883D0 (da) 1983-06-17
DK281883A DK281883A (da) 1984-01-07
DK158947B true DK158947B (da) 1990-08-06
DK158947C DK158947C (da) 1991-01-21

Family

ID=25691256

Family Applications (1)

Application Number Title Priority Date Filing Date
DK281883A DK158947C (da) 1982-07-06 1983-06-17 Tetrahydronaphthalin-,benzofuran- og benzothiophenderivater, fremstilling og anvendelse deraf samt rodenticid indeholdende saadanne derivater

Country Status (13)

Country Link
US (4) US4535086A (da)
EP (1) EP0098591B1 (da)
AU (1) AU565382B2 (da)
CA (1) CA1242726A (da)
DE (1) DE3372368D1 (da)
DK (1) DK158947C (da)
EG (1) EG17031A (da)
ES (1) ES8504168A1 (da)
HU (1) HU194020B (da)
IE (1) IE55564B1 (da)
IL (1) IL69121A (da)
NO (1) NO162464C (da)
PT (1) PT76981B (da)

Families Citing this family (61)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2543947B1 (fr) * 1983-04-08 1985-07-26 Centre Nat Rech Scient Nouveaux tetra-alkyl-2,2,5,5 cyclohexanone-4 01-1 et leurs derives sulfonyles, leur preparation et leur application a la synthese de lactones cyclopropaniques
DE3434947A1 (de) * 1984-09-22 1986-04-03 Basf Ag, 6700 Ludwigshafen Isoxazolcarbonsaeure-derivate, ihre herstellung und verwendung
US5084476A (en) * 1986-07-15 1992-01-28 Hoffmann-La Roche Inc. Tetrahydronaphthalene and indane derivatives
ZW10287A1 (en) * 1986-07-15 1988-01-13 Hoffmann La Roche Tetrahydronaphthaline and indane derivatives
US5264578A (en) * 1987-03-20 1993-11-23 Allergan, Inc. Disubstituted acetylenes bearing heterobicyclic groups and heteroaromatic or phenyl groups having retinoid like activity
US5602130A (en) * 1987-03-20 1997-02-11 Allergan Disubstituted acetylenes bearing heteroaromatic and heterobicyclic groups having retinoid like activity
US5183827A (en) * 1989-09-19 1993-02-02 Allergan, Inc. Acetylenes disubstituted with a heteroaromatic group and a 2-substituted chromanyl, thiochromanyl or 1,2,3,4-tetrahydroquinolinyl group having retinoid-like activity
US5272156A (en) * 1989-09-19 1993-12-21 Allergan, Inc. Acetylenes disubstituted with a heteroaromatic group and a 2-substituted 1,2,3,4-tetrahydroquinolinyl group having retinoid-like activity
DE59008356D1 (de) * 1989-12-14 1995-03-09 Ciba Geigy Ag Heterocyclische Verbindungen.
US5264456A (en) * 1989-12-29 1993-11-23 Allergan, Inc. Acetylenes disubstituted with a furyl group and a substituted phenyl group having retinoid like activity
US5302606A (en) * 1990-04-16 1994-04-12 Rhone-Poulenc Rorer Pharmaceuticals Inc. Styryl-substituted pyridyl compounds which inhibit EGF receptor tyrosine kinase
US5196446A (en) * 1990-04-16 1993-03-23 Yissum Research Development Company Of The Hebrew University Of Jerusalem Certain indole compounds which inhibit EGF receptor tyrosine kinase
US5418245A (en) * 1990-04-16 1995-05-23 Rhone-Poulenc Rorer International (Holdings) Inc. Styryl-substituted monocyclic and bicyclic heteroaryl compounds which inhibit EGF receptor tyrosine kinase
FI935280A0 (fi) * 1991-05-29 1993-11-26 Pfizer Dihydroxiindanontyrosinkinasinhibitorer
US5324840A (en) * 1992-06-11 1994-06-28 Allergan, Inc. Method of treatment with compounds having retinoid-like activity and reduced skin toxicity and lacking teratogenic effects
US6172115B1 (en) 1993-02-11 2001-01-09 Allergan Sales, Inc. Method for preventing onset of restenosis after angioplasty employing an RXR-specific retinoid
US5455265A (en) * 1993-02-11 1995-10-03 Allergan, Inc. Method of treatment with compounds having selective agonist-like activity on RXR retinoid receptors
US5475022A (en) * 1993-10-18 1995-12-12 Allergan, Inc. Phenyl or heteroaryl and tetrahydronaphthyl substituted diene compounds having retinoid like biological activity
US5426118A (en) * 1993-12-30 1995-06-20 Allergan, Inc. [4-(1,2-epoxycyclohexanyl)but-3-en-1-ynyl]aromatic and heteroaromatic acids and derivatives having retinoid-like biological activity
US5498755A (en) * 1994-08-23 1996-03-12 Chandraratna; Roshantha A. Disubstituted aryl and heteroaryl imines having retinoid-like biological activity
US5618943A (en) * 1994-12-29 1997-04-08 Allergan Acetylenes disubstituted with a 5 OXO substituted tetrahydronaphthyl group and with an aryl or heteroaryl group having retinoid-like biological activity
US5618931A (en) * 1994-12-29 1997-04-08 Allergan Acetylenes disubstituted with a 5 substituted dihydronaphthyl group and with an aryl or heteroaryl group having retinoid-like biological activity
US5543534A (en) * 1994-12-29 1996-08-06 Allergan Acetylenes disubstituted with a 5 substituted tetrahydronaphthyl group and with an aryl or heteroaryl groups having retinoid-like biological activity
US5514825A (en) * 1994-12-29 1996-05-07 Allergan, Inc. Acetylenes disubstituted with a 5 substituted tetrahydronaphthyl group and with an aryl or heteroaryl group having retinoid-like biological activity
US5534641A (en) * 1994-12-29 1996-07-09 Allergan Acetylenes disubstituted with 2-tetrahydropyranoxyaryl and aryl or heteroaryl groups having retinoid-like biological activity
US5599967A (en) * 1994-12-29 1997-02-04 Allergan Acetylenes disubstituted with a 5 substituted tetrahydronaphthyl group and with an aryl of heteroaryl group having retinoid-like biological activity
US5648514A (en) 1994-12-29 1997-07-15 Allergan Substituted acetylenes having retinoid-like biological activity
US5489584A (en) * 1994-12-29 1996-02-06 Allergan, Inc. Acetylenes disubstituted with a 5-amino or substituted 5-amino substituted tetrahydronaphthyl group and with an aryl or heteroaryl group having retinoid-like biological activity
US5556996A (en) * 1994-12-29 1996-09-17 Allergan Oxiranyls disubstituted with a phenyl group and a substituted chromanyl or tetrahydroquinolinyl group having retinoid like activity
US6025388A (en) * 1995-04-26 2000-02-15 Allergan Sales, Inc. Method for inhibiting gene expression promoted by AP1 protein with RARβ selective retinoids and method for treatment of diseases and conditions with such retinoids
US5616712A (en) * 1995-05-16 1997-04-01 Allergan Acetylenes disubstituted with a phenyl or heteroaryl group and a 2-thio-1,2,3,4-tetrahdroquinolinyl, 2-alkylthio-3,4-dihydroquinolinyl or 2-alkoxy-3,4-dihydroquinolinyl group having retinoid-like biological activity
US5917082A (en) 1995-06-06 1999-06-29 Allergan Sales, Inc. 2,4-pentadienoic acid derivatives having retinoid-like biological activity
US5675033A (en) 1995-06-06 1997-10-07 Allergan 2,4-pentadienoic acid derivatives having retinoid-like biological activity
US6008204A (en) 1995-09-01 1999-12-28 Allergan Sales, Inc. Synthesis and use of retinoid compounds having negative hormone and/or antagonist activities
US5952345A (en) 1995-09-01 1999-09-14 Allergan Sales, Inc. Synthesis and use of retinoid compounds having negative hormone and/or antagonist activities
US6218128B1 (en) 1997-09-12 2001-04-17 Allergan Sales, Inc. Methods of identifying compounds having nuclear receptor negative hormone and/or antagonist activities
US5958954A (en) 1995-09-01 1999-09-28 Allergan Sales, Inc. Synthesis and use of retinoid compounds having negative hormone and/or antagonist activities
AU7598596A (en) * 1995-11-01 1997-05-22 Allergan, Inc. Sulfides, sulfoxides and sulfones disubstituted with a tetrahydronaphthalenyl, chromanyl, thiochromanyl or tetrahydroquinolinyl and substituted phenyl or heteroaryl group, having retinoid-like biological activity
US5726191A (en) * 1995-11-16 1998-03-10 Hoffmann-La Roche Inc. Aromatic carboxylic acid esters
US5663357A (en) * 1995-11-22 1997-09-02 Allergan Substituted heteroarylamides having retinoid-like biological activity
US5675024A (en) * 1995-11-22 1997-10-07 Allergan Aryl or heteroaryl amides of tetrahydronaphthalene, chroman, thiochroman and 1,2,3,4,-tetrahydroquinoline carboxylic acids, having an electron withdrawing substituent in the aromatic or heteroaromatic moiety, having retinoid-like biological activity
US5688957A (en) * 1995-12-29 1997-11-18 Allergan (3"-thioxacyclohex-1"-enyl)!-but-3'-ene-1'-ynyl!aryl and (3"-thioxacyclohex-1"-enyl)!-but-3'-ene-1'-ynyl!heteroaryl carboxylic acids and esters having retinoid-like biological activity
US5965606A (en) 1995-12-29 1999-10-12 Allergan Sales, Inc. Methods of treatment with compounds having RAR.sub.α receptor specific or selective activity
US5723666A (en) * 1996-06-21 1998-03-03 Allergan Oxime substituted tetrahydronaphthalene derivatives having retinoid and/or retinoid antagonist-like biological activity
US5808124A (en) * 1996-06-21 1998-09-15 Allergan O- or S-substituted dihydronaphthalene derivatives having retinoid and/or retinoid antagonist-like biological activity
US5747542A (en) * 1996-06-21 1998-05-05 Allergan Oxo-substituted tetrahydronaphthalene derivatives having retinold and/or retinoid antagonist-like biological activity
US5773594A (en) 1996-06-21 1998-06-30 Allergan Alkyl or aryl substituted dihydronaphthalene derivatives having retinoid and/or retinoid antagonist-like biological activity
US5763635A (en) 1996-06-21 1998-06-09 Allergan Tetrahydronaphthalene derivatives substituted in the 8 position with alkyhidene groups having retinoid and/or retinoid antagonist-like biological activity
US6555690B2 (en) 1996-06-21 2003-04-29 Allergan, Inc. Alkyl or aryl substituted dihydronaphthalene derivatives having retinoid and/or retinoid antagonist-like biological activity
US5741896A (en) 1996-06-21 1998-04-21 Allergan O- or S- substituted tetrahydronaphthalene derivatives having retinoid and/or retinoid antagonist-like biological activity
US5739338A (en) * 1996-11-05 1998-04-14 Allergan N-aryl substituted tetrahydroquinolines having retinoid agonist, retinoid antagonist or retinoid inverse agonist type biological activity
US5728846A (en) * 1996-12-12 1998-03-17 Allergan Benzo 1,2-g!-chrom-3-ene and benzo 1,2-g!-thiochrom-3-ene derivatives
US5760276A (en) * 1997-03-06 1998-06-02 Allergan Aryl-and heteroarylcyclohexenyl substituted alkenes having retinoid agonist, antagonist or inverse agonist type biological activity
US6037488A (en) 1997-04-19 2000-03-14 Allergan Sales, Inc. Trisubstituted phenyl derivatives having retinoid agonist, antagonist or inverse agonist type biological activity
US5919970A (en) 1997-04-24 1999-07-06 Allergan Sales, Inc. Substituted diaryl or diheteroaryl methanes, ethers and amines having retinoid agonist, antagonist or inverse agonist type biological activity
EP1115286A4 (en) * 1998-09-25 2003-07-23 Viropharma Inc METHOD FOR TREATING AND PREVENTING VIRAL INFECTIONS AND DISEASES RELATED TO THEM
US6313107B1 (en) 2000-08-29 2001-11-06 Allergan Sales, Inc. Methods of providing and using compounds having activity as inhibitors of cytochrome P450RAI
US6380256B1 (en) 2000-08-29 2002-04-30 Allergan Sales, Inc. Compounds having activity as inhibitors of cytochrome P450RAI
US6369225B1 (en) 2000-08-29 2002-04-09 Allergan Sales, Inc. Compounds having activity as inhibitors of cytochrome P450RAI
US6720423B2 (en) 2002-04-30 2004-04-13 Allergan, Inc. Dihydrobenzofuran and dihydrobenzothiophene 2,4-pentadienoic acid derivatives having selective activity for retinoid X (RXR) receptors
RU2721283C2 (ru) * 2014-01-14 2020-05-18 Конекшис Лайф Сайенсиз Пвт. Лтд. Замещенные бициклические гетероарильные соединения в качестве агонистов rxr

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3872114A (en) * 1971-02-05 1975-03-18 Hoechst Ag Benzofurane derivatives, process for their manufacture and their use as optical brighteners
LU77254A1 (da) * 1977-05-04 1979-01-18
US4326055A (en) * 1977-12-22 1982-04-20 Hoffmann-La Roche Inc. Stilbene derivatives
DK159967C (da) * 1977-12-22 1991-06-03 Hoffmann La Roche Analogifremgangsmaade til fremstilling af terapeutisk aktive stilbenderivater

Also Published As

Publication number Publication date
PT76981B (fr) 1986-04-11
US4816476A (en) 1989-03-28
AU565382B2 (en) 1987-09-17
US4535086A (en) 1985-08-13
AU1658983A (en) 1984-01-12
IL69121A (en) 1986-07-31
IE831568L (en) 1984-01-06
US4659735A (en) 1987-04-21
NO832459L (no) 1984-01-09
EP0098591A1 (de) 1984-01-18
NO162464C (no) 1990-01-10
DK158947C (da) 1991-01-21
ES523858A0 (es) 1985-04-16
DK281883A (da) 1984-01-07
EP0098591B1 (de) 1987-07-08
CA1242726A (en) 1988-10-04
PT76981A (fr) 1983-08-01
DE3372368D1 (en) 1987-08-13
ES8504168A1 (es) 1985-04-16
NO162464B (no) 1989-09-25
DK281883D0 (da) 1983-06-17
EG17031A (en) 1989-01-30
HU194020B (en) 1988-01-28
US4931458A (en) 1990-06-05
IE55564B1 (en) 1990-11-07
IL69121A0 (en) 1983-10-31

Similar Documents

Publication Publication Date Title
DK158947B (da) Tetrahydronaphthalin-,benzofuran- og benzothiophenderivater, fremstilling og anvendelse deraf samt rodenticid indeholdende saadanne derivater
SU764610A3 (ru) Способ получени производных 2-ароил-3-фенилбензотиофенов или их солей
US6211197B1 (en) Prostaglandin receptor ligands
CA1300161C (fr) Derives de dihydrobenzofuranne - et de chromane - carboxamides, leursprocede de preparation et leur utilisation comme neuroleptiques
EP0471609A1 (fr) Dérivés de Benzofuranne, Benzothiophène, Indole ou Indolizine, leur procédé de préparation ainsi que les compositions les contenant
CA2008341C (fr) Derives d&#39;acides benzocycloalcenyl dihydroxy alcanoiques procedes de preparation et medicaments les contenant
KR910000404B1 (ko) 항응고성 4-하이드록시쿠마린류 화합물의 제조방법
CN107628945B (zh) 一种合成β-溴甲酸酯类化合物的方法
US3574234A (en) Derivatives of 4-hydroxy coumarine
Runde et al. Rearrangement of the alpha-furfuryl group. 2-furylacetic acid and 5-methylfuroic acid
CN107721956A (zh) 苯并丁内酯类衍生物、合成方法及其制备杀菌剂的应用
FR2630110A1 (fr) Nouveaux derives heteroarotinoides, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
TW304194B (da)
JPS5925789B2 (ja) チアゾリリデン−オキソ−プロピオニトリル、その製造法並びに該化合物を含有する殺虫剤
Campaigne et al. Benzo [b] thiophene derivatives. VII. An abnormal substitution product from 3‐chloromethylbenzo [b] thiophene
HU204520B (en) Process for producing pharmaceutically active compounds and pharmaceutical compositions containing them
BE1006226A3 (fr) Derives de la benzofuranylimidazole, leur procede de preparation ainsi qu&#39;une composition therapeutique les contenant.
JPS6014032B2 (ja) ５‐フエネチル‐２‐オキサゾリドン誘導体およびその製法
JPH0774210B2 (ja) ４−ヒドロキシクマリン誘導体
SE420311B (sv) N-alkenyl-2-hydroximetyl-3,4,5-trihydroxipiperidin
US3989718A (en) [1]Benzothieno[3,2-b]furans
SU489334A3 (ru) Способ получени производных тиепина
Snyder et al. Amine Replacement Reactions of α-Dimethylaminomethyl-β-methoxynaphthalene
SU385443A1 (ru) СПОСОБ ПОЛУЧЕНИЯ ПРОИЗВОДНЫХ ИНДОЛА ИЛИ их СОЛЕЙ
CN106749144A (zh) 7‑芳氧乙酰氧基香豆素类化合物及其在农药上的应用

Legal Events

Date Code Title Description
AHB Application shelved due to non-payment
PBP Patent lapsed