Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
• • 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
  • A01N53/00—Biocides, pest repellants or attractants, or plant growth regulators containing cyclopropane carboxylic acids or derivatives thereof
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P3/00—Drugs for disorders of the metabolism
  • A61P3/06—Antihyperlipidemics
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
  • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
  • C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
  • C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
  • C07C45/70—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction with functional groups containing oxygen only in singly bound form
  • C07C45/71—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction with functional groups containing oxygen only in singly bound form being hydroxy groups

Definitions

• the invention relates to new etherified cycloalkanols, in particular those of the formula (I) in which X 1 is oxygen, sulfur or methylene, X 2 oxygen or sulfur, A is an optionally substituted phenyl radical and n is an integer from 1 to 10, and processes for their preparation, and also pharmaceutical preparations containing these compounds and their use preferably in the form of pharmaceutical preparations.
• radicals and compounds designated "lower" in connection with the present description preferably contain up to and with 7 and primarily up to and with 4 carbon atoms.
• a substituted phenyl radical A is a mono-, di- or poly-substituted phenyl radical.
• the following may be mentioned in particular as substituents: halogen to atomic number 35, lower alkyl, lower alkoxy or trifluoromethyl.
• Halogen represents fluorine or bromine, but preferably chlorine.
• X 2 and the hydroxyl group are preferably trans to one another.
• the new compounds have valuable pharmacological properties. So they cause a reduction in lipid content in the - serum, as for example on the male rat, which in each case mg, a dose of 10 to 200 for 3 days / kg of the test substances and at 4 days two such doses is obtained and subsequently determining the cholesterol and Triglyceride concentration in the serum, can be shown. They can thus be used as hypolipidaemics for the treatment of lipid metabolism disorders.
• cyclopropanecarboxylic acid esters which are suitable for combating various animal and vegetable pests, in particular for combating representatives of the Akarina family: Ixodidae, Argasidae, Tetranychidae, Dermanyssidae and insects of the families : Acrididae, Blattidae, Gryllidae, Gryllotalpidae, Tettigoniidae, Cimicidae, Pyrrhocoridae, Reduviidae, Aphididae, Delphaci- dae, Diaphididae, Pseudococcidae, Chrysomilidae, Coccinellidae, Bruchidae, Scarabaide, Noir , Culicidae, Tipulidae, Stomoxydae, Muscidae, Calliphoridae, Trypertidae or Pul
• the invention relates to 1- (4-phenoxy-phenoxy) cyclopentan-2-ol.
• the invention also preferably relates to the compounds of the formula where R is hydrogen or chlorine and n represents the integers 3, 4 or 5 or the compounds of the formula wherein R represents hydrogen or chlorine and n represents the integers 3, 4 or 5.
• the invention particularly relates to the new compounds described in the examples.
• the new compounds are obtained in a manner known per se; for example, a compound of formula (IV) or a salt thereof, with a compound of formula (V) or represent a carbonyldioxy group of the formula -OC. (0) 0-, and split off any protective group which may be present in the compounds obtained, and, if desired, separate an isomer mixture obtainable according to the process into the individual isomers.
• Salts of compounds of formula (IV) are primarily metal, especially alkali metal e.g. Sodium or potassium salts, which are usually prepared in situ.
• a reactive esterified hydroxyl group is in particular one which is esterified with a strong acid, such as a strong inorganic or organic acid.
• a strong acid such as a strong inorganic or organic acid.
• Particularly strong inorganic acids are hydrohalic acids, such as hydrochloric or hydrobromic acid, or sulfuric acid, and organic acids, primarily sulfonic acids, such as a benzenesulfonic acid optionally substituted by halogen, lower alkyl or lower alkoxy; e.g. p-toluenesulfonic acid or p-methoxybenzenesulfonic acid, or an alkanesulfonic acid e.g. Methane or ethanesulfonic acid.
• a protected hydroxy group is especially an esterified hydroxy group, e.g. an acyloxy group such as a lower alkanoyloxy, e.g. Acetoxy or a benzoyloxy group or an etherified hydroxy group, e.g. a tetrahydropyranyloxy or an aralkoxy group such as the benzyloxy group.
• an esterified hydroxy group e.g. an acyloxy group such as a lower alkanoyloxy, e.g. Acetoxy or a benzoyloxy group or an etherified hydroxy group, e.g. a tetrahydropyranyloxy or an aralkoxy group such as the benzyloxy group.
• the reaction is carried out in a manner known per se. It is preferably carried out in the presence of a base, in particular an inorganic base, such as an alkali or alkaline earth metal hydroxide, carbonate or hydride, for example sodium or potassium hydroxide, hydride or carbonate or an organic base, such as piperidine, pyridine, Quinoline or a tri-lower alkylamine, e.g. Trimethylamine, triethylamine or dimethylisopropylamine.
• a carbodiimide such as dicyclohexylcarbodiimide in the presence of copper chloride. It can work in an inert solvent such as acetone or dimethyl sulfoxide.
• the reaction can also be carried out in a high-boiling solvent such as xylene, toluene or quinoline at an elevated temperature, for example 80-200 °, or in the absence of a solvent.
• a protected hydroxy group can be used in a manner known per se, e.g. set free by hydrolysis or hydrogenolysis.
• the starting materials to be used for this reaction are known or can be obtained in a manner known per se.
• the new compounds can, however, also be obtained if a compound of the formula (VI) the keto group is reduced to the carbinol group in a manner known per se and, if desired, a mixture of isomers obtainable according to the process is separated into the individual isomers.
• the reduction can usually be e.g. with catalytically activated hydrogen, e.g. in the presence of Raney nickel or a palladium catalyst such as Pd / C or with metal hydrides such as sodium borohydride, lithium aluminum hydride or diborane, in the presence of an inert solvent such as water, alcohols e.g. Carry out methanol or ethanol, or ethers such as diethyl ether or tetrahydrofuran.
• catalytically activated hydrogen e.g. in the presence of Raney nickel or a palladium catalyst such as Pd / C or with metal hydrides such as sodium borohydride, lithium aluminum hydride or diborane
• an inert solvent such as water, alcohols e.g. Carry out methanol or ethanol, or ethers such as diethyl ether or tetrahydrofuran.
• the starting material used in this process method is obtained in a manner known per se, e.g. by reacting a keto-cycloalkanol or a reactive ester thereof with a compound of formula IV in the manner shown above, or by reacting a compound of formula IV with a reactive ester of 3-hydroxy-cycloalkene and subsequent oxidation of the double bond, e.g. with mercury II nitrate or acetate in water, or a peracid such as peracetic acid.
• the starting material of formula (VI) thus obtained can, if desired, be reduced without isolation.
• the new compounds can be present as isomer mixtures, such as racemates or diastereoisomer mixtures, or in the form of the pure isomers, such as the optically active components.
• the separation of isomer mixtures obtained into the individual isomers can be carried out by known methods. Mixtures of diastereoisomers can be e.g. due to physico-chemical differences, such as those of solubility, e.g. by fractional crystallization or distillation, or by chromatography into the individual isomers.
• Racemates can be obtained, for example, by esterifying the alcohol racemate with an optically active acid, for example optically active camphorsulfonic acid, separating the ester / diastereoisomer mixture thus obtainable and saponifying the ester, or by esterifying the alcohol racemate with a dicarboxylic acid, only one carboxyl group being esterified, Forming a salt of the monoester acid racemate thus obtainable with a suitable optically active base, for example optically active brucine, a-phenylethylamine or ephedrine, splitting the salt diastereoisomer
• an optically active acid for example optically active camphorsulfonic acid
• separating the ester / diastereoisomer mixture thus obtainable and saponifying the ester
• a dicarboxylic acid only one carboxyl group being esterified
• Forming a salt of the monoester acid racemate thus obtainable with a suitable optically active base, for example optically active
• the invention also relates to those embodiments of the process in which one starts from a compound obtainable as an intermediate at any stage of the process and carries out the missing process steps, or terminates the process at any stage, or forms a starting material under the reaction conditions or in the form of a reactive one Derivative or salt used.
• the starting materials used are preferably those which, according to the process, lead to the compounds described above as being particularly valuable.
• the present invention also relates to pharmaceutical preparations which contain compounds of the formula I.
• the pharmaceutical preparations according to the invention are those for enteral, such as oral or rectal, and parenteral administration to warm-blooded animals which use the pharmacological active ingredient alone or together with a pharmaceutically applicable agent - Contain their carrier material.
• the dosage of the active ingredient depends on the WarmblUter species, the age and the individual condition, as well as on the mode of administration.
• Suitable carriers are, in particular, fillers, such as sugar, for example lactose, sucrose, mannitol or sorbitol, cellulose preparations and / or calcium phosphates, for example tricalcium phosphate or calcium hydrogenphosphate, and also binders, such as starch paste using, for example, corn, wheat, rice or potato starch, gelatin , Tragacanth, methyl cellulose, hydroxypropyl methyl cellulose, sodium carboxymethyl cellulope and / or polyvinyl pyrrolidone, and / or if desired.
• fillers such as sugar, for example lactose, sucrose, mannitol or sorbitol, cellulose preparations and / or calcium phosphates, for example tricalcium phosphate or calcium hydrogenphosphate
• binders such as starch paste using, for example, corn, wheat, rice or potato starch, gelatin , Tragacanth, methyl cellulose, hydroxypropyl methyl cellulose, sodium carboxy
• Disintegrants such as the above-mentioned starches, carboxymethyl starch, cross-linked polyvinyl pyrrolidone, agar, alginic acid or a salt thereof, such as sodium alginate.
• Auxiliaries are primarily flow regulators and lubricants, for example silica, talc, stearic acid or salts thereof, such as magnesium or calcium stearate, and / or polyethylene glycol.
• Dragee kernels are provided with suitable, if appropriate gastric juice-resistant, coatings, including concentrated sugar solutions, which may contain arabic gum, talc, polyvinylpyrrodidone, polyethylene glycol and / or titanium dioxide, lacquer solutions in suitable organic see solvents or solvent mixtures Production of gastric juice-resistant surges, solutions of suitable cellulose preparations, such as acetyl cellulose or hydroxypropyl methyl cellulose phthalate. Dyes or pigments can be added to the tablets or dragée coatings, for example for identification or for labeling different doses of active ingredient.
• the pharmaceutical preparations containing from about 0.1% to 100%, in particular from about 1% to about 50% of the active ingredient.
• the single dose for a warm-blooded animal weighing approximately 70 kg is between 0.1 and 0.75 g, the daily dose between 0.2 and 1 g
• the invention also relates to new cyclopropane carboxylic acid esters of the formula (VII) R 1 wherein A, X 1 , X 2 and n have the meaning given above and R 1 , R 2 , R 3 and R 4 each represent hydrogen, methyl or chlorine, their preparation and their use in pest control.
• esters are suitable for combating various types of animal and vegetable pests.
• the compounds of the formula VII are prepared by methods known per se, for example as follows: Hal stands for halogen, especially for chlorine or bromine.
• tertiary amines such as trialkylamines, e.g. Ethyl diiscpropylamine; Pyridine; Dialkylanilines; also inorganic bases, such as hydrides, hydroxides, alkoxides and carbonates of alkali and alkaline earth metals.
• the process is generally carried out at a temperature of about 10 ° C. to 100 ° C., with acid halides mostly at 0 ° C. to 30 ° C. and with acid anhydrides mostly at 70 ° C. to 100 ° C., under normal pressure and in an inert solution -or diluents performed.
• Suitable solvents or diluents are e.g. Benzene, toluene, xylene; Paraffin hydrocarbons such as hexane or heptane; Ethers such as diethyl ether, tetrahydrofuran, dioxane, dimethoxyethane; also esters, such as ethyl acetate.
• insecticidal effect can be broadened considerably by adding other insecticides and / or acaricides and can be adapted to the given circumstances.
• the compounds of formula VII can be used alone or together with suitable carriers and / or additives.
• suitable carriers and additives can be solid or liquid and correspond to the substances commonly used in formulation technology, e.g. natural or regenerated substances, solvents, dispersants, wetting agents, adhesives, thickeners, binders and / or fertilizers.
• the compounds of the formula VII can be processed with dusts, emulsion concentrates, granules, dispersions, sprays, into solutions or slurries in customary formulations which are common knowledge in application technology.
• Agents according to the invention are prepared in a manner known per se by intimately mixing and / or grinding active ingredients of the formula VII with the suitable carriers, optionally with the addition of dispersing agents or solvents which are inert to the active ingredients.
• the active ingredients can be present and used in the following processing forms.
• the content of active ingredients in the agents described above is between 0.1 to 95% by weight.
• the 2- (4-phenoxy-phenoxy) -cyclohexan-l-ol is obtained in an analogous manner, which melts at 62-65 ° after recrystallization from hexane and the 2- (4-benzylphenoxy) -cyclohexan-l-ol that after recrystallization from isopropanol melts at 78-80 °.
• a solution of 12.6 g of 3- (4-phenoxyphenoxy) cyclopent-l-ene in 25 ml is added dropwise to a mixture of 15.9 g of mercury (II) acetate, 35 ml of water and 50 ml of tetrahydrofuran over the course of an hour Tetra.hydrofuran and stirred for about 15 hours at room temperature.
• 50 ml of 3N sodium hydroxide solution are added dropwise within 1 1/2 hours and then 50 ml of a 0.5N solution of sodium borohydride in 3N sodium hydroxide solution within 1 hour.
• the reaction mixture is stirred for 2 hours at room temperature and filtered off from the precipitated mercury. It is poured. Filtrate on ice water, extracted with ether, the organic phase washed with saturated sodium chloride solution, dry
• the compound of formula IV is obtained with a refraction of n 20 D : 1.5542.

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• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
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• Chemical Kinetics & Catalysis (AREA)
• Health & Medical Sciences (AREA)
• Engineering & Computer Science (AREA)
• General Health & Medical Sciences (AREA)
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• Wood Science & Technology (AREA)
• Plant Pathology (AREA)
• Pest Control & Pesticides (AREA)
• Agronomy & Crop Science (AREA)
• Obesity (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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• Agricultural Chemicals And Associated Chemicals (AREA)

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• 1978
  • 1978-07-12 EP EP78100374A patent/EP0000506A3/fr not_active Withdrawn
  • 1978-07-13 US US05/924,315 patent/US4175137A/en not_active Expired - Lifetime
  • 1978-07-17 FI FI782253A patent/FI782253A/fi not_active Application Discontinuation
  • 1978-07-17 DD DD78206764A patent/DD138202A5/xx unknown
  • 1978-07-18 IT IT7850347A patent/IT7850347A0/it unknown
  • 1978-07-18 ES ES471829A patent/ES471829A1/es not_active Expired
  • 1978-07-18 IL IL55163A patent/IL55163A0/xx unknown
  • 1978-07-19 NO NO782492A patent/NO782492L/no unknown
  • 1978-07-19 ZA ZA00784104A patent/ZA784104B/xx unknown
  • 1978-07-19 DK DK322678A patent/DK322678A/da unknown
  • 1978-07-20 JP JP8778178A patent/JPS5422343A/ja active Pending
• 1979
  • 1979-03-22 ES ES478880A patent/ES478880A1/es not_active Expired

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