EP0000506A2 - Substituted phenyl O- or S- etherified cycloalkanols, a process for their preparation and their application as hypolipidemia, their esters with cyclopropanecarboxylic acids and the application of these esters as insecticides - Google Patents

Abstract

Etherified cycloalkanols of the formula <IMAGE> in which X1 is oxygen, sulfur or methylene, X2 oxygen or sulfur, A is an optionally substituted phenyl radical and n is an integer from 1 to 10 and methods for their preparation. These compounds, especially 2- (4-phenoxy-phenoxy) -cyclopentan-1-ol, have a lipid-lowering activity. Furthermore, they are intermediates for the preparation of the insecticidal cyclopropanoic acid esters of the formula <IMAGE> in which A, X1, X2, and n have the meaning given above and R¹, R², R³ and R <4> are each hydrogen, methyl or chlorine.

Description

worin X₁ Sauerstoff, Schwefel oder Methylen, X₂ Sauerstoff oder Schwefel, A einen gegebenenfalls substituierten Phenylrest und n eine ganze Zahl von 1 bis und mit 10 darstellen, sowie Verfahren zu deren Herstellung, wie auch pharmazeutische Präparate enthaltend diese Verbindungen und deren Verwendung vorzugsweise in Form von pharmazeutischen Präparaten.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.

The 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.

• Niederalkyl ist z.B. n-Propyl Isopropyl, n-Butyl, Isobutyl, sek.-Butyl, tert.-Butyl, n-Pentyl, Isopentyl,.n-Hexyl, Isohexyl oder n-Heptyl, aber vor allem Methyl oder Aethyl.
• Niederalkoxy ist z.B. n-Propoxy', Isopropoxy oder n-Butyloxy, besonders aber Methoxy oder Aethoxy.

The general terms can have the following meanings:

• Lower alkyl is, for example, n-propyl isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, .n-hexyl, isohexyl or n-heptyl, but especially methyl or ethyl.
• Lower alkoxy is, for example, n-propoxy ', isopropoxy or n-butyloxy, but especially methoxy or ethoxy.

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.

worin R Wasserstoff oder Chlor und n die ganzen Zahlen 3, 4 oder 5 darstellen.However, they can also serve as intermediates, in particular for the preparation of 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 Pulicidae.

wherein R represents hydrogen or chlorine and n represents the integers 3, 4 or 5.

First and foremost, the invention relates to 1- (4-phenoxy-phenoxy) cyclopentan-2-ol.

worin R Wasserstoff oder Chlor und n die ganzen Zahlen 3, 4 oder 5 darstellen oder auch die Verbindungen der Formel

worin R Wasserstoff oder Chlor und n die ganzen Zahlen 3, 4 oder 5 darstellen.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.

oder ein Salz davon, mit einer Verbindung der Formel (V)

oder eine Carbonyldioxygruppe der.Formel -OC.(0)0- darstellen, und in erhaltenen Verbindungen eine gegebenenfalls vorhandene Schutzgruppe abspalten, und, wenn erwünscht, ein verfahrensgemäss erhältliches Isomerengemisch in die einzelnen Isomeren auftrennen.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. 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.

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. But you can also in the presence of a carbodiimide such as dicyclohexylcarbodiimide in the presence of copper chloride. It can work in an inert solvent such as acetone or dimethyl sulfoxide. However, 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.

die Ketogruppe in an sich bekannter Weise zur Carbinolgruppe reduziert, und, wenn erwünscht, ein verfahrensgemäss erhältliches Isomerengemisch in die einzelnen Isomeren auftrennt.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.

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

The processes described above are carried out according to methods known per se, in the absence or preferably in the presence of diluents or solvents, if necessary, with cooling or heating, under elevated pressure and / or in an inert gas, such as nitrogen atmosphere.

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.

Herstellung von Magensaft-resistenten UebersUgen, Lösungen von geeigneten Cellulosepräparaten, wie Acetylcellulo- sephthalat oder Hydroxypropylmethylcellulosephthalat, verwendet. Den Tabletten oder Dragée-Ueberzügen können Farbstoffe oder Pigmente, z.B. zur Identifizierung oder zur Kennzeichnung verschiedener Wirkstoffdosen, beigefügt werden.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. 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

worin A, X₁, X₂ und n die oben gegebene Bedeutung besitzen und R₁, R₂, R₃ und R₄ je Wasserstoff, Methyl oder Chlor bedeuten, deren Herstellung und ihre Verwendung in der Schädlingsbekämpfung.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.

Because of their action, preference is given to compounds of the formula VII in which A is phenyl, X ₁ and X _{2 are} oxygen. Also preferred are compounds of formula VII, wherein R ₁ , R ₂ , R ₃ and R ₄ mean either hydrogen or methyl. Also to be emphasized are compounds of the formula VII in which R ₁ and R _{2 are} chlorine and R ₃ and R _{4 are} methyl.

As already noted, these esters are suitable for combating various types of animal and vegetable pests.

Hal steht darin für Halogen, insbesondere für Chlor oder Brom.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.

As basic acid acceptors come e.g. in question: 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.

The insecticidal effect can be broadened considerably by adding other insecticides and / or acaricides and can be adapted to the given circumstances.

• - organische Phosphorverbindungen,
• - Nitrophenole und Derivate,
• - Formamidine, Harnstoffe, Carbamate,
• - Chrysanthemumsäure-Derivate oder
• - chlorierte Kohlenwasserstoffreste.

Examples of suitable additives are:

• - organic phosphorus compounds,
• - nitrophenols and derivatives,
• - formamidines, ureas, carbamates,
• - Chrysanthemic acid derivatives or
• - chlorinated hydrocarbon residues.

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. For application, 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 following examples serve to illustrate the invention. Temperatures are given in degrees Celsius.

example 1

6.7 g of 90% potassium hydroxide powder are added to this melt within 25 minutes and the whole is stirred at 130 ° for one hour. After cooling, the reaction mixture is taken up in ether: hexane (1: 1) and the organic solution is washed four times with 10% potassium hydroxide solution and three times with saturated sodium chloride solution. The organic phase is dried over sodium sulfate and concentrated on a rotary evaporator under reduced pressure. The crude product is distilled and the 2- (4-phenoxyphenoxy) -cyclopentan-l-ol is obtained as a colorless oil with a boiling point of Kp _0.001 181-185 ° and a refractive index n ²⁰ _D = 1.5812.

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 °.

Example 2

• das 2-(4-Phenylmercaptophenoxy)-cyclopentan-1-ol als farbloses Oel vom Brechungsindex n²⁰ _D = 1,6217;
• das 2-Benzylphenoxy)cyclopenta-l-ol als Oel vom Bre- chungsindex n²⁰ _D = 1,5794;
• das 2-[4-(4-Chlor-phenoxy)-phenoxy]-cyclopentan-l-ol vom F. = 53-55°;
• das 2-[4-(4-Chlor-phenoxy)-phenoxy]-cyclohexan-l-ol vom F. 82-83°;
• das 2-(4-Phenylmercaptophenoxy)-cyclohexan-1-ol vom F. 79-81°;
• das 2-[4-(2, 4-Dichlor-phenoxy) -phenoxy]-cytlohexan-l-ol vom F. 84-86°;
• das 2-[4-(2,4-Dichlor-phenoxy)-phenoxyl-cyclopentan-l-ol als Oel vom Brechungsindex n²⁰ _D= 1,5946;
• das 2-[4-(2-Methyl-phenoxy)-phenoxyl-cyclohexan=l-ol vom F. 73-75°;
• das 2-(4-(4-Chlor-phenylmercapto)-phenoxyl-cyclohexan-1-ol vom F. 90-92°;
• das 2-(4-Phenoxy-phenylmercapto)-cyclohexan-l-ol als Oel vom Brechungsindex n²⁰ _D = 1,6051;
• das 2-(4-Phenoxy-phenylmercapto)-cyclopentan-l-ol, als Oel vom Brechungsindex n²⁰ _D = 1,6101;
• das 2-[4-(2-Methyl-phenoxy)-phenoxy]-cyclopentan-l-ol, als Oel vom Brechungsindex n²⁰ _D = 1,5757 oder
• das 2-[4-(4-Chlor-phenylmercapto)-phenoxy]-cyclopentan-l-ol, als Oel vom Brechungsindex n²⁰ _D = 1,6212.

Analogously to the process described in Example 1, starting from the corresponding starting materials,

• the 2- (4-phenylmercaptophenoxy) cyclopentan-1-ol as a colorless oil with a refractive index n ²⁰ _D = 1.6217;
• the 2-benzylphenoxy) cyclopenta-l-ol as an oil with the refractive index n ²⁰ _D = 1.5794;
• the 2- [4- (4-chlorophenoxy) phenoxy] cyclopentan-l-ol of mp = 53-55 °;
• the 2- [4- (4-chlorophenoxy) phenoxy] cyclohexan-l-ol of mp 82-83 °;
• the 2- (4-phenylmercaptophenoxy) cyclohexan-1-ol, mp 79-81 °;
• the 2- [4- (2,4-dichlorophenoxy) phenoxy] cytlohexan-l-ol of mp 84-86 °;
• the 2- [4- (2,4-dichlorophenoxy) phenoxyl-cyclopentan-l-ol as an oil with a refractive index n ²⁰ _D = 1.5946;
• the 2- [4- (2-methylphenoxy) phenoxylcyclohexan = 1-ol of mp 73-75 °;
• the 2- (4- (4-chlorophenylmercapto) phenoxylcyclohexan-1-ol, mp 90-92 °;
• the 2- (4-phenoxy-phenylmercapto) cyclohexan-l-ol as an oil with a refractive index n ²⁰ _D = 1.6051;
• the 2- (4-phenoxy-phenylmercapto) cyclopentan-l-ol, as an oil of refractive index n ²⁰ _D = 1.6101;
• the 2- [4- (2-methylphenoxy) phenoxy] cyclopentan-l-ol, as an oil of refractive index n ²⁰ _D = 1.5757 or
• the 2- [4- (4-chlorophenylmercapto) phenoxy] cyclopentan-l-ol, as an oil of refractive index n ²⁰ _D = 1.6212.

Example 3

.Oel vom K_P0.001 181-1850°.A solution of 3-78 g of sodium borohydride in 10 ml of water is added to a solution of 8.04 g of 2- (4-phenoxyphenoxy) cyclopentan-1-one in 60 ml of methanol at room temperature. The reaction mixture is stirred for a further 15 hours at room temperature and then concentrated under reduced pressure. The residue is poured onto ice water and extracted with ether. The organic phase is washed twice with saturated sodium chloride solution, dried over sodium sulfate and concentrated on a rotary evaporator.

.Oil from K _P0.001 181-1850 °.

erhalten:

• Zu einer Lösung von 18,6 g 4-Phenoxypher.cl in 80 ml Aceton werden 15,2 g,wasserfreies Kaliumcarbonat gegeben und das Reaktionsgemisch eine Stunde am Rückfluss gekocht, Man tropft dann 17,3 g 2-Brom-cyclopentanon zu und kocht während 20 Stunden am Rückfluss. Man kühlt das Reaktionsgemisch ab, filtriert und engt das Filtrat am Rotationsvaporisator ein. Man nimmt das erhaltene 0el in Aether auf, wäscht die Lösung viermal mit 10%-iger Kaliumhydroxydlösung und zweimal mit gesättigter Kochsalzlösung, trocknet über Natriumsulfat und engt am Rotationsvaporisator ein. Das erhaltene rohe 2-(4-Phenoxyphenoxy)- cyclopentan-l-on wird ohne weitere Reinigung für die oben beschriebene Um- Setzung verwendet.

The starting material can be

receive:

• 15.2 g of anhydrous potassium carbonate are added to a solution of 18.6 g of 4-phenoxypher.cl in 80 ml of acetone and the reaction mixture is refluxed for one hour. Then 17.3 g of 2-bromo-cyclopentanone are added dropwise and the mixture is boiled at reflux for 20 hours. The reaction mixture is cooled, filtered and the filtrate is concentrated on a rotary evaporator. The oil obtained is taken up in ether, the solution is washed four times with 10% potassium hydroxide solution and twice with saturated sodium chloride solution, dried over sodium sulfate and concentrated on a rotary evaporator. The crude 2- (4-phenoxyphenoxy) cyclopentan-1-one obtained is used for the reaction described above without further purification.

Example 4

Analogously to Example 3 above, starting from the corresponding starting materials, the 2- (4-phenoxyphenoxy) cyclohexa-l-one of F. -103-105 ° is obtained, which, as described above, gives the corresponding 2- (4- Phenoxyphenoxy) cyclohexan-l-ol is reduced from F. - 62-65 °.

Example 5

6.7 g of 90% strength potassium hydroxide powder are added to a solution of 18.6 g of 4-phenoxyphenol in 120 ml of dimethyl sulfoxide with ice cooling and the whole is stirred at room temperature for 1/2 hour. 16.3 g of 2-acetoxy-cyclopentyl chloride are then added over the course of 20 minutes and the mixture is stirred then the reaction mixture at 50 ° approx. 18 hours. It is poured onto ice water, extracted with ether, the organic phase is washed again with water and once with saturated sodium chloride solution, dried over sodium sulfate and concentrated. After fractional distillation, the 1-acetoxy-2- (4-phenoxyphenoxy) cyclopentane obtained is present as a colorless oil with a refractive index of n ²⁰ _D = 1.5560.

A solution of 1.68 g of potassium hydroxide dissolved in 20 ml of water is added dropwise to a solution of 6.24 g of 1-acetoxy-2- (4-phenoxyphenoxy) cyclopentane in 50 ml of ethanol at room temperature, and the mixture is then boiled for 3 hours on the reflux and evaporates after cooling on the rotary evaporator to 1/3 of the original volume. The residue is poured onto ice water, extracted with ether, the organic phase is washed three times with saturated sodium chloride solution, dried over sodium sulfate and concentrated on a rotary evaporator. Distillation of the residue gives the 2- (4-phenoxyphenoxy) -cyclopentan-l-ol as a colorless oil of k _P0.001 181-I85 °.

Example 6

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. Then 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

Example 7

Example 8

Preparation of the compound of the formula

12.1 g of triethylamine are added to a solution of 28.3 g of 2- (4-phenoxy) -phenoxy-cyclohexanol in 150 ml of anhydrous benzene, and 11.5 g of cyclopropanecarboxylic acid chloride are then added dropwise with stirring at 15-20.degree to. The reaction mixture is stirred for a further 24 hours at room temperature, then successively and repeatedly washed neutral with water, dilute hydrochloric acid, 10% sodium carbonate solution and finally with saturated sodium chloride solution. The organic phase is separated. Dried over sodium sulfate and freed from solvent in vacuo. The oily residue is further purified by chromatography on silica gel (eluent: methyl acetate-hexane 1: 4).

The compound of formula IV is obtained with a refraction of n ²⁰ _D : 1.5542.

The following connections are also made in an analogous manner:

Claims (19)

1. Etherified cycloalkanols of the formula

wherein X _{1 is} oxygen, sulfur or methylene. X _{2 is} oxygen or sulfur, A is an optionally substituted phenyl. rest and n represent an integer from 1 to 10. 2. Etherified cycloalkanols of the formula

where R is hydrogen or chlorine and n is the whole number 3 4 or 5. 3. (4-phenoxy-phenoxy) cyclopentan-1-ol. 4. 2- [4- (4-chlorophenoxy) phenoxy] cyclopentan-1-ol. 2- [4- (4-chlorophenoxy) phenoxy] -

6. Etherified cycloalkanols of the formula

wherein R represents hydrogen or chlorine and n represents the integers 3, 4 or 5. 7. 2- (4-phenylmercaptophenoxy)

8. 2- (4-phenylmercaptophenoxy) cyclohexan-1-ol. 9. 2- [4- (4-chlorophenylmercapto) -

tan-l-ol. 10. 2- [4- (4-chlorophenylmercapto) phenoxy] -

xan-l-ol. ll. Etherified cycloalkanols of the formula

wherein R represents hydrogen or chlorine and n represents the integers 3, 4 or 5. 12. 2- (4-benzylphenoxy) cyclopenten-1-ol. 13. 2- (4-benzylphenoxy) cyclohexan-1-ol. 14. Containing pharmaceutical preparations

claims 1-13

a carrier. 15. The use of the compounds claimed in claims 1-13 as hypolipidaemics. 16. Process for the preparation of etherified A cycloalkanols of the formula

wherein X _{1 represents} oxygen, sulfur or methylene, X _{2 represents} oxygen or sulfur, A represents an optionally substituted phenyl radical and n represents an integer from 1 to 10, characterized in that a) a compound of the formula

or a salt thereof, with a compound of the formula

where Y _{1 is} a free or reactive esterified hydroxyl group and Y _{2 is} an optionally protected hydroxyl group or Y ₁ and Y ₂ together are an epoxy group or a carboxyldioxy group of the formula -OC (0) 0-, and in a compound obtained an optionally present protective group splits off or b) in a compound of the formula

the keto group is reduced to the carbinol group in a manner known per se and, if desired, an available one

mixture into the individual isomers

17. Cyclopropanecarboxylic acid ester of the formula

where X _{1 is} oxygen, sulfur or methylene,

or sulfur, A one if appropriate. substituted phenyl radical, n is an integer from 1 to and with 10 and R ₁ , R ₂ , R ₂ and R ₄ each represent hydrogen, methyl or chlorine. Cyclopropanecarboxylic acid esters of the formula (VII) given in claim 17, in which A is phenyl, X ₁ and X ₂ oxygen and n, R ₁ , R ₂ , R ₃ and R _{4 have} the meaning given in claim 17. 19. Cyclopropanecarboxylic acid ester of the formula (VII) given in Claim 17, in which A is phenyl, X ₁ and X _{2 is} oxygen, R ₁ , R ₂ , R ₃ and R _{4 are} either hydrogen or methyl and n has the meaning given above. 20. Use of the cyclopropane carboxylic acid esters claimed in claims 17-19 as insecticides.