US3720676A - [4-(10,11-DIHYDRO-5H-DIBENZO[a,d]CYCLOHEPTEN-10-yL-1-PIPERAZINYL]-ALKYL]-3-ALKYL-2-IMIDAZOLIDINONES AS CNS DEPRESSANTS - Google Patents

[4-(10,11-DIHYDRO-5H-DIBENZO[a,d]CYCLOHEPTEN-10-yL-1-PIPERAZINYL]-ALKYL]-3-ALKYL-2-IMIDAZOLIDINONES AS CNS DEPRESSANTS Download PDF

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US3720676A
US3720676A US00061435A US3720676DA US3720676A US 3720676 A US3720676 A US 3720676A US 00061435 A US00061435 A US 00061435A US 3720676D A US3720676D A US 3720676DA US 3720676 A US3720676 A US 3720676A
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dihydro
dibenzo
methyl
piperazinyl
imidazolidinone
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W Schindler
A Zuest
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Novartis Corp
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Ciba Geigy Corp
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D233/28—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member 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
    • C07D233/30—Oxygen or sulfur atoms
    • C07D233/32—One oxygen atom

Definitions

  • ABSTRACT Compounds of the class of l-[2- and 3-[4-(l0,l1- dihydro-SH-dibenzo[a,d]cyclohepten-l0-yl)-lpiperazinyll-alkyl1-3-alkyl-2 imidazolidinone which can be substituted in 8-position by chloro, methyl or methoxy, and the pharmaceutically acceptable acid addition salts thereof, have a depressant effect on the central nervous system; pharmaceutical compositions comprising these compounds and a method of producing a depressant effect on the central nervous system of warm-blooded animals, are provided; an illustrative embodiment is l-[2-[4-(8-methyl-l0,ll-dihydro-Sl-ldibenzo[a,d]cyclohepten-l0-yl)-1-piperazinyl]-ethyl]- 3-methyl-2-imidazolidinone-bis-maleate.
  • X is hydrogen, chloro, methyl or methoxy
  • R is alkyl having one to four carbon atoms
  • R is hydrogen or methyl
  • n is theinteger 2 or 3; and the pharmaceutically acceptable acid addition salts thereof.
  • R can be the methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec.butyl or the tert.butyl group.
  • a compound of formula I is produced according to the invention by reacting a compound of formula II,
  • Suitable reactive esters of compounds of formula III are, e.g., halides, such as chlorides or bromides, also sulphonic acid esters, e.g., the methanesulphonic acid ester, or the 0- or p-toluenesulphonic acid ester.
  • esters are reacted with the free bases II preferably in the presence of a solvent.
  • Suitable solvents are those which are inert under the reaction conditions, e.g., hydrocarbons such as benzene, toluene or xylene; halogenated hydrocarbons such as chloroform; ethereal liquids such as ether or dioxane; as well as lower alkanones such as acetone, methyl ethyl ketone or diethyl ketone.
  • the reaction temperatures are between ca. 50 and preferably at the boiling point of the applied solvent.
  • one molecular equivalent of acid is split off.
  • This acid can be bound to excess base of formula II, or to the dibasic reaction product.
  • An acid-binding agent is, however, preferably added to the reaction mixture.
  • Suitable acid-binding agents are, e.g., alkali metal carbonates such as sodium or potassium carbonate, also tertiary organic bases such as, e.g., pyridine, triethylamine or N,N- diisopropylethylamine. Excess tertiary bases may also be used as solvent.
  • an alkali metal derivative thereof e.g., a sodium, potassium or lithium derivative
  • the formation of the alkali metal derivatives of the first reactant is preferably performed in situ, e.g., by the addition of at least one molecular equivalent of alkali metal hydride, alkali metal amide, or of an alkali metal organic compound, when initially one molecular equivalent of free base is used.
  • alkali metal hydride alkali metal amide
  • alkali metal organic compound e.g., sodium amide and lithium amide are used as alkali metal amides; sodium hydride as alkali metal hydrides; and phenyl lithium or butyl lithium as alkali metal organic compound.
  • 8- Methyl- 1 0-( l-piperazinyl)-l0,l l-dihydro-Sl-l-dibenzo [a,d]cycloheptene can be obtained by another process, e.g., as follows: Starting with 8-methyl-l0-chloro-l0,l l -dihydro-5H-dibenzo[a,d]cycloheptene, this is condensed in benzene with l-piperazinecarboxylic acid ethyl ester to 4-(8-methyI-l0,1l-dihydro-Sl-I-dibenzo [a,d]cyclohepten-l0-yl)-piperazine-l-carboxylic acid ethyl ester; the condensation product is subsequently hydrolyzed and decarboxylated by heating with potassium hydroxide in ethanol. Further starting materials of formula II can be produced analogously.
  • the second reactant of the process according to the invention are the reactive esters of compounds of formula lll.
  • these compounds for example, l-(2- chloroethyl)- and l-(3-chloropropyl)-3-methyl-2- imidazolidinone, as well as l-(2-chloroethyl)-3-butyl- Z-imidazolidinone are known, and can be produced by various processes. Further compounds of this type can be produced analogously.
  • R has the meaning given under formula I, or with an alkali metal derivative of such a compound; and, optionally, converting the reaction product with an inorganic or organic acid into an addition salt.
  • radical Y of formula IV is preferably chlorine or bromine.
  • the reaction according to the invention of the free bases of formula ll, or of their alkali metal derivatives, with the urea derivatives, or their alkali metal derivatives may be performed in the same solvents or diluents, and at the same reaction temperatures, as in the first process.
  • two molecular equivalents of hydrogen halide are split off, which can also be bound to the same acid-binding agents.
  • Both reactants are used as alkali metal derivatives, e.g., as sodium, potassium or lithium derivatives, preferably in situ, in the process according to the invention.
  • These alkali metal derivatives can be obtained analogously to the alkali metal derivatives of the first process.
  • a starting material which is embraced by formula IV is l-methyl- 3,3-bis-(2-chloroethyl)-urea which can be obtained, e.g., starting with diethanolamine. With l-methylisocyanate, the diethanolamine yields l-methyl-3,3-bis-(2 -hydroxyethyl)-urea, which reacts with thionyl chloride, whereby sulphur dioxide and hydrogen chloride are split off. Further starting materials of formula lV can be produced analogously.
  • Suitable reactive esters of compounds of formula V are, e.g. halides, such as chlorides or bromides, also sulphonic acid esters such as methane-sulphonic acid ester, 0- or p-toluenesulphonic acid ester, or o-chloroor p-chlorobenzenesulphonic acid ester.
  • reaction according to the invention of the free bases, or of their alkali metal derivatives, with the reactive esters can be performed in the same solvents or diluents, and at the same reaction temperatures, as in the first process.
  • one molecular equivalent of free base with one molecular equivalent of reactive ester one molecular equivalent of acid is split off, which can be bound to the same acid-binding agents as in the first process.
  • alkali metal derivatives eg sodium, potassium or lithium derivatives, preferably in situ, in the process according to the invention.
  • These alkali metal derivatives can be obtained analogously to the alkali metal deriva-' tives in the first process.
  • the compounds of formula I obtained using a process according to the invention are, optionally, subsequently converted, in the usual manner, into their addition salts with inorganic and organic acids.
  • a solution of a compound of formula I in an organic solvent is added the acid desired as salt component, or a solution of the acid.
  • organic solvents in which the formed salt is difficulty soluble are, e.g. methanol, acetone, methyl ethyl ketone, acetone/ethanol, methanol/ether or ethanol/ether.
  • the new active substances are administered orally, rectally or parenterally.
  • the dosage depends on the manner of administration, on the species, on the age, and on the individual condition.
  • the daily dosages of the free bases, or of pharmaceutically acceptable salts thereof vary between 0.15 mg/kg and 10.5 mg/kg for warm-blooded animals.
  • Suitable dosage units such as dragees, tablets, suppositories or ampoules, preferably contain 5-200 mg of an active substance according to the invention.
  • Dosage units for oral administration contain as active substance preferably between and 90 percent of a compound of formula I or of a pharmaceutically acceptable salt thereof. They are produced by combining the active substance, e.g., with solid pulverulent carriers such as lactose, saccharose, sorbitol, mannitol; starches such as potato starch, maize starch or amylopectin, also laminaria powder or citrus pulp powder; cellulose derivatives or gelatine, optionally with the addition of lubricants such as magnesium or calcium stearate, or polyethylene glycols, to form tablets or dragee cores.
  • solid pulverulent carriers such as lactose, saccharose, sorbitol, mannitol
  • starches such as potato starch, maize starch or amylopectin, also laminaria powder or citrus pulp powder
  • cellulose derivatives or gelatine optionally with the addition of lubricants such as magnesium or calcium stearate, or polyethylene glycols,
  • the dragee cores are coated, e.g., with concentrated sugar solutions which can also contain, e.g., gum arabic, talcum and/or titanium dioxide; or with a lacquer dissolved in readily volatile organic solvents or mixtures of solvents.
  • Dyestuffs can be added to these coatings, e.g., to distinguish between varying dosages of active substance.
  • Further dosage units suitable for oral administration are hard gelatine capsules, as well as soft closed capsules made from gelatine and a softener, such as glycerin.
  • the hard capsules preferably contain the active substance as a granulate, e.g. in admixture with fillers such as maize starch, and/or lubricants such as talcum or magnesium stearate, and optionally stabilizers such as sodium metabisulphite (Na,S,O or ascorbic acid.
  • the active substance is preferably dissolved or suspended in suitable liquids such as liquid polyethylene glycols, whereby stabilizers may also be added.
  • Suitable dosage units for rectal administration are, e.g., suppositories consisting of a combination of an active substance with a suppository base material.
  • Suitable suppository base materials are, e.g. natural or synthetic triglycerides, paraffin hydrocarbons, polyethylene .glycols, or higher alkanols.
  • gelatine rectal capsules consisting of a combination of the active substance with a base material.
  • Suitable as a base material are, e.g., liquid triglycerides, polyethylene glycols, or paraffin hydrocarbons.
  • Ampoules for parenteral administration especially intramuscular administration, preferably contain a water-soluble salt of an active substance in a concentration of preferably 0.5 5 percent, optionally together with suitable stabilizers and buffer substances, in aqueous solution.
  • a granulate is produced from 250 g of 1-[2-[4-(8- chloro-l0,11-dihydro-5H-dibenzo[a,d]cycloheptenl 0-yl)-1-piperazinyl]-ethyl]-3-methyl-2- imidazolidinone, 17590 g of lactose and the alcoholic solution of 10 g of stearic acid. After the granulate has been dried, it is mixed with 56.60 g of colloidal silicon dioxide, 165 g of talcum, 20 g of potato starch and 2.50 g of magnesium stearate; the mixture is then pressed into 10,000 dragee cores.
  • a suppository foundation mixture is prepared from 2.5 g of l-[2-[4-(8-methyl-l0,l 1-dihydro-5H- dibenzo[a,d]cyclohepten-10-yl)-l-piperazinyl]-ethyl- ]-3-methyl-2-imidazolidinone and 167.5 g of adeps solidus; from this mixture are poured 100 suppositories each containing 25 mg of active substance.
  • dihydro-5H-dibenzo[a,d]cyclohepten-10-y1)-1- piperazinyl]-ethyl]-3-methyl-2-imidazolidirionedihydrochloride in one liter of water is filled into 1000 ampoules, and sterilized.
  • An ampoule contains a 2.5 percent solution of 25 mg of active substance.
  • EXAMPLE 1 a A suspension of 1 1.7 g (0.040 moles) of 8-methyl- 10-( l-piperazinyl)-l0,l l-dihydro-Sl-l-dibenzo [a,d]cycloheptene, 8.46 g (0.044 moles) of 1-(2- chloro-ethyl)-3-methyl-2-imidazolidinone and l 1.0 g (0.08 moles) of potassium carbonate in 80 ml of diethyl ketone is refluxed for 24 hours. The reaction mixture is cooled and filtered off under suction; the precipitate is then washed with acetone, and the filtrate concentrated in vacuo. The residue is taken up in benzene and water, the aqueous phase separated, and the organic phase extracted with l-n methanesulphonic acid.
  • the crystalline residue is recrystallized from ethyl/acetate/pentane.
  • the pure 8- methyl-10-( l-piperaziny1)-10,1 l-dihydro-5H-dibenzo[ a,d]cycloheptene melts at 95-96; yield 4.4 g, 30 percent of the theoretical value; M.P. of the bis-methane sulphonate l94l96.
  • EXAMPLE 2 a Analogously to Example 1 is obtained the following final product: from 11.7 g (0.040 moles) of 8-methyl-l0-(1-piperazinyl)-l0,11dihydro-Sl-l-dibenzo[a,d]cycloheptene and 8.36 g (0.044 moles) of 1-(3-ehloropropyl)-3-ethyl-2- imidazolidinone is obtained: 1-[3-[4-(10,11-dihydro- 5H-dibenzo[a,d]cyclohepten-l0-yl)-1-piperazinyl]- propyl]3-ethyl-2-imidazolidinone; M.P. of the bismaleate, which is produced analogously to Example 1 a), is 113l yield 21.7 g; 80 percent of the theoretical value.
  • EXAMPLE 3 a An amount of 11.9 g (0.049 moles) of 8-methyllO-chl0r0-l0,l l-dihydro-5l-l-dibenzo[a,d]cycloheptene is dissolved in 50 ml of abs. benzene; this solution is then added dropwise at room temperature to a solution of 15.6 g (0.073 moles) of 1-[2-(1-piperazinyl)- ethyl]-3methyl-Z-imidazolidinone in 30 ml of abs. benzene; and the reaction mixture is refluxed for 20 hours.
  • the cooled solution is poured on to 200 ml of ice water; to this are added 20 ml of 2-n sodium hydroxide solution, and the organic phase is separated.
  • the organic phase is washed with water, and extracted with ml of l-n methanesulphonic acid solution.
  • the pH of the aqueous extract is adjusted with concentrated sodium hydroxide solution to 13.
  • the precipitated crude base is extracted with benzene; the benzene solution is washed with water, dried over magnesium sulphate, and concentrated in vacuo.
  • the residue is recrystallized from ethyl acetate/petroleum ether.
  • the 8-methyl-l0-chloro-10,ll-dihydro-SH-dibenzo [a,d]cycloheptene required as starting material is produced as follows:
  • EXAMPLE 4 An amount of 2.92 g (0.01 mole) of 8-methyl-l0-( lpiperazinyl)-10,l l-dihydro-5H-dibenzo[a,d] cycloheptene is refluxed with 2.80 g (0.014 moles) of crude lmethyl-3,3-bis-(2-chloroethyl)urea and 3.6 g (0.026 moles) of anhydrous potassium carbonate in 36 ml of diethyl ketone for 12 hours. A further 2.4 g (0.018 moles) of potassium carbonate are added after 4 hours reaction time, and the same amount is again added after 8 hours reaction time.
  • the reaction mixture is cooled, diluted with ether, filtered, and the filtrate concentrated in vacuo.
  • the residue (5.22 g) is taken up in ether; the solution is then extracted with l-n hydrochloric acid, the acidified extract washed with ether, and excess sodium carbonate added.
  • the precipitated free base is taken up in ether; the ether solution is then washed with water, dried over sodium sulphate, and concentrated by evaporation.
  • the residue is chromatographed on a column of silica gel (Merck, grain size 0.05 0.2 mm), which has been impregnated with 0.5-n sodium hydroxide solution. Chloroform is used as the eluting agent.
  • the product is an oily compound, which is dissolved in acetone, to which an ethereal solution of hydrochloric acid is added until congo-acid reaction sets in.
  • a solid precipitates which is filtered by suction and recrystallized from ethanol/ethylacetate containing a small amount of diethylether, whereby the pure 1-[3- [4-(8-chloro-10,l 1-dihydro-5H-dibenzo[a,d]cyclohepten-l0-yl)- l -piperazinyl]-propyl]-3-butyl-2- imidazolidinone-dihydrochloride is obtained as a twothird hydrate. M.P. 195 197.
  • the 1-(3-chloropropyl)-3-butyl-2-imidazo1idinone required as starting material may be prepared by the following procedure:
  • the mono-maleate melts at l72- 173.
  • This bis-maleate (from absolute ethanol/diethylether melts at 144 146.
  • the 8-methoxy-l0-(l-piperazinyl)-10,ll-dihydro- H-dibenzo[a,d]cycloheptene required as starting material may be obtained by the following procedure: 48.0 g (0.2 mol) of S-methoxy-lO-hydroxy-SH- dibenzo[a,d]-cycloheptene are dissolved in 200 ml of chloroform, 20.7 g (0.26 mol) of pyridine are added to which solution, in the course of 45 minutes at 0 5, a solution of 28.4 g (0.24 mol) of thionylchloride in 100 ml of benzene are dropped. The reaction mixture is stirred at 45 50 for 2 hours while nitrogen gas is fed in and subsequently poured into V1 liter of ice-water.
  • EXAMPLE 8 a Analogously to Example la), 30.8 g (0.01 mol) of crude 8-methoxy-l0-( l-piperazinyl)-l0,l l-dihydro- 5H-dibenzo-[a,dlcycloheptene, obtained according to Example 7c) and d) respectively, and 21.0 g (0.11 mol) of l-(2-chloroethyl)-isopropyl-2-imidazolidinone are reacted to produce l-[2-[4-(8-methoxy-10,l l-dihydro- 5l-l-dibenzo[a,d]cyclohepten-l0-yl)-1-piperazinyl]- ethyl]-3-isopropyl-2-imidazolidinone.
  • the l-(2-chloroethy1)-isopropyl-2-imidazolidinone required as starting material may be obtained by the following procedure:
  • the product is fractionated in a high vacuum, whereby the pure 1-(2-chloroethyl)-3-isopropyl-2- imidazolidinone distills at 88 90/0.02 Torr; n 1.4855.
  • I diethanol is converted by oxalic acid into the di-oxalate. hydrate.
  • M.P. 120 125 (from ethylacetate/ethanol/diet hylether.
  • the bis-maleate. l4 hydrate melts at 125 127.
  • the 1-isopropyl-3 ,3-bis-( 2-chloro-ethyl)-urea required as starting material is prepared by the following method:
  • the 1-isopropyl-3,3-bis-(2-chloroethyl)-urea is ob tained as an oily product.
  • the bis-maleate melts at ethanol/diethyl-ether).
  • the 5-methyl-10-(l-piperazinyl)-10,1l-dihydro-SH- dibenzo[a,d]cycloheptene is prepared in the following manner:
  • the organic layers are dried over magnesium sulphate and the solvents volatilized in vacuo at 45.
  • the oily residue represents the 5-methyl-10-chloro-10,1l-dihydro-SH- dibenzo[a,d]cycloheptene which is used for the subsequent reaction.
  • the residue represents the 5-methyl-10-(1-piperazinyl)-l0,ll-dihydro-5H-dibenzo[a,d]cycloheptene in crude state.
  • the dioxalate. hydrate (precipitated from acetone/diethylether is recrystallized from ethyl acetate containing a small amount of an ethanol/diethylether mixture) melts at 162 168.
  • the dioxalate. as hydrate melts at 120 125 (from ethyl acetate and a small amount of ethanol/diethylether).
  • R is hydrogen or methyl; and Yield: 8.5 g 38 percent of the theoretical value.
  • n is the integer 2 or 3; The di-oxalate.
  • HS hydrate melts at 198 200 (from a 5 and the pharmaceutically acceptable acid addition salts little absolute ethanol/ethylacetate/diethylether). thereof.
  • a compound according to claim 1 which is l-[2- 1.
  • a compound of formula I [4-(8-methyl-l0,l l-dihydro-5H-dibenzo[ "g' c a,d]cyclohepten-lO-yl)-l-piperazinyl]-ethyl]-3- N 1 l methyI-Z-irnidazolidinone, and a pharmaceutically acceptable acid addition salt thereof.
  • Gib-CH H 3 3.
  • a compound according to claim 1 which is 1-[2- O [4-(8-chloro-l0,l l-dihydro-H-dibenzo[a,dlcyclohepten-.l0-yl)-l-piperazinyl]-ethyl]-3-methyl-2- l5 imidazolidinone, and a pharmaceutically acceptable acid addition salt thereof.

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US00061435A 1969-08-11 1970-08-05 [4-(10,11-DIHYDRO-5H-DIBENZO[a,d]CYCLOHEPTEN-10-yL-1-PIPERAZINYL]-ALKYL]-3-ALKYL-2-IMIDAZOLIDINONES AS CNS DEPRESSANTS Expired - Lifetime US3720676A (en)

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CH1212069A CH513189A (de) 1969-08-11 1969-08-11 Verfahren zur Herstellung von neuen Imidazolidinonderivaten

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Cited By (2)

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EP0040310A3 (de) * 1980-04-12 1982-02-03 Hoechst Aktiengesellschaft Fungizide, heterocyclisch substituierte Thioglykolsäureanilide, Verfahren zu ihrer Herstellung und diese enthaltende Schädlingsbekämpfungsmittel
US4376773A (en) * 1980-03-08 1983-03-15 Basf Aktiengesellschaft 10-Substituted 5-cyanomethylene-10,11-dihydro-dibenzo-[a,d]-cycloheptenes, their preparation, and therapeutic agents containing these compounds

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FR2278340A1 (fr) * 1974-07-17 1976-02-13 Delalande Sa Nouveau derive de la n-(trimethoxy-3,4,5 cinnamoyl) piperazine, ses sels d'addition d'acides, son procede de preparation et son application en therapeutique
US4878236A (en) * 1988-12-02 1989-10-31 Ray Donald K Automatic emergency locator system and method

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US3320247A (en) * 1964-02-28 1967-05-16 Asta Werke Ag Chem Fab Phenthiazine compounds
US3496182A (en) * 1965-12-28 1970-02-17 Rhone Poulenc Sa Substituted 10- or 11-piperazino dibenzo-cycloheptadiene derivatives
US3646037A (en) * 1969-03-28 1972-02-29 Ciba Geigy Corp Imidazolidinone derivatives
US3646039A (en) * 1968-06-20 1972-02-29 Geigy Chem Corp 4 5-dihydrothieno(2 3-b)(1)benzothiepin derivatives as cns depressants

Patent Citations (4)

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Publication number Priority date Publication date Assignee Title
US3320247A (en) * 1964-02-28 1967-05-16 Asta Werke Ag Chem Fab Phenthiazine compounds
US3496182A (en) * 1965-12-28 1970-02-17 Rhone Poulenc Sa Substituted 10- or 11-piperazino dibenzo-cycloheptadiene derivatives
US3646039A (en) * 1968-06-20 1972-02-29 Geigy Chem Corp 4 5-dihydrothieno(2 3-b)(1)benzothiepin derivatives as cns depressants
US3646037A (en) * 1969-03-28 1972-02-29 Ciba Geigy Corp Imidazolidinone derivatives

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4376773A (en) * 1980-03-08 1983-03-15 Basf Aktiengesellschaft 10-Substituted 5-cyanomethylene-10,11-dihydro-dibenzo-[a,d]-cycloheptenes, their preparation, and therapeutic agents containing these compounds
EP0040310A3 (de) * 1980-04-12 1982-02-03 Hoechst Aktiengesellschaft Fungizide, heterocyclisch substituierte Thioglykolsäureanilide, Verfahren zu ihrer Herstellung und diese enthaltende Schädlingsbekämpfungsmittel

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DE2039722A1 (de) 1971-02-25
IE34450L (en) 1971-02-11
FR2068484A1 (enrdf_load_stackoverflow) 1971-08-27
ES382621A1 (es) 1972-11-16
NL7011529A (enrdf_load_stackoverflow) 1971-02-15
AU1859270A (en) 1972-02-17
ZA705502B (en) 1971-04-28
ES382618A1 (es) 1972-11-16
DE2039722B2 (de) 1973-08-02
DK127117B (da) 1973-09-24
CH513191A (de) 1971-09-30
GB1325354A (en) 1973-08-01
AT294080B (de) 1971-11-10
NO128070B (enrdf_load_stackoverflow) 1973-09-24
FR2068484B1 (enrdf_load_stackoverflow) 1974-02-22
DE2039722C3 (de) 1974-03-07
CH513189A (de) 1971-09-30
IL35087A (en) 1973-01-30
ES382619A1 (es) 1972-11-16
IL35087A0 (en) 1970-10-30
CH513190A (de) 1971-09-30
US3798325A (en) 1974-03-19
BE754642A (fr) 1971-02-10

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