DK158655B - PROCEDURE FOR THE PREPARATION OF ESTERS OF (A) -CYCLOPROPANCARBOXYLIC ACIDS, WHICH ARE RACEMIC OR OPTICALLY ACTIVE WITH 1R, 3R, 1S, 3S, 1R, 3S- OR 1S, 3R CONFIGURATION, AND ALSO (R) -configuration - Google Patents
PROCEDURE FOR THE PREPARATION OF ESTERS OF (A) -CYCLOPROPANCARBOXYLIC ACIDS, WHICH ARE RACEMIC OR OPTICALLY ACTIVE WITH 1R, 3R, 1S, 3S, 1R, 3S- OR 1S, 3R CONFIGURATION, AND ALSO (R) -configuration Download PDFInfo
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- DK158655B DK158655B DK401677A DK401677A DK158655B DK 158655 B DK158655 B DK 158655B DK 401677 A DK401677 A DK 401677A DK 401677 A DK401677 A DK 401677A DK 158655 B DK158655 B DK 158655B
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- 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
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Description
iin
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Opfindelsen angår en særlig fremgangsmåde til fremstilling af estere af cyclopropancarboxylsyrer og optisk 25 aktivt allethrolon ud fra allethrolonsulfonater med antipodal konfiguration.This invention relates to a particular process for preparing esters of cyclopropane carboxylic acids and optically active allethrolone from allethrolone sulfonates of antipodal configuration.
Opfindelsen angår nærmere betegnet en fremgangsmåde til fremstilling af estere med den i krav l's indledning angivne almene formel I, og denne fremgangsmåde er ejen-30 dommelig ved det i krav l's kendetegnende del anførte.More particularly, the invention relates to a process for the production of esters of the general formula I set forth in claim 1, and this method is peculiar to the characterizing part of claim 1.
Denne fremgangsmåde betegnes fremgangsmåde cC,This process is called process cC,
Det salt af (A)-cyclopropancarboxylsyre, der benyttes ved fremgangsmåden ifølge opfindelsen, vælges fortrinsvis fra en gruppe bestående af alkalimetalsaltene, jordalkali-35 metalsaltene, de tertiære basers salte og ammoniumsaltet.The salt of (A) -cyclopropane carboxylic acid used in the process of the invention is preferably selected from a group consisting of the alkali metal salts, the alkaline earth metal salts, the tertiary bases salts and the ammonium salt.
Det er særlig fordelagtigt som salt af (A)-cyclo-propancarboxylsyré at benytte et alkalimetalsalt.It is particularly advantageous as salt of (A) -cyclopropane carboxylic acid to use an alkali metal salt.
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Ifølge en foretrukket udførelsesform for fremgangsmåden ifølge opfindelsen er saltet af (A)-cyclopropancarboxylsyre natrium-eller kaliunsaltet.According to a preferred embodiment of the process of the invention, the salt of (A) -cyclopropane carboxylic acid is the sodium or potassium salt.
Blandt de syrer, som fremgangsmåden ifølge opfindelsen kan 5 anvendes, skal især nævnes 2,2-diirethyl-3-(2,-methyl-l,-propenyl)--cyclopropan-l-carboxylsyrerne, 2,2-dimethyl-3-(2*,2’-dichlorvinyl)--cyclopropan-1-carboxylsyreroe, 2,2 -dimethy1-3-(2,2-dibromvinyl)--oyclopropan-l-carboxylsyrerne, 2,2-dimethyl-3-(2 *,2 *-difluorvinyl)--cyclopropan-l-carboxylsyrerne, 2,2-dimethyl-3-(2’-methyl-3'-methoxy-10 -1*(E)-propeny3)-cyclopropan-l-carboxylsyrerne, 2,2-dimethyl-3-(21 - -etbyl-3*-oxo-1*-butenyl)-cyclopropan-l-carboxylsyrerne, 2,2-dime-thyl-3-(cyclcpentylidenmethyl)-c3fclopropan-l-carboxylsyrerne, 2,2--dimethyl-3-(2’-oxo-31-oxacyclopentylidenmethyl)-cyclopropan-l-carb-oxylsyrerne, 2,2-dimethyl-3-(2 *-oxo-3‘-thiacyolopentylidenmethyl)-15 -cyclopropan-l-carboxylsyrerne, idet de ovennævnte syrer kan være raceniske eller optisk aktive, og specielt de i eksemplerne i den eksperimentelle del benyttede syrer.Among the acids to which the process according to the invention can be used are especially mention 2,2-diethyl-3- (2, -methyl-1,1-propenyl) -cyclopropane-1-carboxylic acids, 2,2-dimethyl-3- (2 *, 2'-dichlorovinyl) - cyclopropane-1-carboxylic acid, 2,2-dimethyl-3- (2,2-dibromovinyl) oyclopropane-1-carboxylic acids, 2,2-dimethyl-3- (2 *, 2 * -Difluorovinyl) -cyclopropane-1-carboxylic acids, 2,2-dimethyl-3- (2'-methyl-3'-methoxy-10 -1 * (E) -propenyl) -cyclopropane-1-carboxylic acids , 2,2-Dimethyl-3- (21-Ethyl-3 * -oxo-1 * -butyl) -cyclopropane-1-carboxylic acids, 2,2-dimethyl-3- (cyclopentylidenemethyl) -cyclopropane-1-carboxylic acid the carboxylic acids, 2,2-dimethyl-3- (2'-oxo-31-oxacyclopentylidene methyl) -cyclopropane-1-carboxylic acids, 2,2-dimethyl-3- (2 * -oxo-3'-thiacyolopentylidene methyl) - The 15-cyclopropane-1-carboxylic acids, the aforementioned acids being racenic or optically active, and especially the acids used in the examples in the experimental part.
Det organiske opløsningsmiddel eller den blanding af organiske opløsningsmidler, bvori kondensationen af allethrolonsulfonatet 20 og saltet af (A)-cyelopropancarboxylsyre udføres ifølge opfindelsen, vælges fortrinsvis blandt dimethylformamid, hexamethylphosphorotri-amid, dimethylsulfoxid, dimethoxyethan, aoetonitril, aliphatiske ketoner med 3-6 carbonatomer, alkanoler, monocykliske aromatiske carbonhydrider eller en blanding af disse opløsningsmidler.The organic solvent or mixture of organic solvents wherein the condensation of the allethrolone sulfonate 20 and the salt of (A) -cyclopropane carboxylic acid is carried out according to the invention is preferably selected from dimethylformamide, hexamethylphosphorotriamide, dimethylsulfoxide, dimethoxyethane, dimethoxyethane, alkanols, monocyclic aromatic hydrocarbons or a mixture of these solvents.
25 Ifølge foretrukne udførelsesformer for fremgangsmåden iføl ge opfindelsen er dette opløsningsmiddel hexamethylphosphorotriamid, dimethylsulfoxid eller dimethylformamid,According to preferred embodiments of the process of the invention, this solvent is hexamethylphosphorotriamide, dimethylsulfoxide or dimethylformamide,
San kan med fordel som opløsningsmiddelblanding benytte en blanding af toluen og dimethylsulfoxid.San may advantageously use as a solvent mixture a mixture of toluene and dimethyl sulfoxide.
30 Ifølge andre foretrukne udførelsesformer for fremgangsmåden ifølge opfindelsen er den ved fremgangsmåden ifølge opfindelsen benyttede opløsningsmiddelblanding en blanding af toluen og sekundær eller tertiær alkanol med 4-6 carbonatomer, specielt en blanding af toluen og tert.-butanol.According to other preferred embodiments of the process according to the invention, the solvent mixture used in the process according to the invention is a mixture of toluene and secondary or tertiary alkanol having 4-6 carbon atoms, especially a mixture of toluene and tert-butanol.
35 Sulfonaterne af optisk aktivt allethrolon med den almene formel II, der benyttes som udgangsprodukt ved fremgangsmåden ifølge opfindelsen, er beskrevet i fransk patentansøgning 76-19087 af 23/6 1976.The sulfonates of optically active allethrolone of the general formula II used as the starting product of the process according to the invention are described in French patent application 76-19087 of 23/6 1976.
Bisse sulfonater fremstilles, idet man i et organisk opløsningsmiddel eller en blanding af organiske opløsningsmidler i nærvæ-Pieces of sulfonates are prepared by mixing in an organic solvent or a mixture of organic solvents in the presence of
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relse af et basisk middel omsætter sulfonsyrechloridet med den almene formel IVof a basic agent, the sulfonic acid chloride of the general formula IV is reacted
X*S02C1 (IV) hvor Xf har samme betydning som ovenfor, dvs. betegner en alkylgrup-5 pe med 1-3 carbonatomer såsom methyl, ethyl, propyl eller isopropyl, en phenylgruppe, som eventuelt er substitueret i p-stillingen med en methylgruppe eller med et fluor-, chlcr- eller bromatom, med optisk aktivt allethrolon med (R)- eller (S)-konfiguration.X * SO 2 Cl (IV) where Xf has the same meaning as above, i. represents an alkyl group having 1-3 carbon atoms such as methyl, ethyl, propyl or isopropyl, a phenyl group optionally substituted at the β-position with a methyl group or with a fluorine, chlorine or bromine atom, with optically active allethrolone having (R) or (S) configuration.
Det basiske middel, hvori man udfører denne kondensation, 10 er fortrinsvis en tertiær base og navnlig triethylamin.The basic agent in which this condensation is carried out is preferably a tertiary base and especially triethylamine.
let organiske opløsningsmiddel eller den blanding af organiske opløsningsmidler, som benyttes til udførelse af denne kondensation, vælges fortrinsvis blandt aliphatiske ketoner med 3-6 carbonatomer, monocykliske aromatiske carbonhydrider, oxidethere og 15 chlorerede opløsningsmidler.light organic solvent or the mixture of organic solvents used to perform this condensation is preferably selected from aliphatic ketones of 3-6 carbon atoms, monocyclic aromatic hydrocarbons, oxide ethers and 15 chlorinated solvents.
Fordelagtige arbejdsmåder består i som opløsningsmiddel at benytte enten acetone eller toluen,Advantageous working methods consist of using either acetone or toluene as a solvent,
Sulfonsyrechlorideme IV, der benyttes, er fortrinsvis methansulfonylchlorid eller p-toluensulfonylchlorid.The sulfonic acid chlorides IV used are preferably methanesulfonyl chloride or p-toluenesulfonyl chloride.
20 Eksempler på fremstilling af sulfonat af optisk aktivt al lethrolon er angivet nedenfor i den eksperimentelle del.Examples of the preparation of sulfonate of optically active all lethrolone are given below in the experimental section.
Ifølge en foretrukket udførelsesform for fremgangsmåden ifølge opfindelsen benytter man allethrolonsulfonatet i opløsning uden at isolere det fra det reaktionsmilieu, hvori det er dannet.According to a preferred embodiment of the process according to the invention, the allethrolone sulfonate is used in solution without isolating it from the reaction environment in which it is formed.
25 Man benytter da fortrinsvis som opløsningsmiddel til frem stilling af sulfonatet af optisk aktivt allethrolon et monocyklisk aromatisk carbonhydrid.Preferably, then, as a solvent is used to prepare the sulfonate of optically active allethrolone a monocyclic aromatic hydrocarbon.
Saltet af cyclopropancarboxylsyren fremstilles efter gængse metoder ved indvirkning af syre på den tilsvarende base i et orga-30 nisk opløsningsmiddel.The salt of the cyclopropane carboxylic acid is prepared by conventional methods by the action of acid on the corresponding base in an organic solvent.
Ifølge en foretrukket udførelsesform for opfindelsen benytter man saltet af cyclopropancarboxylsyre i opløsning uden isolering fra det reaktionsmilieu, hvori det er dannet.According to a preferred embodiment of the invention, the salt of cyclopropane carboxylic acid is used in solution without isolation from the reaction environment in which it is formed.
Man benytter da fortrinsvis til fremstilling af saltet af 35 (A)-cyclopropancarboxylsyre et opløsningsmiddel eller en blanding af opløsningsmidler, som vælges blandt dimethylformamid, dimethyl-sulfoxid, hexamethylphosphorotriamid, dimethoxyethan, acetonitril, aliphatiske ketoner med 3-6 carbonatomer, alkanoler, monocykliske aromatiske carbonhydrider eller en blanding af disse opløsningsmidler,Preferably, then, in the preparation of the salt of 35 (A) -cyclopropane carboxylic acid, a solvent or mixture of solvents selected from dimethylformamide, dimethylsulfoxide, hexamethylphosphorotriamide, dimethoxyethane, acetonitrile, aliphatic ketones of 3-6 carbon atoms, alkanols, alkanols, alkanes, hydrocarbons or a mixture of these solvents,
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Fremgangsmåden ifølge opfindelsen anvendes især i det tilfælde, hvor (A)-cyclopropancarboxylsyren er 2,2-dimethyl-3R-(2t--methyl-l’-propenylJ-cyclopropan-lR-carboxylsyre, 2,2-dimethyl-3S--(2'-methyl-11-propenyl)-cyclopropan-lR-carboxylsyre, 2,2-dimethyl-5 -3R-(cyclopentylidenmethyl)-cyclopropan-lR-carboxylsyre, (IR,trans)--2,2-dimethyl-3-(2',21-dichlorvinyl)-cyclopropan-l-carboxylsyre, (IR,trans)-2,2-dimetfcy1-3-(2’,2 *-difluorvinyl)-cyclopropan-l-carboxylsyre og (3R,cis)-2,2-dimethyl-3-(2',2’-difluorvinyi)-cyclopropan--1-carboxylsyre.The process according to the invention is used especially in the case where the (A) -cyclopropane carboxylic acid is 2,2-dimethyl-3R- (2t-methyl-1'-propenylJ-cyclopropane-1R-carboxylic acid, 2,2-dimethyl-3S). (2'-methyl-11-propenyl) -cyclopropane-1R-carboxylic acid, 2,2-dimethyl-5 -3R- (cyclopentylidenemethyl) -cyclopropane-1R-carboxylic acid, (IR, trans) - 2,2-dimethyl 3- (2 ', 21-Dichlorovinyl) -cyclopropane-1-carboxylic acid, (1R, trans) -2,2-dimethyl-3- (2', 2 * -difluoro-vinyl) -cyclopropane-1-carboxylic acid and (3R, cis) -2,2-dimethyl-3- (2 ', 2'-difluorvinyi) cyclopropane - 1-carboxylic acid.
10 Ret er kendt, at estere af oyclopropancarboxylsyrer og op tisk aktivt allethrolon med (S)-konfiguration har en insekticid aktivitet, som er langt større end virkningen af estere af cyclopropan-carboxylsyrer og allethrolon, som har (R)-konfiguration eller er racemisk med (R,S)-konfiguration.It is well known that esters of oyclopropane carboxylic acids and optically active allethrolone with (S) configuration have an insecticidal activity far greater than the action of esters of cyclopropane carboxylic acids and allethrolone which have (R) configuration or are racemic with (R, S) configuration.
15 Til fremstilling af esterne af oyclopropancarboxylsyrer og optisk aktivt allethrolon med (S)-konfiguration har den eneste hidtil kendte metode bestået i at esterificere en cyclopropancarboxyl-svre eller et af dens funktionelle derivater med optisk aktivt allethrolon med (S)-konfiguration. Optisk aktivt allethrolon med (S)-kon- 20 figuration har længe været utilgængeligt på industrielt plan. Rer eksisterer nu fremgangsmåder til spaltning af racemisk (R,S)-allethrolon, som gør det muligt at opnå allethrolon med (S)-konfiguration, se fransk patentskrift 2.166.503, med vægtudbytter, som naturligvis ikke kan overstige 50$ i forhold til det racemiske ud- 25 gangsallethrolon.To prepare the esters of oyclopropane carboxylic acids and optically active allethrolone with (S) configuration, the only known method has been to esterify a cyclopropane carboxylic acid or one of its functional derivatives with optically active allethrolone with (S) configuration. Optically active allethrolone with (S) configuration has long been unavailable at the industrial level. There are now methods for cleavage of racemic (R, S) -allethrolone enabling allethrolone to be obtained with (S) configuration, see French Patent 2,166,503, with weight yields which, of course, cannot exceed $ 50 relative to the racemic starting salethrolone.
Ret optisk aktive allethrolon med (R)-konfiguration hidrørende fra denne spaltning udgør altså et· produkt uden praktisk anvendelighed, og det har stor industriel interesse at kunne gøre brug af dette allethrolon med (R)-konfiguration igen.Thus, optically active allethrolone with (R) configuration resulting from this cleavage constitutes a product of no practical utility, and it is of great industrial interest to be able to make use of this allethrolone with (R) configuration again.
30 Renne fremgangsmåde ifølge opfindelsen frembyder en særlig fordelagtig løsning på dette vigtige industrielle problem. I virkeligheden gør den det muligt i et eneste simpelt reaktionstrin direkte ud fra allethrolon med (R)-konfiguration at opnå esterne af cyclopropancarboxylsyrerne med (S)-konfiguration med et højt udbytte.The pure process according to the invention presents a particularly advantageous solution to this important industrial problem. In fact, in a single simple reaction step directly from the allethrolone with (R) configuration, it is possible to obtain the esters of the high yield (S) cyclopropane carboxylic acids.
35 Ren frembyder den fordel i forhold til de allerede kendte fremgangsmåder ikke som mellemprodukt at ende med et isoleret allethrolon med (S)-konfiguration, som man derpå må esterificere med den passende cyclopropancarboxylsyre (som man i forvejen må omdanne til syrechlorid). Fremgangsmåden ifølge opfindelsen frembyder naturligvis en særlig interesse, når udgangsallethrolonet er allethro-Pure does not offer the advantage over the already known methods of ending up with an isolated allethrolone with (S) configuration, which must then be esterified with the appropriate cyclopropane carboxylic acid (which must be converted into acid chloride in advance). Of course, the process of the invention presents a particular interest when the starting alethrolone is allethroic.
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Ion med (R)-konfiguration*Ion with (R) configuration *
Desuden er fremgangsmåderne til spaltning af allethrolon ikke kvantitative og giver i praksis ved siden af det ønskede allethrolon med (S)-konfiguration en blanding af allethrolon med (E)~ 5 -konfiguration og allethrolon med (S)-konfiguration, som er rigt på allethrolon med (R)-konfiguration.In addition, the methods of cleavage of allethrolone are not quantitative and in practice, in addition to the desired allethrolone with (S) configuration, yields a mixture of allethrolone with (E) ~ 5 configuration and allethrolone with (S) configuration which is rich in allethrolone with (R) configuration.
Efter omdannelse af disse blandinger til sulfonat får man en blanding af sulfonat af allethrolon med (R)-konfiguration og sulfonat af allethrolon med (S)-konfiguration, som er rigt på allethrc-10 Ion med (H)-konfiguration.After converting these mixtures into sulfonate, a mixture of sulfonate of allethrolone with (R) configuration and sulfonate of allethrolone with (S) configuration rich in allethrc-10 ion with (H) configuration are obtained.
Fremgangsmåden ifølge opfindelsen benyttes på disse blandin ger.The process of the invention is applied to these mixtures.
Opfindelsen angår altså en fremgangsmåde ifølge den almene fremgangsmåde a, som er ejendommelig ved, at sulfonatet af optisk 15 aktivt allethrolon, der benyttes som udgangsprodukt, udgøres af en blanding af sulfonat af allethrolon med (S)-konfiguration og sulfonat af allethrolon med (R)-konfiguration, som er rigt på sulfonat med (R)-konfiguration.The invention thus relates to a process according to the general process a, characterized in that the sulfonate of optically active allethrolone used as a starting product is constituted by a mixture of sulfonate of allethrolone with (S) configuration and sulfonate of allethrolone with (R ) configuration which is rich in sulfonate with (R) configuration.
Fremgangsmåden ifølge opfindelsen har en uventet karakter.The method according to the invention has an unexpected character.
20 Skønt man allerede kendte nogle eksempler på inversion af optisk aktive aliphatiske alkoholer ved indvirkning af et acetat på tosylatet af alkoholen, var inversionen af asymmetricentret af allethrolon skønt frembydersde en betydelig industriel interesse aldrig blevet realiseret under anvendelse af denne type af fremgangs-25 måden.Although some examples of inversion of optically active aliphatic alcohols by the action of an acetate on the tosylate of the alcohol were already known, the inversion of the asymmetric center of allethrolone, although of considerable industrial interest, was never realized using this type of method.
Vellykketheden af en sådan inversionsfremgangsmåde i tilfælde af allethrolon var i virkeligheden på forhånd yderst tvivlsom, først og fremmest fordi adgangen til allethrolonsulfonaterne frem-byder vanskeligheder. Således er det kendt, at man ved behandlingen 30 af allethrolon med methansulfonylchlorid i nærværelse af en svag base som pyridin får det chlorerede derivat og ikke sulfonatet.Indeed, the success of such an inversion method in the case of allethrolone was highly questionable in the first place, primarily because access to the allethrolone sulfonates presents difficulties. Thus, it is known that the treatment of allethrolone with methanesulfonyl chloride in the presence of a weak base such as pyridine gives the chlorinated derivative and not the sulfonate.
Allethrolonsulfonaterne, således som de er beskrevet i opfindelsen, er skrøbelige produkter, som er følsomme over for varme i nærværelse af uorganiske eller organiske baser, som får dem til 35 at tabe sulfonylgruppen og fører til epaltningsprodukter ved Diels--Alder's reaktionThe allethrolone sulfonates, as described in the invention, are fragile products which are sensitive to heat in the presence of inorganic or organic bases which causes them to lose the sulfonyl group and lead to epaling products by Diels - Alder's reaction
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„,/CC"/ CC
(ikke isolerbar) j|(not insulable) j |
Disse sulfonater er ligeledes følsomme over for tilstedevæ- 10 reisen af hydrochlorider af baser såsom hydrochloridet af triethyl-amin, som medfører dannelsen af det ehlorerede derivat.These sulfonates are also sensitive to the presence of hydrochlorides of bases such as the hydrochloride of triethylamine which results in the formation of the ehlorated derivative.
Fremstillingen af de i opfindelsen beskrevne allethrolon-sulfonater gør det følgelig nødvendigt, at de nævnte vanskeligheder afhjælpes ved passende løsninger, hvilket vil sige, at reaktio- 1 *5 nen udføres ved lav temperatur under begrænset alkaliske betingelser, og at man benytter et reaktionsopløsningsmiddel, hvori det tri-ethylaminhydrochlorid, som dannes i løbet af sulfoneringen, uopløse-liggøres, hvilket gør det uegnet til at reagere hurtigt med alle-throlonsulfonatet, ? ΩAccordingly, the preparation of the allethrolone sulfonates described in the invention necessitates that the said difficulties be remedied by suitable solutions, i.e., the reaction is carried out at low temperature under limited alkaline conditions and the use of a reaction solvent is used. wherein the triethylamine hydrochloride formed during the sulphonation is insoluble, which makes it unsuitable to react rapidly with the all-throlone sulphonate, Ω
Reaktionen af allethrolonsulfonatet med et cyclopropancarb-oxylsyresalt frembyder ligeledes flere risikomomenter: - Dels udviklingen af sulfonatet i retning af dannelsen af spaltningsprodukter som følge af den alkalinitet, som hidføres af cyclopropancarboxylsyresaltet,The reaction of the allethrolone sulfonate with a cyclopropane carboxylic acid salt also presents several risks: - Firstly, the development of the sulfonate towards the formation of cleavage products due to the alkalinity imparted by the cyclopropane carboxylic acid salt,
2 S2 S
- dels en ufuldstændig epimerisering, som ville føre til en delvis racemisering af allethrolonets asymmetricenter.- partly an incomplete epimerization, which would lead to partial racemization of the asymmetric center of allethrolone.
Fremgangsmåden ifølge opfindelsen gør det muligt på bemærkelsesværdig måde at reducere de frygtede sidereaktioner og fører med meget store udbytter (både ud fra et kemisk og et optisk synspunkt) 30 til de rene produkter.The process of the invention makes it possible to remarkably reduce the dreaded side reactions and leads with very large yields (both from a chemical and an optical point of view) to the pure products.
Ved fremgangsmåden ifølge opfindelsen kan følgende forbindelser fremstilles: - 2,2-dimethyl-3R-(cyclopentylidenmethyl)-cyclopropan-lS--earboxylsyre-(3)-allethrolonester, 35 - 2,2-dimethyl-3S-(21,2f-dichlorvinyl)-cyclopropan-lR-carb- oxylsyre-(S)-allethrolonester eller (lR,trans)-2,2-dimethyl-3-(2 * ,2*--diehlorvinyl)-cyolopropan-l-earboxylsyre-(S)-allethrolonester, - 2,2-dimethyl-33-(21,2 f-difluorvinyl)-cyclopropan-lR-carb~ oxylsyre-(S)-allethrolonester eller (IR,trans)-2,2-dimethyl-3-(2’,21 --difluorvinyl)-cyclopropan-l-carboxyisyre-(S)-allethrolonester ogBy the process of the invention, the following compounds can be prepared: - 2,2-dimethyl-3R- (cyclopentylidenemethyl) -cyclopropane-1S - earboxylic acid (3) -allethrolone ester, 2,2-dimethyl-3S- (21,2f dichlorovinyl) -cyclopropane-1R-carboxylic acid (S) -allethrolone ester or (1R, trans) -2,2-dimethyl-3- (2 *, 2 * -dichlorovinyl) -cyolopropane-1-earboxylic acid (S ) -allethrolone ester, - 2,2-dimethyl-33- (21,2 f-difluorovinyl) -cyclopropane-1R-carboxylic acid (S) -allethrolone ester or (IR, trans) -2,2-dimethyl-3- (2 ', 21-Difluorovinyl) -cyclopropane-1-carboxylic acid (S) -allethrolone ester and
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- 2,2-dimethyl-3R-(2',2’-difluorvinyl)-cyclopropan-lR-carb- oxylsyre-(S)-allethrolonester eller (IR,cis )-2,2-dimethyl-3-(2 f,2 * — -difluorvin;;,l)-cyelopropan-l-carboxylsyre-(3 )-allethrolonester,- 2,2-dimethyl-3R- (2 ', 2'-difluorovinyl) -cyclopropane-1R-carboxylic acid (S) -allethrolone ester or (IR, cis) -2,2-dimethyl-3- (2 , 2 * - -Difluorovin ;; 1) -cyelopropane-1-carboxylic acid (3) -allethrolone ester,
Rer insekticide aktivitet af de fire ovennævnte 5 forbindelser er vist i en undersøgelse nedenfor.Insecticidal activity of the four above-mentioned compounds is shown in a study below.
Således bar disse produkter vist sig at have en knock-down--evne (eller evne til at slå insekterne ned), som ligger særdeles . højt, medens de besidder en god letal virkning.Thus, these products were found to have a knock-down ability (or ability to knock down the insects), which is extremely valuable. high, while possessing a good lethal effect.
De finder navnlig anvendelse i husholdningen. De kan lige-10 ledes benyttes i landbruget, Navnlig i dette sidste tilfælde kan man benytte dem i forbindelse med andre pyrethrinoide forbindelser. Ren insekticide virkning af disse produkter har f.eks, kunnet påvises ved forsøg med knock-down-aktivitet eller ved forsøg med letal virkning på stuefluer samt ved forsøg på Aedes aegypti, 15 I dette sidste tilfælde har man benyttet dem, idet man har inkorporeret dem i røgudviklende produkter.They are particularly applicable in the household. They can also be used in agriculture, especially in this latter case they can be used in conjunction with other pyrethrinoid compounds. Pure insecticidal activity of these products has been demonstrated, for example, by tests with knock-down activity or by tests with lethal effect on houseflies and by experiments with Aedes aegypti. 15 In this last case they have been used, having incorporated those in smoke developing products.
De fire ovennævnte forbindelser kan med fordel anvendes i forbindelse med et synergistisk middel såsom piperonylbutoxid eller N-(ethylheptyl-2-)-bicyclo-(2,2,l)-5-hepten-2,3-dicarboxiimid,The four above compounds may advantageously be used in conjunction with a synergistic agent such as piperonylbutoxide or N- (ethylheptyl-2-) bicyclo- (2,2,1) -5-hepten-2,3-dicarboxyimide,
Den eller de aktive bestanddele kan eventuelt tilsættes et eller flere andre pesticide midler. Disse produkter kan foreligge i form af pudder, granulater, suspensioner, emulsioner, opløsninger, opløsninger til aerosoler, brændbare strimler, lokkemad eller andre præparater, som normalt anvendes til nyttiggørelse af denne 25 slags forbindelser,The active ingredient (s) may optionally be added to one or more other pesticidal agents. These products may be in the form of powders, granules, suspensions, emulsions, solutions, solutions for aerosols, combustible strips, baits or other preparations usually used to recover this kind of compound,
Foruden den aktive bestanddel indeholder disse præparater \In addition to the active ingredient, these preparations contain \
8 DK 158655 B8 DK 158655 B
normalt et bærestof og/eller et ikke-ionisk overfladeaktivt stof, som desuden sikrer en ensartet fordeling af de bestanddele, som udgør blandingen. Det benyttede bærestof kan være en væske såsom vand, ethanol, carbonhydrider eller andre organiske opløsningsmid -5 ler, en mineralolie eller animalsk eller vegetabilsk olie, et pudder såsom talkum, ler, silicater, kiselgur eller et fast brændbart stof såsom pyrethrumkvas.usually a carrier and / or a nonionic surfactant which furthermore ensures a uniform distribution of the constituents constituting the mixture. The carrier used may be a liquid such as water, ethanol, hydrocarbons or other organic solvents, a mineral oil or animal or vegetable oil, a powder such as talc, clay, silicates, diatomaceous earth or a solid combustible material such as pyrethrum quas.
Disse insekticide præparater indeholder fortrinsvis 0,01-95 vægtprocent aktiv bestanddel.These insecticidal compositions preferably contain 0.01-95% by weight of active ingredient.
10 Anvendelsen af de fire ovennævnte forbindelser i form af røgudviklende præparater er særlig interessant.10 The use of the four above-mentioned compounds in the form of smoke-producing compositions is particularly interesting.
Disse produkter kan især udgøres af en insekticid spiral indeholdende fortrinsvis 0,01-10 vægtprocent af i det mindste en af de fire ovennævnte forbindelser som aktiv bestanddel og et indif-15 ferent brændbart bærestof, som især udgøres af f.eks. pyrethrumkvas, pulver af bladene af Machilus thumbergii, pulver af pyrethrum-stilk, pulver af cedernåle, træpulver, f.eks. fyrresavsmuld, stivelse og pulver af skaller af kokosnød.In particular, these products may be constituted by an insecticidal coil containing preferably 0.01 to 10% by weight of at least one of the four above-mentioned compounds as an active ingredient and an inert flammable carrier which is constituted in particular by e.g. pyrethrum kvass, powder of the leaves of Machilus thumbergii, powder of pyrethrum stalk, powder of cedar needles, wood powder, e.g. pine sawdust, starch and powder of coconut shells.
De kan ligeledes fås, idet man inkorporerer i det mindste en 20 af de fire forbindelser i en koncentration på 0,01-95 vægtprocent i et ubrændbart fibrøst substrat, og idet man anbringer det således opnåede røgpræparat i et opvarmningsapparat, f.eks. et elektrisk myggeudryddelsespræparat, som har til formål at fordampe den aktive bestanddel, hvilket giver anledning til en fordampning, som kan 25 forlænges efter ønske.They can also be obtained by incorporating at least one of the four compounds at a concentration of 0.01-95% by weight in an incombustible fibrous substrate, and placing the thus obtained smoke preparation in a heating apparatus, e.g. an electric mosquito extermination composition which aims to evaporate the active ingredient, giving rise to an evaporation which can be extended as desired.
Man kan således til opnåelse af et sådant præparat fremstille en forstøvbar olie indeholdende fortrinsvis 0,01-95 vægtprocent af i det mindste en af de nævnte forbindelser, idet denne olie kan gennemvæde vægen i en lampe og underkastes forbrænding, hvilket li-30 geledes bevirker fordampning af den aktive bestanddel, 2.2- dimethyl-3S-(2f,2’-difluorvinyl)-cyclopropan-lR-carbox-ylsyre-(S)-allethrolonester eller (lEjtransJ^^-dimethyl^-^*^*--difluorvinyl)-cyclopropan~l-carboxylsyre-(S)-allethrolonester og 2.2- dimethyl-3D-(2',2'-difluorvinyl)-cyclopropan-lR-carbox-35 ylsyre-(S)-allethrolonester eller (111,018)-2,2-(3111^1^1-3-(2^2^ -difluorvinyl)-cyclopropan-l-carboxylsyre-(S)-allethrolonester har en særlig interessant aktivitet, når de benyttes i form af røgudviklende præparater,Thus, to obtain such a composition, an atomizable oil containing preferably 0.01-95% by weight of at least one of said compounds can be prepared, this oil being able to soak the wick in a lamp and subject to combustion, which also causes evaporation of the active ingredient, 2,2-dimethyl-3S- (2f, 2'-difluorovinyl) -cyclopropane-1R-carboxylic acid (S) -allethrolone ester or (1 H ) -cyclopropane-1-carboxylic acid (S) -allethrolone ester and 2,2-dimethyl-3D- (2 ', 2'-difluorovinyl) -cyclopropane-1R-carboxylic acid (S) -allethrolone ester or (111,018) -2 , 2- (3111 ^ 1 ^ 1-3- (2 ^ 2 ^ -difluorovinyl) -cyclopropane-1-carboxylic acid (S) -allethrolone ester has a particularly interesting activity when used in the form of smoke-generating preparations,
Nedenstående eksempler illustrerer fremgangsmåden ifølge opfindelsen.The following examples illustrate the method of the invention.
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Eksempel 1.Example 1.
2.2-d imethy 1-3 R-( 21 -methyl-1 * -propenyl) -cyclopropan-lR-oarboxyl-syre-2-allyl-5-methyl-4R-hydroxy-2-cyclopent-l-on eller d-trans--ohrvsanthemins.vre-(R)-alle throlones ter ud fra methansulfonat af 5 (S)-allethrolon, I 33 ml hexamethylphosphorotriamid indfører man 12,5 g me-thansulfonsyre-(S)-allethrolonester, tilsætter 9*65 g natriumsalt af d-trans-chrysantheminsyre, omrører i 10 minutter, tilsætter en blanding af 1 li natriumhydroxid opløsning, vand og n-heptan, rører 10 om, fraskiller den organiske fase ved dekantering, ekstraherer den vandige fase med heptan, forener de organiske faser, vasker dem, tørrer dem og får 12,94 g d-trans-chrysantheminsyre-(R)-allethrolon-ester,2,2-dimethyl 1-3 R- (21-methyl-1 * -propenyl) -cyclopropane-1R-oreboxylic acid-2-allyl-5-methyl-4R-hydroxy-2-cyclopent-1-one or d- trans - ohranthanthemic acid (R) -all throlones ter from methanesulfonate of 5 (S) -allethrolone, Into 33 ml of hexamethylphosphorotriamide 12.5 g of methanesulfonic acid (S) -allethrolone ester are added, 9 * 65 g sodium salt of d-trans-chrysanthemic acid, stirring for 10 minutes, adding a mixture of 1 L sodium hydroxide solution, water and n-heptane, stirring 10, separating the organic phase by decantation, extracting the aqueous phase with heptane, combining the organic phases , wash them, dry them and get 12.94 g of d-trans-chrysanthemic acid (R) -allethrolone ester,
Cirkulær diohroisme (dioxan); 15 Vendepunkt 345 nm Δε = - 1,18 max 332 nm Δε = - 2,41 max 321 nm Δε = - 2,73 vendepunkt 310 nm Δε = - 2,08 max 230 nm Δε = +15,9 20 Methansulfonsyre-(S)-allethrolonesteren, der benyttes, kan fremstilles på følgende måde:Circular Diohroism (dioxane); Turning Point 345 nm Δε = - 1.18 max 332 nm Δε = - 2.41 max 321 nm Δε = - 2.73 turning point 310 nm Δε = - 2.08 max 230 nm Δε = +15.9 Methanesulfonic acid - ( The S) -allethrolone ester used can be prepared as follows:
Man opløser 7,35 g (S)-allethrolon i 7,5 ml acetone, afkøler til -15°C, tilsætter 8,4 ml triethylamin og derefter langsomt 4,3 ml methansulfonylchlorid opløst i 11 ml acetone, omrører i 15 25 minutter, hælder reaktionsblandingen i en blanding af 23 il 1 N saltsyre, 56 ml vand og 23 ml methylenchlorid, omrører i 15 minutter, fraskiller ved dekantering den organiske fase, ekstraherer den vandige fase med methylenchlorid, forener de organiske faser, vasker dem, tørrer dem, inddamper dem til tørhed og får 12,5 g methansul-30 fonsyre-(S)-allethrolonester i rå tilstand, som umiddelbart benyttes til kondensationen i eksempel 1.Dissolve 7.35 g of (S) -allethrolone in 7.5 ml of acetone, cool to -15 ° C, add 8.4 ml of triethylamine and then slowly 4.3 ml of methanesulfonyl chloride dissolved in 11 ml of acetone, stir for 15 minutes , pour the reaction mixture into a mixture of 23 µl of 1N hydrochloric acid, 56 ml of water and 23 ml of methylene chloride, stir for 15 minutes, separate by decanting the organic phase, extract the aqueous phase with methylene chloride, combine the organic phases, wash them, dry them , evaporates them to dryness to obtain 12.5 g of crude methane sulfonic acid (S) -allethrolone ester, which is used immediately for the condensation of Example 1.
Natriumsaltet af chrysantheminsyre, der benyttes i eksempel 1, kan fremstilles på følgende måde: I en opløsning af 16,8 g 2,2-dimethyl-3R-(2?-methyl-1'-pro-35 penyl)-cyclopropan-lR-carboxylsyre i 50 ml acetone indfører man den fornødne mængde 10 N vandig natriumhydroxidopløsning til opnåelse af phenolphthaleins omslag, isolerer ved frasugning den dannede udfældning, vasker den, tørrer den og får 18,6 g natriumsalt af 2,2--d imethy 1-3 R-( 2'-methyl-1'-propenyl)-cyclopropan-lR-carboxylsyre, som umiddelbart benyttes til kondensation i eksempel 1.The sodium salt of chrysanthemic acid used in Example 1 can be prepared as follows: In a solution of 16.8 g of 2,2-dimethyl-3R- (2β-methyl-1'-propenyl) -cyclopropane-1R -carboxylic acid in 50 ml of acetone introduces the required amount of 10 N aqueous sodium hydroxide solution to obtain the phenolphthalein's cover, isolates by suctioning the precipitate formed, it is washed, dried and obtained 18.6 g of sodium salt of 2.2-d imethy-1 3 R- (2'-methyl-1'-propenyl) -cyclopropane-1R-carboxylic acid, which is used immediately for condensation in Example 1.
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Eksempel 2.Example 2.
2 > 2 -dimethy l-3R-( 2 1 -methyl-1 * -propenyl) -cyclopropan-lR-carboxylsyre--(S)-allethrolb.nester ud fra methansulfonsyre-(R)-allethrolonester. Idet man arbejder i analogi med eksempel 1 ud fra methan-5 sulfonsyre-(R)-allethrolonester, får man med samme udbytte 2,2-di-methyl-3R-(2 f -methyl-1’-propenyl)-cyclopropan-lR-carboxylsyre-(S)- OO r\ -allethrolonester, or- -50° (o = 5$, toluen)*2> 2-Dimethyl 1-3R- (2L-methyl-1 * -propenyl) -cyclopropane-1R-carboxylic acid (S) -allethrolone ester from methanesulfonic acid (R) -allethrolone ester. Working in analogy to Example 1 from methanesulfonic acid (R) -allethrolone ester, 2,2-dimethyl-3R- (2-methyl-1'-propenyl) -cyclopropane-2 1R-Carboxylic Acid (S) - OO r -allethrolone ester, or- -50 ° (o = 5 $, toluene) *
Eksempel 5.Example 5
10 2.2-d imeth.vl-3R-( 2«-methyl-1' -propenyl) -cyclopropan-lR-carboxylsyre- -(R)-allethrolon ud fra methansulfons.yre-(S)-allethrolont2,2-Dimethyl-3R- (2 '-methyl-1' -propenyl) -cyclopropane-1R-carboxylic acid - (R) -allethrolone from methanesulfonic acid (S) -allethrolone
Til den nedenfor opnåede opløsning af kaliumsalt ud fra 110 g d-trans-chrysantheminsyxe sætter man hurtigt ved 15°C en opløsning af 165 g metbansulfonsyre-(S)-allethrolon i 350 ml dimetfcyl-15 sulfoxid, omrører i 24 timer ved 20°C, tilsætter ICO ml heptan og 500 ml vand, rører om, fraskiller ved dekantering den organiske fase, ekstraherer den vandige fase med heptan, forener hept&nfaserne, vasker dem med en 1 E vandig natriumhydroxidopløsning og derefter med vand, ekstraherer de vandige vaskevæsker med heptan, forener hep-20 tanfraktionerne, tørrer dem, inddamper dem til tørhed ved destilla tion og får 169 g 2,2-dimethyl-3R-(2t-methyl-l,-propenyl)-eyclo- ΛΛ _ propan-lR-carboxylsyre-(R)-allethrolonester, oT-^ = +11° (c = 1$, ethanol).To the solution of potassium salt obtained from 110 g of d-trans-chrysanthemic acid below, a solution of 165 g of methanesulfonic acid (S) -allethrolone in 350 ml of dimethyl sulfoxide is stirred rapidly at 24 ° C. C, add ICO ml of heptane and 500 ml of water, stir, separate by decanting the organic phase, extracting the aqueous phase with heptane, combining the heptane phases, washing them with a 1 E aqueous sodium hydroxide solution and then with water, extracting the aqueous washing liquids with heptane , the heptane fractions are combined, dried, evaporated to dryness by distillation to obtain 169 g of 2,2-dimethyl-3R- (2t-methyl-1,1-propenyl) -eyclo-ΛΛ-propane-1R-carboxylic acid. (R) -allethrolone ester, oT- = + 11 ° (c = 1 $, ethanol).
U.V.spektrum (ethanol)i 25 Max ved 225 nm, E^ = 600, max ved 295 nm, = 3.U.V. spectrum (ethanol) in 25 Max at 225 nm, E ^ = 600, max at 295 nm, = 3.
Cirkulær dichroisme (dioxan):-max 230 nm Δε = +15 vendepunkt 310 nm Δε = - 2,15 max 320 nm Δε = - 2,70 30 vendepunkt 330 nm Δε = - 2,43 vendepunkt 345 nm Δε = - 1,14Circular dichroism (dioxane): - max 230 nm Δε = +15 turning point 310 nm Δε = - 2.15 max 320 nm Δε = - 2.70 30 turning point 330 nm Δε = - 2.43 turning point 345 nm Δε = - 1, 14
Methansulfonsyre-(S)-allethrolonester, der benyttes som udgangsprodukt i eksempel 3, kan fremstilles på følgende måde: I 200 ml acetone opløser man 200 g (S)-allethrolon med kp.Methanesulfonic acid (S) -allethrolone ester used as the starting product in Example 3 can be prepared as follows: 200 g of acetone dissolve 200 g (S) -allethrolone with b.p.
35 115°C/0,6 mm Hg og -- +14° (o = 1,3$# chloroform), U.V.absorp115 ° C / 0.6 mm Hg and - + 14 ° (o = 1.3 $ # chloroform), U.V.absorp
tion (ethanol): max ved 229 nm, = 810, tilsætter ved -15°Ction (ethanol): max at 229 nm, = 810, add at -15 ° C
114,5 ml triethylamin, rører om, indfører mellem 0 og 5°C en opløsning af 86,5 g methansulfonylchlcrid i 180 ml vandfri acetone i løbet af ca. 20 minutter, omrører i 20 minutter ved -10°C, indfører ved -15°C 200 ml methylenchlorid og derpå en blanding af 50 ml114.5 ml of stirred triethylamine introduces between 0 and 5 ° C a solution of 86.5 g of methanesulfonyl chloride in 180 ml of anhydrous acetone over approx. 20 minutes, stirring for 20 minutes at -10 ° C, introducing at -15 ° C 200 ml of methylene chloride and then a mixture of 50 ml
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vandig 18,8 E saltsj/re, rører om, fraskiller ved dekantering den organiske fase, ekstraherer den vandige fase med methylenchlorid, forener de organiske faser, vasker dem med vand, ekstraherer de vandige vaskevæsker med methylenchlorid, forener methylenchloridopløs -5 ningerne, vasker dem, tørrer dem, inddamper dem til tørhed under formindsket tryk og får 165 g methansulfonat af (S)-allethrolon i rå tilstand, som umiddelbart benyttes til kondensationen i eksempel 3 med kaliumsaltet af d-trans-chrysantheminsyre.aqueous 18.8 U hydrochloric acid, stir, separate by decanting the organic phase, extracting the aqueous phase with methylene chloride, combining the organic phases, washing them with water, extracting the aqueous washing liquids with methylene chloride, combining the methylene chloride solutions, washing drying them, evaporating them to dryness under reduced pressure and obtaining 165 g of crude (S) -allethrolone methane sulfonate which is used immediately for the condensation of Example 3 with the potassium salt of d-trans-chrysanthemic acid.
Opløsningen af kaliumsaltet af d-trans-chrysantheminsyre, 10 der benyttes i eksempel 3, kan fremstilles på følgende måde: I en blanding af 100 ml dimethylsulfoxid og 30 ml vand indfører man 110 g 2,2-dimethyl-3R-(2,-methyl-l’-propenyl)-cyclopropan--lR-carboxylsyre, = +36,7° (dimet hylf ormamid), tilsætter 2 dråber alkoholisk opløsning af phenolphthalein, tilsætter ved 15°C den for-15 nødne mængde 50° Bé vandig kaliumhydroxidopløsning til opnåelse af omslag til rosa af phenolphthalein (ca, 49,5 ml), tilsætter 0,7 ml vand og får en opløsning indeholdende kaliumsaltet af 2,2-dimethyl--3R-(21-methy1-1’-propenyl)-eyclopropan-lR-carboxylsyre.The solution of the potassium salt of d-trans-chrysanthemic acid 10 used in Example 3 can be prepared as follows: Into a mixture of 100 ml of dimethylsulfoxide and 30 ml of water 110 g of 2,2-dimethyl-3R- (2 methyl-1'-propenyl) -cyclopropane - 1R-carboxylic acid, = + 36.7 ° (dimethylformamide), add 2 drops of alcoholic solution of phenolphthalein, add at 15 ° C the required amount of 50 ° B aqueous potassium hydroxide solution to obtain the phenolphthalein pink wrapper (approx. 49.5 ml), add 0.7 ml of water and obtain a solution containing the potassium salt of 2,2-dimethyl-3R- (21-methyl-1'-propenyl) -eyclopropan-R-carboxylic acid.
20 Eksempel 4.Example 4.
2«2-d imethyl-5R-(2>-methyl-lt-propen.vl)-c.vclopropan-lR-carboxvlsvre--2-allyl-3-methyl-4S-hydroxy-2-c.yclopent-l-onester eller d-trans--chrysanthemins.yre-(S)-allethrolonester ud fra methansulfonat af (R)-allethrolon.2'-2-Dimethyl-5R- (2> -methyl-1t-propenyl) -cyclopropane-1R-carboxylic acid - 2-allyl-3-methyl-4S-hydroxy-2-cyclopent-1 -one ester or d-trans - chrysanthemic acid (S) -allethrolone ester from methanesulfonate of (R) -allethrolone.
25 Til en opløsning af kaliumsaltet af d-trans-chrysanthemin- syre fremstillet ovenfor ud fra 11 g d-trans-chrysantheminsyre sætter man ved 15°C en opløsning af 16 g methansulfonat af (R)-alle-throlon i 35 ml dimethylsulfoxid, omrører i 24 timer ved 20°C, tilsætter vand og heptan, omrører, fraskiller ved dekantering den or-30 ganiske fase, genekstraherer den vandige fase med heptan, forener de organiske faser, vasker dem med 1 E natriumhydroxidopløsning og derefter med vand, tørrer dem, inddamper dem til tørhed og får 16,1 g 2,2-dimethyl-3R-(2’-methyl-l'-propenyl)-cyclopropan-lR-carb-oxylsyre-(S)-allethrolonester.To a solution of the potassium salt of d-trans-chrysanthemic acid prepared above from 11 g of d-trans-chrysanthemic acid is added at 15 ° C a solution of 16 g of methanesulfonate of (R) -altrolone in 35 ml of dimethyl sulfoxide. stir for 24 hours at 20 ° C, add water and heptane, stir, separate by decanting the organic phase, re-extract the aqueous phase with heptane, combine the organic phases, wash them with 1 E sodium hydroxide solution and then with water, dry evaporating them to dryness to give 16.1 g of 2,2-dimethyl-3R- (2'-methyl-1'-propenyl) -cyclopropane-1R-carboxylic acid (S) -allethrolone ester.
35 U.V.spektrum (ethanol):Spectrum (ethanol):
Max 227-228 nm e = 17.400Max 227-228 nm e = 17,400
Deraf udleder man en kemisk renhed af allethrolonchrysanthe-mat på 94$.From this, a $ 94 chemical purity of allethrolone chrysanthemum is deduced.
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Cirkulær dichroisme (dioxan):Circular dichroism (dioxane):
Max 227,5 nm Δε = -24,5 vendepunkt 310 nm Δε = + 1,87 max 320 nm Δε = + 2,40 5 max 332 nm Δε = + 2,16 vendepunkt 345 nm Δε = + 1,02Max 227.5 nm Δε = -24.5 turning point 310 nm Δε = + 1.87 max 320 nm Δε = + 2.40 max 332 nm Δε = + 2.16 turning point 345 nm Δε = + 1.02
Denne dichroisme svarer til: 90# (S)-allethrolonester 4# (R)-allethrolonester plus: 6$ urenheder (ifølge U.V«spektrum), 10 - som ikke påvirker den cirkulære dichroisme.This dichroism corresponds to: 90 # (S) -allethrolone ester 4 # (R) -allethrolone ester plus: 6 $ impurities (according to U.V «spectrum), 10 - which do not affect circular dichroism.
Den optiske renhed af esterei er altså 90 : (90+4) = oa.95,8#. Værdien for stereoomdannelse fra (R)-allethrolon til (S)-al-lethrolonester er altså kvantitativ 95,8 : 95,5.The optical purity of ester egg is thus 90: (90 + 4) = oa.95.8 #. The value for stereo conversion from (R) -allethrolone to (S) -all-lethrolone ester is thus quantitative 95.8: 95.5.
15 Det som udgangsprodukt i eksempel 4 benyttede methansulfonat af (R)-allethrolon kan fremstilles på følgende måde:The methane sulfonate of (R) -allethrolone used as the starting product in Example 4 can be prepared as follows:
Man benytter et (R)-allethrolon med = -15° +1° (c = 1#, chloroform), som ifølge sin cirkulære dichroisme indeholder 95,5# (R)-isomer og 4,5# (S)-isomer.An (R) -allethrolone with = -15 ° + 1 ° (c = 1 #, chloroform) is used, which according to its circular dichroism contains 95.5 # (R) isomer and 4.5 # (S) isomer .
20 Man opløser 10 g (R)-allethrolon i 20 ml acetone, afkøler til -15°C, tilsætter 11,4 ml triethylamin og derefter under opretholdelse af temperaturen under 0°C en blanding af 18 ml acetone og 5,8 ml methansulfonylchlorid, omrører i 20 minutter til -10°C, indfører methylenchlorid, syrner ved tilsætning af en vandig opløsning 25 af 1 IT saltsyre, rører om, fraskiller den organiske fase ved dekantering, ekstraherer atter den vandige fase med methylenchlorid, forener methylenchloridfaserne, vasker dem med vand, tørrer dem, inddamper dem under formindsket tryk og får 16 g methansulfonat af (R)-allethrolon i rå tilstand, som umiddelbart benyttes i eksempel 4. 30 Opløsningen af kaliumsalt af d-trans-chrysantheminsyre, der benyttes i eksempel 4, kan fremstilles på følgende måde:20 g of (R) -allethrolone are dissolved in 20 ml of acetone, cool to -15 ° C, 11.4 ml of triethylamine is added and then, while maintaining the temperature below 0 ° C, a mixture of 18 ml of acetone and 5.8 ml of methanesulfonyl chloride , stirring for 20 minutes to -10 ° C, introducing methylene chloride, acidifying by adding an aqueous solution 25 of 1 IT hydrochloric acid, stirring, separating the organic phase by decantation, again extracting the aqueous phase with methylene chloride, combining the methylene chloride phases, washing them with water, drying them, evaporating them under reduced pressure to give 16 g of crude (R) -allethrolone methane sulphonate immediately used in Example 4. The solution of potassium salt of d-trans-chrysanthemic acid used in Example 4, can be prepared as follows:
Man opløser 11 g (XR,3R)-d-trans-chrysantheminsyre i 10 ml dimethylsulfoxid, tilsætter 3 ml vand og en dråbe alkoholisk opløsning af phenolphthalein og indfører kaliumhydroxidopløsning ind-35 til omslag af phenolphthalein.11 g (XR, 3R) -d-trans-chrysanthemic acid is dissolved in 10 ml of dimethyl sulfoxide, 3 ml of water and a drop of alcoholic solution of phenolphthalein are added and potassium hydroxide solution is introduced to cover phenolphthalein.
13 DK 158655B13 DK 158655B
Eksempel 5, 2,2-dimethyl-3R-(2 »-methyl-l’ -propenyl)-oyolopropan«-lR-carbox.vlsyre--(S)-allethrolonester ud fra methansulfonat af (R)-allethrolon (uden Isolering af det som mellemprodukt dannede methansulfonat).Example 5, 2,2-Dimethyl-3R- (2'-methyl-1'-propenyl) -oyolopropane '- 1R-carboxylic acid - (S) -allethrolone ester from methanesulfonate of (R) -allethrolone (without Isolation of the methane sulfonate formed as intermediate).
5 Ved 20°C indfører man hurtigt den opløsning af methansulfo nat af (R)-allethrolon, der er fremstillet nedenfor ud fra 250 g (R)-allethrolon i opløsningen af kaliumsaltet af d-trans-chrysanthe-minsyre fremstillet nedenfor ud fra 293 g d-trans-chrysantheminsyre, omrører i 24 timer ved 20°C, tilsætter i løbet af 10 minutter ved 10 oa, 20°C 750 ml vand, rører om, fraskiller ved dekantering den organiske fase , ekstraherer den vandige fase med toluen, vasker de forenede organiske faser med vand, med en vandig 1 H natriumhydroxid -opløsning og med vand, tørrer over magnesiumsulfat, filtrerer, tilsætter 250 g aluminiumoxid, rører om, filtrerer, inddamper til tør-15 hed under formindsket tryk og får 400,7 g 2,2-dimethyl-3R-(2’-me-thyl-1’-propenyl)-cyclopropan-lR-carboxylsyre-(S)-allethrolonester, a2° = -49° (c = 5#, toluen).At 20 ° C, the solution of methanesulfonate of (R) -allethrolone prepared below from 250 g of (R) -allethrolone is rapidly introduced into the solution of the potassium salt of d-trans-chrysanthemic acid prepared below from 293 g of d-trans-chrysanthemic acid, stirring for 24 hours at 20 ° C, adding over 10 minutes at 10 ° C, 20 ° C 750 ml of water, stirring, separating by decanting the organic phase, extracting the aqueous phase with toluene, wash the combined organic phases with water, with an aqueous 1 H sodium hydroxide solution and with water, dry over magnesium sulfate, filter, add 250 g of alumina, stir, filter, evaporate to dryness under reduced pressure to give 400.7 g of 2,2-dimethyl-3R- (2'-methyl-1'-propenyl) -cyclopropane-1R-carboxylic acid (S) -allethrolone ester, α2 ° = -49 ° (c = 5 #, toluene).
Den som udgangsprodukt i eksempel 5 benyttede opløsning af methansulfonat af (R)-allethrolon fremstilles på følgende måde: 20 Man opløser 250 g (R)-allethrolon, a2^ = -10,5° (c = 10$, chloroform), i 750 ml toluen, indfører i løbet af ca, 10 minutter ved -13°C 225 g methansulfonylchlorid og derefter i løbet af ca, 2 timer ved -8°C en opløsning af 217,5 g triethylamin i 200 ml toluen, onrører i 15 minutter, tilsætter ved -5°C i løbet af ca, 30 minutter 25 1000 ml vand, rører om, fraskiller ved dekantering den organiske fase, ekstraherer den vandige fase med toluen, forener toluenfaserne, vasker dem med vand, ekstraherer de vandige vaskevæsker med toluen, forener toluenopløsningeme, tørrer dem og får en toluenopløsning af methansulfonat af (R)-allethrolon, som umiddelbart benyttes 30 i eksempel 5.The solution of methanesulfonate of (R) -allethrolone used as the starting product in Example 5 is prepared as follows: 250 g of (R) -allethrolone, α2 = -10.5 ° (c = 10 $, chloroform), are dissolved in 750 ml of toluene, introduces 225 g of methanesulfonyl chloride over about 10 minutes at -13 ° C and then, over about 2 hours at -8 ° C, a solution of 217.5 g of triethylamine in 200 ml of toluene, stirring for 15 minutes. minutes, add at -5 ° C over about 30 minutes 25 ml of water, stir, separate by decanting the organic phase, extracting the aqueous phase with toluene, combining the toluene phases, washing them with water, extracting the aqueous washing liquids with toluene, combines the toluene solutions, dries them and obtains a toluene solution of methanesulfonate of (R) -allethrolone, which is immediately used in Example 5.
Opløsningen af kaliumsalt af d-trans-ohrysantheminsyre, der benyttes i eksempel 5, kan fremstilles på følgende måde: I 500 ml dimethylsulfoxid opløser man 293 g 2,2-dirnethyl--3R-(2’-rnethy1-1’-propenyl)-cyclopropan-lR-carboxylsyre, indfører 35 ved 40°C i løbet af ca, 30 minutter 184,2 g 50° Bé vandig kaliumhydroxid opløsning, omrører i 30 minutter ved 40°C og får en opløsning af kaliumsaltet af 2,2-diraethyl-3R-(2’-methyl-1’-propenyl)--cyclopropan-lR-carboxvlsyre.The solution of potassium salt of d-trans-ohrysanthemic acid used in Example 5 can be prepared as follows: Dissolve 293 g of 2,2-dirnethyl-3R- (2'-trimethyl-1'-propenyl) in 500 ml of dimethyl sulfoxide. -cyclopropane-1R-carboxylic acid, introduces 35 at 40 ° C over about 30 minutes 184.2 g of 50 ° B aqueous potassium hydroxide solution, stirs for 30 minutes at 40 ° C and obtains a solution of the potassium salt of 2.2 diraethyl-3R- (2'-methyl-1'-propenyl) - cyclopropane-R-carboxylic acid.
14 DK 158655 B14 DK 158655 B
Eksempel 6.Example 6
2.2- dimethyl-3R-(2 ’-meth.yl-1 *-propenyl)-cyolopropan-lR-carboxylsyre--(R)-allethrolonester ud fra methansulfonatet af (S)-allethrolon (uden isolering af det som mellemprodukt dannede methansulfonat).2,2-Dimethyl-3R- (2 '-methyl-1 * -propenyl) -cyolopropane-1R-carboxylic acid - (R) -allethrolone ester from the methanesulfonate of (S) -allethrolone (without isolation of the intermediate methanesulfonate) ).
5 Ud fra 250 g (S)-allethrolon, α2° = +14° (c = 1,3/«, chloro form), fremstiller man en toluenopløsning af methansulfonat af (£)--allethrolon, idet man arbejder i analogi med eksempel 5 og efter kondensation med kaliumsaltet af d-trans-chrysantheminsyre, benyttet i opløsning, efter en arbejdsmåde i analogi med eksempel 5, 10 får 397 g 2,2-dimefhyl-3R-(2’-methyl-1’-propenyl)-oyclopropan-lR--carboxvlsyre-(R)-allethrolonester, α ^ = -4° (c = 5/, toluen).From 250 g of (S) -allethrolone, α2 ° = + 14 ° (c = 1.3 / «, chloroform), a toluene solution of methanesulfonate of (£) - allethrolone is prepared, working in analogy with Example 5 and after condensation with the potassium salt of d-trans-chrysanthemic acid, used in solution, following a procedure analogous to Examples 5, 10, 397 g of 2,2-dimethyl-3R- (2'-methyl-1'-propenyl) are obtained. -oyclopropane-1R - carboxylic acid (R) -allethrolone ester, α ^ = -4 ° (c = 5 /, toluene).
Eksempel 7« 2.2 -d imeth.vl-5R-( 2 * -methyl-1T -propenyl )-oycloprcpan-lR-carboxylsyre-15 (S)-allethrolonester ud fra methansulfonatet af (R)-allethrolon (uden isolering af det som mellemprodukt dannede methansulfonat).Example 7 2,2-Dimethyl-5R- (2 * -methyl-1T-propenyl) -ocyclopropane-1R-carboxylic acid-15 (S) -allethrolone ester from the methanesulfonate of (R) -allethrolone (without isolating it as intermediate formed methanesulfonate).
I den nedenfor ud fra 82,8 g d-trans-chrysantheminsyre fremstillede opløsning af kalium-d-trans-chrysantbemat indfører man ved 18-20°C i løbet af nogle minutter den nedenfor ud fra 50 g (R)-alle-20 throlon fremstillede opløsning af methansulfonat af (E)-allethrolcn, omrører energisk i 35 timer ved 18-20aC, tilsætter 150 ml vand, fraskiller ved dekantering toluenfasen, ekstraherer den vandige fase med toluen, forener toluenfaserne, vasker dem med vand, forener toluenfaserne, vasker dem indtil fravær af chrysantheminsyre, 25 idet man benytter en vandig opløsning indeholdende 5/ natriumbicar-bonat og 5/ natriumcarbonat, og derefter med vand indtil neutralitet, tørrer, filtrerer, sætter C,1 g hydrcquinon til filtratet, inddamper til tørhed ved destillation under formindsket tryk og får 92,9 g 2.2- dimethyl-3R-(2'-methyl-1’-propenyl)-cyclopropan-lR-carboxylsyre-30 -(S)-alletbrolonester, a2p = -50,5° (c = 5/, toluen).In the solution of potassium d-trans-chrysanthemate obtained from 82.8 g of d-trans-chrysanthemic acid prepared below, at 18-20 ° C, for a few minutes, the below from 50 g (R) -all-20 is introduced. throlone prepared solution of methanesulfonate of (E) -allethroline, stirring vigorously for 35 hours at 18-20aC, adding 150 ml of water, separating by decanting the toluene phase, extracting the aqueous phase with toluene, combining the toluene phases, washing them with water, combining the toluene phases, wash them until the absence of chrysanthemic acid, using an aqueous solution containing 5 / sodium bicarbonate and 5 / sodium carbonate, and then with water until neutrality, dry, filter, add C, 1 g of hydroquinone to the filtrate, evaporate to dryness by distillation under reduced pressure to obtain 92.9 g of 2,2-dimethyl-3R- (2'-methyl-1'-propenyl) -cyclopropane-1R-carboxylic acid 30 - (S) -allethane brolone ester, α2β = -50.5 ° (c = 5 /, toluene).
Den i eksempel 7 benyttede opløsning af methansulfonat af (R)-allethrolon fremstilles på følgende måde: X 150 ml toluen indfører man 50 g (£)-allethrolon og derefter i løbet af ea, 10 minutter ved 0°C 45 g methansulfonylchlorid, 35 tilsætter derpå i løbet af ca. 1 time ved C°C en opløsning af 43,5 g triethylamin i 40 ml toluen, omrører i 30 minutter ved 0°C, indfører ved 0°C i løbet af ca. 30 minutter 200 ml vand, rører om, fraskiller ved dekantering toluenfasen, vasker den med vand indtil fravær af ohlorid, idet man arbejder vec en tempera„tur under 5°C, tørrer toluenopløsningen, filtrerer og får en opløsning af methansulfo-The solution of methanesulfonate of (R) -allethrolone used in Example 7 is prepared as follows: X 150 ml of toluene is introduced with 50 g of (?) -Allethrolone and then within a period of 10 minutes at 0 ° C 45 g of methanesulfonyl chloride, 35 g. then adds over the course of approx. For 1 hour at C, a solution of 43.5 g of triethylamine in 40 ml of toluene, stirring for 30 minutes at 0 ° C, introducing at 0 ° C over approx. 30 minutes 200 ml of water, stir, separate by decanting the toluene phase, washing it with water until absent of chloride, working at a temperature below 5 ° C, drying the toluene solution, filtering and obtaining a solution of methanesulfonic acid.
is DK 158655Bis DK 158655B
nat af (R)-allethrolon, som umiddelbart benyttes i eksempel 7- til kondensation med kaliumsaltet af cbrysantheminsyre.per night of (R) -allethrolone used immediately in Example 7- for condensation with the potassium salt of cbrysanthemic acid.
Den i eksempel 7 benyttede opløsning af kaliumsaltet af d-trans-chrysantheminsyre kan fremstilles på følgende måde: 5 I en blanding af 100 ml tert,-butanol og 100 ml toluen indfører man ved 20°C 24,9 g 90,8^’s kaliumhydroxidopløsning, tilsætter i løbet af ca# 30 minutter ved 25-30°C 82,8 g 2,2-dimethyl--3R-(2’-methyl-l’-propenyl)-cyelopropan-lR-carboxylsyre, omrører i 2 timer 30 minutter ved 25-30°C, afkøler til 20°C og får en op-10 løsning af kaliumsaltet af 2,2-dimethyl-3R-(2’-methyl-l’-propenyl)--cyclopropan-lR-carboxylsyre, som umiddelbart benyttes i eksempel 7«The solution of the potassium salt of d-trans-chrysanthemic acid used in Example 7 can be prepared as follows: In a mixture of 100 ml of tert, butanol and 100 ml of toluene, 24.9 g of 90.8 g are added at 20 ° C. s potassium hydroxide solution, adds about 82.8 g of 2,2-dimethyl-3R- (2'-methyl-1'-propenyl) -cyclopropane-1R-carboxylic acid in about # 30 minutes at 25-30 ° C, stirring in 2 hours 30 minutes at 25-30 ° C, cool to 20 ° C and obtain a solution of the potassium salt of 2,2-dimethyl-3R- (2'-methyl-1'-propenyl) -cyclopropane-1R -carboxylic acid, which is used immediately in Example 7 «
Eksempel 8» 2,2-dlmethyl-3S-(21-methyl-1,-propenvl)~cyolopropan-lR-carboxylsyre-15 -(S)-allethrolonester ud fra methansulfonatet af (R)-allethrolon (uden isolering af det som mellemprodukt dannede methansulfonat).Example 8 »2,2-Dimethyl-3S- (21-methyl-1, -propenyl) -cyolopropane-1R-carboxylic acid-15 - (S) -allethrolone ester from the methanesulfonate of (R) -allethrolone (without isolating it as intermediate formed methanesulfonate).
I en blanding af 20 ml toluen og 20 ml tert.-butanol indfører man 10 g natriumsa.lt af 2,2-diméthyl-3S-(2 1-methyl-l,-propenyl)--cyclopropan-lR-carboxylsyre og derefter hurtigt 31,8 ml tcluenop-20 løsning på 1,1 mol pr. liter af methansulfonat af (R)-alletbrolon, omrører i 2 timer, tilsætter 30 ml toluen og 20 ml tert.-butanol, omrører i 65 timer, tilsætter vand, ekstraherer med ether, vasker etherekstrakterne med vand, med en fortyndet vandig ammoniakopløsning og med vand, tørrer, inddamper til tørhed ved destillation un-25 der formindsket tryk og får 9,94 g rå ester, som man renser ved cbromatcgrafi på silicagel under eluering med en blanding af cyclo-hexan og ethylacetat (9:1) og får 7,38 g 2,2-dimethyl-3S-(2,-methvl--1’-propenyl)-cyclopropan-lR-carboxylsyre-(S)-allethrolonester, a2·^ - +39,5° (c = 0,8fo, chloroform.), 30 Cirkulær dichroisme (dioxan): Δε = -9,85 ved 231 nm Δε s +2,68 ved 320 nm Δε = +2,38 ved 332 nmTo a mixture of 20 ml of toluene and 20 ml of tert-butanol is introduced 10 g of sodium salt of 2,2-dimethyl-3S- (2 L-methyl-1,1-propenyl) cyclopropane-1R-carboxylic acid and then fast 31.8 ml tcluenop solution of 1.1 moles per ml. liters of methanesulfonate of (R) -allet brolone, stir for 2 hours, add 30 ml of toluene and 20 ml of tert-butanol, stir for 65 hours, add water, extract with ether, wash the ether extracts with water, with a dilute aqueous ammonia solution and with water, dries, evaporates to dryness by distillation under reduced pressure to give 9.94 g of crude ester which is purified by chromatography on silica gel eluting with a mixture of cyclohexane and ethyl acetate (9: 1) and 7.38 g of 2,2-dimethyl-3S- (2,1-methyl-1'-propenyl) -cyclopropane-1R-carboxylic acid (S) -allethrolone ester, α2 · + - 39.5 ° (c = 0 , 8fo, chloroform.), 30 Circular dichroism (dioxane): Δε = -9.85 at 231 nm Δε s + 2.68 at 320 nm Δε = +2.38 at 332 nm
Eet i eksempel 8 benyttede natriumsalt af cis-chrysanthemin- 35 syre fremstilles på følgende måde: I 200 ml ethanol indfører man 20 g 2,2-dimethyl-5S-(2f-me-thyl-1’-propenyl)-cyclopropan-lR-carboxylsyre og nogle phenolphtfca-leinkrystaller, tilsætter langsomt koncentreret natriumhydroxidopløsning indtil omslag til rosa, eliminerer opløsningsmidlerne ved destillation under formindsket tryk og får 22 g natriumsalt afThe sodium salt of cis-chrysanthemic acid used in Example 8 is prepared as follows: 20 g of 2,2-dimethyl-5S- (2f-methyl-1'-propenyl) -cyclopropane-1R are introduced into 200 ml of ethanol. -carboxylic acid and some phenolphtfca clay crystals, slowly add concentrated sodium hydroxide solution until wrapped to pink, eliminate the solvents by distillation under reduced pressure and obtain 22 g of sodium salt of
16 DK 158655B16 DK 158655B
2,2-aimethyl-3S-(2'-methyl-l'-propenylJ-oyclopropan-lE-oarboxylsyre,2,2-aimethyl-3S- (2'-methyl-l'-propenylJ-oyclopropan-le-oarboxylsyre,
Den i eksempel 8 benyttede tolueno-pløsning af methansulfona,t af (R)-allethrolon fremstilles på følgende måde: I 105 ml toluen indfører man 35 g frisk rektificeret (R)-5 -allethrolon (kp. 97°0/0,2 mm Hg), omrører, afkøler til 2°C, tilsætter i løbet af 15 minutter ved 2°C 22 ml methansulfonylchlorid, indfører i løbet af 1 time ved 2°C en blanding af 28 ml toluen og 42 ml triethylamin, omrører i 30 minutter ved 0°C, tilsætter i løbet af 10 minutter ved 0°C 35 ml iskoldt vand, dernæst på én gang 10 100 ml iskoldt vand, rører om, fraskiller ved dekantering den van dige fase fra den organiske, vasker den organiske fase med vand ved 0°G, tørrer toluenfasen, filtrerer og opbevarer den opnåede opløsning ved 0°C. Terme opløsning indeholder 1,13 mol methansulfonat af allethrolon pr. liter.The toluene solution of methanesulfona, t of (R) -allethrolone used in Example 8 is prepared as follows: In 105 ml of toluene 35 g of freshly rectified (R) -5-allethrolone (b.p. 97 ° 0 / 0.2) is introduced. , stirring, cooling to 2 ° C, adding 22 ml of methanesulfonyl chloride over 15 minutes at 2 ° C, introducing a mixture of 28 ml of toluene and 42 ml of triethylamine over a period of 1 hour at 2 ° C, stirring for 30 minutes. minutes at 0 ° C, over 10 minutes at 0 ° C, add 35 ml of ice-cold water, then at one time 10 100 ml of ice-cold water, stir, separate by decanting the usual phase from the organic, washing the organic phase with water at 0 ° G, drying the toluene phase, filtering and storing the obtained solution at 0 ° C. Thermal solution contains 1.13 moles of methanesulfonate of allethrolone per liter.
1515
Eksempel 9« 2 c2-dimethyl-5S-(2 * -methyl-11 -propenyl)-c.yolopropan-lR-oarboxyl-Syre-(S)-allethrolonester..ud fra, p-toluensulfonat af (R)-allethrolon.Example 9 «2 C2-Dimethyl-5S- (2 * -methyl-11-propenyl) -cyolopropane-1R-oreboxylic acid (S) -allethrolone ester from p-toluenesulfonate of (R) -allethrolone .
I en blanding af 20 ml dimethylsulfoxid og 2 ml vana indfø-20 rer man 2,28 g natriumsalt af 2,2-dimetfcyl-3S-(2f-methyl-l,-prope-nyl)-cyclopropan-lR-carboxylsyre og derefter 3,4 g p-toluensulfonat af (R)-allethrolon, omrører i 2 timer ved stuetemperatur, hælder i saltsyre, rører om, ekstraherer den vandige fase med petroleums-ether (kp. 35-75°C), vasker de organiske ekstrakter med vand, tør-25 rer, inddamper til tørhed og får 3,4 g rest, som man chromatografe-rer på silicagel under eluering med en blanding af benzen og ethyl-acetat (9:1) og får 2,06 g 2,2-dimethyl-3S-(2’-methyl-lt-propenyl)--cyclopropan-lR-carboxylsyre-(S)-allethrolonester.To a mixture of 20 ml of dimethyl sulfoxide and 2 ml of vana is introduced 2.28 g of sodium salt of 2,2-dimethylcyl-3S- (2f-methyl-1,1-propanol) cyclopropane-1R-carboxylic acid and then 3.4 g of p-toluenesulfonate of (R) -allethrolone, stir for 2 hours at room temperature, pour in hydrochloric acid, stir, extract the aqueous phase with petroleum ether (bp 35-75 ° C), wash the organic extracts with water, dry, evaporate to dryness to obtain 3.4 g of residue which is chromatographed on silica gel eluting with a mixture of benzene and ethyl acetate (9: 1) to give 2.06 g of 2, 2-dimethyl-3S- (2'-methyl-t-propenyl) - cyclopropane-LR-carboxylic acid (S) -allethrolonester.
Cirkulær dichroisme (dioxan); 30 Δε = -7,8 ved 233 nm Λ,ε = +2,4 ved 320 nm Δε = +2,1 ved 332 nmCircular dichroism (dioxane); 30 Δε = -7.8 at 233 nm Λ, ε = +2.4 at 320 nm Δε = + 2.1 at 332 nm
Det i eksempel 9 benyttede uatriumsalt af cis-chrysanthe-minsyre fremstilles på samme måde som i eksempel 8.The sodium salt of cis-chrysanthemic acid used in Example 9 is prepared in the same manner as in Example 8.
35 Det i eksempel 9 benyttede p-toluensulfonat af (R)-alle- tkrclon fremstilles på følgende måde: I 100 ml tetrahydrofuran indeholdende 11,6 g (R)-allethro-lon indfører man ved -50°C under indifferent atmosfære 11,6 g triethylamin og derefter 21,9 g p-toluensulfonylchlorid, omrører i 48 timer ved 5°C, hælder reaktionsblandingen i 0,1 i< saltsyre, rørerThe p-toluenesulfonate of (R) -altreclone used in Example 9 is prepared as follows: Into 100 ml of tetrahydrofuran containing 11.6 g (R) -allethrolone is introduced at -50 ° C under inert atmosphere 11, 6 g of triethylamine and then 21.9 g of p-toluenesulfonyl chloride, stir for 48 hours at 5 ° C, pour the reaction mixture into 0.1 L of hydrochloric acid, stir
IV DK 158655BIV DK 158655B
om, ekstraherer den vandige fase med chloroform, vasker de organiske ekstrakter med vand, tørrer, inddamper til tørhed, ehromatograferer resten (29 g) på silicagel under eluering med en "blanding af benzen og ethylacetat (955 5) og får 6,8 g p-toluensulfonat af (R)-allethro-5 Ion.about, extracting the aqueous phase with chloroform, washing the organic extracts with water, drying, evaporating to dryness, ehromatographing the residue (29 g) on silica gel eluting with a mixture of benzene and ethyl acetate (955 5) to obtain 6.8 g p-toluenesulfonate of (R) -allethro-5 ion.
Eksempel 10.Example 10.
2,2-dimeth.vl-3S-(2 '-methyl-l'-propenyl^o.yolopropan-lR-carbox.yls.yre--(S)-allethrolonester ud fra p-brombenzensulfonat af (R)-allethrolon. 10 I en blanding af 38 ml dimethylsulfoxid og 3,8 ml vand ind fører man 3,8 g natriumsalt af 2,2-dimethyl-3S-(2'-methyl-l,-prope-nyl)-cyclopropan-lR-carboxylsyre, indfører 3,77 g p-brombenzensulfonat af (R)-allethrolon og 5 ml dimethylsulfoxid, rører om i 30 minutter, lader henstå i 15 minutter, tilsætter 1 E saltsyre, eks-15 traherer den vandige fase med petroleumsether (kp, 35-75°C), vasker de organiske faser med 1 E natriumhydroxidopløsning og med vand, tørrer, inddamper til tørhed og får 1,02 g rest, som man chromato-graferer på silicagel under eluering med en blanding af petroleums-ether (kp. 35-75°C) og ethylether (7:3), og man får 0,422 g 2,2-di-20 methyl-38-(21-methyl-1’-propenyl)-cyclopropan-lR~carboxylsyre-(3)- -allethrolonester.2,2-Dimethyl-3S- (2'-methyl-1'-propenyl) oyolopropane-1R-carboxylacetic acid (S) -allethrolone ester from p-bromobenzene sulfonate of (R) -allethrolone To a mixture of 38 ml of dimethyl sulfoxide and 3.8 ml of water is introduced 3.8 g of sodium salt of 2,2-dimethyl-3S- (2'-methyl-1,1-propanyl) -cyclopropane-1R- carboxylic acid, introduces 3.77 g of p-bromobenzene sulfonate of (R) -allethrolone and 5 ml of dimethylsulfoxide, stirs for 30 minutes, leaves for 15 minutes, adds 1 E hydrochloric acid, extracts the aqueous phase with petroleum ether (b.p. 35-75 ° C), wash the organic phases with 1 E sodium hydroxide solution and with water, dry, evaporate to dryness and obtain 1.02 g of residue which is chromatographed on silica gel eluting with a mixture of petroleum ether (bp 35-75 ° C) and ethyl ether (7: 3) to give 0.422 g of 2,2-dimethyl-38- (21-methyl-1'-propenyl) -cyclopropane-1R-carboxylic acid (3 ) - -allethrolone ester.
Cirkulær diohroisme (dioxan): Δε = -3,4 ved 233 nm Δε s +1,5 ved 321 nm 25 Δε = +1,7 ved 332 nmCircular Diohroism (dioxane): Δε = -3.4 at 233 nm Δε s + 1.5 at 321 nm 25 Δε = +1.7 at 332 nm
Ret i eksempel 10 benyttede natriumsalt af cis-ehrysanthe-minsyre fremstilles på samme måde som i eksempel 8,The sodium salt of cis-ehrysanthemic acid used in Example 10 is prepared in the same manner as in Example 8,
Ret i eksempel 10 benyttede p-brombenzensulfonat af (R)--allethrolon fremstilles på følgende måde: 30 I 25 ml tetrahydrofuran indfører man 2,5 g (R)-allethrolon, afkøler til 0°C, tilsætter 2,5 g triethylamin og derefter 6,3 g p-brombenzensulfonylchlorid, omtører 6 timer ved 5°C, tilsætter fort. saltsyre, rører om, ekstraherer med methylenohlorid, vasker de forenede organiske faser med vand, tørrer, inddamper til tørhed og 35 får 7,47 g p-brombenzensulfonat af (R)-allethrolon i rå tilstand, som man umiddelbart benytter i eksempel 10,P-bromobenzene sulfonate of (R) - allethrolone used in Example 10 is prepared as follows: In 25 ml of tetrahydrofuran 2.5 g of (R) -allethrolone are cooled, cooled to 0 ° C, 2.5 g of triethylamine is added and then 6.3 g of p-bromobenzene sulfonyl chloride, stirring for 6 hours at 5 ° C, is added rapidly. hydrochloric acid, stir, extract with methylene chloride, wash the combined organic phases with water, dry, evaporate to dryness and give 7.47 g of crude p-bromobenzene sulfonate of (R) -allethrolone, which is used immediately in Example 10,
is DK 158655Bis DK 158655B
Eksempel 11, 2.2-d imethyl-3R-(o.yolopent.vlidenmeth.yl)-cyolopropan-lR-carbox.yls.yre--2-all.yl-3-methyl-4S-hydrox.y-2-oyclopent-l-onester ((S )-allethro-lonesteren) ud fra methansulfonatet af (R)-allethrolon.Example 11, 2,2-Dimethyl-3R- (oyolopentylidene methyl) -cyolopropane-1R-carboxylic acid 2-allyl-3-methyl-4S-hydroxy-2-oyclopent -l-ester ((S) -allethro-lone ester) from the methanesulfonate of (R) -allethrolone.
5 Man opløser de 0,530 g methansulfonat af (R)-allethrolon fremstillet nedenfor ud fra 0,362 g (R)-allethrolon i 10 ml dime-thylformamid, afkøler til 5°0, tilsætter de 0,576 g kaliumsalt, som fås nedenfor ud fra 2,2-dimethyl-3R-(cyelopentylidenmethyl)-lR--carboxyisyre, omrører ved 5°C i 1 time, hælder i vand, syrner til 10 en pH-værdi på 4 ved tilsætning af fortyndet saltsyre, ekstraherer med petroleumsether, tørrer den organiske fase og inddamper, chro-matograferer resten på silicagel under eluering med en blanding af benzen og ethylaeetat (95 s5) og isolerer 0,443 g 2,2-dimethyl-3R--(cy clopentylidenmethyl)-cyelopropan-lR-carboxylsyre-(S )-allethrolon-15 ester med = -38° +2,5° (c = 0,6$, chloroform).The 0.530 g of methanesulfonate of (R) -allethrolone prepared below is dissolved from 0.362 g of (R) -allethrolone in 10 ml of dimethylformamide, cooled to 5 ° 0, the 0.576 g of potassium salt obtained below is added, 2-dimethyl-3R- (cyclopentylidene methyl) -1R - carboxylic acid, stirring at 5 ° C for 1 hour, pouring into water, acidifying to 10 a pH of 4 by adding dilute hydrochloric acid, extracting with petroleum ether, drying the organic phase and evaporator, chromatograph the residue on silica gel eluting with a mixture of benzene and ethyl acetate (95 s5) and isolating 0.443 g of 2,2-dimethyl-3R - (cy clopentylidene methyl) -cycelopropane-1R-carboxylic acid (S) -allethrolone ester with = -38 ° + 2.5 ° (c = 0.6 $, chloroform).
Cirkulær dichroisme (dioxan): vendepunkt ved 345 nm Δε = + 1,09 max ved 332 nm Δε =+ 2,32 max ved 320 nm Δε = + 2,-60 20 vendepunkt ved 310 nm Δε = + 1,97 max ved 230 nm Δε = -26,7Circular dichroism (dioxane): turning point at 345 nm Δε = + 1.09 max at 332 nm Δε = + 2.32 max at 320 nm Δε = + 2, -60 20 turning point at 310 nm Δε = + 1.97 max at 230 nm Δε = -26.7
Methansulfonatet af (R)-allethrolon, der benyttes som udgangsprodukt i eksempel 11, kan fremstilles på følgende måde:The methanesulfonate of (R) -allethrolone used as the starting product in Example 11 can be prepared as follows:
Man opløser 0,362 g (R)-allethrolon (som efter sin eirku-25 lære dichroisme har en optisk renhed på 97-98^) i 4 ml blanding af benzen og ether (50:50), afkøler til -6°C, tilsætter 0,46 ml triet hylamin og derefter langsomt 0,2 ml methansulfonylchlorid opløst i 2,7 ml blanding af benzen og ether (50:50), omrører i 2 timer ved -10°C, hælder i fortyndet saltsyre, fraskiller den organiske fase 30 ved dekantering, ekstraherer den vandige fase med ether, forener de organiske faser, vasker dem med vand, tørrer dem, inddamper dem til tørhed ved destillation under formindsket tryk og får 0,530 g methansulfonat af (R)-allethrolon i rå tilstand, som umiddelbart benyttes i eksempel 11.Dissolve 0.362 g (R) -allethrolone (which, after its circular dichroism, has an optical purity of 97-98 °) in 4 ml mixture of benzene and ether (50:50), cool to -6 ° C, add 0.46 ml of triethylamine and then slowly 0.2 ml of methanesulfonyl chloride dissolved in 2.7 ml of mixture of benzene and ether (50:50), stirring for 2 hours at -10 ° C, pouring in dilute hydrochloric acid, separating the organic phase By decantation, the aqueous phase is extracted with ether, combines the organic phases, washed with water, dried, evaporated to dryness under reduced pressure and obtained 0.530 g of methane sulfonate of (R) -allethrolone in the crude state, which immediately is used in Example 11.
35 Kaliumsaltet af 2,2-dimethyl-3R-(cyclopentylidenmethyl)-cy- clopropan-lR-carboxylsyre, der benyttes i eksempel 11, fremstilles på følgende måde:The potassium salt of 2,2-dimethyl-3R- (cyclopentylidene methyl) -cyclopropane-1R-carboxylic acid used in Example 11 is prepared as follows:
Lian fremstiller 0,576 g 2,2-dimethyl-3R-(cyclopentylidenmethyl )-cyclopropan-lR-carboxylsyrekaliumsalt ved neutralisation af en methanolisk opløsning af 2,2-dimethyl-3R-(eyclopentyliden-Lian produces 0.576 g of 2,2-dimethyl-3R- (cyclopentylidene methyl) -cyclopropane-1R-carboxylic acid potassium salt by neutralizing a methanolic solution of 2,2-dimethyl-3R- (eyclopentylidene)
19 DK 158655B19 DK 158655B
methyl)-cyclopropan-lR-oarboxylsyre med methanolisk kaliumhydroxid -opløsning (omslag af phenolphthalein), destillation til tørhed under formindsket tryk og overdestillation ved hjælp af benzen, 5 Eksempel 12.methyl) -cyclopropane-1R-oreboxylic acid with methanolic potassium hydroxide solution (phenolphthalein wrap), distillation to dryness under reduced pressure and over distillation by benzene, Example 12.
2,2-dimeth,yl-3S-(2,,2t-dichlorvinyl)-cyolopropan-lR-carbox.ylsyre--(S)-allethrolonester eller (lR<trans)-2,2-dimethvl-5-(2,.2t-di-chlorvibyl)-c.vclopropan-l-carboxylsyre-(S)-allethrolonester ud fra methansulfonat af (R)-allethrolon (uden isolation af det som mel-10 lemprodukt dannede methansulfonat), I en blanding af 20 ml toluen og 20 ml tert.-butanol indfører man 10 g natriumsalt af (IR,trans)-2,2-dimethyl-3-(21,2»-di-chlorvinyl)-cyclopropan-l-carboxylsyre og derefter 26,2 ml toluenopløsning af methansulfonat af (R)-allethrolon med en styrke på 15 1,3 mol pr, liter, omrører 2 timer, tilsætter 30 ml toluen og 20 ml tert,-butanol, omrører i 65 timer, behandler i analogi med eksempel 8, får 9,26 g rå ester, som man chromatograferer på silicagel under eluering med en blanding af cyclohexan og ethylacetat (9:1) og får 7,91 g (IR,trans)-2,2-dimethyl-3-(2*,2’-dichlorvinyl)-cyclo-20 propan-l-carboxylsyre-(S)-allethrolonester, a^ = -26 (c = 0,5$, chloroform),2,2-dimethyl, yl-3S- (2,2,2-dichlorovinyl) -cyolopropane-1R-carboxylic acid - (S) -allethrolone ester or (1R <trans) -2,2-dimethyl-5- (2 2,2-D-Chloro-Vibyl) -cyclopropane-1-carboxylic acid (S) -allethrolone ester from methanesulfonate of (R) -allethrolone (without isolation of the methanesulfonate formed as an intermediate), in a mixture of 20 10 ml of sodium salt of (IR, trans) -2,2-dimethyl-3- (21,2'-dichlorovinyl) -cyclopropane-1-carboxylic acid and then 26.2 ml of toluene and 20 ml of tert-butanol are introduced. ml of toluene solution of methanesulfonate of (R) -allethrolone at a strength of 1.3 moles per liter, stirring 2 hours, adding 30 ml of toluene and 20 ml of tert -butanol, stirring for 65 hours, treating by analogy with Example 8 gives 9.26 g of crude ester which is chromatographed on silica gel eluting with a mixture of cyclohexane and ethyl acetate (9: 1) to give 7.91 g (IR, trans) -2,2-dimethyl-3- (2 *, 2'-dichlorovinyl) -cyclopropane-1-carboxylic acid (S) -allethrolone ester, α a = -26 (c = 0.5 $, chloroform),
Cirkulær diohroisme (dioxan): Δε = -23,6 ved 228 nm Δε = +2,62 ved 321 nm 25 Δε = +2,32 ved 332 nmCircular Diohroism (dioxane): Δε = -23.6 at 228 nm Δε = +2.62 at 321 nm 25 Δε = +2.32 at 332 nm
Det i eksempel 12 benyttede natriumsalt af (lR,trans)-2,2~ -dimethyl-3-(2!,2’~dichlorvinyl)-cyclopropan-l-carboxylsyre fås på følgende måde: I 200 ml ethanol indfører man 20 g (IR,trans )-2,2-dimethyl-30 -3-'(2%2t-dichlorvinyl)-cyclopropan-l-carboxylsyre, nogle phenol-phthaleinkrystaller, tilsætter langsomt natriumhydroxid indtil omslag til rosa, inddamper til tørhed ved destillation under formindsket tryk, tilsætter benzen, inddamper til tørhed, foretager denne operation en gang mere og får 22,6 g natriumsalt af (IR,trans)-2,2-35 -dimethyl-3-(2 *,2’-dichlorvinylj-cyclopropan-l-carboxylsyre.The sodium salt of (1R, trans) -2,2 ~ -dimethyl-3- (2,1,2'-dichlorovinyl) -cyclopropane-1-carboxylic acid used in Example 12 is obtained as follows: 20 g of ethanol are introduced into 20 g. (IR, trans) -2,2-Dimethyl-30-3 - (2% 2t-dichlorovinyl) -cyclopropane-1-carboxylic acid, some phenol-phthalein crystals, slowly add sodium hydroxide until pink, evaporates to dryness by distillation under reduced pressure, add benzene, evaporate to dryness, perform this operation once more and obtain 22.6 g of sodium salt of (IR, trans) -2,2-35-dimethyl-3- (2 *, 2'-dichlorovinyl] cyclopropane -l-carboxylic acid.
Den i eksempel 12 benyttede toluenopløsning af methansulfonat af (R)-allethrolon fremstilles på samme måde som i eksempel 8,The toluene solution of methanesulfonate of (R) -allethrolone used in Example 12 is prepared in the same manner as in Example 8,
so DK 158655Bso DK 158655B
Eksempel 13« 2.2- dimethyl-3S-(2f ,2 »-dichlorvinyl^cyolopropan-lR-carboxylsyre--(S)-allethrolonester eller (lR«trans)-242-dimetfayl-5~(2>,2t«.di-chlorvinyl )-cyclopropan-l-®arboxyl3.vre-( S )-allethrolonester ud fra 5 p-toluensulfonat af (R)-allethrolon.Example 13 "2.2-Dimethyl-3S- (2f, 2" -dichlorovinyl) cyolopropane-1R-carboxylic acid - (S) -allethrolone ester or (1R "trans) -242-dimethylphayl-5 ~ (2>, 2t") -chlorvinyl) -cyclopropane-1-arboxyl3-acid (S) -allethrolone ester from 5 p-toluenesulfonate of (R) -allethrolone.
I en ‘blanding af 20 ml dimethylsulfoxid og 2 ml vand indfører man 2,78 g natriumsalt af (lR,trans)-2,2-dimethyl-5-(2,,2,-di-chlorvinyl)-cyclopropan-l-carboxylsyre og dernæst 3,4 g p-toluensulfonat af (R)-allethrolon, omrører i 2 timer ved stuetemperatur, 10 syrner, ekstraherer med petroleumsether (kp. 35-75°C), vasker de organiske faser med 1 R natriumhydroxid og dernæst med vand, tørrer dem, inddamper dem til tørhed og får 3 g rest, som man chromatogra-ferer på silicagel under eluering med en blanding af benzen og ethylacetat (9:1), og man får 2,31 g (lR,trans)-2,2-dimethyl-3-(2’, 15 2 *-d ichlorvinyl)-cyclopropan-l-carboxylsyre-(S)-allethrolonester.To a mixture of 20 ml of dimethyl sulfoxide and 2 ml of water is added 2.78 g of sodium salt of (1R, trans) -2,2-dimethyl-5- (2,2,2-di-chlorovinyl) -cyclopropane-1-one. carboxylic acid and then 3.4 g of p-toluene sulfonate of (R) -allethrolone, stir for 2 hours at room temperature, 10 acids, extract with petroleum ether (bp 35-75 ° C), wash the organic phases with 1 R sodium hydroxide and then with water, dry them, evaporate them to dryness and give 3 g of residue which is chromatographed on silica gel eluting with a mixture of benzene and ethyl acetate (9: 1) to give 2.31 g (1R, trans) -2,2-dimethyl-3- (2 ', 2 * -dichlorovinyl) -cyclopropane-1-carboxylic acid (S) -allethrolone ester.
Ratriumsaltet af (IR,trans)-2,2-dimethyl-3-(2:,21-dichlorvinyl )-cyclopropan-l-carboxylsyre fås på samme måde som i eksempel 12.The rat sodium salt of (IR, trans) -2,2-dimethyl-3- (2:, 21-dichlorovinyl) -cyclopropane-1-carboxylic acid is obtained in the same manner as in Example 12.
Ren i eksempel 13 benyttede p-toluensulfonsyre-(R)-allethro-20 lonester fås som i eksempel 9.P-toluenesulfonic acid (R) -allethrolone ester used in Example 13 is obtained as in Example 9.
Eksempel 14.Example 14.
2.2- dimethyl-3S-(21,2t-difluorvinyl)-oyolopropan-lR-carboxylsyre--(S)-allethrolonester eller (lR.trans)-2.2-dimethyl-3-(2*.2*-di- 25 fluorvin.vl)-cyolopropan-l-oarboxylsyre-(S)-allethrolonester ud fra me-thansulfonatet af (R)-allethrolon (uden isolation af det som mellemprodukt dannede methansulfonat).2,2-Dimethyl-3S- (21,2t-difluorovinyl) -oyolopropane-1R-carboxylic acid - (S) -allethrolone ester or (1R.trans) -2,2-dimethyl-3- (2 *, 2 * -difluorobenzine) .vl) -cyolopropane-1-oreboxylic acid (S) -allethrolone ester from the methanesulfonate of (R) -allethrolone (without isolation of the intermediate methanesulfonate).
I en blanding af 36 ml toluen og 36 ml tert.-butanol indfører man 18,26 g natriumsalt af (lR,trans)-2,2-dimethyl-3-(21,2’-di-30 fluorvinyl)-cyclopropan-l-carboxylsyre og tilsætter i løbet af 1 minut 54,5 ml toluenopløsning af methansulfonat af (R)-allethrolon med en styrke på 1,13 mol pr. liter, omrører i 76 timer ved 20°C, behandler på samme måde som i eksempel 8 og får 18,69 g rå ester, som man chromatograferer på silicagel under eluering med en blanding 35 af cyclohexan og ethylacetat (9:1), og man får 15,1 g (lR,trans)-2,2--dimethyl-3-(2 *,2 *-difluorvinyl)-cyclopropan-l-carboxylsyre-(3)--allethrolonester, α ^ = -24,5° (c = 1$, chloroform).In a mixture of 36 ml of toluene and 36 ml of tert-butanol 18.26 g of sodium salt of (1R, trans) -2,2-dimethyl-3- (21,2'-difluorovinyl) cyclopropane are added. 1-carboxylic acid and in 1 minute add 54.5 ml of toluene solution of methanesulfonate of (R) -allethrolone at a strength of 1.13 moles per ml. liters, stirred for 76 hours at 20 ° C, treated in the same manner as in Example 8 to obtain 18.69 g of crude ester which is chromatographed on silica gel eluting with a mixture of cyclohexane and ethyl acetate (9: 1), and 15.1 g (1R, trans) -2,2 - dimethyl-3- (2 *, 2 * -difluorovinyl) -cyclopropane-1-carboxylic acid (3) -allethrolone ester, α 5 ° (c = 1 $, chloroform).
Cirkulær dichroisme (dioxan): Δε = -22,6 ved 225 nm Δε = + 2,51 ved 320 nm Δε = + 2,23 ved 332 nmCircular dichroism (dioxane): Δε = -22.6 at 225 nm Δε = + 2.51 at 320 nm Δε = + 2.23 at 332 nm
21 DK 158655 B21 DK 158655 B
U,V,spektrum (ethanol); max ved 228 nm ε = 15,300U, V, spectrum (ethanol); max at 228 nm ε = 15,300
Det i eksempel 14 benyttede natriumsalt fremstilles i analogi med fremstillingen af natriumsaltet i eksempel 8, Ud fra 17 g 5 (IR, trans )-2,2-dimethyl-3-(2 *,2,-difluorvinyl)-cyclopropan-l-carb-oxylsyre får man 18,27 g natriumsalt.The sodium salt used in Example 14 is prepared by analogy with the preparation of the sodium salt of Example 8. From 17 g of 5 (IR, trans) -2,2-dimethyl-3- (2 *, 2, -difluorovinyl) -cyclopropane-1- carboxylic acid gives 18.27 g of sodium salt.
Toluenopløsningen af methansulfonat af (R)-allethrolon, som benyttes i eksempel 14, fås på samme måde som i eksempel 8, 10 Eksempel 15.The toluene solution of methanesulfonate of (R) -allethrolone used in Example 14 is obtained in the same manner as in Example 8, Example 15.
2«2-dimethyl-5R-(21.2,~difluorvin.yl)--cyolopropan-lR-oarboxylsyre--(S)-alletkrolonester eller (lR<cis)-2<2-dimethyl-5-(2t.2t-difluor-vinyl)-cyclopropan~l~oarboxylsyre-(S)-allethrolonester ud fra me-thansulfonatet af (E)-allethrolon (uden isolation af det som mel-15 lemprodukt dannede methansulfonat).2'-2-Dimethyl-5R- (21.2, ~ difluorovinyl) - cyolopropane-1R-oreboxylic acid - (S) -alethololone ester or (1R <cis) -2 <2-dimethyl-5- (2t.2t difluoro-vinyl) -cyclopropane-1-oreboxylic acid (S) -allethrolone ester from the methanesulfonate of (E) -allethrolone (without isolation of the methanesulfonate formed as an intermediate).
I en blanding af 23 ml toluen og 23 ml tert,-butanol indfører man 11,5 g natriumsalt af (lR,cis)-2,2-dimethyl-3-(2’,2’-difluor· vinyl)-cyclopropan-l-carboxylsyre, tilsætter i løbet af 1 minut 35 ml toluenopløsning af methansulfonat af allethrolon med en styr-20 ke på 1,13 mol pr, liter, omrører i 76 timer ved 20°C, behandler i analogi med eksempel 8 og får 12,25 g rå ester, som man renser ved chromatografi på silioagel under eluering med en blanding af cyclo-hexan og etfcylacetat (9:1), og man får 9,61 g (lR,cis)-2,2-dimethyl--3-(2',2’-difluorvinyl)-cyclopropan-l-carboxylsyre-(S)-allethroloneste 25 a2^ ~ +5° (c = 0,8^, chloroform).To a mixture of 23 ml of toluene and 23 ml of tert-butanol is added 11.5 g of sodium salt of (1R, cis) -2,2-dimethyl-3- (2 ', 2'-difluoro-vinyl) cyclopropane. 1-carboxylic acid, in 1 minute add 35 ml of toluene solution of methanesulfonate of allethrolone at a strength of 1.13 moles per liter, stir for 76 hours at 20 ° C, treat in analogy with Example 8 and obtain 12 25 g of crude ester which is purified by chromatography on silio gel eluting with a mixture of cyclohexane and ethyl acetate (9: 1) to give 9.61 g (1R, cis) -2,2-dimethyl 3- (2 ', 2'-Difluorovinyl) -cyclopropane-1-carboxylic acid (S) -allethrolone ester α 2 + + 5 ° (c = 0.8 +, chloroform).
Cirkulær dichroisme (dioxan): Δε = -18,1 ved 226 nm Δε = + 2,6 ved 321 nm Δε = + 2:,3 ved 332 nm 30 U,V,spektrum (ethanol): max ved 228 nm ε = 15.200Circular dichroism (dioxane): Δε = -18.1 at 226 nm Δε = + 2.6 at 321 nm Δε = + 2:, 3 at 332 nm 30 U, V, spectrum (ethanol): max at 228 nm ε = 15200
Det i eksempel 15 benyttede natriumsalt fremstilles i analogi med natriumsaltet i eksempel 8, Ud fra 10,57 g (lR,cis)-2,2--dimethyl-3-(2f,2'-difluorvinylj-cyclopropan-l-carboxylsyre får man 35 11,65 g natriumsalt.The sodium salt used in Example 15 is prepared by analogy with the sodium salt of Example 8. From 10.57 g (1R, cis) -2,2 - dimethyl-3- (2f, 2'-difluorovinyl) cyclopropane-1-carboxylic acid is obtained. 11.65 g of sodium salt.
Toluenopløsningen af methansulfonatet af (R)-allethrolon, som benyttes i eksempel 15, er identisk med den i eksempel 8 fremstillede.The toluene solution of the methanesulfonate of (R) -allethrolone used in Example 15 is identical to that of Example 8.
22 DK 158655 B22 DK 158655 B
Eksempel 16.Example 16.
Fremstilling af et emulgerbart koncentrat.Preparation of an emulsifiable concentrate.
Man blander grundigt: - lE.,trans-2,2-dimethyl-3-(2 ’,2f-difluorvinyl)-cyclo- 5 propan-l-carboxylsyre-(S)-allethrolonester G,3 g - piperonylbutoxid 3 g - Topanol A 0,1 g - xylen 96,6 g 10 Eksempel 17«Thoroughly mix: - 1E., Trans-2,2-dimethyl-3- (2 ', 2f-difluorovinyl) -cyclopropane-1-carboxylic acid (S) -allethrolone ester G, 3 g - piperonylbutoxide 3 g - Topanol A 0.1 g - xylene 96.6 g Example 17
Fremstilling,af en røgspiral.Manufacture, of a smoke coil.
Man inkorporerer med omhu en opløsning af 0,1 g lR,trans--2,2-dimethyl-3-(2*,2’-difluorvinyl)-cyclopropan-1-carboxylsyre--(S)-allethrolonester i 5 ml methanol i en blanding bestående af 15 30 g pyrethrumkvas, 12 g pyrethrumstilkpulver, 51»! g kokosskal pulver og 6 g opløselig stivelse« Man blander det opnåede pulver med ca, 100 g vand, tørrer det og formgiver det til en spiral med en tykkelse på ca, 0,4 cm og 1 diameter på ca, 12 cm.Carefully incorporate a solution of 0.1 g of 1R, trans - 2,2-dimethyl-3- (2 *, 2'-difluorovinyl) cyclopropane-1-carboxylic acid (S) -allethrolone ester in 5 ml of methanol in a mixture of 15 30 g of pyrethrum quasi, 12 g of pyrethrum powder, 51 »! g of coconut shell powder and 6 g of soluble starch «The obtained powder is mixed with about 100 g of water, dried and shaped into a spiral with a thickness of about 0.4 cm and 1 diameter of about 12 cm.
20 Eksempel 18.Example 18.
Frenstilling af en røgspiral.Removal of a smoke coil.
Man inkorporerer med omhu en opløsning af 0,15 g lR,cis--2,2-dimethyl-3-(2,,2,-difluorvinyl)-cyclopropan-l-carboxylsyre--(S)-allethrolonester i 5 ml methanol i en blanding af 43 g pyre-25 thrumstiIkpulver, 52 g kokosskalpulver og 4,4 g opløselig stivelse, Man blander det opnåede pulver med ca. 100 g vand, tørrer det og former det til en spiral med en tykkelse på ca. 0,4 cm og en diameter på ca. 12 cm.Carefully incorporate a solution of 0.15 g of 1R, cis-2,2-dimethyl-3- (2,2,2-difluorovinyl) -cyclopropane-1-carboxylic acid (S) -allethrolone ester in 5 ml of methanol in a mixture of 43 g of pyro-thrumstick powder, 52 g of coconut peel powder and 4.4 g of soluble starch. 100 g of water, dry it and form it into a spiral with a thickness of approx. 0.4 cm and a diameter of approx. 12 cm.
30 Eksempel 19.Example 19.
Fremstilling af et produkt beregnet til elektrisk opvarmning.Manufacture of a product for electric heating.
Man adsorberer en opløsning af 0,2 g lR,trans-2,2-dimethyl--3-(2 *,2 *-difluorvinyl)-cyclopropan-l-carboxylsyre-(S)-allethrolon-ester i 5 ml toluen på overfladen af et stykke asbest med dimensio-35 nerne 2 x 2 x 0,8 cm. Man anbringer på asbeststykket et andet stykke asbest med samme dimensioner. Han får således et fordampningspræparat, som skal anvendes ved opvarmning på en plade med en elektrisk modstand.A solution of 0.2 g of 1R, trans-2,2-dimethyl-3- (2 *, 2 * -difluorovinyl) -cyclopropane-1-carboxylic acid (S) -allethrolone ester is adsorbed in 5 ml of toluene. the surface of a piece of asbestos with the dimensions 2 x 2 x 0.8 cm. Another piece of asbestos with the same dimensions is placed on the piece of asbestos. He thus obtains an evaporative composition which is to be used for heating on a plate with an electrical resistance.
23 DK 158655 B23 DK 158655 B
Undersøgelse af den insekticide virkning af 2,2-dimethyl--5R-(oyclo-pentylidenmethyl)-oyolopropan-lR-carbox.ylsyre-(S )-allethrolonester (forbindelse A), af lR.trans-2<12-dimeth.yl-3-j(2tt2t--dichlorvin,yl)--cyclopropan-l-carboxyls.yre-(S )-allethrolonester (forb.B). ,af 5 IR, trans -2,2 -d imethy1-5-( 2^21^ if luorvin.yl) -cyclopropan-l-carbox- yls.yre-(S)-allethrolonester (forb,.O) og af..lR,,cis-2,2-dimethyl---3-(2’,2 ’-difluorvin.vl)-cyclopropan-l-oarboxyls.vre (S)-allethrolon-ester (forbindelse D).Investigation of the insecticidal effect of 2,2-dimethyl-5R- (oyclopentylidenemethyl) -oyolopropane-1R-carboxylic acid (S) -allethrolone ester (compound A), of 1R.trans-2 <12-dimeth. yl-3-j (2tt2t - dichlorovin, yl) - cyclopropane-1-carboxylic acid (S) -allethrolone ester (compound B). , of 5 IR, trans -2,2-d-dimethyl-5- (2,221 µl of fluorovinyl) -cyclopropane-1-carboxylic acid (S) -allethrolone ester (forb, O) and of 1R 1, cis-2,2-dimethyl --- 3- (2 ', 2' -difluorovinyl) -cyclopropane-1-oreboxylic acid (S) -allethrolone ester (compound D).
A) Undersøgelse af knock-down-virkningen på stueflue, 10 Porsøgsinsekterne er 3 dage gamle hunstuefluer. Man arbej der ved direkte forstøvning i Kearns og March’s kammer, idet man som opløsningsmiddel benytter en blanding af lige rumfang acetone og petroleum (mængde af benyttet opløsning: 500 mg).A) Investigation of the knock-down effect on housefly, 10 The test insects are 3 day old female flies. They work by direct atomization in Kearns and March's chamber, using as a solvent a mixture of equal volumes of acetone and petroleum (amount of solution used: 500 mg).
Man benytter ca, 50 insekter pr, behandling. Man foretager 15 kontrol hvert minut indtil 15 minutter.About 50 insects are used per treatment. 15 checks are performed every minute until 15 minutes.
Resultatet udtrykkes i KT 50, som er den fornødne tid til at slå 50$ af insekterne ned med en bestemt dosis af det produkt, som undersøges. Denne tid er desto kortere jo mere aktivt produktet er, 20 De opnåede forsøgsresultater fremgår af følgende tabel: 25 30 35The result is expressed in KT 50, which is the time needed to knock down $ 50 of the insects with a specific dose of the product being tested. This time is shorter the more active the product is, 20 The experimental results obtained are shown in the following table: 25 30 35
24 DK 158655 B24 DK 158655 B
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25 , DK 158655 B25, DK 158655 B
B) Undersøgelse af letal virkning på stueflue.B) Investigation of lethal effect on housefly.
Forsøgsinsekterne er stuefluer af blandet køn. Man arbejder ved topisk applikation af 1 μΐ acetoneopløsning på insekternes dorsale thorax. Man benytter 50 individer pr. behandling. Man fore-5 tager kontrol for dødelighed 24 timer efter behandlingen.The experimental insects are mixed-sex living flies. Topical application of 1 μΐ acetone solution to the insect's dorsal thorax is performed. 50 individuals are used per day. treatment. Mortality is checked at 24 hours after treatment.
Ben forbindelse, som skal undersøges, synergetiseres af pi-peronylbutoxid (10 vægtdele piperonylbutoxid for hver vægtdel af det produkt, som skal undersøges).Bone compound to be tested is synergetized by piperonyl butoxide (10 parts by weight of piperonyl butoxide for each part by weight of the product to be tested).
1010
Boser i $ dødelighed Bl 50 i ng ng aktivt efter 24 timer pr. insekt materiale pr. flue _ _ 15Bosses in mortality Bl 50 in ng active after 24 hours per day. insect material per fly _ _ 15
Forbindelse A 50 90,9 25 72,5 17,5 12.5 28,2Compound A 50 90.9 25 72.5 17.5 12.5 28.2
Forbindelse B 250 100 20 100 86,7 38,0 50 65,6Compound B 250 100 20 100 86.7 38.0 50 65.6
Forbindelse C 25 100 12.5 53,3 10,1 25 6,25 16,7Compound C 25 100 12.5 53.3 10.1 25 6.25 16.7
Forbindelse B 175 100 50 90 25,4 25 46,6 30 Konklusion: Forbindelserne har en god letal virkning på stueflue.Compound B 175 100 50 90 25.4 25 46.6 30 Conclusion: The compounds have a good lethal effect on housefly.
26 DK 158655B26 DK 158655B
G) Undersøgelse af insekticid virkning af forbindelserne P..g.gJ?.G) Investigation of insecticidal effect of the compounds P..g.gJ ?.
•på Aedes aegypti i form af røgpræparat.• on Aedes aegypti in the form of smoke preparation.
Man undersøger knock-down-virkningen og den letale virkning af den forbindelse, som skal undersøges, på hunner af Aedes 5 aegypti.The knock-down effect and the lethal effect of the compound to be examined are investigated on females of Aedes 5 aegypti.
Man benytter metoden med lukket cylinder ifølge Dainippon, og man lader en røgspiral indeholdende den pågældende forbindelse brænde fra enden i 1 minut i en lukket cylinder med 20 cm diameter og 43 cm højde og indeholdende 20 hunner af Aedes aegypti.The closed-cylinder method according to Dainippon is used and a smoke coil containing the compound in question is fired from the end for 1 minute in a closed cylinder of 20 cm diameter and 43 cm height and containing 20 females of Aedes aegypti.
10 Knock-down-virkningen iagttages hvert 30. sekund i 5 minut ter. Resultaterne udtrykkes i K3? 50, dvs, den fornødne tid til at slå 50$ af insekterne ned med en bestemt dosis aktivt stof. Denne tid er desto kortere, jo mere aktivt produktet er.The knock-down effect is observed every 30 seconds for 5 minutes. The results are expressed in K3? 50, that is, the required time to knock down $ 50 of the insects with a specific dose of active substance. This time is shorter the more active the product.
Man foretager ligeledes tælling af de døde individer efter 15 24 timers forløb og udtrykker resultaterne for letal virkning i $ dødelighed.The dead individuals are also counted after 15 24 hours and the lethal effect results are expressed in $ mortality.
Man foretager tre .på hinanden følgende rækker forsøg og bestemmer gennemsnittene for disse forsøg.Three consecutive rows of tests are performed and the averages of these tests are determined.
Man foretager forsøgene parallelt med et referenceprodukt, 20 som er kendt for sin høje knock-down-virkning, nemlig d-trans-chry-santheminsyre (S)-allethrolonester (forbindelse E).The experiments are carried out in parallel with a reference product 20 known for its high knock-down effect, namely d-trans-chry-santhemic acid (S) -allethrolone ester (compound E).
De opnåede forsøgsresultater fremgår af følgende tabel.The experimental results obtained are shown in the following table.
25 30 3525 30 35
27 DK 158655 B27 DK 158655 B
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Claims (15)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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FR7627288A FR2364199A1 (en) | 1976-09-10 | 1976-09-10 | PROCESS FOR THE PREPARATION OF OPTICALLY ACTIVE CARBOXYLIC CYCLOPROPANE ACID ESTERS OF ALLETHROLONE FROM ANTIPODAL CONFIGURATION ALLETHROLONE |
FR7627288 | 1976-09-10 |
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DK401677A DK401677A (en) | 1978-03-11 |
DK158655B true DK158655B (en) | 1990-07-02 |
DK158655C DK158655C (en) | 1991-01-14 |
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DK401677A DK158655C (en) | 1976-09-10 | 1977-09-09 | PROCEDURE FOR THE PREPARATION OF ESTERS OF (A) -CYCLOPROPANCARBOXYLIC ACIDS, WHICH ARE RACEMIC OR OPTICALLY ACTIVE WITH 1R, 3R, 1S, 3S, 1R, 3S- OR 1S, 3R CONFIGURATION, AND ALSO (R) -configuration |
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AU (1) | AU512196B2 (en) |
BE (1) | BE858555A (en) |
BR (1) | BR7706029A (en) |
CH (1) | CH626320A5 (en) |
DE (1) | DE2740701C2 (en) |
DK (1) | DK158655C (en) |
EG (1) | EG13016A (en) |
ES (1) | ES462242A1 (en) |
FR (1) | FR2364199A1 (en) |
GB (1) | GB1583600A (en) |
GR (1) | GR71905B (en) |
HU (1) | HU177736B (en) |
IE (1) | IE45486B1 (en) |
IL (1) | IL52785A (en) |
IT (1) | IT1091136B (en) |
LU (1) | LU78102A1 (en) |
NL (1) | NL188690C (en) |
PH (1) | PH21134A (en) |
PT (1) | PT67015B (en) |
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FR2247140A5 (en) * | 1973-10-06 | 1975-05-02 | Bosch Gmbh Robert | |
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JPS6443126U (en) * | 1987-09-10 | 1989-03-15 | ||
JP5892105B2 (en) | 2013-04-12 | 2016-03-23 | 株式会社デンソー | A / F sensor element and manufacturing method thereof |
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EG14503A (en) * | 1973-04-21 | 1983-12-31 | Sumitomo Chemical Co | Novel insecticidal composition |
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1976
- 1976-09-10 FR FR7627288A patent/FR2364199A1/en active Granted
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1977
- 1977-08-01 SE SE7708768A patent/SE437152B/en not_active IP Right Cessation
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- 1977-08-25 ZA ZA00775153A patent/ZA775153B/en unknown
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- 1977-09-08 HU HU77RO940A patent/HU177736B/en not_active IP Right Cessation
- 1977-09-08 PT PT67015A patent/PT67015B/en unknown
- 1977-09-08 GR GR54321A patent/GR71905B/el unknown
- 1977-09-09 NL NLAANVRAGE7709966,A patent/NL188690C/en not_active IP Right Cessation
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1978
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1987
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Also Published As
Publication number | Publication date |
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DK158655C (en) | 1991-01-14 |
DE2740701A1 (en) | 1978-03-16 |
IL52785A0 (en) | 1977-10-31 |
JPS6238345B2 (en) | 1987-08-17 |
JPS5334756A (en) | 1978-03-31 |
GR71905B (en) | 1983-08-11 |
PT67015A (en) | 1977-10-01 |
DK401677A (en) | 1978-03-11 |
EG13016A (en) | 1980-07-31 |
CH626320A5 (en) | 1981-11-13 |
LU78102A1 (en) | 1978-06-01 |
IT1091136B (en) | 1985-06-26 |
SE437152B (en) | 1985-02-11 |
NL7709966A (en) | 1978-03-14 |
IE45486B1 (en) | 1982-09-08 |
FR2364199A1 (en) | 1978-04-07 |
ES462242A1 (en) | 1978-06-01 |
IE45486L (en) | 1978-03-10 |
PH21134A (en) | 1987-07-27 |
NL188690C (en) | 1992-09-01 |
DE2740701C2 (en) | 1987-03-26 |
FR2364199B1 (en) | 1979-10-12 |
PT67015B (en) | 1979-09-12 |
SU1178310A3 (en) | 1985-09-07 |
ZA775153B (en) | 1978-09-27 |
AU512196B2 (en) | 1980-09-25 |
AU2869477A (en) | 1979-03-15 |
BE858555A (en) | 1978-03-09 |
IL52785A (en) | 1982-11-30 |
GB1583600A (en) | 1981-01-28 |
BR7706029A (en) | 1978-06-06 |
HU177736B (en) | 1981-12-28 |
SU1713436A3 (en) | 1992-02-15 |
NL188690B (en) | 1992-04-01 |
SE7708768L (en) | 1978-03-11 |
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