Chrysanthemic acid methyl ester

Esters of chrysanthemic acid are rapidly acting insecticides with a comparatively low toxicity for human and mammalian organisms. Retrosynthetic disconnection of the cyclopropane ring following the path of a 1,3-elimination leads to a carbanion with the leaving group X in an allyl position. Provided that X stabilizes the carbanion by electron-withdrawing [(-)-M-effect], the intermediate on its part arises from a MICHAEL addition of the dimethylallyl-X-compound to the methyl ester of senecionic acid (3-methyl-2-butenoic acid). 

When canying out the synthesis 3,3,6-trimethyl-4-/ -tolylsulfonyl-5-heptenoic acid methyl ester proves to be an appropriate synthetic equivalent of die intermediate. This precursor arises from Michael addition of (3-methyl-2-buten-l-yl)-/7-tolylsulfone to senecionic acid methyl ester. The / -tolylsulfone is obtained from sodium /7-toluensuUmate and l-bromo-3-methyl-2-butene by an Sn reaction and subsequent cationotropic 1,2-shift. l-Bromo-3-mefliyl-2-butene is prepared by nucleophilic bromination of 3-methyl-2-buten-l-ol, which is produced by an allyl 

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Franck-Neumann et al. 61) have succeeded in preparing m-chrysanthemic acid methyl ester (8) by selective catalytic hydrogenation of the corresponding cyclo-propene derivative 7 (Eq. 7). 

Miscellaneous Reactions of Methylenephosphoranes.—The synthesis of three-membered rings by means of phosphorus ylides has been reviewed and there have been several new reports of this type of reaction. Optically active a,p-un-saturated esters have been converted into cyclopropanes highly stereoselectively by reaction with isopropylidenetriphenylphosphorane as the key step in syntheses of both (li ,3 )-chrysanthemic acid methyl ester (53) and the (IR) cis-gem dibromovinyl analogue (54). The addition of reactive phosphonium ylides to functionalized 1,3-butadienylphosphonates provides a new synthesis of 2-cyclopen ten-1 -ylphosphonates (5 5). ... 

In a large number of carbene and carbenoid addition reactions to alkenes the thermodynamically less favored jjyn-isomers are formed The finding that in the above cyclopropanation reaction the an/i-isomer is the only product strongly indicates that the intermediates are organonickel species rather than carbenes or carbenoids. Introduction of alkyl groups in the 3-position of the electron-deficient alkene hampers the codimerization and favors isomerization and/or cyclodimerization of the cyclo-propenes. Thus, with methyl crotylate and 3,3-diphenylcyclopropene only 16 % of the corresponding vinylcyclopropane derivative has been obtained. 2,2-Dimethyl acrylate does not react at all with 3,3-dimethylcyclopropene to afford rranj-chrysanthemic acid methyl ester. This is in accordance with chemical expectations since in most cases the tendency of alkenes to coordinate to Ni(0) decreases in the order un-, mono-< di- tri- < tetrasubstituted olefines. 

Isopropylidene-D-glyceraldehyde (readily obtained from D-raannose) has been used to prepare the -unsaturated ester (77) by a Wittig reaction, and hence the cyclopropyl derivatives (1R,3R)-caronaldehyde metnyl ester (78) and (1R,3R)-chrysanthemic acid methyl ester (79) following isopropylidene addition to the double bond (Scheme 15). The same intermediate (77) has been utilized... 

In conclusion, all of the eight stereoisomers of norchrysanthemic acid methyl esters were synthesized in stereoselective manner starting from (1/ )-inmv-chrysanthemic acid or (+)-3-carene. All stereoisomers of metofluthrin were synthesized in our laboratory. Their structure-activity relationship will be published elsewhere. 

The columns labeled PI reflect the total of pyrethrin I and cinerin I just as in the AO AC procedure. The gas chromatographic results are in terms of the total amount of the mixture but were analyzed as the methyl ester of chrysanthemic acid. The present state of the determination of PII (pyrethrin II plus cinerin II) is not complete because of the erratic extractability of the dicarboxylic acids from the hydrolysis mixture. The gas chromatographic pattern is distinct and straightforward. As the extraction procedure for PII is improved, the gas chromatographic method will be more applicable. The present recovery of PII is in the range of 80 to 90%. The average of the values shown in Table II for PI is 98.0%. 

For the synthesis of permethric acid esters 16 from l,l-dichloro-4-methyl-l,3-pentadiene and of chrysanthemic acid esters from 2,5-dimethyl-2,4-hexadienes, it seems that the yields are less sensitive to the choice of the catalyst 72 77). It is evident, however, that Rh2(OOCCF3)4 is again less efficient than other rhodium acetates. The influence of the alkyl group of the diazoacetate on the yields is only marginal for the chrysanthemic acid esters, but the yield of permethric acid esters 16 varies in a catalyst-dependent non-predictable way when methyl, ethyl, n-butyl or f-butyl diazoacetate are used77). 

Much effort this year has been expended on chrysanthemic acid syntheses. Aratani et al. have extended earlier work on asymmetric synthesis (Vol. 6, p. 21) by decomposing various alkyl diazoacetates in 2,5-dimethylhexa-2,4-diene in the presence of chiral copper complexes to yield up to 92% of rrans-chrysanthemic acid in 88% dextrorotatory enantiomeric excess. Mitra has used ozonolysis of (+)-a-pinene to obtain, stereospecifically, the bromo-ketone (104) which undergoes Favorskii rearrangement to yield the anticipated ester (105) from which (+)-trans-chrysanthemic acid is readily obtained a second paper reports another route from (+)-car-3-ene initially to methyl (—)-c/s-chrysanthemate or to (—)-dihydro-chrysanthemolactone (106), both of which are convertible into (+)-rra s-chrysan-... 

Bu3SnLi adds to ,/3-unsaturated esters, and the resulting Li-enolate reacts with 3-methyl-2-butenal to afford 7-hydroxyalkyl tins which are treated with BF3-OEt2 to produce vinyl cyclopropane carboxylic esters (chrysanthemic acid) (Equation (111)).280... 

When phosphane-free nickel complexes, such as bis(cycloocta-l,5-diene)nickel(0) or te-tracarbonylnickel, are employed in the codimerization reaction of acrylic esters, the codimer arising from [2-1-1] addition to the electron-deficient double bond is the main product. The exo-isomer is the only product in these cyclopropanation reactions. This is opposite to the carbene and carbenoid addition reactions to alkenes catalyzed by copper complexes (see previous section) where the thermodynamically less favored e Jo-isomers are formed. This finding indicates that the reaction proceeds via organonickel intermediates rather than carbenoids or carbenes. The introduction of alkyl substituents in the /I-position of the electron-deficient alkenes favors isomerization and/or homo-cyclodimerization of the cyclopropenes. Thus, with methyl crotonate and 3,3-diphenylcyclopropene only 16% of the corresponding ethenylcyc-lopropane was obtained. Methyl 3,3-dimethylacrylate does not react at all with 3,3-dimethyl-cyclopropene, so that the methylester of tra 5-chrysanthemic acid cannot be prepared in this way. This reactivity pattern can be rationalized in terms of a different tendency of the alkenes to coordinate to nickel(O). This tendency decreases in the order un-, mono- < di-< tri- < tet-... 

The starting ester has been prepared3 by the reaction of methallyl chloride, acetylene, and methanol in the presence of nickel carbonyl followed by treatment with base. Reaction with (4) gives the methyl ester of ( )-rran.v-chrysanthemic acid in 72.5% yield. 

The active substances of pyrethrum (rethrins) are pyrethrin I (9) which is the ( + )-3-penta-l,3-dienyl-2-methyl-4-oxo-cyclopent-2-en-l-yl ester of ( + )-( / , 3/ )-( )-chrysanthemic acid, pyrethrin II (10), the ( + )-3-penta-l,3-dienyl-2-methyl-... 

Chrysauthemie esters. Belgian chemists noted that chrysanthemic acid could be formed from two isopropylidene units and, indeed, they obtained /rnns-methyl chrysanthemate (2) in 60% yield by reaction of methyl trans A-oxobutenoate (1) with isopropylidenetriphenylphosphorane (—78->20°). Cyclopentylidenetriphenylphosphorane reacts with (1) in the same way, but other dialkylmethylenetriplienylphosphoranes react to form dienoic esters. 

The first step is conjugate addition of the highly stabilized anion. The intermediate enolate then closes the three-membered ring by favourable nucleophilic attack on the allyUc carbon. The leaving group is the sulfinate anion and the stereochemistry comes from the most favourable arrangement in the transition state for this ring closure. The product is the methyl ester of the important chrysanthemic acid found in the natural pyrethrum insecticides. 

CAS 28434-01-7 EINECS/ELINCS 209-542-4 Synonyms (5-Benzyl-3-furyl) methyl(1 R)-trans-chrysanthemate 1 R-trans-2,2-Dimethyl-3-(2-methylpropenyl) cyclopropane carboxylic acid (5-benzyl-3-furyl) methyl ester (5-(Phenylmethyl)-3-furanyl) methyl-1 R-trans-2,2-dimethyl-3-(2-methylpropenyl)... 

Synonyms Chrysanthemum monocarboxylic acid pyrethrolone ester Cyclopropanecarboxylic acid, 2,2-dimethyl-3-(2-methylpropenyl)-, ester with 4-hydroxy-3-methyl-2-(2,4-pentadienyl)-2-cyclopenten-1-one Pyrethrolone, chrysanthemum monocarboxylic acid ester (+)-Pyrethronyl (+)-trans-chrysanthemate Classification Pyrethrins (natural)... 

A project directed towards the synthesis of chrysanthemic acid enantiomers illustrates some of our recent work on cyclopropano-pyranosides. The sequence (Scheme 40) that had worked so well (25) for the preparation of the simple cyclopropyl ketone (169) from the methanol adduct (168) was not adaptable for preparation of the gem-dimethyl analogue (171). The photoaddition of isopropanol to (83) gave an excellent yield of (170), but efforts to convert this into (171) were not encouraging. However, the Wittig cyclopropanation (24) of epoxide (51) gave the ester (172) whose stereochemistry was deduced by two pieces of nmr data (a) the value J12 < 1 Hz (76) (see Scheme 4), and (b) a ten percent Nuclear Overhauser Effect between H-1 and the methyl protons. 

Cyclopropanes are occasionally found in Nature, and one class of naturally occurring cyclopropanes, the pyrethroids, are useful insecticides. These compounds are highly toxic to insects but not to mammals, and because they are rapidly biodegraded, cyclopropanes do not persist in the environment. The naturally occurring pyrethroids are found in members of the chrysanthemum family and are formally derived from chrysanthemic acid. Many modified pyrethrins not found in Nature have been made in the laboratory and several are widely used as pesticides. The molecule known as pyrethrin I has the systematic name 2,2-dimethyl-3-(2-methyl-l-propenyl)cyclopropanecarboxylic acid 2-methyl-4-oxo-3-(Z-2,4-dipentadienyl)-2-cyclopenten-1-yl ester. See why the shorthand is used ... 

It was only from FTNMR that chemical kinetics and structural analyses of the acid-catalyzed rearrangement of trans-mt hy chrysanthemate to methyl lavandulyl esters could be accurately analyzed. 

The Michael addition, i.e the fusion of an enolate with an a,P-unsaturated aldehyde, ketone, ester, carboxamide, or nitrile, belongs to the most prominent organic reactions/ " The literature abounds with impressive examples as is the manufacture of chrysanthemic acid from two isoprene building blocks, namely, ethyl P,P-dimethylacrylate and 4-chlorophenyl prenyl (3-methyl-2-butenyl) sulfone. ... 

Figure 2. Infrared spectrum of methyl-trans-chrysanthemate Prepared from DL-trans-chrysanthemum acid and collected as pure ester from gas chromatograph...

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