Trans cyclopropane carboxylic acid

Factors Influencing the Application of Literature Methods Toward the Preparation of a Chiral trans-Cyclopropane Carboxylic Acid Intermediate During Development of a Melatonin Agonist... 

AI3-29062 Anchimanaito 20S Anvil Anvil 2 2 ULV Anvil 10 10 ULV Benzyl alcohol, m-phenoxy-, 2,2-dimethyl-3-(2-methylpropenyl)cyclopropanxxboxylate Caswell No. 652B CCRIS 2602 Cyclopropanecarboxylic xid, 2,2-dimethyl-3-(2-methyl-1-propenyl)-, 3-(phenoxy-phenyl)methyl ester, cis,trans-( )- Cyclopropane-carboxylic acid, 2,2-dimethyl-3-(2-methyl-1-propenyl)-,... 

The specific feature of the bonds also affects its chemical behaviour and the stereochemistry of substitution reactions. For example in the conversion of (-) trans -2, 3 diphenyl cyclopropane carboxylic acid into (+) 1, 3 diphenylallene the optical activity is retained. 

The synthesis of compounds 39, 41, and 43 by the ODPM rearrangement opens a novel photochemical route to chrysanthemic acid and other cyclopropane carboxylic acids present in pyrethrins and pyrethroids [52]. In fact, aldehyde 43 can be transformed to tran -chrysanthemic acid by simple oxidation. This new synthetic route to ecologically benign insecticides competes with the one previously described by us using the 1-ADPM rearrangement of p,y-unsaturated oxime acetates [30,53]. 

C4H602)t Ci s-crotonic, trans-crotonic 3-butenoic, methacrylic and cyclopropane carboxylic acids 210 g, n 425... 

R and R may be H, methyl, cyclopropyl, cyano, or ester groups. The phenylcarbene formed on irradiation of trans-l,2-diphenyloxirane has been trapped and identified in the form of a cyclopropane derivative in methanol in the presence of benzyl methyl ether and alkenes. Photolysis in the presence of 2,3-dimethyl-2-butene proceeds by cycloaddition with the formation of cyclopropane-carboxylic acid and oxetane derivatives (Eq. 368). ... 

More investigations have been performed with cyclopropyl ketones. The isomerization of the cis-cyclopropyl ketone 209 to its trans isomer 210 was only achieved by means of the rather basic dimsyl sodium in dimethyl sulfoxide at 60°C . Similarly, esters of cyclopropane carboxylic acids have been isomerized ... 

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)... 

The importance of this non-flat structure, thus deduced and implying that the hydrophilic (polar) group is out of the plane of the lipophilic (nonpolar) ring system, was accentuated by the fact that of different other pairs of cis-trans acids, only the cis-form proved to be active [naphthalene-i-acrylic acid (XVIII-XIX), tetralydeneacetic acid (XX XXI), phenyl-cyclopropane-carboxylic acid o (XXII-XXIII)]. 

The cyclobutanones mentioned in Reaction schemes 83 and 84 can be halogenated and subjected to the Faworski rearrangement with aqueous alkah to give free cyclopropane carboxylic acid, predominantly the trans-isomer [917] (Reaction scheme 87). 

The bark of Croton eluteria (Euphorbiaceae) yields, on steam distillation, cascarilla essential oil which is used as a tonic. The main component of the acid fraction of this oil is cascarillic acid ([aJo -10.5°, methyl ester), a cyclopropane carboxylic acid (123) (79). The stereochemistry of the cyclopropane ring was established as trans by comparing H-NMR spectra and retention times on gas chromatograms of methyl esters of the synthetic trans- and cw-isomers with those of the natural compound (147). It is interesting that compounds with closely related structures have been found in an algae and in an insect. Dictyopterene A (124) was isolated from the essential oil of algae of the genus Dictyopteris (77) and (Z)-3-decenoic acid from carpet beetle, Anthrenus flavipes, as a sex pheromone (41). 

Permethrinic acid has two enantiomer pairs and four isomers (2" = 4) (Table B33, Appendix B). The acid leaving group for permethrin, cypermethrin, and cyfluthrin is permethrinic acid. The structure of this acid is given in Table 3. Angerer and Ritter (1997) separated the methyl esters of cis- and trans-permethrinic acid on a polysiloxane capillary column by GC (Table C18, Appendix C). The carboxylic acids of several of these pyrethroids were also listed as trans- or cw-3-(2, 2-dichlorovinyl)-2, 2-dimethyl cyclopropane carboxylic acid. The acids may be separated on a CHIREX phase 3005 column (Phenomenex, 2320 W 205th Street, Torrance, CA 90501) by HPLC. 

Humans eliminated conjugates of 3-phenoxybenzoic acid (CAS no. 3739-38-6), 3-(4 -hydroxyphenoxy) benzoic acid (CAS no. 35065-12-4), and cyclopropane-carboxylic acid (DCCA CAS no. 55701-05-8) in urine according to Woollen et al. (1992). In the Woollen et al. study, cypermethrin was administered orally to six male volunteers as a single dose (3.3 mg cis trans 1 1) and dermally to six volunteers at a dose of 31 mg/800 cm (cis trans 56 44) of skin. Cypermethrin was orally absorbed between 27 and 57% (mean of 36%) based on the elimination of DCCA and four times greater based on the recovery of benzoic acid conjugates. In the case of the dermal studies, 1.2% of the appUed dose was recovered in urine as benzoic acid conjugates. 

Hydrolysis of the pyrethroids may occur prior to hydroxylation. For dichloro groups (i.e., cyfluthrin, cypermethrin and permethrin) on the isobutenyl group, hydrolysis of the trans-isomers is the major route, and is followed by hydroxylation of one of the gem-dimethyls, the aromatic rings, and hydrolysis of the hydroxylated esters. The cis-isomers are not as readily hydrolyzed as the tran -isomers and are metabolized mainly by hydroxylation. Metabolism of the dibromo derivative of cypermethrin, deltamethrin, is similar to other pyrethroids (i.e., cyfluthrin, cypermethrin, and permethrin) that possess the dichloro group. Type 11 pyrethroid compounds containing cyano groups (i.e., cyfluthrin, cypermethrin, deltamethrin, fenvalerate, fenpropathrin, and fluvalinate) yield cyanohydrins (benzeneacetonitrile, a-hydroxy-3-phenoxy-) upon hydrolysis, which decompose to an aldehyde, SCN ion, and 2-iminothia-zolidine-4-carboxylic acid (TTCA). Chrysanthemic acid or derivatives were not used in the synthesis of fenvalerate and fluvalinate. The acids (i.e., benzeneacetic acid, 4-chloro-a-(l-methylethyl) and DL-valine, Af-[2-chloro-4-(trifluoromethyl) phenyl]-) were liberated from their esters and further oxidized/conjugated prior to elimination. Fenpropathrin is the oifly pyrethroid that contains 2,2,3,3-tetramethyl cyclopropane-carboxylic acid. The gem-dimethyl is hydroxylated prior to or after hydrolysis of the ester and is oxidized further to a carboxylic acid prior to elimination. 

Ethyl chrysanthemate (ethyl 2,2-dimethyl-3 c and t -[2-methylpropenyl]-cyclopropane carboxylate) [97-41-6] M 196.3, b 98-102 /llmm, 117-121 /20mm. Purified by vacuum distn. The free trans-acid has m 54° (from, EtOAc) and the free cis-acid has m 113-116° (from EtOAc). The 4-nitrophenyl ester has m 44-45° (from pet ether) [Campbell and Harper J Chem Soc 283 1945 IR Allen et al. JOrg Chem 21 29 1957]. 

A solution of the above ester (207.8 grams) and 64.5 grams of sodium hydroxide in 80 cc of water and 600 cc of ethanol is refluxed for 9 hours. The carboxylic acid of 2-phenyl-cyclopropane is liberated with 200 cc of concentrated hydrochloric acid. The 2-phenyl-cyclopropanecarboxylic acid contains 3 to 4 parts of the trans isomer to 1 part of the cis isomer. The acid is recrystallized from hot water. The pure trans isomer comes out as crystalline material (solid) while the cis isomer stays in solution. 

A second example of the use of ionic chiral auxiliaries for asymmetric synthesis is found in the work of Chong et al. on the cis.trans photoisomerization of certain cyclopropane derivatives [33]. Based on the report by Zimmerman and Flechtner [34] that achiral tmns,trans-2,3-diphenyl-l-benzoylcyclopropane (35a, Scheme 7) undergoes very efficient (0=0.94) photoisomerization in solution to afford the racemic cis,trans isomer 36a, the correspondingp-carboxylic acid 35b was synthesized and treated with a variety of optically pure amines to give salts of general structure 35c (CA=chiral auxiliary). Irradiation of crystals of these salts followed by diazomethane workup yielded methyl ester 36d, which was analyzed by chiral HPLC for enantiomeric excess. The results are summarized in Table 3. 

Numerous studies of the photoreactions of dihydrofurans have been described. On irradiation 2,3-dihydrofurans are known to undergo conversion to acylcyclopropanes by a pathway involving initial carbon-oxygen bond homolysis. The /i-enamino ester (162), for example, affords the cyclopropane (163) on triplet-sensitized irradiation.138 Similar transformations have been observed in 2,2,4-triacyl-2,3-dihydrofurans,139 and a synthesis of a cis-trans mixture of chrysanthemum carboxylic acid has been accomplished in this way.140 The conversion of the 2-thiazolines(164) to the iV-alkenylthio-amides (165) presumably involves an analogous carbon-sulfur bond homolysis, followed by a 1,2-hydrogen shift in the resulting biradical (166).141... 

Fig. 3.18. Mechanistic details on the transition-metal catalyzed (here Cu-catalyzed) cyclopropanation of styrene as a prototypical electron-rich alkene. The more bulky the substituent R of the ester group C02R, the stronger is the preference of transition state A over D and hence the larger the portion of the trans-cyclo-propane carboxylic acid ester in the product mixture.—The zwitterionic resonance form B turns out to be a better presentation of the electrophilic character of copper-carbene complexes than the (formally) charge-free resonance form C or the zwitterionic resonance form (not shown here) with the opposite charge distribution ( a to the C02R substituent, on Cu) copper-carbene complexes preferentially react with electron-rich alkenes.

Photochemical Fe(CO)5-induced rearrangement of silylated allyl amine 9 gave N-silylated enamine 1015, which on subsequent Cu-catalyzed cyclopropanation by methyl diazoacetate afforded cyclopropane derivative 11. The use of an optically active catalyst gave an asymmetric induction of 56% ee for the cis isomer and 20% ee for the trans isomer. Further acid-induced ring cleavage afforded the -formyl ester 12, whereas reduction and desilylation produced aminocyclopropane carboxylic acid 13 (equation 2). 

The addition products 125 cyclized upon treatment with base to form the corresponding cyclopropane carboxylates which underwent spontaneous de-hydrohalogenation at room temperature to form dihaloalkenes 126 as a mixture of cis/trans diastereoisomers. Hydrolytic cleavage from the support then gave the product acids 127 [ 18]. 

The data in Table 2 show that the rotations of cis-substituted cyclopropanes are often considerably smaller than those of the corresponding trans compounds. If the cyclopropane bears a phenyl ring the relationship between the magnitude of the rotations of cis and trans compounds is not obvious. For instance, the rotation of the cis-phenylcyclopropane carboxylic acid 23 is small compared with the rotation of the trans compound 22 and also the rotation of the cis-phenylcyclopropane 32 is rather small. On... 

Determinations of absolute configurations of trans-cyclopropane-l,2-dicarboxylic acids on the basis of a definite Cotton effect seem to be possible for carboxylic acid thioamides. In these molecules, such as 123a and 123b, there is a Cotton effect near 330 nm which results from the (n, n ) excitation of the thioamide chromophore . In the... 

Hunsdiecker reaction of the silver salts of both cis-(56) and trans-2-methylcyclopropanecarboxylic acid (57) yielded the same mixture of cis- (58) and trans-1-bromo-2-methylcyclopropane (59), thus demonstrating that the 2-methylcyclopropyl radical was incapable of maintaining its configuration . Brominative decarboxylation of the silver salts of exo- (60) and em/o-norcarane-7-carboxylic acid (61) produced the same mixture (16 84) of exo- (62) and entio-7-bromonorcarane (63)". Similarly, cis- and trans-silver 1,2-cyclopropanedicarboxylate gave rise to the same isomer ratio (24 76) of cis- and fraws-1,2-dibromocyclopropane. Consistent with these results is the report that the Hunsdiecker reaction with the silver salt of trans-2,2,3-d3-cyclopropanecarboxylic acid (64) gives an equimolar mixture of cis- (65) and rrans-2,2,3-d3-cyclopropane (66) . 

Cyclopropanation of a,jS-unsaturated AT-methoxy-AT-methylamides 5 with dimethyloxo-sulfonium methanide afforded the cyclopropanecarboxamides 6 in yields far superior to those obtained with the corresponding a,/J-unsaturated ketones. In almost all cases, the trans-isomer was exclusively obtained in analogy to the cyclopropanation of the corresponding unsaturated ketones. The oxygen atom of the methoxy group on the A -methoxy-A -methyl-amide 5 was found to facilitate the reaction. The substituted amides 6 can be converted to ketones (methylmagnesium bromide), aldehydes (diisobutylaluminum hydride) and carboxylic acids (potassium rerf-butoxide/water). It is noteworthy that cyclopropanecarbaldehydes and -carboxylic acids, which are not directly accessible from the corresponding a,)8-unsaturated systems under standard cyclopropanation reactions, can be obtained indirectly by this method. 

At 50% conversion, the product contains three esters, the two cis- 142s and the (I.V,3.V)-/ran.Y ester together with a little (15,35) -trans acid and all of the (I / ,3/ )-permethrinic acid 143. The ratio of these last two is 10 90 but one recrystallisation from petrol gives (l/ ,3/ )-permethrinic acid 143 in 98% ee. This approach works for several different cyclopropane-based carboxylic acids in much the same way. 

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