Cyclopropane carboxylates, from

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]. 

Preparation of 2-Cyclopropylcarbony/amido-5-Chlorobenzophenone To 400.5 g (1.73 mols) of 2-amino-5-chlorobenzophenone dissolved in 220 g (2.18 mols) of triethylamine and 3.5 liters of tetrahydrofuran is added cautiously 181 g (1.73 mols) of cyclopropane-carboxylic acid chloride. The reaction is refluxed 2 /2 hours and allowed to cool to room temperature. The solvent is then removed under vacuum to obtain 2-cyclopropylcarbonyl-amido-5-chlorobenzophenone as a residue which is dissolved in 1 liter of methylene chloride, washed twice with 5% hydrochloric acid, and then twice with 10% potassium hydroxide. The methylene chloride solution is then dried over anhydrous magnesium sulfate, filtered and the solvent removed under vacuum. The residue is recrystallized from 1,500 ml of methanol, charcoal-treating the hot solution to give 356 g of 2-cyclopropylcarbonylamido-5-chlorobenzophenone, MP 105° to 105.5°C (69% yield). 

Nitrocyclopropane-l-carboxylate is prepared in 71% yield by nitration of the enolate derived from the cyclopropane carboxylate with isoamyl nitrate (Eq. 2.24). It is a precursor of... 

Diazomethane is also decomposed by N O)40 -43 and Pd(0) complexes43 . Electron-poor alkenes such as methyl acrylate are cyclopropanated efficiently with Ni(0) catalysts, whereas with Pd(0) yields were much lower (Scheme 1)43). Cyclopropanes derived from styrene, cyclohexene or 1-hexene were formed only in trace yields. In the uncatalyzed reaction between diazomethane and methyl acrylate, methyl 2-pyrazoline-3-carboxylate and methyl crotonate are formed competitively, but the yield of the latter can be largely reduced by adding an appropriate amount of catalyst. It has been verified that cyclopropane formation does not result from metal-catalyzed ring contraction of the 2-pyrazoline, Instead, a nickel(0)-carbene complex is assumed to be involved in the direct cyclopropanation of the olefin. The preference of such an intermediate for an electron-poor alkene is in agreement with the view that nickel carbenoids are nucleophilic 44). 

Scheme 31. Isomer distribution [%] of Rh CFjCOO -catalyzed cyclopropanation of substituted benzenes with methyl diazoacetate at 22 °C. The numbers refer to the percentage of 1,3,5-cyelohepta-triene-7-carboxylate from the total cycloheptatriene isomers.

Finally, an entirely different approach to milnacipran (2) was recently reported in the literature (Scheme 14.6). In this case, the general strategy is based on position-selective deprotonation of cyclopropane carboxamides. Thus, cyclopropane amide 27, which was easily prepared from commercially available cyclopropane carboxylic acid, underwent... 

The checkers obtained cyclopropylcarbinol from the Aldrich Chemical Company, Inc. It can be readily prepared by the reduction of cyclopropane-carboxylic acid with lithium aluminum hydride. ... 

Compounds that affect Host Reactions. Examples of compounds which enhance or induce host reactions to pathogens include 2,2-dichloro-3,3-dimethyl-cyclopropane carboxylic acid (DDCC), probenazole, and fosetyl-Al (4). Although these chemicals do not stop the fungus from penetrating the plant, they are quite effective at preventing colonization through the enhancement of the host s resistance mechanisms. Further studies are needed to elucidate how these resistance mechanisms are triggered. 

Cyancyclopropane,or the nitrile of cyclopropane-carboxylic acid,is easily obtained from -chlor-... 

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]. 

Cyclopropanation of alkenes carrying electron-withdrawing groups with dihalo-carbenes does not take place under the normal reaction conditions unless the dihalocar-bene is generated from trihalomethylphenylmercury compounds. By this procedure acrylonitrile was converted into l-cyano-2, 2-dichlorocyclopropane in 78% yield and other acrylic derivatives are transformed into dichloromethyl cyclopropane carboxylates (186) (equation 46). Treatment of electron-deficient olefins with dibromomethane in the presence of Ni(0) complex/Zinc/Lewis acid seems to be very effective for cyclopropanation. ... 

Weinstock reaction of NaNs with the mixture of the acid (14) and ethyl chloroformate instead of the acid chloride prevented isomerization of the cyclopropane-carboxylic acid chloride (16, R = H) which occasionally occurred with the former procedures. No isomerizations were reported when the azide (15) was prepared via the hydrazide from the ester. 

The acyl azide - isocyanate rearrangement is known to proceed stereospecifically with retention of both optical and geometrical (cis-tranSy endo-exo) configuration. Thus, optically active aminocyclopropanes were obtained from optically active cyclopropane carboxylic acid derivatives A lot of exo-amiobicyclo[n.l.O]alkanes or... 

Prior to the advent of DDT and the organophosphates, the natural pyrethrins (32.33) found considerable use but were limited by their instability. The discovery of permethrin by Michael Elliot (3 4) proved a turning point for the new synthetic pyrethroids. Here were very active compounds that did not suffer from the stability problems of the natural compounds. And even now pyrethroid-like compounds continue to interest synthetic chemists due to their high insecticidal activity and relatively low mammalian toxicity. You would think that by now most of the very active compounds would have been found. but it seems that persistence and originality pay off. Workers at du Pont and FMC detail the structure-activity relationships for two groups of new pyrethroid-like compounds. Chemists at Dow reveal some of the intricacies in the synthesis of the cyclopropane carboxylate end of the molecule. 

The catalytic activity of low-valent ruthenium species in carbene-transfer reactions is only beginning to emerge. The ruthenium(O) cluster RujCCO), catalyzed formation of ethyl 2-butyloxycyclopropane-l-carboxylate from ethyl diazoacetate and butyl vinyl ether (65 °C, excess of alkene, 0.5 mol% of catalyst yield 65%), but seems not to have been further utilized. The ruthenacarborane clusters 6 and 7 as well as the polymeric diacetatotetracarbonyl-diruthenium (8) have catalytic activity comparable to that of rhodium(II) carboxylates for the cyclopropanation of simple alkenes, cycloalkenes, 1,3-dienes, enol ethers, and styrene with diazoacetic esters. Catalyst 8 also proved exceptionally suitable for the cyclopropanation using a-diazo-a-trialkylsilylacetic esters. ... 

The synthetic compounds are obviously esters of a cyclopropane carboxylic acid and a cyanohydrin 202. Enantioselective transesterification of butanol and the acetate 201 of the cyanohydrin using immobilised lipases gives the required (S)-alcohol 202 and the unreacted enantiomer of the acetate (R) -201 easily racemised with Et3N. Reports using different lipases appeared at the same time CHIRAZYME L-6, the lipase from Pseudomonas immobilised on sephadex DEAE was used in i-Pr20 and the racemisation carried out with Et3N under reflux in the same solvent.55... 

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