Cyclopropanecarboxylate compounds

Recently, a series of triorganotin butyrates and cyclopropanecarboxylates were reported to be effective against the second instar stage of the Cx. P. quinquefasciatus mosquito. The toxicities, in ppm, ranged from 0.39 to 3.21 for the butyrates, while the cyclopropanecarboxylate compounds had toxicities that ranged from 0.31 to 1.09 ppm. ... 

The first nonintroductory section of the text starts with the observation made early in this century that cyclopropanes have significant olefinic character. That is, corresponding ethylene and cyclopropane derivatives have significant similarities. There are literature comparisons of the thermochemistry of direct counterparts such as the parent species (1 and 2, X = H), propene and methylcyclopropane with X = Me, and of methyl acrylate and methyl cyclopropanecarboxylate 8 with X = COOMe. But the chemistry of substituted eth-ylenes is far richer than just that of vinyl compounds. One can retrieve enthalpy of formation data for cumulenes ( cumulenated olefins) such as allene (3) and both cis- and trans-2,3,4-hexatriene (4a and 4b), and for conjugated olefins such as 1,3-butadiene (5) and both (Z)- and (E)-1,3,5-hexatriene (6a and 6b). For the cyclopropane chemist it is natural to... 

We acknowledge that methylcyclopropane is no less a substituted cyclopropane as is methyl cyclopropanecarboxylate. However, for the former species we use the hydrocarbon equation 3 with nc = 4, and for the latter species we use the substituted compound equation 4 with b = 10.5 (for esters) and flc = 5 (remember the carbonyl carbon in calculating the number of nonquaternary carbons). 

Similarly, 144 has been obtained from the reaction of 1-trimethylsilylcyclopropyl methyl selenide with n-BuLi The a-bromosilane 147 underwent lithiation with n-BuLi in THF at —78 °C to provide 144 with superior efficiency to any other method, Eq. (46))81). 147 was prepared in large quantities by the Hunsdiecker degradation of the 1-trimethylsilylcyclopropanecarboxylic acid 146, obtained by successively reacting the commercially available cyclopropanecarboxylic acid with -BuLi (2 equivalents) and ClSiMe3 82). Uneventfully, 144 added to carbonyl compounds, except for cyclopentanone where enolate anion formation competed the 1-trimethylsilylcyclo-propylcarbinols 148 underwent acid-induced dehydration to the expected 1-trimethyl-silylvinylcyclopropanes 149 79-81) while base induced elimination (KH, diglyme, 90 °C) led to cyclopropylidenecycloalkanes 150 77), Eq. (47). 

As mentioned in the last paragraph, the methodology employing Lewis acids for activation of siloxycyclopropanes has certain restrictions with regard to the substitution pattern. Therefore an alternative path to prepare hydroxyalkylated adducts would be most valuable. It can actually be achieved via enolates of methyl 2-siloxy-cyclopropanecarboxylates, which add cleanly to many carbonyl compounds (Eq. 83)96). 

The procedure described here for compound 1 is a scaleup of a published method.6 Phase-transfer catalysis7 and concentrated alkali are used to effect a one-pot conversion of diethyl malonate to the cyclopropane diacid, which is easily obtained by crystallization. Apparently alkylation of the malonate system occurs either at the diester or monocarboxylate, monoester stage since the method fails when malonic acid itself is used as the starting material. This method of synthesizing doubly activated cyclopropanes has been extended to the preparation of 1-cyanocyclopropanecar-boxylic acid (86%) by the use of ethyl cyanoacetate and 1-acetyl-cyclopropanecarboxylic acid (69%) by use of ethyl acetoacetate.6... 

J. S. Chickos, D. G. Hesse, J. F. Liebman and S. Y. Panshin, J. Org. Chem., 53, 3435 (1988). In the absence of a literature value suggested for a desired enthalpy of vaporization for a substituted hydrocarbon, this CHLP protocol will be used implicitly to estimate the desired quantity. We acknowledge that methylcyclopropane is no less a substituted cyclopropane as is methyl cyclopropanecarboxylate. However, for the former species we use the hydrocarbon equation 3 with Pic = 4, and for the latter species we use the substituted compound equation 4 with Z = 10.5 (for esters) and fic= 5 (remember the carbonyl carbon in calculating the number of nonquaternary carbons). 

The strain energy of the cyclopropane ring is determined from thermochemical measurements on two closely related compounds the /r-butyl ester of cyclopropanecarboxylic acid and the methyl ester of cyclohexanecarboxylic acid. Both compounds can be synthesized from the appropriate acid chlorides, and their heats of combustion measured with a bomb calorimeter. 

Cyclopropanecarboxylic acids and their derivatives generally achieve bisected conformations VI so that the n systems of the carboxy group and the A-component of the 3e orbital of 112 can interact conjugatively " This type of interaction is depicted for the HOMO of a cyclopropanecarboxylic acid in XXIII. In the liquid phase mostly mixtures of cis and trans (VIII, VI) conformers of cyclopropanecarboxylic acids are found. In the parent compound, cyclopropanecarboxylic acid, the cis form seems to be preferred For substituted cyclopropanecarboxylic acids, however, different conformer populations may... 

For the preparation of long chain alkanes from fatty acids it is useful to extract the electrolyte contin-ously with a high-boiling nonpolar solvent, e.g. 2-methylheptane. Cyclopropanecarboxylic acids in some cases have been dimerized, e.g. or (15) in other cases the radical is further oxidized to a carbocation which then undergoes ring opening and solvoiysis to allylic compounds. Specifically substituted 1,2-diphenyiethanes have been prepared from phenylacetic acids (Table 2, entries 22 and 23). A variety of 2,3-disubstituted succinic acids and their derivatives have become accessible from malonic... 

The cyclopropanation of gaseous alkenes, butadiene, and allene (see Section 1.2.1.2.4.2.6.3.3., Table 11, entry 1) by diazoacetic esters can be achieved by passing a vapor-gas mixture of the alkene and the diazo compound at atmospheric pressure through a tubular continuous flow reactor which contains a copper catalyst (ca. 10%) deposited on pumice. In this manner, alkyl cyclopropanecarboxylates were obtained in yields of up to 50% with cop-per(II) sulfate (typical reaction temperature 65-110"C, contact time 3.6 s) or copper(II) oxide (85-200°C, 5s) as catalysts. 

Dicarbonyl compounds can be cleaved oxidatively using peracids this protocol has been used to prepare cyclopropanecarboxylic acids from a dicyclopropylethanedione, e.g. 2 from 1 and several 2-cyclopropyl-2-oxoacetic acids. " An appropriately substituted 1,3-diketone has also been converted to a cyclopropanecarboxylic acid by basic hydrolysis. When a hydroxy group is attached p to the carbonyl group of an alkyl cyclopropyl ketone, periodate oxidation afforded a similar acid in quantitative yield. ... 

Cyclopropyl ketones and lactams as well as amides of cyclopropanecarboxylic acids were converted to the corresponding thiocarbonyl compounds on reaction with 2,4-bis(4-methoxyphenyl)-l,3,2,4-dithiadiphosphetane-2,4-dithione (Lawesson s reagent) in benzene or toluene the yields were good. For example, reaction of lactam 1 to give thione 2. Thiones were also formed when hydrazones were treated with sulfur monochloride. ... 

Thioamides of two cyclopropanecarboxylic acids undergo coupling reactions with diazomethane derivatives in refluxing benzene containing rhodium(II) acetate. The reaction conceivably takes place via a thiirane intermediate which undergoes reductive elimination by reaction with excess diazo compound. An example of an intramolecular reaction is the formation of indolizine 2. If the diazo compound is not in excess a thiol is formed, this can be removed by Raney nickel desulfurization. ... 

The carbenoid reaction between alkyl diazoacetates and enol ethers, enol acetates and silyl enol ethers furnishes P-oxycyclopropane carboxylates (see Tables 2, 4, 5, 6, 7 and Scheme 5). The recently recognized synthetic versatility of these donor/acceptor-substituted cyclopropanes i 2,io3) (precursors of 1,4-dicarbonyl and P, 7-unsaturated carbonyl compounds, 4-oxocarboxylic acids and esters, among others) gave rise to the synthesis of a large number of such systems with a broad variation of substituents p-acetoxycyclopropanecarboxylates , p-alkoxy- or p-aryloxysubstituted cyclopropanecarboxylates 2-alkoxy-1-methyl-1-cy-... 

This method of asymmetric cyclopropanation using copper catalysts which are chirally modified with salicylaldimines of optically active amines has been intensively investigated and numerous modifications of the ligands have been tested24-40-43. The use of chiral amino alcohols derived from amino acids is exceptionally successful. Thus, 2-methylpropene with ethyl diazoacetate in the presence of R-7644 (Sumitomo catalyst) gives ethyl (LS)-2,2-dimethyl-1-cyclopropanecarboxylate (2) with 92% ee, on an industrial scale24. This compound is used as a precursor of cilastm, an enzyme inhibitor. 

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