Cyclopropanecarboxylic acid, and

The solution is then cooled in an ice bath and acidified by 200 g. of concentrated sulfuric acid (sp. gr. 1.84) previously mixed with 300 g. of cracked ice. The solution is again cooled in an ice bath. The thick floating layer of cyclopropanecarboxylic acid and various polymers is separated and the cold aqueous solution extracted once with 1 1. of ether, using a stirrer instead of shaking (Note 5). The extract and crude acid are combined and dried over SO g. of Drierite, and the solvent is removed in a 500-ml. modified Claisen flask2 on a steam bath. The residue is then distilled under reduced pressure. The yield of acid boiling at 94-95°/26 mm. or 117—118°/75 mm. is 63.5-68 g. (74-79%) (Note 6). 

In the examples given the preparative value depends upon the ready availability of the required methyl ketone thus pinacolone (Expt 5.98), cyclopropyl methyl ketone (Expt 7.1) and mesityl oxide (Expt 5.213) are converted into 2,2-dimeth-ylpropanoic acid, cyclopropanecarboxylic acid and 3,3-dimethylacrylic acid respectively (Expts 5.124 and 5.125). 

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. 

Since the two esters I and II are not available commercially, they will be synthesized by a procedure that is basically that of Jeffeiy and Vogel. The starting materials for the syntheses are the free acids, cyclopropanecarboxylic acid and cyclohexanecarboxylic acid. Each is first converted to the acid chloride with thionyl chloride, and the acid chloride is then allowed to react with the appropriate alcohol to form the ester. Alternatively the acid chlorides can be obtained commercially from Aldrich Chemical Co., Inc., Milwaukee, Wisconsin, and the first part of the syntheses can be dropped. The purity of the two esters is checked by refractometry, infrared spectroscopy, and vapor-phase chromatography and the heats of combustion are determined with a bomb calorimeter. It is suggested that each student in the team synthesize and check the purity of one of the esters and that both work together on the calorimetric measurements. 

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... 

The configurations of these hydroxy acids were assigned by NMR spectroscopy and comparison with the data of some alkylated cyclopropanecarboxylic acids and 1-hydroxycyclo-propanecarboxylic acids. Chemical evidence for the exo configuration of the carboxy group and endo configuration of the hydroxy group resulted from the preparation and reaction of a norcarene-7-carboxylic acid, i.e. the 7-hydroxy-cw-bicyclo[4.1.0]hept-3-ene-exo-7-carboxylic acid (10a). 

The Curtius rearrangement has been extensively utilized for the synthesis of numerous cyclo-propylamines 4 from cyclopropanecarboxylic acids 1. The necessary acyl azides 2 are most conveniently obtained by reaction of sodium azide with the mixed anhydride of the cyclopropanecarboxylic acid and ethyl chloroformate. ... 

Various cyclopropanecarboxylic acids and esters have been converted to various amides, TV-alkylated amides, and hydrazides by treatment with ammonia, alkylamines, - and hydrazines, respectively. In many cases the acids have been converted via the corresponding acid chlorides generated in situ. Diethyl esters of a variety of cyclopropane-1,1-dicarboxylic acids also react with urea. Generally, all these reactions proceed smoothly and in fairly good yield and give only very small amounts of byproducts due to opening of the cyclopropane ring. 

The etiolate of cyclopropanecarboxylic acid and its derivatives is an important building block for organic synthesis.However, the strained methylenecyclopropane structure of the enolate renders this species not only difficult to prepare, but also unstable. A rather simple method for the preparation of substituted 2-cyclopropylidene-5,5-dimethyl-l,3-dioxanes 15 is the thermolysis of the corresponding 2-alkylidenecyclopropanone acetals 14 which rearrange at 150 °C to the hydrolytically unstable ketene acetals. 

R. erythropolis AJ270 Cyclopropane, oxirane, aziridine carbonitriles Enantiopure trans- and cis-cyclopropanecarboxylic acids and carboxamides, oxirane and aziridine carboxamides Chemoenzymatic synthesis of various building blocks [100-104]... 

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. 

Twenty-four grams (0.11 mole) of red mercuric oxide (Note 1) and 60 ml. of freshly distilled 1,1,2,2-tetrachloroethane are placed in a 250-ml. three-necked flask equipped with a dropping funnel, a reflux condenser, and a stirrer. A solution of 32.2 g. (0.20 mole) of bromine and 17.2 g. (0.20 mole) of cyclopropanecarboxylic acid in SO ml. of tetrachloroethane is added dropwise to the stirred suspension of mercuric oxide over a period of 45 minutes, the flask being kept in a water bath at 30-35° (Note 2). The mixture is stirred after the addition of the reactants until the evolution of carbon dioxide ceases. 

The protocol is effective in preparation of hydrazides of 5 carbons or less. Cyclopropanecarboxylic acid hydrazide15 and isobutyric acid hydrazide16 were prepared from their corresponding acid chlorides in 64% and 71% yields, respectively. However, when this method was applied to cyclohexanecarboxylic acid chloride, the bis-acylhydrazide was the predominant product, and the mono-acylhydrazide17 was isolated in 25% yield.18... 

In contrast to the synthesis of carbocyclic rings, the Cope rearrangement has been used sparsely for generating azepinones. Recently, the enantioselectivity of the conversion of 2-aza-divinylcyclopropane 286 has been investigated. The synthesis started from the optically active cyclopropanecarboxylic acid (90% ee), which had been converted into the isocyanate 286 by initial azidation to 285 and a consecutive Curtius rearrangement. Furthermore, the conditions of the iso-... 

GABAc receptors are defined by their insensitivity to bicuculline and their activation by conformationally restricted analogues of GABA such as CACA and (+)-CAMP (15, 2i -2-(aminomethyl)cyclopropanecarboxylic acid). They are blocked by picrotoxin but can be selectively antagonised by TPMPA (l,2,5,6-tetrahydropyridin4-ylphosphinic acid). Unlike GABAa receptors, they are not affected by benzodiazepines, barbiturates or anaesthetics (Barnard et al. 1998 Bormann 2000 Chebib and Johnston 2000). 

Martel J, Tessier J, Demoute JP (1978) New esters of cyclopropanecarboxylic acids with a polyhalogenated substituent, preparation and pesticidal compositions. Ger Offen 2,742,546... 

In a recent study, chiral separations for pyrethroic acids, which are the chiral building blocks of synthetic pyrethroids and the primary metabolites of the acid part of these potent ester insecticides, have been developed [62], For example, a polar-organic mobile phase allowed the complete baseline resolution of all four stereoisomers of chrysanthemic acid (2,2-dimethyl-3-(2-methylprop-l-enyl)-cyclopropanecarboxylic acid) on a 0-9-(tcrt-butylcarbamoyl)quinine-based CSP(acjj = 1.20, oLtrans = 1-35, critical Rs = 3.03) (Figure 1,32a). This chiral acid is the precursor of pyrethroids like allethrin, phenothrin, resmethrin, and tetramethrin but not excreted as metabolite. The primary acid metabolite of these pyrethroids is chrysanthemum dicarboxylic acid (3-[(l )-2-carboxyprop-l-enyl]-2,2-dimethylcyclopropanecarboxylic acid) the stereoisomers of which could also be resolved with a reversed-phase eluent (acetonitrile— 30-mM ammonium acetate buffer 90 10, v/v pHa = 6.0) and employing an O-9-(2,6-diisopropylphenylcarbamoyl)quinine-based CSP ads = 1-09, atrans = 1-50,... 

Table III. Biological Activity of Bridged Biphenyl and Heteroaromatic Bridged Biphenyl Esters of cis-3-(2 Chloro3.3,3-trifluoro-l-propenyl)-2,2-dimethyl-cyclopropanecarboxylic acid...

Some variations of the method have been used to prepare cyclopropyl and cyclobutyl halides. Simultaneous addition of bromine and 3-bromocyclobutanecarboxylic acid to the suspension of mercuric oxide gives 1,3-dibromocyclobutane in good yield.7 Similarly, cyclopropanecarboxylic acid gives bromo-cyclopropane,9 and 3-(bromomethyl)cyclobutanecarboxylic acid gives 3-(bromomethyl)cyclobutyl bromide.10 In the latter reaction, it was found desirable to remove the water from the reaction as it is formed in order to obtain high yields. Another variation is the addition of a mixture of the acid and mercuric oxide to excess bromine in bromotrichloromethane.6... 

In the following we shall focus on heterogeneous acid-base reactions. One of the best known case studies is the reaction of crystalline benzoic acid with ammonia to form 1 1 ammonium salts [19, 20]. Crystalline p-chlorobenzoic anhydride reacts with gaseous ammonia to give the corresponding amide and ammonium salt [22] a similar reaction has been investigated in the case of optically active cyclopropanecarboxylic acid crystals [23]. 

Recently, the cyclopropanation of (Z)-4-benzyIidene-2-phenyl-5(4//)-oxazolone 621 with phenyldiazomethane was reported to give the spirocyclopropane, rac- 21 in very high yield. Subsequent ring opening and hydrolysis of rac- 21 generated frani-l-amino-2,3-diphenyl-l-cyclopropanecarboxylic acid, rac-828 (cadiPhe) (Scheme 7.256). This new, constrained phenylalanine analogue induces a y-tum in the sohd state when incorporated into model dipeptides. The enantiomers of the Al-Boc (Boc = tert-butyloxycarbonyl) methyl ester of 828 have been resolved by HPLC. 

The trapping of lithiohalocyclopropanes by carbon dioxide, aldehydes and acid chlorides, respectively, constitutes a useful route to the corresponding cyclopropanecarboxylic acids, alcohols and ketones. In the case of ketones an intramolecular loss of lithium bromide may take place yielding spiroepoxides which in turn may be isomerized to cyclobutanones. 

The cyclopropane ester was prepared by the reaction between 16 g (t)-butyl 2,5-dimethoxy-4-methylcinnamate and dimethylsulfoxonium methylide, prepared as described in the Kaiser reference in the acknowledgements. Hydrolysis of this ester gave 53% trans-2-(2,5-dimethoxy-4-methylphenyl)cyclopropanecarboxylic acid which, after recrystallization from a MeOH/... 

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