Cyclopropanecarboxylic acid synthesis

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-... 

CYCLOPROPANECARBOXYLIC ACID, cis-2-PHENYL-, 50, 94 Cyclopropane derivatives, synthesis, 52, 22, 33, 132 Cyclopropenes, 50, 30 Cyclopropenone, di-tert-buty1-,... 

Cyclopentanes, synthesis, 66, 10 CYCLOPEKTANONE SYNTHESIS, 66, 87, 92, 93 Cyclopentanone, 2-carbomethoxy-3-vinyl, 66, 56 Cyclopentanone, 2-ethenyl-2-methyl (88729-76-4), 66, 94 2-CYCLOPENTEN-l-ONE, 3-METHYL-2-PENTYL-, 65, 26 Cyclopropane, l-trimethy1s1lyloxy-1-ethoxy-, 56, 44 Cyclopropanecarboxylic acid chloride, 66, 176... 

Cyclopropanecarboxylic acid may be prepared by a malonic ester synthesis, as retrosynthetic analysis shows. 

Aratani, T. (1985) Catalytic asymmetric synthesis of cyclopropanecarboxylic acids an application of chiral copper carbenoid reaction. Pure Appl. Chem., 57, 1839. 

The 1-ADPM reaction has been used as the key step in the synthesis of a series of cyclopropanecarboxylic acids present in insecticidally-active pyrethrins and pyrethroids [63]. Thus, acetophenone-sensitized irradiation... 

Cyclopropanecarboxylic acid, 1-amino-, deuteriated, enantiospeciflc synthesis, 57, 263... 

The procedme for preparing cyclohexanecarboxyhc acid chloride is exactly the same as that described above for the preparation of cyclopropanecarboxylic acid chloride. In this case f f. 9 g (0.10 mol) of freshly distilled or reagent-grade thionyl chloride and 7.66 g (0.06 mol) of cyclohexanecarboxyhc acid are used. Cyclohexanecarboxyhc acid is a sohd that melts at 31°C, but it is easier to handle as a liquid. As an effective and safe (under normal precautions) method of melting the acid for weighing and addition to the thionyl chloride, apply steam to the exterior of the bottle or the dropping funnel. As with the previous synthesis, one may distiU this acid chloride (bp 125°C/760 Torr), or one may use it without distillation in the next step. 

S. Abele, P. Seiler, D. Seebach, Synthesis, Crystal Structures, and Modelling of P-Oligopeptides Consisting of l-(Aminomethyl)cyclopropanecarboxylic Acid Ribbon-Type Arrangement of Eight-Membered H-Bonded Rings , Helv. Chim. Acta 1999, 82, 1559 - 1571. 

The cyanoacetic ester synthesis with ethylene bromide is preferred to the malonic ester synthesis for the preparation of cyclopropanecarboxylic acid. ... 

In a similar manner, the 2-cyano-6-oxazolopiperidine synthon is useful for the chiral synthesis of in-dolizidine (monomerine piperidine [(+)- and (-)-coniine and dihydropinidine] and quinolizidine alkaloids.2-Hydroxymethyl-1-amino-1-cyclopropanecarboxylic acid (-)-(2I )-hydroxy-(3S)-nonylamine and a-substituted phenylethylamines are obtained in optically active form from (-)-N-cyanomethyl-4-phenyloxazolidine. 

Cleavage of acetates. DePuy used methyllithium in the first and last step of a general method for the synthesis of cyclopropanols from cyclopropanecarboxylic acids, for example traus-2-phenylcyclopropanecarboxylic acid (1). Reaction with 2... 

An aldehyde synthesis utilizing ethylenimine is illustrated by the following example. Reaction of cyclopropanecarboxylic acid chloride with ethylenimine and triethylamine in ether at 0° gives a precipitate of triethylamine hydrochloride and a solution of the 1-acylaziridine (3), which is reduced by lithium aluminum hydride... 

A methodically related transformation, the copper(Il)-mediated transfer of a cyano(ethoxycar-bonyl)methylene unit from ethyl cyanoacetate to alkenes, is presented in Section I.2.I.2.4.2.9. The copper-mediated synthesis of cyclopropyl ketones from a,a-dibromo ketones and alkenes seems to be of very limited scope and even less efficient than the corresponding synthesis of cyclopropanecarboxylic acids from o ,a-dibromoacetates (vide supra). The reaction (toluene, 100°C, 93 h) of cyclooctene (4.0 mmol), dibromomethyl phenyl ketone (8.0mmol), and commercial grade copper powder (18 mmol) activated with iodine (0.2 mmol) gave exy-9-benzoyl-bicyclo[6.1.0]nonane (7, 12%) and (2-oxo-2-phenylethyl)cyclooct-l-ene (8, 3%). ° A similar treatment of styrene gave l-benzoyl-2-phenylcyclopropane in only 2% yield [ratio (cisjtrans) 1 l.b]. " ... 

As the reaction of 2-bromocyclobutanone with 1,2-phenylenediamine was carried out in 80% acidic aqueous methanol, ring contraction of a 2-bromocyclobutanone hydrate, hemiacetal or dimethyl acetal to cyclopropanecarboxylic acid (Section 4.1.2.2.4), followed by a Philipps-type benzimidazole synthesis could explain the formation of the 2-cyclopropylbenzimidazole (8). However, the reaction proceeded equally well in an aprotic solvent such as chloroform. Therefore, direct ring contraction of a 2-bromo-l,l-(l,2-phenylenediamino)-... 

The Wolff rearrangement of six- and five-membered a-diazocycloalkanones has been extensively applied to the synthesis of highly strained frameworks. The rearrangement of an (x-diazo-cyclobutanone was reported from 2-diazo-3,4-bis(diphenylmethylene)cyclobutanone (1). The diazo ketone (1) was prepared by treatment of the 3,4-bis(diphenylmethyl-ene)cyclobutane-l,2-dione tosylhydrazone with alumina in 95% overall yield from the corresponding cyclobutanedione. Irradiation in the presence of water, alcohols and aniline afforded 1-carboxy-, 1-alkoxycarbonyl- and 1-phenylcarbamoyl-substituted 2,3-bis(diphenyl-methylene)cyclopropanes 2, respectively, in 13-87% yields. Thermal decomposition in aqueous dioxane afforded the cyclopropanecarboxylic acid 2 (X = OH) in 52% yield. ... 

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. ... 

Table 2. Stereoselective Synthesis of Aminocyclopropanes by the Curtins Rearrangement of Cyclopropanecarboxylic Acids...

With the correct choice of reaction conditions, however, the asymmetric synthesis of cis-suh-stituted cyclopropanecarboxylic acid derivatives is achieved. Stereoselective methylene transfer to (Z)-a, -unsaturated acyl systems bonded to optically active carbonyl()j -cyclopen-tadienyl)triphenylphosphanyliron 2 and oxidative decomplexation of the products gave cis-substituted cyclopropanecarboxamides 3. High asymmetric induction (up to 92% de) was observed with bromine/l-phenylethylamine as decomplexation agent. When the decomplexation was carried out with A-bromosuccinimide/ethanol, racemic cw-substituted cyclopropanecarboxylic acid esters were obtained. 

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. 

Janecki, T., A convenient synthesis of substituted 2-cyano-l,3-butadienes, Synthesis. 167, 1991. Ting, P.C., and Solomon, D.M., Synthesis of spiro[4, 5, 10,11-tetrahydro-5//-dibenzo[a,d]cyclohep-ten-5-yl-2 (37/)-furans] as potential cytokine inhibitors, J. Heterocycl. Chem., 32, 1027, 1995. Armesto, D., flail ego, M.G., Horspool, W.M., and Agarrabeitia, A.R., A new photochemical synthesis of cyclopropanecarboxylic acids present in pyrethroids by the aza-di-Jt-methane reanangement. Tetrahedron, 51, 9223, 1995. 

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