Cyclohexanone-2-carboxylic esters

The a-arylation of ketones, such as cyclohexanone, can be achieved using different methods. A convenient route by Pinhey et al.89), reacts cyclohexanone-2-carboxylic esters with aryllead triacetates in pyridine. The protection of the P-carboxylic ester prevents a,a-di- or even higher arylations in a -positions. The ester group can be removed by basic hydrolysis and mild thermal decarboxylation or by heating in wet dimethylsulfoxide with sodium chloride (120-180 °C)90). Barton et al. 91) have found a similar a-arylation route using the less electrophilic triphenylbismuth carbonate. In both cases probably the lead- or bismuth-enolates, respectively, are the first inter-... 

Cyclohexanone-2-carboxylic esters. The reagent acts as a condensation catalyst for twofold Michael additon of a donor to an acrylate ester and Dieckmann cyclization of the 1 2 adducts. However, NaOMe has the same capability therefore, Na2pe(CO)4 is not unique. 

Intramolecular Claisen condensations, called Dieckmann condensations, are ringclosing reactions that yield 2-cyclopentanone carboxylic esters (Figure 10.52) or 2-cyclohexanone carboxylic esters. The mechanism of the Dieckmann condensation is, of course, identical to the mechanism of the Claisen condensation (Figure 10.51). To ensure that the Dieckmann condensation goes to completion, the presence of a stoichiometric amount of base is required. As before, the neutral /3-ketoester (B in Figure... 

In competition with these amination reactions, intramolecular aminations can occur, and they become the main reaction in certain cases. The oxaz-iridine 61, derived from cyclohexanone, reacts with methoxide to give the phenylhydrazine carboxylic ester, and with cyclohexylamine to the sub-... 

The action of peroxyacids, such as Caro s acid, on cyclic ketones affords co-hydroxy carboxylic acids or their lactones, the latter being convertible into co-hydroxy carboxylic esters by the action of an alcohol and an acid cyclohexanone, for instance, gives a 6-hydroxyhexanoic ester in this way 126,127... 

The Gewald synthesis of 2-aminothiophen-3-carboxylic acid derivatives has been extended to cyanoacetic acid hydrazides. In the base-catalysed reaction with cyclohexanone and sulphur, the hydrazides yielded the thienopyrimidone derivative (24), which could be hydrolysed to the 2-aminothiophen-3-carboxylic acid hydrazide (24a). A series of substituted 2-aminothiophen-3-carboxylic esters have been prepared by a... 

This cyano-ester is hydrolysed by boiling with concentrated hydrochloric acid with the formationof pentane-ay -tricarboxylic acid, CO H. CH (CHj. CHj. COjH) andiwhen the sodium salt of this acid is heat with acetic anhydride and distilled, decomposition takes place with the formation of 8-ketohexahydrobenzoic acid or cyclohexanone-4-carboxylic acid—... 

The next step was to convert cyclohexanone-4-carboxylic acid into l-methyl-cyclohexanol-4-carboxylic acid, and this is readily accomplished by heating the ester of the ketonic acid with magnesium methyliodide in the usual manner—... 

By oxidation with chromic acid, this is converted into cyclohexanone-3-carboxylic acid, in which the —CH. OH— group is converted into the —CO— group. This is converted into its ethyl ester and treated with magnesium methyl iodide, and the product, on hydrolysis, yields l-methyl-cyclohexane-l-ol-3-carboxylic acid, which is converted byhydro-bromic acid into 1-bromo-l - methyl - cyclohexane - 3 - carboxylic acid. When this is digested with pyridine, hydrobromic acid is eliminated and yields l-methyl-A -cyclohexane-3-carboxylic acid of the formula—... 

Most carbonyl compounds exist almost exclusively in the keto form at equilibrium, and it s usually difficult to isolate the pure enol. For example, cyclohexanone contains only about 0.0001% of its enol tautomer at room temperature, and acetone contains only about 0.000 000 1% enol. The percentage of enol tautomer is even less for carboxylic acids, esters, and amides. Even though enols are difficult to isolate and are present only to a small extent at equilibrium., they are nevertheless responsible for much of the chemistry of carbonyl compounds because they are so reactive. 

Brominate cyclohexanone-2-COOH (JACS 72,2127(1950)) and cover to the ethyl ester. Add 1M ethyl-3-Br-cyclohexanone-2-carboxylate to 2M p-methoxy-aniline in cold benzene. Recrystallize the product from ether-petroleum ether and reflux sixteen hours in presence of ZnCl2 in dry ethanol. Filter, evaporate in vacuum and recrystallize-petroleum ether. Dehydrogenate with 5% palladium-... 

The starting point for the 5-fluoropentanecarboxylic esters was cyclohexanone, which was oxidized to 5-hydroxypentane-carboxylic acid by a modification of Robinson and Smith s method.3 This was then converted into the bromo acid by means of hydrogen bromide and sulphuric acid.4... 

Salicylic acid, upon reaction with amyl alcohol and sodium, reduces to a ring-opened aliphatic dicarboxylic acid, ie, pimelic acid (eq. 5). The reaction proceeds through the intermediate cyclohexanone-2-carboxylic acid. This novel reaction involves the fission of the aromatic ring to tfj-hexahydrosalicylic acid when salicylic acid is heated to 310°C in an autoclave with strong alkali. Pimelic acid is formed in 35—38% yield and is isolated as the diethyl ester. 

Highly stereoselective aldol reactions of lithium ester enolates (LiCR1 R2CC>2R3) with (/0-2-(/ -tolylsulfiny I (cyclohexanone have been attributed to intermediacy of tricoordinate lithium species which involve the enolate and the sulfinyl and carbonyl oxygens of the substrates.43 The O-metallated /<-hydroxyalkanoatcs formed by aldol-type reaction of carbonyl compounds with enolates derived from esters of alkanoic acids undergo spontaneous intramolecular cyclization to /1-lactones if phenyl rather than alkyl esters are used the reaction has also been found to occur with other activated derivatives of carboxylic acids.44... 

This microflow processing was also demonstrated using other P-keto esters such as ethyl 2-chloro-3-oxobutanoate [309,273] or ethyl 2-methyl-3-oxobutanoate [273]. Five-and six-ring P-ketoester derivatives such as 3-acetyl-3,4,5-trihydrofuran-2-one (1) [273], 2-acetyl cyclohexanone [273] and ethyl 2-oxocydohexane carboxylate (2) [273] were directly fluorinated as well. 

Favorskii rearrangement of cyclic 2-bromoketones leads to ring contraction and this has become one of the most fruitful uses of the rearrangement in synthesis. Bromination of cyclohexanone is a simple reaction (Chapter 21) and treatment with methoxide gives the methyl ester of cyclopentane carboxylic acid in good yield. 

Oxygen donor substrates continue to be extensively studied. Conformations of esters, (427) aldehydes and ketones, (428, 429) ketones, (430, 431) cyclohexanones, (432, 433) carboxylates, (434) benzene-1,2-dioxydiacetate, (435) borneols, (436) troponeiron tricarbonyl, (437) and nitrosopiperidines (438) have been deduced. It is... 

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