2-Cyclohexanone carboxylic acid esters

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. 

This represents probably one of the earliest interests in the chemistry of Ti compounds." Ketones, like cyclohexanone, are easily dimethylated by MeTiCb, Me2 IlCl2 and Me2Zn/riCU- " Depending upon the molecular ratio of Mc2Zn and TiCU, various products (43), (154) and (155) are obtained from cyclohexanone (equation 57), as is reported in Table 1S. The reaction proceeds dirough cationic intermediates various functionalities (e.g. carboxylic acid esters, primary and secondary alkyl halides) are well tolerated. Some problems arise when a,3-unsaturated ketones are utilized, because of the formation of two distinct dimethylated products (equation 58). ... 

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—... 

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... 

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. 

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... 

Initially, cyclohexane is oxidized to the intermediate cyclohexyl hydroperoxide, CHHP. Then, the obtained CHHP is decomposed into the desired components cyclohexanone and cyclohexanol however, it is also partly decomposed into undesired by-products. A part of the formed cyclohexanol is further oxidized to cyclohexanone and a part of the formed cyclohexanone is converted to by-products. Part of the cyclohexane oxidation by-products are further destroyed (not shown in this figure). The by-products finally obtained include, in various amounts, acids such as adipic acid, e-hydroxycaproic acid, glutaric acid, succinic acid, valeric acid, caproic acid, propionic acid, acetic acid, formic acid, and noncondensable gases such as CO and CO2. In addition, several esters are formed between mainly cyclohexanol and the various carboxylic acids. The destinations of these by-products are quite diverse and depend on the producer for example, some of these byproducts are fed to combustion units for heat recovery purposes, while others are used as feedstock for chemicals such as 1,5-pentanediol, 1,6-hexanediol (HDO), and caprolactone. In general cyclohexanol is recovered from esters in a biphasic saponification step. 

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... 

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