Cyclohexanone carboxylation

Changing the functionality on the alicyclic ring from an amine to a carboxylic acid leads to a compound that shows antiallergic activity, acting possibly by means of inhibition of the release of allergic mediators. Thus, condensation of acylated indole with cyclohexanone carboxylic acid affords directly oxarbazole (29). ... 

One of the most powerful strategies for asymmetric ring construction is to desymmelrize a preformed ring. Yasamusa Hamada of Chiba University in Japan has reported (J. Am. Chem. Soc. 2004, /26, 3690) that the inexpensive diaminophosphine oxide 2 nicely catalyzes the asymmetric alkylation of the cyclohexanone carboxylate 1 to give 3. Although no examples were given, this asymmetric alkylation would probably work as well with heterocyclic P-ketoesters. 

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... 

The reaction of 4-indolyllead triacetate with substituted methyl 2-cyclohexanone-carboxylates, which has been investigated as a route to the natural product N-mefhylwelwitindolinone C isothiocyanate, afforded the desired coupled product in excellent yield and diastereoselectivity (Scheme 13.12) [40]. 

A number of studies of the acid-catalyzed mechanism of enolization have been done. The case of cyclohexanone is illustrative. The reaction is catalyzed by various carboxylic acids and substituted ammonium ions. The effectiveness of these proton donors as catalysts correlates with their pK values. When plotted according to the Bronsted catalysis law (Section 4.8), the value of the slope a is 0.74. When deuterium or tritium is introduced in the a position, there is a marked decrease in the rate of acid-catalyzed enolization h/ d 5. This kinetic isotope effect indicates that the C—H bond cleavage is part of the rate-determining step. The generally accepted mechanism for acid-catalyzed enolization pictures the rate-determining step as deprotonation of the protonated ketone ... 

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—... 

Ketones are inert to most oxidizing agents but undergo a slow cleavage reaction when treated with hot alkaline KMnO The C-C bond next to the carbonyl group is broken, and carboxylic acids are produced. The reaction is useful primarily for symmetrical ketones such as cyclohexanone because product mixtures are formed from unsymmetrical ketones. 

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. 

Bromosulfone 303 was found to react with ethyl cyclohexanone-2-carboxylate by preferential attack of the a-sulfonyl carbanion on the carbonyl group to give tricyclic compound 304382. 

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... 

Cycloalkenone-2-carboxylates tautomerize to conjugated dienols in the presence of either acids or bases. Iron(III) catalysts have also been found to promote enone-dienol equilibration, and, at room temperature, dimerization64. Thus, treating 87 with 1 mol% iron(III) chloride hexahydrate in methylene chloride at room temperature affords 88 in 81% yield (equation 46). The cyclohexadiene-cyclohexanone is in a rapid equilibrium with its triendiol tautomer, 89 (equation 47). 

Cyclohexene TlCl04/HCl04-(Pt) tI(cio4)3 Cyclopentane-1-carboxylic acid, Cyclohexanone, Cyclohexane-1,2-dione, Cyclohexane-1,2-diol 247... 

We were interested in applications of the high level of stereocontrol associated with the asymmetric Birch reduction-alkylation to problems in acyclic and heterocyclic synthesis. The pivotal disconnection of the six-membered ring is accomplished by utilization of the Baeyer-Villiger oxidation (Scheme 7). Treatment of cyclohexanones 25a and 25b with MCPBA gave caprolactone amides 26a and 26b with complete regiocon-trol. Acid-catalyzed transacylation gave the butyrolactone carboxylic acid 27 from 26a and the bis-lactone 28 from 26b cyclohexanones 31a and 31b afforded the diastereomeric lactones 29 and 30. ... 

Oxidative ring cleavage of cyclohexanones is achieved in ethanol at a platinum anode. Cleavage of the carbon-carbonyl bond occurs and the carbonyl centee is trapped as the carboxylic acid. The radical centre formed after bond cleavage is oxidised to the carbocation. This rearranges to the most stable centre and is then trapped by the carboxyl group to form a lactone [4, 5], An identical process is... 

The common name caprolactam comes from the original name for the Ce carboxylic acid, caproic acid. Caprolactam is the cyclic amide (lactam) of 6-aminocaproic acid. Its manufacture is from cyclohexanone, made usually from cyclohexane (58%), but also available from phenol (42%). Some of the cyclohexanol in cyclohexanone/cyclohexanol mixtures can be converted to cyclohexanone by a ZnO catalyst at 400°C. Then the cyclohexanone is converted into the oxime with hydroxylamine. The oxime undergoes a very famous acid-catalyzed reaction called the Beckmann rearrangement to give caprolactam. Sulfuric acid at 100-120°C is common but phosphoric acid is also used, since after treatment with ammonia the by-product becomes... 

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