Cycloalkanones acids

Synthesis from Aldehydes and Ketones. Treatment of aldehydes and ketones with potassium cyanide and ammonium carbonate gives hydantoias ia a oae-pot procedure (Bucherer-Bergs reactioa) that proceeds through a complex mechanism (69). Some derivatives, like oximes, semicarbazones, thiosemicarbazones, and others, are also suitable startiag materials. The Bucherer-Bergs and Read hydantoia syntheses give epimeric products when appHed to cycloalkanones, which is of importance ia the stereoselective syathesis of amino acids (69,70). 

Compounds i, ii, and iii can be prepared by an acid-catalyzed reaction of a diol and the cycloalkanone in the presence of ethyl orthoformate and mesitylenesul-fonic acid. The relative ease of acid-catalyzed hydrolysis [0.53 M H2SO4, H2O, PrOH (65 35), 20°] for compounds i, iii, acetonide, and ii is C5 C7 > ace-... 

The reaction conditions (neutral, acidic or basic) do have an affect on the regioselectivity of the reaction. Acidic reaction conditions have also been shown to preferentially provide one regioisomer over basic conditions for reactions of aryl hydrazines. Extensive studies with 2-perfluoroacylcycloalkanones and mono-substituted hydrazines were studied to determine the selectivity of various alkyl-, aryl-, and heteroaryl-substituted hydrazines. Reactions of the aryl hydrazine 21 with the trifluoromethyl-substituted cycloalkanone 22 under neutral conditions (methanol, reflux) gave a mixture of isomers 23 and 24, whereas the reaction of the pyridyl hydrazine 25 was shown to give exclusively 26. 

A novel ring closure was discovered by Stork (6) in which the pyrrolidine enamine of a cycloalkanone reacts with acrolein. The scheme illustrates the sequence in the case of 1-pyrrolidino-l-cyclohexene, and the cyclopentane compound was found to undergo the reaction analogously. The procedure details the preparation of the bicyclo adduct and its cleavage to 4-cyclooctenecarboxylic acid. 

Notable examples of general synthetic procedures in Volume 47 include the synthesis of aromatic aldehydes (from dichloro-methyl methyl ether), aliphatic aldehydes (from alkyl halides and trimethylamine oxide and by oxidation of alcohols using dimethyl sulfoxide, dicyclohexylcarbodiimide, and pyridinum trifluoro-acetate the latter method is particularly useful since the conditions are so mild), carbethoxycycloalkanones (from sodium hydride, diethyl carbonate, and the cycloalkanone), m-dialkylbenzenes (from the />-isomer by isomerization with hydrogen fluoride and boron trifluoride), and the deamination of amines (by conversion to the nitrosoamide and thermolysis to the ester). Other general methods are represented by the synthesis of 1 J-difluoroolefins (from sodium chlorodifluoroacetate, triphenyl phosphine, and an aldehyde or ketone), the nitration of aromatic rings (with ni-tronium tetrafluoroborate), the reductive methylation of aromatic nitro compounds (with formaldehyde and hydrogen), the synthesis of dialkyl ketones (from carboxylic acids and iron powder), and the preparation of 1-substituted cyclopropanols (from the condensation of a 1,3-dichloro-2-propanol derivative and ethyl-... 

The lithium enolates of cyclopentanone and cyclohexanone undergo addition-elimination to the 2,2-dimethylpropanoic acid ester of ( )-2-nitro-2-hepten-l-ol to give 2-(l-butyl-2-nitro-2-propenyl)cycloalkanones with modest diastereoselection. An analogous reaction of the enolate ion of cyclohexanone with the 2,2-dimethylpropanoic acid ester of (Z)-2-nitro-3-phenyl-2-propenol to give 2-(2-nitro-l-phenyl-2-propenyl)cyclohexanones was also reported. The relative configuration of these products was not however determined6. 

Oxidation of 4-methylcyclohexanone by addition of nitric acid at about 75°C caused a detonation to occur. These conditions had been used previously to oxidise the corresponding alcohol, but although the ketone is apparently an intermediate in oxidation of the alcohol, the former requires a much higher temperature to start and maintain the reaction. An OTS report, PB73591, mentions a similar violent reaction with cyclohexanone [1], Presence of nitrous acid is essential for the smooth oxidation of cycloalkanones with nitric acid to a, rw-hcxanedioic acids. Because high-purity nitric acid (free of nitrous acid) is now commonly available, addition of a little sodium or potassium nitrite to the acid is necessary before its use to oxidise cycloalkanones [2],... 

Ring enlargement. Treatment of an a-(silylmethyl)cycloalkanecarbaldehyde (2) with a Lewis acid results in a one-carbon ring enlargement to a cycloalkanone... 

Cycloalkanones were reacted with diethyl aminomethylenemalonate (13) in boiling toluene or xylene in the presence of dichloroacetic acid or p-toluenesulfonic acid monohydrate under nitrogen or argon for 2.5-7 days, and under a water separator, to give N-( 1 -cycloalkenyDaminomethy-lenemalonates (275, R = R1 = —(CH,)n—, n = 6-10) (88EUP270494). 

Cycloalkanones are oxidatively cleaved to yield dicarboxylic acids, together with their chlorinated derivatives [23]. The initial a-chlorination is followed by solvolysis... 

Aqueous NaOCl (10%, 400 ml) is added with stirring to the cycloalkanone (0.1 mol) and Aliquat (4 g, 10 mmol) at 10°C. The mixture is stirred and the pH is maintained at 12.0 by the addition of aqueous NaOH (0.5 M). On completion of the reaction, the aqueous phase is separated, washed with CH2C12 (200 ml), and acidified to pH 2.0 with HC1 (2M). The acidic solution is cooled to 0°C to cause precipitation of the dicarboxylic acids (e.g. cyclohexanone yields a mixture of adipic acid 63%, succinic acid 9%, glutaric acid 17%, and a,a-dichloroadipic acid 5%). 

The derivatives 24 were synthesised by the acylation of trans-2-aminocy-clopentanol (n=l) or frans-2-aminocyclohexanol (n=2) with 3,3-ethylene-dioxydodecanoic acid in the presence of EDC, DMAP and DIPEA followed by acidolysis with THF in DCM. The cycloalkanone analogues 25 were obtained by Swern oxidation of the corresponding cycloalkanols 24 (Scheme 10). 

Pyridinium fluorochromate oxidizes cycloalkanones to the corresponding 1,2-diketones. " The kinetics have been studied in aqueous acetic-perchloric acid mixtures relative reactivities are explained in terms of conformational and steric... 

An annulation protocol has been elaborated that uses lithiated 3,3-dichloropropene 124 generated in situ by deprotonation as a key intermediate. When added to a cycloalkanone, the homoallylic alcohol 125 forms upon aqueous workup. Its subsequent treatment with trifluoroacetic acid brings about elimination of water and dissociation of a chloride anion. 

Enantlomerically pure B-suhstituted carbonyl compounds serve as useful intermediates in the synthesis of many chiral organic compounds. The enantloselective synthesis of acyclic 0-substituted carboxylic acids has been reported by Meyers, Mukaiyama, and Koga. However, no effective, general method for the enantio-controlled preparation of P-substituted cycloalkanones was available prior to the investigations by the submitters. For example, poor enantloselectivity was observed in conjugate additions of organometallic... 

Types of Reaction. The net result of a-cleavage in cycloalkanones is the formation of an unsaturated aldehyde and/or a saturated ketene which subsequently reacts with nucleophiles. These types of reaction can be illustrated by the photochemistry of menthone (Formula 224). Irradiation of menthone in aqueous ethanol gives a saturated acid (Formula 225) and an unsaturated aldehyde which is either Formula 226 or 227 (86). In the absence of nucleophiles, irradiation of cyclopentanone... 

Applications to Steroids and Terpenes. The photochemical cleavage of cycloalkanones to acids in aqueous acetic acid has found some application in structure determination. Greater use should be made of this technique in the future. 

Keywords bicarboxylic acid, decarboxylation, graphite, microwave irradiation, cycloalkanone... 

The oxidation of D-fructose with cerium(IV) in sulfuric acid medium is inhibited by an increase in the acidity. A cationic surfactant, CTAB, catalyses the reaction, whereas SDS has no effect. The catalytic role of CTAB has been explained using the pseudophase model of Menger and Portnoy. A mechanism involving the formation of an intermediate complex between /3-D-fructopyranose and Ce(S04)32- has been proposed.61 The oxidation of cycloalkanones with cerium(IV) in sulfuric acid medium showed a negligible effect of acidity. Formation of an intermediate complex, which decomposes in the rate-determining step, has been suggested.62... 

The cyclic /J-ketoester E subsequently can be saponified in acidic medium. The acid obtained then decarboxylates via the mechanism of Figure 13.27 to provide the ester-free cycloalkanone D. Product D represents the product of a CH2 insertion into the starting ketone. 

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