Dicarboxylic acids from cyclic ketones

For preparation of cyclic ketones from dicarboxylic acids see... 

Acetic anhydride pyridine Cyclic ketones from dicarboxylic acids... 

We have already considered the use of mixed anhydrides and so in this section we shall be concerned with homocarboxylic anhydrides. The use of anhydrides constitutes the most frequently reported method after the use of an acyl chloride and aluminum chloride. Anhydrides from monocarboxylic acids yield ketones, and cyclic anhydrides derived from dicarboxylic acids afford keto acids. Very nucleophilic aromatic compounds react with trifluoroacetic anhydride in the absence of a catalyst. The confirmation of aromatic character invariably involves establishing reactivity towards a range of electrophiles. Trifluoroacetic anhydride reacts with homoazulene in the presence of an excess of triethylamine to afford 1-tri-fluoroacetylhomoazulene in 91-95% yield. The preparations of 3-aroylpropanoic acids from succinic anhydride and 4-aroylbutanoic acids from glutaric anhydride have been known for many years. Maleic anhydride can be used in a similar way to prepare 3-aroylacrylic acids. We will now concentrate our attention on more recent examples. 

The autoxidation of cyclic ketones with dirhenium decacarbonyl under basic catalytic conditions produces dicarboxylic acids (68-73%) bicyclic ketones are converted into keto carboxylic acids and, when one ring is aromatic, quinones are obtained, e.g. 1-tetralone produces 2-hydroxy-1,4-naphthaquinone (93%), and H02C(CH2)4C0(CH2)3C02H (85%) is obtained from 1-decalone via a cyclic triketone [5]. 

A mixture of palladium chloride and triphenylphosphine effectively catalyzes carboxylation of linoleic and linolenic acids and their methyl esters with water at 110°-140°C and carbon monoxide at 4000 psig. The main products are 1,3-and 1,4-dicarboxy acids from dienes and tricarboxy acids from trienes. Other products include unsaturated monocar-boxy and dicarboxy acids, carbomethoxy esters, and substituted a,J3-unsaturated cyclic ketones. The mechanism postulated for dicarboxylation involves cyclic unsaturated acylr-PdCl-PhsP complexes. These intermediates control double bond isomerization and the position of the second carboxyl group. This mechanism is consistent with our finding of double bond isomerization in polyenes and not in monoenes. A 1,3-hydrogen shift process for double bond isomerization in polyenes is also consistent with the data. 

Cyclic ketones containing up to 31 C-atoms in the ring have been prepared from the corresponding dicarboxylic acids. By the Clemmensen reduction (Reaction LVIII. (c)) the ketones have been converted into cyclic hydrocarbons. These large ring compounds are remarkably stable. (H. Acta, 11, 496,670 13,1152 17,78.)... 

Clearly such a method is of limited preparative value, but an important exception is the oxidation of cyclic secondary alcohols which on oxidation with nitric acid give good yields of dicarboxylic acids by way of the intermediate cyclic ketone, e.g. adipic acid from cyclohexanone, Expt 5.123. 

The boron atom dominates the reactivity of the boracyclic compounds because of its inherent Lewis acidity. Consequently, there have been very few reports on the reactivity of substituents attached to the ring carbon atoms in the five-membered boronated cyclic systems. Singaram and co-workers developed a novel catalyst 31 based on dicarboxylic acid derivative of 1,3,2-dioxaborolane for the asymmetric reduction of prochiral ketones 32. This catalyst reduces a wide variety of ketones enantioselectively in the presence of a co-reductant such as LiBH4. The mechanism involves the coordination of ketone 32 with the chiral boronate 31 and the conjugation of borohydride with carboxylic acid to furnish the chiral borohydride complex 34. Subsequent transfer of hydride from the least hindered face of the ketone yields the corresponding alcohol 35 in high ee (Scheme 3) <20060PD949>. 

The ability to accept electrons from donors is particularly pronounced in acrylic acid derivatives [85] its alkyl esters [78, 87, 88], acrylonitrile [88], acrylamide, hydroxylacrylates [85], and further in styrenes substituted with an electronegative atom or group m-nitrostyrene, 2,6-dichlorostyrene [86], / -nitrostyrene [89] bicyclobutane-1-carbonitrile [89] lactones /J-propio-Iactone [85], sulfolactone vinyl ketones [87] unsaturated dicarboxylic acids and their derivatives diethyl fumarate, fumaronitrile [90], ROOC—N— N—COOR [86], cyclic anhydrides of diacids [91 ], particularly maleic anhydride [78, 92] ethylenes substituted with electronegative groups [93, 95]... 

Despite problems with acyclic ketones, the reaction is quite useful for cyclic ketones and the corresponding secondary alcohols, the dicarboxylic acid being prepared in good yield. The formation of adipic acid from cyclohexanone (shown above) is an important industrial procedure. Acid dichromate and permanganate are the most common oxidizing agents, although autoxidation (oxidation with... 

The octahydroquinolines 24 and decahydroacridines were obtained from dimedone. On montmorillonite KSF clay, acridine derivatives 25 were obtained. Reaction of arylidenemalononitriles with cyclic ketones gave 2-amino-3-cyanopyridines 26. Reaction of diphenylamine and dicarboxylic acids or arylacetic acids was catalyzed by zinc chloride to give acridines. Pyrimido[4,5-Z>]quinolines 27 were synthesized. ... 

The direct oxidation of ketones to carboxylic acids usually implies a carbon-carbon bond cleavage [249]. Product mixtures are often obtained. However, for the preparation of dicarboxylic acids from cyclic ketones this reaction has proven to be synthetically very useful. 

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