Diethyl carbonate ketones

In a reaction related to the mixed Claisen condensation nonenolizable esters are used as acylatmg agents for ketone enolates Ketones (via their enolates) are converted to p keto esters by reaction with diethyl carbonate... 

Finar and coworkers (B-76MI40402) have made a detailed study of the pyrazolyl Grignard reagent (505). In addition to alcohols and ketones, the hydrocarbons (506) and (507) could be isolated, the first by heating the Grignard reagent (505) and the second by reaction with diethyl carbonate. 

Difunctional electrophiles such as diethyl carbonate and diethyl oxalate also react with perfluorooctyllithium and perfluoroalkyletherlithium compounds to yield ketones, diketones, and keto esters [39, 79] (equations 38 1). 

Acylation of ketones (Section 21.4) Diethyl carbonate and diethyl oxalate can be used to acylate ketone enolates to give p-keto esters. 

In an altogether different type of approach, the hydrazone is formed in situ as a lithium salt. Wilson et al. (80JHC389) described this approach in the one-pot synthesis of 5-aryl-2-phenylpyrazol-3-ones 72a-f from the corresponding hydrazones 65a-f (Scheme 20). The latter were obtained by condensing ketones 64a-f with phenylhydrazine. Treatment of hydrazones 65a-f with n-butyllithium in dry THF, followed by the addition of half a molar equivalent of diethyl carbonate 67 and then quenching the reaction mixture with hydrochloric acid, produced pyrazol-3-ones 72a-f, along with products 71. The yields of the products 72 are in the range 22-97%. Four intermediates—66a-f, 68a-f, 69a-f, and 70a-f— were proposed for this reaction. 

Several methods for the carbethoxylation of cyclic ketones via their enolates have been described. The methods differ primarily in the nature of the acylating agent employed. Thus, diethyl oxalate, diethyl carbonate, and ethyl diethoxyphosphinyl... 

The product supplied by Matheson, Coleman and Bell was used as received. Lower yields were obtained when a molar equivalent of diethyl carbonate was utilized, possibly because of self-condensation of the ketone. 

This procedure has been patterned after the method by which the carbethoxy group is introduced into a few alicyclic ketones 6 and several cyclic ketones. Cyclohexanone has been reported to yield 50% of 2-carbethoxycyclohexanone when treated with sodium hydride and diethyl carbonate using ether as the solvent.7 The preparation of 2-carbethoxycycloheptanone using potassium f-butoxide and diethyl carbonate in benzene has been reported in 40% yield.8 Jacob and Dev report an 80% yield of the latter compound using sodium hydride as the base.9... 

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-... 

Ketones are converted to (3-ketoesters by acylation with diethyl carbonate or diethyl oxalate, as illustrated by Entries 4 and 5 in Scheme 2.16. Alkyl cyanoformate can be used as the acylating reagent under conditions where a ketone enolate has been formed under kinetic control.227... 

Substituted 4-hydroxycoumarins result from the reaction of o-hydroxyphenyl ketones with diethyl carbonate (48JCS174) and with ethyl chloroformate (81JCS(P1)1697). 

Unfortunately neither reaction will work The black route requires a controlled condensation between two different enolizable esters—a recipe for a mixture of products. The simple alkylation route above removes the need for control. The green route requires a condensation between an unsymmetrical ketone and diethyl carbonate. This condensation will work all right, but not to give this product. As you saw on p. 730, Claisen condensations prefer to give the less substituted dicarbonyl compound, and condensation would occur at the methyl group of the ketone on the right to give the other unsymmetrical keto-ester. 

For example, reaction of an ester enolate with diethyl carbonate yields a p-diester (Reaction [1]), whereas reaction of a ketone enolate with ethyl chloroformate forms a p-keto ester (Reaction [2]). 

I blem bas two possible solutions by direct acylation, labelled A and B in the diagrams. A o be controlled as the straight-chain ester could self-condense, but B needs no control imM Ketone can enolize, diethyl carbonate, CO(OEt)2, is more electrophilic than a ketone, i.oe wanted product can enolize again and form a stable enolate under the reaction IS. However, route B adds only one carbon atom in the key step. 

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