Ketones decarboxylation

Ketonic decarboxylation, in which two molecules of acid are thermally converted to a symmetrical ketone plus carbon dioxide and water, has been reviewed.316 Radical, f >-keto acid, and concerted mechanisms are considered, with the reviewer favouring the last, albeit not conclusively. It is suggested that development of bifunctional catalysts may be the best way to improve the energetics of the process, and hence its synthetic utility and green credentials. 

Control in this reaction is likely to be exerted stereoclectronically hy the enzyme as it was in the pyridoxal reactions above. Since the OR bond is held parallel to the p orbitals of the ketone, R migration occurs, but if the C02H group were to be held parallel to the p orbitals of the ketone, decarboxylation would occur. Next, a simple reduction with NADPH converts tine ketone into an alcohol and prepares the way for a second rearrangement. 

C,3R,5- H2]mevalonic acid is [3Hi while lophenol is [ Hn, " 5]. It must be concluded that, contrary to earlier reports, the 4a-methyl group is lost first. This result is further substantiated by the incorporation of 4a-hydroxy-methyl-4j3-methylcholestan-3j8-ol but not the 4jff-hydroxymethyl isomer. Furthermore, 4j9-methylcholestan-3)S-ol is largely inert. The sequence of events would seem to be that the 4a-methyl is oxidised to a carboxyl group and the 3)3-hydroxyl to a 3-ketone. Decarboxylation of the jS-keto acid is followed by rapid reduction of the 3-ketone back to a 3/9-alcohol. In the presence of tritiated water C-3 and C-4 become radioactive. ... 

Renz, M Corma, A. Ketonic decarboxylation catalysed by w eak bases and its application to an optically pure substrate. European Journal of Org anic Chemistry 2004 2036-2039. 

This process is very similar to the process we discussed for 1,3-dicarboxyhc acids. In the first step, a pericyclic reaction forms an enol, which then undergoes tautomerization to form a ketone. Decarboxylation can occur because the carboxyhc acid exhibits a carbonyl group in the (3 position, which enables the pericyclic reaction shown above. Below is an example of an acetoacetic ester synthesis. 

Wikipedia, The Free Encyclopedia. Ketonic Decarboxylation. Revised 12 Dec 2013. Retrieved 22 Jul 2013. 

By the ketonic hydrolysis of substituted acetoacetic esters this is brought about by the action of dilute alkali in the cold, followed by acidification and boiling. The free substituted acetoacetic acid is produced, which readily undergoes decarboxylation (since it has a carboxyl and a carbonyl group on the same carbon atom) to give a ketone, for example ... 

The glycidic esters are of interest primarily because upon hydrolysis aud decarboxylation they aflFord aldehydes (if ClCHjCOOEt is used) or ketones (if substituted chloroacetic esters- ClCHRCOOEt are employed) having a higher carbon content than the original aldehyde or ketone. Thus (I) gives o-phenyl-propionaldehyde or hydratropaldehyde (II) ... 

The addition of active methylene compounds (ethyl malonate, ethyl aoeto-acetate, ethyl plienylacetate, nltromethane, acrylonitrile, etc.) to the aP-double bond of a conjugated unsaturated ketone, ester or nitrile In the presence of a basic catalyst (sodium ethoxide, piperidine, diethylamiiie, etc.) is known as the Michael reaction or Michael addition. The reaction may be illustrated by the addition of ethyl malonate to ethyl fumarate in the presence of sodium ethoxide hydrolysis and decarboxylation of the addendum (ethyl propane-1 1 2 3-tetracarboxylate) yields trlcarballylic acid ... 

Suggestions as to the methods for identifying the above classes of compounds will be found under Class Reactiona in Section XI,7. Some fimther remarks upon enolic compounds (see Table IV,1I4A) may be made here. Enols may be divided into (a) p-keto esters and (b) 1 3-diketones. With 5 per cent, sodium hydroxide solution, a p-keto ester yields the salt of the corresponding acid, which when heated with dilute hydrochloric acid is decarboxylated to a ketone ... 

Svndiesis (Crombie, J. Chem. Soc. (C), 1969, 1016). The acetylenic bromide corresponding to allyl bromide is called propargyl bromide and is reactive and readily available. We shall need to protect the ketone before we make the acetylene anion. It turns out tliat protection and decarboxylation can be done in one step. 

Geranyl acetoacetate (685) is converted into geranylacetone (686). On the other hand, a mixture of E- and Z-isomers of 688 is obtained from neryl acetoacetate (687). The decarboxylation and allylation of the allyl malonate or cyanoacetate 689 affords the o-allylated acetate or nitriie[447]. The trifluoromethyl ketone 691 is prepared from cinnamyl 4.4,4-trifluoroacetoace-tate (690)[448],... 

Ailyl enol carbonates derived from ketones and aldehydes undergo Pd-cat-alyzed decarboxylation-elimination, and are used for the preparation of a, /3-unsaturated ketones and aldehydes. The reaction is regiospecific. The regio-isomenc enol carbonates 724 and 726, prepared from 723, are converted into two isomeric enones, 725 and 727. selectively. The saturated aldehyde 728 can be converted into the a,/3-unsaturated aldehyde 730 via the enol carbonate 729[459]. 

The compounds most frequently encountered m this reaction are (3 keto acids that is carboxylic acids m which the (3 carbon is a carbonyl function Decarboxylation of (3 keto acids leads to ketones... 

The thermal decarboxylation of p keto acids is the last step in a ketone synthesis known as the acetoacetic ester synthesis The acetoacetic ester synthesis is discussed in Section 21 6... 

The carbon-carbon bond forming potential inherent m the Claisen and Dieckmann reac tions has been extensively exploited m organic synthesis Subsequent transformations of the p keto ester products permit the synthesis of other functional groups One of these transformations converts p keto esters to ketones it is based on the fact that p keto acids (not esters ) undergo decarboxylation readily (Section 19 17) Indeed p keto acids and their corresponding carboxylate anions as well lose carbon dioxide so easily that they tend to decarboxylate under the conditions of their formation... 

The sequence begins with a Claisen condensation of ethyl pentanoate to give a p keto ester The ester is hydrolyzed and the resulting p keto acid decarboxylates to yield the desired ketone... 

Section 21 5 Hydrolysis of p keto esters such as those shown m Table 21 1 gives p keto acids which undergo rapid decarboxylation forming ketones... 

The anion of a p keto ester may be alkylated at carbon with an alkyl halide and the product of this reaction subjected to ester hydrolysis and decarboxylation to give a ketone... 

In addition to formation from a ketone, the hydra2ones can be obtained from dicarbonyl compounds by a Japp-Klingemann reaction. This is especially useful for P-ketoesters and P-ketoacids, which undergo either deacylation or decarboxylation. 

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