Decarboxylation, ketonic

The synthesis may thus be seen to be an intramolecular Claisen ester condensation, which is known as the Dieckmann reaction. The procedure is an important method for the synthesis of five- and six-membered ring systems, and the cyclic /2-keto ester product may be converted into the corresponding cyclic ketone by hydrolysis followed by decarboxylation (ketonic hydrolysis, see Section 5.8.5, p. 619). The base catalyst used in Expt 7.8 is sodium ethoxide, but sodium hydride as a 50 per cent dispersion in oil is a recommended alternative. 

GVL 73, itself a potential biofuel, is also a starting material for pentanoate esters ( valeric biofuels ) that have been shown to have outstanding fuel properties [213]. GVL-derived pentanoic acid 80 can be catalytically upgraded by decarboxylative ketonization to 5-nonanone 81, which can then be variously processed to nonane 82 and other hydrocarbons [214, 215], GVL has also been converted to butenes over a silica-alumina catalyst, which are then oligomerized on H-ZSM-5 or Amberlyst-70 to give a mixture of Cg-Cie alkenes that can be hydrogenated to drop-in fuels (Scheme 27) [216]. 

The biosynthesis of fatty acids is accomplished two carbons at a time by an enzyme complex called fatty acid synthetase. The biochemical reactions involved in fatty acid synthesis are described in Special Topic E WileyPLUS). Each of these biochemical reactions has a counterpart in synthetic reactions you have studied. Consider the biochemical reactions involved in adding each —CH2CH2— segment during fatty acid biosynthesis (those in Special Topic E that begin with acetyl-S-ACP and malonyl-S-ACP, and end with butyryl-S-ACP). Write laboratory synthetic reactions using reagents and conditions you have studied (not biosynthetic reactions) that would accomplish the same sequence of transformations (i.e., the condensation-decarboxylation, ketone reduction, dehydration, and alkene reduction steps). 

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. 

Diethyl Ketone. Diethyl ketone [96-22-0] (3-pentanone) is isomeric with methyl / -propyl ketone (2-pentanone), which has similar solvent and physical properties. Diethyl ketone is produced by the decarboxylation of propionic acid over Mn02—alumina (165), Zr02 (166), or Zr02 or Th02 on Ti02 (167,168). Diethyl ketone can also be produced by the hydrocarbonylation of ethylene (169—171). It is used as a solvent and a reaction intermediate. 

Reactions. Heating an aqueous solution of malonic acid above 70°C results in its decomposition to acetic acid and carbon dioxide. Malonic acid is a useful tool for synthesizing a-unsaturated carboxyUc acids because of its abiUty to undergo decarboxylation and condensation with aldehydes or ketones at the methylene group. Cinnamic acids are formed from the reaction of malonic acid and benzaldehyde derivatives (1). If aUphatic aldehydes are used acryhc acids result (2). Similarly this facile decarboxylation combined with the condensation with an activated double bond yields a-substituted acetic acid derivatives. For example, 4-thiazohdine acetic acids (2) are readily prepared from 2,5-dihydro-l,3-thiazoles (3). A further feature of malonic acid is that it does not form an anhydride when heated with phosphorous pentoxide [1314-56-3] but rather carbon suboxide [504-64-3] [0=C=C=0], a toxic gas that reacts with water to reform malonic acid. 

Reactions. The chemical properties of cyanoacetates ate quite similar to those of the malonates. The carbonyl activity of the ester function is increased by the cyano group s tendency to withdraw electrons. Therefore, amidation with ammonia [7664-41-7] to cyanoacetamide [107-91-5] (55) or with urea to cyanoacetylurea [448-98-2] (56) proceeds very easily. An interesting reaction of cyanoacetic acid is the Knoevenagel condensation with aldehydes followed by decarboxylation which leads to substituted acrylonitriles (57) such as (29), or with ketones followed by decarboxylation with a shift of the double bond to give P,y-unsaturated nitriles (58) such as (30) when cyclohexanone [108-94-1] is used. 

P-Peroxylactones undergo thermal decarboxylation to carbonyl compounds by the initial formation of a 1,5-diradical (238). a-Peroxylactones undergo similar decarboxylation, emitting light since the ketone is generated in the triplet excited state (85,239,240) ... 

PUtzing erReaction. Quinoline-4-carboxyhc acids are easily prepared by the condensation of isatin [91-56-5] (16) with carbonyl compounds (50). The products may be decarboxylated to the corresponding quinolines. The reaction of isatin with cycHc ketones has been reported, eg, the addition of cyclohexanone gives the tricycHc intermediate (17) [38186-54-8] which upon oxidation produces quinoline-2,3,4-tricarboxyhc acid [16880-83-4] (51). 

Condensation of campholenic aldehyde with ethyl acetoacetate with subsequent saponification and decarboxylation gives the intermediate unsaturated ketones. 

Constitution of Yohimbine and its Isomerides. The yohimb alkaloids are methyl esters of acids. Yohimbine, yohimbene, mesoyohimbine (isoyohimbine) and y-yohimbine (table, p. 502) are hydrolysed to four, distinct, monocarboxylic acids, C2,yH2402N2, each of which on decarboxylation by heating with soda-lime yields yohimbol, long supposed to be a secondary alcohol, Ci,yH240N2, but which Witkop has shown to be a ketone and has re-named yohimbone, C18H22ON2, m.p. 307° (dec.),... 

Early efforts to partially synthesize 20-keto and 17a-hydroxy-20-keto steroids led to ring D-expanded products isomeric with the desired compounds. Darzens condensation of 3/5-hydroxyandrost-5-en-17-one acetate (75) with ethyl a,a-dichloropropionate, followed by alkali treatment and decarboxylation, gives both the expected 3j5-hydroxypregn-5-en-20-one (78) and an isomer now known to be 17a-methyl-D-homo-17-ketone (79).36,37a alternative route for the introduction of the two carbon side chain, Ruzicka... 

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