Ethyl acetoacetate relative acidity

The properties of diethyl malonate that make the malonic ester synthesis a useful procedure are the same as those responsible for the synthetic value of ethyl acetoacetate The hydrogens at C 2 of diethyl malonate are relatively acidic and one is readily removed on treatment with sodium ethoxide... 

However, the reaction is not quite that simple, and to understand and utilize the Claisen reaction we have to consider pAT values again. Loss of ethoxide from the addition anion is not really favourable, since ethoxide is not a particularly good leaving group. This is because ethoxide is a strong base, the conjugate base of a weak acid (see Section 6.1.4). So far then, the reaction will be reversible. What makes it actually proceed further is the fact that ethoxide is a strong base, and able to ionize acids. The ethyl acetoacetate prodnct is a 1,3-dicarbonyl componnd and has relatively acidic protons on the methylene between the two carbonyls (see Section 10.1). With... 

Problem 17.12 Compare the relative acid strengths of 2,4-pentanedione, CHjCOCHjCOCHj (I) ethyl acetoacetate, CHiCOCH COOC.H, (II) and diethyl malonate, C2H,OOCCH2COOC2H5 (III). Explain your ranking. <... 

Skaddan and co-workers employed the Hantzsch synthesis in their preparation of isotopically labeled l- -pyrrole-2,3,5-tricarboxylic acid, a metabolic by-product of the breakdown of melatonin. Labeled -H-pyrrole-2,3,5-tricarboxylic acid is currently under investigation as a tool to study the effectiveness of new hyper pigmentation drugs. C-Labeled ethyl acetoacetate 19 and 2-chloroethanal 20, when treated with -labeled aqueous ammonium hydroxide, produced pyrrole 21 in 35% yield. The authors chose to use this approach due to the relatively low cost and availability of the reagents required to prepare this compound. 

Depending on the respective reaction partner, acetic acid esters can react either as C-H acidic compounds or as acylating agents. Both are illustrated by the self-condensation of ethyl [ 1 acetate in the presence of 0.5 equivalent of sodium ethoxide or triphenymethyl sodium to give ethyl [1,3- C2]acetoacetate (Claisen condensation). In the first case, however, because of the relatively low radiochemical yields (40-45%) obtained by this procedure, it is of minor importance for the preparation of labeled ethyl acetoacetate. The deprotonation of alkyl acetates with LiHMDS followed by acylation with unlabeled or labeled acyl halides to labeled give /3-keto esters is discussed in Section 6.4. Claisen condensation of alkyl [ CJacetates with esters lacking a-hydrogens (i.e. ethyl formate, diethyl oxalate, aromatic/heteroaromatic carboxylic acid esters) proceed unidirectionally and are valuable pathways in the synthesis of ethyl [ C]formyl acetate (521. diethyl [ C]-oxaloacetate (53) and ethyl 3-oxo-3-pyrid-3-yl[2- C]acetate (54). The last example... 

BINAP-ligated complexes 17-19, which are functionahzed with hydrophilic ammonium units, and successfully apphed them as catalyst for AH in aqueous phase. For instance, complex 17 enables the AH of ethyl acetoacetate in water, providing 100% conversion with 94% ee under relatively mild conditions (40 bar H2 at 50 °C for 16 h), and the catalyst could be recycled at least three times [79a]. In the AH of ethyl trifluoroacetoacetate, a challenging substrate, with Ru-BINAP or its derivatives, the complex 18 dehvered 95% conversion with 70% ee in an acidic aqueous medium (1.0m L water, 0.13 m L acetic acid, and 0.125 m L trifluoroacetic acid) [79c]. 

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