Ethyl isobutyrate condensation

In this section primarily reductions of aldehydes, ketones, and esters with sodium, lithium, and potassium in the presence of TCS 14 are discussed closely related reductions with metals such as Zn, Mg, Mn, Sm, Ti, etc., in the presence of TCS 14 are described in Section 13.2. Treatment of ethyl isobutyrate with sodium in the presence of TCS 14 in toluene affords the O-silylated Riihlmann-acyloin-condensation product 1915, which can be readily desilylated to the free acyloin 1916 [119]. Further reactions of methyl or ethyl 1,2- or 1,4-dicarboxylates are discussed elsewhere [120-122]. The same reaction with trimethylsilyl isobutyrate affords the C,0-silylated alcohol 1917, in 72% yield, which is desilylated to 1918 [123] (Scheme 12.34). Likewise, reduction of the diesters 1919 affords the cyclized O-silylated acyloin products 1920 in high yields, which give on saponification the acyloins 1921 [119]. Whereas electroreduction on a Mg-electrode in the presence of MesSiCl 14 converts esters such as ethyl cyclohexane-carboxylate via 1922 and subsequent saponification into acyloins such as 1923 [124], electroreduction of esters such as ethyl cyclohexylcarboxylate using a Mg-electrode without Me3SiCl 14 yields 1,2-ketones such as 1924 [125] (Scheme 12.34). 

Base catalyzed condensation reactions of esters and ketones have an additional factor of importance in determining the product, and this is the fact that the overall reaction, as well as the intermediate steps, is highly reversible. The final product may be rate or equilibrium determined, and in the latter case the result may depend on the relative acidity of the various possible products. In a highly basic medium the product will be partly in the form of a salt and the stability of the salt is then a product-determining factor. Failure of a condensation to take place may be due either to an insufficiently high concentration of carbanions or to the instability of the product. The reactions of ethyl isobutyrate will illustrate both points.419... 

I. The Condensation of Ethyl Isobutyrate to Ethyl Isobutyryl-isobutyrate. 

For esters with only one a-hydrogen, such as ethyl 2-methyl propanoate (ethyl isobutyrate), a more powerful base (e.g. sodium triphenylmethide, Ph3CeNa ) is required to affect the condensation reaction [the forced Claisen ester condensation, e.g. the synthesis of ethyl 2,2,4-trimethyl-3-oxopentanoate (ethyl iso-butyrylisobutyrate), Expt 5.176]. In this case the reaction sequence is completed in the step corresponding to (ii) above since the /1-keto ester (24) has no a-hydro-gen for step (iii), and the powerful base is required to force the equilibrium (i) to the right. 

Esters with only one a hydrogen generally give poor yields in the Claisen condensation. Propose a mechanism for the Claisen condensation of ethyl isobutyrate, and explain why a poor yield is obtained. 

An inspection of the mechanism of the condensation of ethyl isobutyrate with ethyl benzoate reveals that the essential feature of the acceptor molecule (ethyl benzoate) is that it be able to lose a negative ion (ethoxide ion in this case) in step 13 to form the 0-ketoester, Accordingly it has been found possible to carry out successful Claisen condensations between ethyl isobutyrate and other acceptor molecules such as benzoyl chloride, or benzoic anhydride.22 For all of these reactions we may generalize step 13 as follows ... 

The base is useful for promoting sterically hindered condensations, for example ethyl isobutyrate---> ethyl isobutyrylisobutyrate (30%). It is useful for effecting... 

Three esters (ethyl isovalerate, ethyl r-butylacetate, and ethyl isobutyrate) do notundergo this type of condensation under normal conditions with sodium ethoxide, presumably due to the steric hindrance. However, their condensation proceeds readily when mesitylmagnesium bromide is applied as the base. In addition, the acetoacetic ester condensation has been improved to give high yields using some quaternary ammonium salts of long aliphatic chains as the phase transfer catalyst in benzene. ... 

Ethyl acetate [141-78-6] is produced commercially by the Tischenko condensation of acetaldehyde using an aluminum ethoxide catalyst (60). The Tischenko reaction of acetaldehyde with isobutyraldehyde [78-84-2] yields a mixture of ethyl acetate, isobutyl acetate [110-19-0] and isobutyl isobutyrate [97-85-8] (61). 

Ethyl Benzoyl-diethylacetate to Ethyl Benzoate and Ethyl Isobnt5rryl-isobutyrate in the IPresence of Sodium Ethoxide and Triphenylmethane. The Reversibility of the Claisen Type of Condensation. J. Amer. chem. Soc. 62, 62 (1940),... 

NOTE Acetals of acetaldehyde, propionaldehyde, and n- and isobutyr-aldehyde are prepared by condensation with PVA in the presence of sulfuric acid in ethanol. Acetals of 2-ethyl butyraldehyde, Az-hexaldehyde, n-heptaldehyde, and 2-ethyl hexaldehyde are prepared in a mixture of dioxane and ethanol. Some typical results are shown in Table X. 

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