Alkyl acetoacetates replacement

Routes 1-6 can also be used for the preparation of a broad range of carbon-14-labeled /8-keto esters and acids by replacing [ C]acetyl chloride with other acyl chlorides. Alternatively, higher homologs can be prepared by alkylation of doubly deprotonated alkyl acetoacetates (see Section 6.4.1)... 

Ethylmalonic Acid.—Like acetoacetic ester (see p. 83), diethylmalonate contains the gioup CO.CHj.CO. By the action of sodium or sodium alroholate, the hydrogen atoms of the methylene group are successively replaceable by sodium. The sodium atoms are in turn replaceable by alkyl or acyl groups. Thus, in the present preparation, ethyl malonic ester is obtained by the action of ethyl iodide on the monosodium compound. If this substance be treated with a second molecule of sodium alcoholate and a second molecule of alkyl iodide, a second radical would be in roduced, and a compound formed of the general formula... 

R., 262 J. pr., [2], 51, 186.)—Cyanoacetic, CH CNICOOCjHj, has similar properties to malonic and acetoacetic esters, inasmuch as the methylene hydrogen atoms are successively replaceable by sodium and this latter by alkyl and acyl radicals. 

The second hydrogen on the methylene unit of acetoacetic ester can also be replaced by an alkyl group, creating a disubstituted acid. To accomplish this conversion, the reaction product in step 2 above would be reacted with a very strong base to create a carbanion. 

In planning an acetoacetic ester synthesis, as in planning a malonic ester synthesis, our problem is to select the proper alkyl halide or halides. To do this, wc have only to look at the structure of the ketone we want. For example, 5-methyI-2-hexanone can be considered as acetone in which one hydrogen has been replaced by an isobutyl group. In order to prepare this ketone by the acetoacetic ester synthesis, we would have to use isobutyl bromide as the alkylating agent ... 

When the sodium derivative of acetoacetic ester is warmed with an alkyl halide, the metallic atom is replaced by an alkyl group. The stable form of these substances appears to have the keto structure. The reaction is usually effected by treating an alcoholic solution of acetoacetic ester with the calculated quantity of sodium ethylate, which converts the ester into its sodium derivative —... 

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