Esters acetoacetic, synthesis

Product of the j Two components needed malonic ester synthesis I - - 

Sample Problem 23.3 What starting materials are needed to prepare 2-methylhexanoic acid [CH3CH2CH2CH2CH(CH3)COOH] 

The target molecule has two different alkyl groups bonded to the a carbon, so three components are needed for the synthesis  

Problem 23.23 What alkyl halides are needed to prepare each carboxylic acid by the malonic ester synthesis  

Problem 23.24 Explain why each of the following carboxylic acids cannot be prepared by a malonic ester synthesis (a) (CH3)3CCH2C00H (b) CgHsCHgCOOH (c) (CH3)gCCOOH. 

Problem 23.25 Explain why each of the following carboxylic acids cannot be prepared by a malonic ester 

The acetoacetic ester synthesis is a stepwise method for converting ethyl acetoacetate into a ketone having one or two alkyl groups on the a carbon. 

The steps in the acetoacetic ester synthesis are exactly the same as those in the malonic ester synthesis. Because the starting material, CH3COCH2COOEt, is a p-keto ester, the final product is a ketone, not a carboxylic acid. 

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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... 

This reaction sequence is called the acetoacetic ester synthesis It IS a standard... 

The acetoacetic ester synthesis brings about the overall transformation of an alkyl halide to an alkyl derivative of acetone... 

The malonic ester synthesis is conceptually analogous to the acetoacetic ester synthesis The overall transformation is... 

Section 21 6 The acetoacetic ester synthesis is a procedure in which ethyl acetoac etate is alkylated with an alkyl halide as the first step in the preparation... 

Section 21 7 The malonic ester synthesis is related to the acetoacetic ester synthesis Alkyl halides (RX) are converted to carboxylic acids of the type RCH2COOH by reaction with the enolate ion derived from diethyl mal onate followed by saponification and decarboxylation... 

Acetoacetic ester synthesis (Section 21 6) A synthetic method for the preparation of ketones in which alkylation of the enolate of ethyl acetoacetate... 

This reaction sequence is called the acetoacetic ester synthesis. It is a standard procedure for the preparation of ketones from alkyl halides, as the conversion of 1-bromobutane to 2-heptanone illustrates. 

Related and equally important reactions are the acetoacetic ester synthesis and the eyanoaeetie ester synthesis Here too the initial substituted product can be hydrolyzed and decarboxylated, to yield a ketone 11 (i.e. a substituted acetone) from acetoacetic ester 10, and a substituted acetonitrile 14 from eyanoaeetie ester 13 respectively. Furthermore a substituted acetoacetic ester can be cleaved into a substituted acetic ester 12 and acetate by treatment with strong alkali ... 

Just as the malonic ester synthesis converts an alkyl halide into a carboxylic acid, the acetoacetic ester synthesis converts an alkyl halide into a methyl ketone having three more carbons. 

Using the Acetoacetic Ester Synthesis to Prepare a Ketone... 

How would you prepare 2-pentanone by an acetoacetic ester synthesis ... 

Strategy The acetoacetic ester synthesis yields a methyl ketone by adding three carbons to an alkyl halide. 

Thus, the acetoacetic ester synthesis of 2-pentanone must involve reaction of bromoethane. 

Which of the following compounds cannot be prepared by an acetoacetic ester synthesis Explain. 

Both the malonic ester synthesis and the acetoacetic ester synthesis are easy to cany out because they involve unusually acidic dicarbonyi compounds. As a result, relatively mild bases such as sodium ethoxide in ethanol as solvent can be used to prepare the necessary enolate ions. Alternatively, however, it s also possible in many cases to directly alkylate the a position of monocarbonyl compounds. A strong, stericaliy hindered base such as LDA is needed so that complete conversion to the enolate ion takes place rather than a nucleophilic addition, and a nonprotic solvent must be used. 

Alpha hydrogen atoms of carbonyl compounds are weakly acidic and can be removed by strong bases, such as lithium diisopropylamide (LDA), to yield nucleophilic enolate ions. The most important reaction of enolate ions is their Sn2 alkylation with alkyl halides. The malonic ester synthesis converts an alkyl halide into a carboxylic acid with the addition of two carbon atoms. Similarly, the acetoacetic ester synthesis converts an alkyl halide into a methyl ketone. In addition, many carbonyl compounds, including ketones, esters, and nitriles, can be directly alkylated by treatment with LDA and an alkyl halide. 

The cyclic /3-keto ester produced in a Dieckmann cyclization can be further alkylated and decarboxylated by a series of reactions analogous to those used in the acetoacetic ester synthesis (Section 22.7). For example, alkylation and subsequent decarboxylation of ethyl 2-oxocyclohexanecarboxylate yields a 2-alkylcvclohexanone. The overall sequence of (1) Dieckmann cyclization, (2) /3-keto ester alkylation, and (3) decarboxylation is a powerful method for preparing 2-substituted cyclohexanones and cyclopentanones. 

Another alternative for preparing a primary amine from an alkyl halide is the Gabriel amine synthesis, which uses a phthalimide alkylation. An imide (—CONHCO—) is similar to a /3-keto ester in that the acidic N-H hydrogen is flanked by two carbonyl groups. Thus, imides are deprotonated by such bases as KOH, and the resultant anions are readily alkylated in a reaction similar to the acetoacetic ester synthesis (Section 22.7). Basic hydrolysis of the N-alkylated imide then yields a primary amine product. The imide hydrolysis step is analogous to the hydrolysis of an amide (Section 21.7). 

Step 2 of Figure 29.11 Decarboxylation The TPP addition product, which contains an iminium ion j8 to a carboxylate anion, undergoes decarboxylation in much the same way that a jB-keto acid decarboxylates in the acetoacetic ester synthesis (Section 22.7). The C=N+ bond of the pyruvate addition product acts... 

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