Acetals Acetoacetic ester synthesis

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 ... 

It is obvious that many carboxylic acids of the formulas RCH2COOH and RR CHCOOH can be synthesized by this method (for some other ways of preparing such acids, see 10-106, 10-108, and 10-109). Another important example is the acetoacetic ester synthesis, in which Z is COOEt and Z is COCH3. In this case the product can be decarboxylated with acid or dilute base (12-38) to give a ketone or cleaved with concentrated base (12-41) to give a carboxylic ester and a salt of acetic acid ... 

Malonic esters have two ester groups, each of which may react as in the acetoacetic ester synthesis due to their similar structure (see the preceding section). The malonic ester synthesis provides a method for preparing a substituted acetic acid. Figure 15-14 shows the structure of one type of malonic ester. Figure 15-15 outlines the basic malonic ester synthesis. May repeat in that figure refers to the reaction with a second molecule of RX (or R X). 

The malonic ester synthesis is similar to the acetoacetic ester synthesis. It begins with deprotonation of diethyl malonate (pKa = 11) to produce an enolate anion that is the synthetic equivalent of the enolate anion derived from acetic acid ... 

Show how the malonic ester synthesis makes substituted acetic acids, and how the acetoacetic ester synthesis makes substituted acetones. Give mechanisms for these reactions. 

Tseou, H.-F., Wang, Y.-T. Abnormal acetoacetic ester synthesis. I. The reaction of sodium with allyl, benzohydryl and cinnamyl acetates. J. Chinese Chem. Soc. 1937, 5, 224-229. 

A useful counterpart of the acetoacetic ester synthesis —one that allows the synthesis of mono- and disubstituted acetic acids— is called the malonic ester synthesis. The starting compound is the diester of a j8-dicarboxylic acid, called a malonic ester. The most commonly used malonic ester is diethyl malonate. 

Historically, as early as 1937, the first enolate Claisen rearrangement, though it was not formally recognized as such, was documented. Tseou and Wang [12] reported the formation of 4-pentenoic acid in low yields on heating neat allyl acetate with sodium metal for 3 h to ca. 100°C while attempting the acetoacetic ester synthesis (Scheme 5.1.1). 

As with the acetoacetic ester synthesis, we have already encountered all the important chemistry of the malonic ester synthesis, although not in this particular pattern. Let us illustrate this synthesis by choosing 5-methoxypentanoic acid as a target molecule. The two carbons shown in color are provided by diethyl malonate. The remaining three carbons and the methoxy group represent the —R group of a monosubstituted acetic acid. 

Acetoacetic ester synthesis (Section 22.7) The synthesis of a methyl ketone by alkylation of an alkyl halide with ethyl aceto-acetate, followed by hydrolysis and decarboxylation. 

The malonate ester synthesis resembles the acetoacetate ester synthesis. It is used to prepare alkylated derivatives of acetic acid and other carboxylic acids rather than derivatives of acetone or other ketones prepared by the acetoacetic ester synthesis. The a-hydrogen atom of diethyl malonate is sufficiently acidic to be deprotonated by ethoxide ion. Subsequent alkylation with a primary or secondary alkyl halide yields an alkylated malonate ester. 

Still another possibility in the base-catalyzed reactions of carbonyl compounds is alkylation or similar reaction at the oxygen atom. This is the predominant reaction of phenoxide ion, of course, but for enolates with less resonance stabilization it is exceptional and requires special conditions. Even phenolates react at carbon when the reagent is carbon dioxide, but this may be due merely to the instability of the alternative carbonic half ester. The association of enolate ions with a proton is evidently not very different from the association with metallic cations. Although the equilibrium mixture is about 92 % ketone, the sodium derivative of acetoacetic ester reacts with acetic acid in cold petroleum ether to give the enol. The Perkin ring closure reaction, which depends on C-alkylation, gives the alternative O-alkylation only when it is applied to the synthesis of a four membered ring ... 

Aminopyrans 244, spiro-conjugated with an polycyclic N,0,S-system, have been synthesized using N,S-acetal derivatives of actylacetone and acetoacetic ester 245 (00PS(160)105). Diacetyl derivative 245 (Z = COMe) undergoes deacetylation in the course of pyran synthesis (Scheme 93). 

Synthesis of substituted acetic acids via acetoacetic ester Acetoacetic ester, an ester formed by the self-condensation of ethyl acetate via a Claisen condensation, has the following structure ... 

Synthesis of substituted acetic acids via acetoacetic ester... 146 Synthesis of substituted acetic acid via malonic ester. .. 150 a halo acids, a hydroxy acids, and a, (3 unsaturated acids.. .153... 

Similarly, the a-methylene group of acetoacetic ester is oximinated by the action of sodium nitrite in glacial acetic acid (63%). Nitrosation of alkylated malonic, acetoacetic, and benzoyl acetic esters with subsequent cleavage affords an excellent synthesis for a-oximino esters, RC(=-NOH)COjC2Hj. A survey of several possible procedures for this conversion has been made." If a /3-keto acid is nitrosated, then the Carboxyl group is lost and an a-oximino ketone is formed, viz.,... 

As a synthetic route, this organoborane synthesis parallels the aoetoaoetic ester and malonic ester syntheses. An acetone unit is furnished by acetoacetic ester or, here, by bromoacetone an acetic add unit is furnished by malonic ester or, here, by bromoacetic ester. In these syntheses, bromine plays the same part that the —COOEt group did by increasing the acidity of certain a-hydrogens, it determines where in the molecule reaction will take place it is easily lost from the molecule when its job is done. Unlike the loss of —COOEt, the departure of —Br is an integral part of the alkylation process. 

When treated with concentrated alkali, acetoacetic ester is converted into two moles of sodium acetate, (a) Outline all steps in a likely mechanism for this reaction. (Hint See Sec. 21.11 and Problem 5.8, p. 170.) (b) Substituted acetoacetic esters also undergo this reaction. Outline the steps in a general synthetic route from acetoacetic ester to carboxylic acids, (c) Outline the steps in the synthesis of 2-hexanone via acetoacetic ester. What acids will be formed as by-products Outline a procedure for purification of the desired ketone. (Remember that the alkylation is carried out in alcohol that NaBr is formed that aqueous base is used for hydrolysis and that ethyl alcohol is a product of the hydrolysis.)... 

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