Acetic acetoacetate esters

Simple esters (e.g., ethyl acetate) undergo the acetoacetic ester condense tion (compare Section 111,151). The effective condensing agent is sodium ethoxide, produced by the action of sodium upon traces of alcohol present in the ester ... 

The formation of acyloins (a-hydroxyketones of the general formula RCH(OH)COR, where R is an aliphatic residue) proceeds best by reaction between finely-divided sodium (2 atoms) and esters of aliphatic acids (1 mol) in anhydrous ether or in anhydrous benzene with exclusion of oxygen salts of enediols are produced, which are converted by hydrolysis into acyloins. The yield of acetoin from ethyl acetate is low (ca. 23 per cent, in ether) owing to the accompanying acetoacetic ester condensation the latter reaction is favoured when the ester is used as the solvent. Ethyl propionate and ethyl ji-butyrate give yields of 52 per cent, of propionoin and 72 per cent, of butyroin respectively in ether. 

Diethyl 3-oxoheptanedioate, for example, is clearly derived from giutaryl and acetic acid synthons (e.g. acetoacetic ester M. Guha, 1973 disconnection 1). Disconnection 2 leads to acrylic and acetoacetic esters as reagents. The dianion of acetoacetic ester could, in prin-ciple,be used as described for acetylacetone (p. 9f.), but the reaction with acrylic ester would inevitably yield by-products from aldol-type side-reactions. 

Manufacture and Uses. Acetoacetic esters are generally made from diketene and the corresponding alcohol as a solvent ia the presence of a catalyst. In the case of Hquid alcohols, manufacturiag is carried out by continuous reaction ia a tubular reactor with carefully adjusted feeds of diketene, alcohol, and catalyst, or alcohol—catalyst blend followed by continuous purification (Fig. 3). For soHd alcohols, an iaert solvent is used. Catalysts used iaclude strong acids, tertiary amines, salts such as sodium acetate [127-09-3], organophosphoms compounds, and organometaHic compounds (5). 

On treatment with alkoxide bases, esters undergo self-condensation to give a p-keto ester and an alcohol. Ethyl acetate, for exanple, undergoes a Claisen condensation on treatment with sodium ethoxide to give a p-keto ester known by its common nane ethyl ace-toacetate (also called acetoacetic ester) ... 

Ethyl acetoacetate (acetoacetic ester), available by the Claisen condensation of ethyl acetate, has properties that make it a useful starting material for the preparation of ketones. These properties are... 

The formation of ethyl acetoacetate occurs, according- to Claisen, in four steps. The presence of a small quantity of alcohol gives lise to sodium ethylate, which forms an additive compound with ethyl acetate. The latter unites with a second molecule of ethyl acetate yielding the sodium salt of ethyl acetoacetate, and splitting off alcohol, which reacts with fresh metallic sodium. The sodium salt on acidifying passes into the tautomeric (ketonic) form of acetoacetic ester. 

Add I c.c. of a saturated alcoholic solution of cupric acetate to a few drops of the ester, a bluish-green crystalline precipitate of copper acetoacetic ester, (CoH903), Cu, is formed. See Appendix, p. 248. i . ... 

Orthoformic ester and acetoacetic ester in presence of acetic anhydride form a hydroxyniethylene ester (Claisen),... 

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 ... 

See Cephradine for preparation of D-2-amino-2-(1,4-cyclohexadienyl)acetic acid and then its methyl acetoacetic ester enamine as the starting material. 

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 ... 

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 ... 

Arthur Lachman. The Spirit of Organic Chemistry (New York Macmillan, 1899) 71. Also see Russell, "Specialism and Its Hazards," 2021 and Ihde, The Development of Modern Chemistry, who notes that while Wilhelm Wislicenus in 1896 isolated two ethyl formyl phenyl acetates that had keto and enol properties, it was only in 1911 that each form of acetoacetic ester was isolated free of contamination by the other at temperatures around - 78°C (330). 

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). 

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). 

To prepare hexaaluminates for ceramic applications a slightly different sol-gel process was proposed by Debsikbar.19 Ba-hexaaluminates were prepared via hydrolysis of Al di(isopropoxide) acetoacetic ester chelate and anhydrous Ba acetate obtained by reaction between BaC03 and glacial acetic acid. The substitution of Al(i-OC3H7)3 with the alkoxy ester was intended to control the chemical polymerization during gel formation. The reaction was performed in 1-butanol. The formation of the gel slowly occurred at room temperature in about 10 h. To obtain the final phase the gel precursor was dried at 70 °C for about 2 weeks, ground and calcined at 1200°C for 2 h. However no data on the morphology of the final materials were reported by the author. 

Acetoacetic Ester can be prepared by the condensation of ethyl acetate, called the Acetoacetic Ester Condensation Reaction, a Claisen Condensation-. 

An interesting variation of the Dieckmann cyclization involves vinylogous activation of a methyl group in a 2-butenyl ester. Reaction of an a-halo ester with the enethiol formed by treatment of an acetoacetic ester, which may be substituted at the a-position, with hydrogen sulfide produces (92) in satisfactory yield. Treatment of these compounds with sodium in benzene produced the 4-hydroxythiophene-2-acetic acids (94) (40JCS1385). The product undoubtedly involved the intermediate (93), in which the activated methyl goup has condensed with the ethoxycarbonyl group in typical Claisen fashion. 

In a 12-I. round-bottom flask, fitted with an efficient mechanical stirrer, is placed 5 l. of a 5 per cent solution of sodium hydroxide (6.25 moles). To this is added the crude ethyl w-butylaceto-acetate (about 925 g.) (p. 36) obtained from 5 moles of ethyl acetoacetate. The mixture is stirred at room temperature for four hours, during which time the mono-substituted acetoacetic ester is completely saponified and passes into solution. The mixture is then allowed to stand until the unsaponified material separates completely as an oily layer. The aqueous layer is separated (Note r) and transferred to a flask provided with a stopper fitted with a separatory funnel and a large bent glass tube leading to a condenser set for distillation. 

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