Ester condensation mixed

Diethylene glycol method. Place 0-5 g. of potassium hydroxide pellets, 3 ml. of diethylene glycol and 0 5 ml. of water in a 10 or 25 ml. distilling flask heat the mixture gently until the alkali has dissolved and cool. Add 1-2 g. of the ester and mix well. Fit the flask with a thermometer and a small water-cooled condenser in the usual way. Heat the flask over a small flame whilst shaking gently to mix the contents. When only one liquid phase, or one hquid phase and one solid phase, remains in the flask, heat the mixture more strongly so that the alcohol distils. Identify the alcohol in the distillate by the preparation of the 3 5 dinitrobenzoate (Section 111,27,2). 

The Claisen reaction is a carbonyl condensation that occurs between two ester molecules and gives a /3-keto ester product. Mixed Claisen condensations... 

Mixed condensations of esters are subject to the same general restrictions as outlined for mixed aldol reactions (Section 2.1.2). One reactant must act preferentially as the acceptor and another as the nucleophile for good yields to be obtained. Combinations that work best involve one ester that cannot form an enolate but is relatively reactive as an electrophile. Esters of aromatic acids, formic acid, and oxalic acid are especially useful. Some examples of mixed ester condensations are shown in Section C of Scheme 2.14. Entries 9 and 10 show diethyl oxalate as the acceptor, and aromatic esters function as acceptors in Entries 11 and 12. 

The sol-gel process involves the preparation of inorganic matrices via three steps. Components of the sol-gel cocktail are the sol-gel precursor (e.g. tetramethoxysilane), water, a catalyst (acids or bases), the indicator chemistry and a solvent such as ethanol. Mixing these components causes hydrolysis of the ester, silanol-ester condensation, and silanol-silanol condensation of the precursors ... 

In these Claisen condensations OCjH, is displaced from the COOCjH, group by the a-carbanion formed from another ester molecule. Mixed Claisen condensations are feasible only if one of the esters has no a H. 

When a mixture of two dissimilar esters (R -CH2 C02Et and R2-CH2 C02Et) is treated with sodium as the ethoxide, a mixed / -keto ester (R -CH2 C0 CH(R2)-C02Et or R2-CH2 CH(R1) C02Et) may be formed. However the disadvantage which is common to all mixed reactions, i.e. the formation of both symmetrical and crossed products, reduces its preparative value. Exceptions are provided in those cases where one of the esters contains no a-hydrogens. An important example is provided by the use of esters of oxalic acid in such mixed Claisen ester condensations (e.g. Section 5.14.3, p. 735, and Expt 8.37). 

The forward synthetic reaction (formulated in Expt 7.9) is thus an initial mixed Claisen ester condensation, followed by a Dieckmann cyclisation, hydrolysis and decarboxylation. Indane-l,3-dione is used for the synthesis of the trione, ninhydrin (Expt 5.99). 

The synthesis of the disubstituted malonic ester cannot be achieved by successive ethylation and phenylation procedures [cf. Section 5.11.6, p. 680] since for the latter reaction the aryl halide is not sufficiently reactive. The procedure described below (formulated in Expt 8.37) provides a suitable indirect alternative route. This involves a mixed Claisen ester condensation (cf. Section 5.14.3, p. 738) between ethyl phenylacetate and diethyl oxalate, followed by decarbony-lation of the a-keto diester on heating to 175 °C. 

Crossed Claisen condensations can be chemoselective even when the nonenolizable ester is not a better electrophile than the enolizable ester. This can be accomplished by a suitable choice of reaction conditions. The nonenolizable ester is mixed with the base and the enoliz-able ester is added slowly to that mixture. The enolate of the enolizable ester then reacts mostly with the nonenolizable ester for statistical reasons it reacts much less with the noneno-lized form of the enolizable ester, which is present only in rather small concentration. Carbonic acid esters and benzoic acid esters are nonenolizable esters of the kind just described. 

As was the case with the aldol condensation, mixed ester condensations can be useful if one of the components can only act as the electrophile—that is, if it cannot form an enolate anion (no hydrogens on the o-carbon). The following esters are most commonly employed in this role ... 

The crude bromo ester is mixed with 82.5 ml. (0.70 mole) of pure quinoline (Note 3) in a 250-ml. round-bottomed flask equipped with an air condenser, and the mixture is heated for 3 hours with an oil bath maintained at 160-170°. The black mixture is cooled, treated with 150 ml. of 20% hydrochloric acid, then shaken thoroughly with 200 ml. of petroleum ether (Note 2) until most of the tarry material has dissolved (Note 4). The aqueous phase is separated and washed with an additional 200 ml. of petroleum ether, and the combined organic extracts are washed with 10% hydrochloric acid and then with water. This washing cycle is repeated until the washes are colorless (two acid washes usually suffice) finally, the petroleum ether solution is washed once more with water. The organic layer is dried over anhydrous sodium sulfate, the solvent is flash-distilled as described above, and the residual liquid ester is distilled through a 61-cm. Pod-bielniak-type column (Note 5). The colorless unsaturated ester (Note 6) distils at 153-154°/14.5 mm. after a small fore-run. The yield is 22-27 g. (70-85.5% based on 2-methyldodecanoic acid), 1.4520-31, Xmax 214 me 12,300, in hexane (Note 7), Xmax 217 mii, e 12,800, in 95% ethanol. 

The over-all yields (R equals w-C,-Q, -C , and -C ) from the esters vary from 55% to 78%. Certain heterocyclic ketones, namely, 8-acetyl-quinoline and /3-acetylpyridine, have been prepared through a mixed ester condensation. (3) If acetoacetic ester is acylated in the form of its sodium enolate and carefully hydrolyzed, a new /3-keto ester is formed. Alkylation of this keto ester followed by hydrolysis gives ketones of the type RCOCH,R. ... 

An example is the synthesis of ethyl a-ethoxalylpropionate (R = CH,) in 70% yield. Ethyl oxalate and ethyl succinate form ethyl a-ethoxalyl-succinate (83%). In a mixed ester condensation, the use of a more reactive ester, such as the phenyl or biphenyl ester, helps to prevent side reactions. Simple heterocyclic esters, namely, ethyl nicotinate and ethyl 8-quinolinecarboxylate, undergo the mixed ester condensation in good yields. The internal condensation of ethyl adipate to give 2-carbethoxycyclopentanone (Dieckmann reaction) is an example of cyclization (81%). ... 

The Claisen reaction is a carbonyl condensation that occurs between two ester components and gives a /3-keto ester product. Mixed Claisen condensations between two different esters are successful only when one of the two partners has no acidic a hydrogens (ethyl benzoate and ethyl formate, for instance) and thus can function only as the acceptor partner. Intramolecular Claisen condensations, called Dieckmann cyclization reactions, provide excellent syntheses of five- and six-membered cyclic /3-keto esters starting from 1,6- and 1,7-diesters. 

Analogous to mixed aldol condensations, mixed Claisen condensations involve carbon-carbon bond formation between the a-carbon atom of one ester and the carbonyl carbon of another. 

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