Esters Dieckmann reaction

Esters of dicarboxyUc acids having hydrogen on tbe 8 or e carbon atoms undergo intramolecular cyclisation when heated with sodium or with sodium ethoxide. This cyclisation is known as the Dieckmann reaction. It is essentially an application of the Claiseu (or acetoacetic eater) condensation to the formation of a ring system the condensation occurs internally to produce s... 

Benzilic acid rearrangement Benzoin reaction (condensation) Blanc chloromethylation reaction Bouveault-Blanc reduction Bucherer hydantoin synthesis Bucherer reaction Cannizzaro reaction Claisen aldoi condensation Claisen condensation Claisen-Schmidt reaction. Clemmensen reduction Darzens glycidic ester condensation Diazoamino-aminoazo rearrangement Dieckmann reaction Diels-Alder reaction Doebner reaction Erlenmeyer azlactone synthesis Fischer indole synthesis Fischer-Speior esterification Friedel-Crafts reaction... 

Synthesis This cyclisation version of the Claisen ester condensation is sometimes called the Dieckmann Reaction. 

The carbon-car bon bond-fonrring potential inherent in the Claisen and Dieckmann reactions has been extensively exploited in organic synthesis. Subsequent transfonnations of the p-keto ester products permit the synthesis of other functional groups. One of these transformations converts p-keto esters to ketones it is based on the fact that p-keto acids (not esters ) undergo decarboxylation readily (Section 19.17). Indeed, p-keto acids, and their- conesponding carboxylate anions as well, lose carbon dioxide so easily that they tend to decarboxylate under the conditions of their formation. 

Should there be two ester functions in the same molecule, then it is possible to achieve an intramolecular Claisen reaction, particularly if this results in a favourable five- or six-membered ring. This reaction is usually given a separate name, a Dieckmann reaction, but should be thought of as merely an intramolecular extension of the... 

The reverse Claisen reaction is common, especially with cyclic P-ketoesters, such as one gets from the Dieckmann reaction (see Section 10.8). If one only wants to hydrolyse the ester, it thus becomes necessary to use the rather less effective acid-catalysed hydrolysis method (see Section 7.9.2). 

Nucleophilic addition to C=0 (contd.) ammonia derivs., 219 base catalysis, 204, 207, 212, 216, 226 benzoin condensation, 231 bisulphite anion, 207, 213 Cannizzaro reaction, 216 carbanions, 221-234 Claisen ester condensation, 229 Claisen-Schmidt reaction, 226 conjugate, 200, 213 cyanide ion, 212 Dieckmann reaction, 230 electronic effects in, 205, 208, 226 electrons, 217 Grignard reagents, 221, 235 halide ion, 214 hydration, 207 hydride ion, 214 hydrogen bonding in, 204, 209 in carboxylic derivs., 236-244 intermediates in, 50, 219 intramolecular, 217, 232 irreversible, 215, 222 Knoevenagel reaction, 228 Lewis acids in, 204, 222 Meerwein-Ponndorf reaction, 215 MejSiCN, 213 nitroalkanes, 226 Perkin reaction, 227 pH and, 204, 208, 219 protection, 211... 

The mechanism of the Claisen and Dieckmann reactions is the ordinary tetrahedral mechanism,1694 with one molecule of ester being converted to a nucleophile by the base and the other serving as the substrate. 

C-alkyl derivatives (280) are obtained by direct addition of an alkyl halide at the end of the Dieckmann reaction, in benzene or xylene. O-Alkyl derivatives (281) are obtained by reacting sodium amide with ester 278, previously isolated, in benzene, followed by addition of the... 

The conversion of esters (278) to 3(2//)-benzofuranones (279) by hydrolysis and decarboxylation (KOH in alcohol)279,668,674 is sometimes difficult. Direct conversion of esters (277) into benzofurans has recently been achieved by the action of NaBH4 on the product of the Dieckmann reaction (not isolated), followed by acidic hydrolysis (70% yield).681,682... 

The synthesis may thus be seen to be an intramolecular Claisen ester condensation, which is known as the Dieckmann reaction. The procedure is an important method for the synthesis of five- and six-membered ring systems, and the cyclic /2-keto ester product may be converted into the corresponding cyclic ketone by hydrolysis followed by decarboxylation (ketonic hydrolysis, see Section 5.8.5, p. 619). The base catalyst used in Expt 7.8 is sodium ethoxide, but sodium hydride as a 50 per cent dispersion in oil is a recommended alternative. 

Intramolecular ester condensation reactions are called Dieckmann condensations and are very useful ring-forming reactions. Examples are shown in the following equations. In the second equation the yield is only 54% if sodium ethoxide is used as the base. 

The intramolecular version of the Claisen ester condensation is sometimes known as the Dieckmann reaction, It provides an excellent route to heterocyclic ketones (cyclic ketones with heteroatoms in the ring very important in. . 

Dieckmann reaction (Section 23.9) the intramolecular Claisen condensation reaction of a 1,6-or 1,7-diester, yielding a cyclic p-keto ester. 

A method for the enantioselective synthesis of the ftmctionalised carbapenam core 38 from D-serine-derived pyrrolidines has been reported <03JOC187>. Disubstituted pyrrolidines, obtained from the retro Dieckmann reaction of azabicyclo[2.2.1]heptan-2-one-1-carboxylic acid methyl esters, have been used as starting materials to develop concise syntheses of all four stereoisomers of carbapenam-3-carboxylic acid methyl esters <03JOC2889>. The synthesis of 1-methylcarbapenams 39 by intramolecular attack of lactam nitrogen on a 77 -propargylpalladium complex has been reported <03JOC8068>. 

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%). ... 

Intramolecular Claisen reactions of dlesters form five- and six-membered rings. The enolate of one ester is the nucleophile, and the carbonyl carbon of the other is the electrophile. An intramolecular Claisen reaction is called a Dieckmann reaction. Two types of diesters give good yields of cyclic products. 

Problem 24.21 What two p-keto esters are formed in the Dieckmann reaction of the following diester ... 

The Dieckmann reaction of Et02C(CH2)4CH(CH3)C02Et yields only one of the two possible cyclic p-keto esters. Draw structures for both possible products and explain why only one is formed. 

After converting A -Phth-protected amines into the corresponding 2-(pyrrolidinocarbon-yl)benzamide derivative, Dieckmann reactions, ester hydrolysis, and transesterfication can be carried out. This strategy of pyrrolidine-based deactivation of phthaloyl-protected anoines followed by reclosure of the phthaloyl group has successfully been applied in the synthesis of (3-lactam antibiotics.P l... 

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