Claisen ester condensation intramolecular

Carboxylic esters 1 that have an a-hydrogen can undergo a condensation reaction upon treatment with a strong base to yield a /3-keto ester 2. This reaction is called the Claisen ester condensation or acetoacetic ester condensation, the corresponding intramolecular reaction is called the Dieckmann condensation ... 

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... 

Frequently the basic conditions used cause the initial Michael adduct to undergo intramolecular transformations, as for example in the synthesis of dimedone (Expt 7.11). This involves a Michael reaction between mesityl oxide and diethyl malonate followed by an internal Claisen ester condensation. 

The intramolecular carbon-carbon bond-forming reactions considered in this section are based on the aldol condensation (see Section 5.18.2, p. 799), the Claisen-Schmidt reaction (see Section 6.12.2, p. 1032), the Claisen ester condensation (see Section 5.14.3, p. 736), and the Claisen reaction (see Section 6.12.2, p. 1032). Since these carbonyl addition reactions are reversible, the methods of synthesis are most successful for the formation of the thermodynamically stable five- and six-membered ring systems. The preparation of the starting materials for some of these cyclisation reactions further illustrates the utility of the Michael reaction (see Section, 5.11.6, p. 681). 

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. 

However, even this is not the end as, if the reaction is done in this way, those two molecules of ethoxide released from 48 catalyse an intramolecular Claisen ester condensation 54 and the main product is the ketoester 55. 

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. . 

So far the mechanism is almost the same as that of the Robinson annelation but the cyclization is now the attack of a ketone enolate on an ester group (it doesn t matter which one as they are equivalent) and so it is an intramolecular Claisen ester condensation (Chapter 28). The intermediate must be redrawn to allow cyclization. 

The acylation of RLi or RMgBr by nitriles (cyanides) is an effective way to make ketones (Chapr and here we see the cyanide version of an intramolecular Claisen ester condensation. One cy-makes an enolate , which attacks the other. The resulting imine tautomerizes to the coni. . enamino nitrile. 

X -.".e third case, cyclopentanone has self-condensed and ignored the enone to which it was to add in a conjugate fashion and continue with a Robinson annelation (p. 761). The liiis - - again is to use a specific enolate such as an enamine though the simplest here is a keto-ester can be easily prepared by intramolecular Claisen ester condensation (p. 727). 

The next stage is an intramolecular Claisen ester condensation. We can easily discover which enolate reacts with which ester by drawing the starting material in the shape of the product. The alternatives are three- or sbt-membered rings five-membered rings are more stable than three- and more rapidly formed than six-membered. Under the reaction conditions there is no stereochemistry as the product exists as a stable conjugated enolate ion (p. 724). 

The rest of the synthesis is straightforward no protection is needed in the favourable Claisen ester condensation to give 47 and the formation of the enol ether, being intramolecular, requires only heating with acid. This treatment also hydrolyses the remaining ester. 

When the Claisen ester condensation is intramolecular, it goes by the name of the Dieckmann condensation. As with the intramolecular aldol reactions, only processes that give rise to five- or six-membered rings are favorable (Figure 17.33). This process has been used in the total synthesis of prostaglandin A2 (Figure 17.34). 

Esters of dicarboxylic acids having hydrogen on the 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 Claisen (or acetoacetic ester) condensation to the formation of a ring system the condensation occurs internally to produce a... 

Intramolecular condensation of 6a-esters, thioesters, or amides (339 X = O, S, or NH R = Me or Ph), under the enolising influence of sodium hydride, affords the novel 4,6-fused furano- (340), thiopheno- (341), and pyrrolo- (342) derivatives, respectively. The reactions comprise a Claisen-like condensation. 

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