Carboxylic esters Dieckmann condensation

Step 1 Intramolecular condensation of two esters (Dieckmann condensation). Step 2 Saponification of the ethyl ester provides the P-keto carboxylic acid. 

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 ... 

In the case of the dicarboxylic esters of adipic and pimelic acids, intramolecular condensation gives cyclic esters of /8-keto-carboxylic acids (Dieckmann) ... 

Fiessdmann and Pfeiffer" passed HCl at 0° through acetoacetic ester and thioglycolic ester in dcohol to obtain triethyl y3, -bis(carbo-methoxymethylthio)butyrate (169) Dieckmann condensation reportedly furnish ethyl 3,4-dihydroxy-6a-methyl-3a,6a-dihydro-thieno(2,3-b]-thiophene-2-carbOxylate (170) [Eq. (48)]. 

Acylation of Carboxylic Esters by Carboxylic Esters. The Claisen and Dieckmann Condensations Alkoxycarbonylalkyl-de-alkoxy-substitution... 

Intramolecular Claisen condensations, called Dieckmann condensations, are ringclosing reactions that yield 2-cyclopentanone carboxylic esters (Figure 10.52) or 2-cyclohexanone carboxylic esters. The mechanism of the Dieckmann condensation is, of course, identical to the mechanism of the Claisen condensation (Figure 10.51). To ensure that the Dieckmann condensation goes to completion, the presence of a stoichiometric amount of base is required. As before, the neutral /3-ketoester (B in Figure... 

Intramolecular attack of the enamino carbonyl is possible too. Ethyl 3-hydro-xypyrrolecarboxylate and 3-hydroxyindole-2-carboxylate derivatives can be synthesized by Dieckmann condensation of an enamino ester derived from glycine ester and a / -ketoester. Transformation to the 2-pyrrolin-4-on system is easy198 (equation 139). 

The indole-2-carboxylate (70.2) undergoes a Dieckmann condensation usine sodium in benzene. An excess of lithium bis(trimethyl ily )atni()Q (LB At thf at -78 C for 5 min cyclizes the thio ester (70.3) to the stereoisomer shown as the only product. The same base has been used (30671 to svnthe ir biologically promising carbapenems. 

Carboxylic Acids and their Derivatives.—2,3-Seco-A -unsaturated dicarboxylic acids (443), obtained by ozonolysis of 2-hydroxymethylene-4-en-3-ones, have been considered rather resistant to cyclisation to form the A-nor-3-en-2-one system (444). Two convenient methods for achieving such a reaction are now described. Dieckmann condensation of the dimethyl ester (445) was successful with sodium hydride, in toluene containing a little methanol. The 5-methoxy-carbanion (446), resulting from conjugate addition of methoxide ion, is suggested as a possible activated intermediate. Alternatively, the diacid (in the B-nor-series)... 

Cyclohexanone-2-carboxylic esters. The reagent acts as a condensation catalyst for twofold Michael additon of a donor to an acrylate ester and Dieckmann cyclization of the 1 2 adducts. However, NaOMe has the same capability therefore, Na2pe(CO)4 is not unique. 

Recall from Section 18.4C that hydrolysis of an ester in aqueous sodium hydroxide (saponification) followed by acidification of the reaction mixture with aqueous HCl converts an ester to a carboxylic acid. Also recall from Section 17.9 that j8-ketoacids and j8-dicarboxylic adds (substituted malonic acids) readily undergo decarboxylation (lose CO2) when heated. Both the Claisen and Dieckmann condensations yield esters of j8-ketoacids. The following equations illustrate the results of a Claisen condensation followed by hydrolysis of the ester, acidification, and decarboxylation. 

The Ti- and Zr- Claisen and Dieckmann condensations exhibit powerful reactivity to realize C-C bond formations between various carboxylic esters under mild reaction conditions. This characteristic merit would promise a large ring closing with higher concentrations and speed. 

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... 

Pyrido[2,3-(7]pyrimidincs 23, unsubstituted in the 2,4-positions, have been synthesized by condensation of ethyl 4-aminopyrimidine-5-carboxylate with several esters, phenylacetonitrile, phenylacetamide, or malonic ester chloride.173 In the first step, the 4-amino group reacts with the ester, nitrile, or acid chloride function of the cyclization partner, ring closure then being effected by a Dieckmann-type cyclization. 

A process which should have produced norlupinane was worked through by Clemo and Ramage. They condensed ethyl piperidine-2-carboxylate withy-bromobutyronitrile and, as the resultingy-2-carbethoxy-piperidinobutyronitrile could not be cyclised, hydrolysed it with alcoholic hydrogen chloride to the dicarboxylic ester (XXIII), which by the Dieckmann reaction, gave ethyl l-ketooctahydropyridocoline-2-carboxylate (XXIV). This on boiling with dilute sulphuric acid furnished 1-kcto-... 

---