Knoevenagel condensation, Doebner

Knoevenagel condensation Doebner modification. Condensation of aldehydes or ketones with active methylene compounds (specifically malonic ester) in the presence of ammonia or amines the use of malonic acid and pyridine is known as the Doebner modification. 

The formation of 39 has been interpreted by assuming a Knoevenagel-Doebner reaction. The C-glycoside 40, obtained via the Knoevenagel condensation of the... 

The Doebner Modification (or Knoevenagel Condensation), which is possible in the presence of carboxylic acid groups, includes a pyridine-induced decarboxylation. 

Malonic acid undergoes Knoevenagel condensations with nearly every type of aldehyde and with very reactive ketones. If condensations with malonic acid are performed in ethanolic ammonia below 70 C, the methylenemalonic acids are usually obtained. If, however, the condensations are performed in pyridine (Doebner modification), decarboxylation normally takes place and the acrylic or cinnamic acid is... 

Knoevenagel condensation is also known as Doebner Condensation . 

In the formation of the first synthetic intermediate in Sequence D, the very effective Verley-Doebner modification of the fundamental Knoevenagel condensation is used. This modification uses malonic acid in place of the conventional ester to promote enoUzation. In addition, the heterocyclic amine, pyridine, functions as both the base catalyst and the solvent. A cocatalyst, P-alanine (an amino acid), is also introduced. Mechanistically, the reaction closely resembles the aldol condensation in that in both cases a carbanion is generated by abstraction, by base, of a proton alpha to a carbonyl group. The resulting carbanion is stabilized as an enolate anion (see below). 

Verley-Doebner modification of the Knoevenagel condensation. This method was somewhat forgotten for many years, until it was rediscovered by Haley and Maitland in 1951 and Prout in 1953. Prout carried out... 

The Doebner condensation (or reaction) is a slight modification of the Knoevenagel reaction and consists in warming a solution of the aldehyde and... 

KNOEVENAGEL OOEBNER STOBBE Condensation Base catalyzed aldol condensation of aldehydes or ketones with an activated methylene group of a malonic ester (Knoevenagel Doebner) or a succinic ester (Stobbe)... 

When the reactant is of the form ZCH2Z, aldehydes react much better than ketones and few successful reactions with ketones have been reported. However, it is possible to get good yields of alkene from the condensation of diethyl malonate, CH2(COOEt)2, with ketones, as well as with aldehydes, if the reaction is run with TiCU and pyridine in THF. In reactions with ZCH2Z, the catalyst is most often a secondary amine (piperidine is the most common), though many other catalysts have been used. When the catalyst is pyridine (to which piperidine may or may not be added) the reaction is known as the Doebner modification of the Knoevenagel reaction. Alkoxides are also common catalysts. 

The forward synthetic reaction is a base-catalysed condensation reaction between two carbonyl compounds, the aldol condensation leading to -hydroxy-aldehydes or / -hydroxyketones followed by dehydration. This sequence is one of the most important carbon-carbon bond forming reactions, and aldol-type condensation reactions are considered in a number of other sections of the text, for example, the Doebner reaction (Section 5.18.3, p. 805), the Knoevenagel reaction (Section 5.11.6, p. 681), the Perkin reaction (Section 6.12.3, p. 1036) and the Robinson annelation reaction (Section 7.2). 

Condensation reactions of the aldol type play an important part in heterocyclic chemistry. There are a large number of condensation reactions that are closely related to the aldol condensation. Each of these reactions has its own name Claisen, Dieckmann, Doebner, Knoevenagel, Perkin, to mention a few, but the chemistry is essentially the same as that of the aldol condensation. 

The condensation of 4-fluorobenzylsulfonylacetic acid with 2-pyridinecarboxaldehyde in the presence of benzylamine and acetic acid occurs by the Knoevenagel-Doebner reaction and is reviewed (1). 

---