Doebner reaction

Ootonic acid may be prepared by condensing acetaldehyde with malonic acid in pyridine solution in the presence of a trace of piperidine (Doebner reaction see discussion following Section IV,123). 

This preparation is another example of the condensation of an aldehyde with malonic acid and pyridine to 3neld ultimately an ap-unsaturated acid (Doebner reaction). It is included here because, unlike the acids prepared from many of the lower aUphatic aldehydes, the product consists largely (about 95 per cent.) of the ap-isomeride and only about 5 per cent, of the PY-isomeride is present ... 

Sorbic acid is prepared by the condensation of crotonaldehj de with malonic acid ill the presence of pyridine at 100° (Doebner reaction) ... 

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... 

The Doebner reaction is a three component coupling of an aniline (1), pyruvic acid (2), and an aldehyde (3) to provide a 4-carboxyl quinoline (4). That product can be decarboxylated to furnish quinoline 5. 

In 1883, Bottinger described the reaction of aniline and pyruvic acid to yield a methylquinolinecarboxylic acid. He found that the compound decarboxylated and resulted in a methylquinoline, but made no effort to determine the position of either the carboxylic acid or methyl group. Four years later, Doebner established the first product as 2-methylquinoline-4-carboxylic acid (8) and the second product as 2- methylquinoline (9). Under the reaction conditions (refluxing ethanol), pyruvic acid partially decarboxylates to provide the required acetaldehyde in situ. By adding other aldehydes at the beginning of the reaction, Doebner found he was able to synthesize a variety of 2-substituted quinolines. While the Doebner reaction is most commonly associated with the preparation of 2-aryl quinolines, in this primary communication Doebner reported the successful use of several alkyl aldehydes in the quinoline synthesis. 

A possible mechanism is shown. Condensation of 6 and 3 provides 11, which can be attacked by the enol of 2 (12) to provide 13. Intramolecular condensation yields 16, which is then oxidized to 17. A common variant of the Doebner reaction involves first... 

The electronic properties of the aniline are important in the Doebner reaction. The reaction works best with electronic donating groups. Anilines substituted with a chlorine at the meta position consistently give low yields, but fluorine at the meta position seems... 

The Doebner reaction can provide the 4-carboxyl quinoline when the Pfitzinger reaction does not." Pfiztinger reaction of pinnacolone with isatin did not provide the desired quinoline. Doebner reaction of aniline with acetaldehyde and pyruvic acid did furnish the quinoline, albeit in only 8% yield. 

The method constitutes a simple preparation of ethanol-in-soluble cinnamic acids, of a high degree of purity when compared with the Perkin reaction 6 or the usual procedure for the Doebner reaction,6 which uses a large excess of pyridine. A useful modification of this reaction is to warm the reactants on a steam plate in the absence of alcohol.7 8... 

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

Dodecenoic acid, 37, 31 DodECYLAMINE, N methyl, 36, 48 n Dodecyl fluoride, 36, 42 Doebner reaction, 31, 35... 

Doebner Reaction (Beyer Synthesis, Beyer Method for Quinolines)... 

Disulphides, 1078 dialkyl, 496, 498 Dithizone, 955 Di-p-tolyl ketone, 930, 931 Dixon gauze rings, 97 n-Dodecane, 237 n-Dodecyl bromide, 282 n-Dodecyl chloride, 275 n-Dodecyl p-toluenesuiphonate, 825 Doebner reaction, 463, 465, 710, 711, 719... 

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). 

While the individual scaffolds are not new, this combinatorial evaluation of the Doebner reaction yielded a deeper and more complete understanding of this MCR and the dependence of the expected products on the structure of the used starting materials was evaluated in a very short time. 

Scheme 10.5. Rational modification of the classical Doebner reaction yielded a novel four-component reaction.

Distillation apparatus, 31, 70 Doebner reaction, 31, 35 Drying methods, diethyl phthalate, 31,2 magnesium ethoxide, 31, 2 Dulcin, 31, 10... 

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