Doebner condensation decarboxylation with

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... 

An earlier version of this reaction condensed 4.18 and malonic acid to give 4.19. Refluxing 4.19 led to the monomer 4.20), which decarboxylated under the reaction conditions to give 3-amino-3-phenylpropanoic acid, 4.21. Doebner condensation with malonic acid itself sometimes leads to very poor yields of product, as seen above. An improvement in the reaction used nitro-ester 4.22 rather than malonic acid, and 4.23 [ethyl 3-(N-phenylamino)-2-nitroprop-2E-enoate] was produced in good yield. 

This reaction type leading to oc,/ -unsaturated acids and esters is exemplified in the Perkin reaction (Section 6.12.3, p. 1036) and the Knoevenagel reaction (Section 5.11.6, p. 681). The Doebner reaction, which is illustrated in this section, is the condensation of an aldehyde with malonic acid in pyridine solution, often in the presence of a trace of piperidine. The reaction mechanism involves the addition of a malonate anion to the aldehydic carbonyl carbon atom followed by the elimination of water accompanied by decarboxylation. 

The recently discovered antimicrobial activity of canthin-6-one (12) has provided the impetus for renewed synthetic studies. Of the new, efficient syntheses reported " one involves the direct formation of canthin-6-one by a Doebner reaction on /S-carboline-1 -carboxaldehyde, for which an improved preparation was developed the overall yield of canthin-6-one from tryptophan is 15%. Alternatively, condensation of /S-carboline-1-carboxaldehyde with malonic ester, followed by hydrolysis and decarboxylation of the product, affords canthin-6-one in 19% overall yield from... 

The condensation of aldehydes or ketones, with active methylene compounds (especially malonic ester) in presence of a weak base like ammonia or amine (primary or secondary) is known as Knoevenagel reaction. However, when condensation is carried out in presence of pyridine as a base, decarboxylation usually occurs during the condensation. This is known as Doebner modification. Some examples are given (Scheme 37). 

---