Esters, 1,3-keto Knoevenagel reaction

Keywords phenol, /1-keto ester, Pechmann reaction, Knoevenagel reaction, cou-marin... 

Knoevenagel Reaction. This involves the reaction of an aldehyde with malonic ester or /3-keto esters. The reaction is catalyzed by amines. 

Knoevenagel reaction. As surrogate for benzaldehyde in the condensation with active methylene compounds, the benzenesulfonimine is superior. In the presence of EtjN in chloroform the reaction with, inter alia, /8-diketones, )3-keto esters, a-sulfonyl ketones, a-nitro esters, and malononitrile proceeds at room temperature. 

Under similar conditions, 2-furyl vinylcarbonyl systems (ketones, esters, acids) also produce keto esters. For example, 3-(2-furyl)acrylic acid 38, which is easily accessible from 2-furaldehyde by a decar-boxylating Knoevenagel reaction with malonic acid, yields the 3-oxoheptanedicarboxylic ester 39 (Marckwald cleavage) [9] ... 

Good yields of dihydropyran-2-ones may be had by a TiCU-catalysed Knoevenagel reaction of -keto esters. ... 

With 8-keto esters HCHO is known to undergo Knoevenagel reaction to give 2-acylacrylates, key intermediates in the Hantzsch dihydropyridine synthesis. Application... 

The preparation of (83) (Expt 8.29) is an example of the Hantzsch pyridine synthesis. This is a widely used general procedure since considerable structural variation in the aldehydic compound (aliphatic or aromatic) and in the 1,3-dicarbonyl component (fi-keto ester or /J-diketone) is possible, leading to the synthesis of a great range of pyridine derivatives. The precise mechanistic sequence of ring formation may depend on the reaction conditions employed. Thus if, as implied in the retrosynthetic analysis above, ethyl acetoacetate and the aldehyde are first allowed to react in the presence of a base catalyst (as in Expt 8.29), a bis-keto ester [e.g. (88)] is formed by successive Knoevenagel and Michael reactions (Section 5.11.6, p. 681). Cyclisation of this 1,5-dione with ammonia then gives the dihydropyridine derivative. Under different reaction conditions condensation between an aminocrotonic ester and an alkylidene acetoacetate may be involved. 

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