Hann-Lapworth mechanism

The Knoevenagel condensation is a base-catalyzed aldol-type reaction, and the exact mechanism depends on the substrates and the type of catalyst used. The first proposal for the mechanism was set forth by A.C.O. Hann and A. Lapworth Hann-Lapworth mechanism) In 1904." When tertiary amines are used as catalysts, the formation of a p-hydroxydlcarbonyl Intermediate is expected, which undergoes dehydration to afford the product. On the other hand, when secondary or primary amines are used as catalyst, the aldehyde and the amine condense to form an Imlnlum salt that then reacts with the enolate. Finally, a 1,2-ellmlnatlon gives rise to the desired a,p-unsaturated dicarbonyl or related compounds. The final product may undergo a Michael addition with the excess enolate to give a bis adduct. 

Hann-Lapworth mechanism with tertiary amines as catalysts ... 

A few years after Knoevenagel proposed his mechanism for the reaction that came to bear his name, Hann and Lapworth showed that primary or secondary amines were not required for the transformation to take place, as Knoevenagel had claimed, but that tertiary amines could indeed promote the reaction between menthylacetoacetate 15 and aldehydes (although they were less efficient)." The use of a tertiary amine obviously precludes the possibility of an aminal or imine intermediate, therefore Hann and Lapworth proposed direct reaction between the enolized dicarbonyl compound and the aldehyde (Hann-Lapworth mechanism). This mechanism would proceed similarly to that proposed by Knoevenagel, but without aminal formation, and proceeding through a P-hydroxy dicarbonyl compound such as 18, rather than a P-amino dicarbonyl compound (e.g., 13). 

Clear evidence for both mechanisms exists, as both the P-amino dicarbonyland P-hydroxy dicarbonylintermediates been isolated in some cases. It can be safely assumed that if the reaction is promoted by a tertiary base, the Hann-Lapworth mechanism is operative, but in the presence of primary or secondary amines, either mechanism may occur. 

Lapworth, A. and Hann, A. (1902) The mutarotation of camphorquinonehy-drazone and mechanism of simple desmotropic change. J. Chem. Soc., 81, 1508-1519. 

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