Lapworth mechanisms

Both parts of the Lapworth mechanism enol formation and enol halogenation are new to us Let s examine them m reverse order We can understand enol halogenation by analogy to halogen addition to alkenes An enol is a very reactive kind of alkene Its carbon-carbon double bond bears an electron releasing hydroxyl group which makes it electron rich and activates it toward attack by electrophiles... 

Although the catalysis of the dimerization of aldehydes to acyloins by thiazolium ion has been known for some tlrae, the development of procedures using anhydrous solvents which give satisfactory yields of acyloins on a preparative scale was first realized in the submitters laboratories. The mechanism proposed by Breslow - for the thiazolium ion-catalyzed reactions is similar to the Lapworth mechanism for the benzoin condensation with a thiazolium ylide replacing the cyanide ion. Similar mechanisms are involved... 

The mechanism of the cyanide- and thioazolium ion-catalyzed conjugate addition reactions is considered to be analogous to the Lapworth mechanism for the cyanide-catalyzed benzoin condensation. Thus the cyano-stabilized carbanion resulting from deprotonation of the cyanohydrin of the aldehyde is presumed to be the actual Michael donor. After conjugate addition to the activated olefin, cyanide is eliminated to form the product and regenerate the catalyst. 

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 ... 

The first two steps of the Lapworth mechanism are the same as the general mechanism of acid-catalyzed enolization (Mechanism 20.5, p. 899). Formation of the enol is rate-determining. Once formed, the enol reacts rapidly with bromine in step 3 to give, after transferring a proton to water in step 4, the a-bromo ketone. 

Lapworth mechanism for acid-catalyzed a-halogenation of a ketone. 

The widely accepted Lapworth mechanism for the cyanide-catalyzed condensation and Breslow mechanism for the heterocyclic carbene-... 

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. 

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