Knoevenagel reaction mechanism

The term Knoevenagel reaction however is used also for analogous reactions of aldehydes and ketones with various types of CH-acidic methylene compounds. The reaction belongs to a class of carbonyl reactions, that are related to the aldol reaction. The mechanism is formulated by analogy to the latter. The initial step is the deprotonation of the CH-acidic methylene compound 2. Organic bases like amines can be used for this purpose a catalytic amount of amine usually suffices. A common procedure, that uses pyridine as base as well as solvent, together with a catalytic amount of piperidine, is called the Doebner modification of the Knoevenagel reaction. 

The Knoevenagel reaction is a carbonyl condensation reaction of an ester with an aldehyde or ketone to yield an a,j8-unsaturated product. Show the mechanism of the Knoevenagel reaction of diethyl malonate with benzaldchyde. 

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Two mechanisms have been proposed for the Knoevenagel reaction. In one, the role of the amine is to form an imine or iminium salt (378) which subsequently reacts with the enolate of the active methylene compound. Under normal circumstances elimination of the amine would give the cinnamic acid derivative (379). However, when an o-hydroxy group is present in the aromatic aldehyde intramolecular ring closure to the coumarin can occur. The timing of the various steps may be different from that shown (Scheme 118). 

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. 

Knoevenagel reactions (for their mechanism, see Section 13.4.2) end with H20 being eliminated from the initially formed alcohol in the basic medium. The elimination takes place via an Elcb mechanism, an example of which is shown in Figure 4.38. In a fast exergonic reaction, nitroalcohol shown is deprotonated quantitatively to give a nitronate. In the following slower second reaction step, an OH group leaves, and a nitroalkene is produced. It is preferentially formed as the trans-isomer because of product development control. 

Fig. 13.52. Mechanism of the Knoevenagel reaction of active-methylene compounds -H indicates the migration of a proton.

Fig. 13.53. Mechanism of a Knoevenagel reaction with nitromethane. Alkaline aluminum oxide powder is sufficiently basic to deprotonate nitromethane. The small amount of the anion generated from nitromethane suffices for the addition to aldehydes to proceed. The elimination of water via an Elib mechanism follows quickly if a conjugated C=C double bond is formed, as in the present case.

Benzaldehyde itself could be the electrophile in this Knoevenagel reaction. However, it is also possible that the piperidinium salt derived from benzaldehyde acts as the electrophile. Similarly, several plausible mechanisms can be formulated for the decarboxylation step—they depend, among other things, on the stage at which it may occur. Because of these ambiguities, we do not want to discuss any of the details of these reaction steps. Instead, we want to focus on a mechanistic detail of the first step and that is the question of which species acts as the nucleophile and initiates the C—C bond formation. 

Scheme 3 Deactivation mechanism of aminopropyl-grafted silicas in the Knoevenagel reaction...

The Knoevenagel reaction, the condensation of 1,3-dicarbonyl compounds with aldehydes to give unsaturated compounds, is catalyzed by 2° amines. A perfectly reasonable mechanism involving deprotonation of the 1,3-dicarbonyl compound by base, aldol reaction with the ketone, and Elcb elimination of H2O can be drawn. However, the Knoevenagel reaction does not proceed nearly so well using 3° amines, suggesting that the amine does not simply act as a base. 

The important point, however, is that no reasonable mechanism for the elimination of water can be written until step 5 is complete, and step 5 requires the presence of a proton donor (an acid). These considerations have been nicely verified in the Knoevenagel reaction (pp. 182, 183), where it has been found that a base alone is not as effective a catalyst as it is in the presence of acetic acid. 

Scheme 2 Proposed reaction mechanisms of Knoevenagel condensation on the pair site consisting of the Si-NHz and the neighboring Si-OH. The neighboring Si-OH functions as an acid site to activate the carbonyl group.

However the mechanism of the action of the catalyst was not demonstrated. The aim of our study is to understand the role of the amine function linked on MTS surface with the opportunity of benefitting from the unique pore structure and surface of this recently discovered family of mesoporous materials. Oiu previous works on the Knoevenagel reaction (scheme... 

Q Outline the full mechanism for the Knoevenagel reaction of benzaldehyde with diethyl malonate. 

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