Organic Knoevenagel reaction

Knoevenagel reaction. The condensation of an aldehyde with an active methylene compound (usually malonic acid or its derivatives) in the presence of a base is generally called the Knoevenagel reaction. Knoevenagel found that condensations between aldehydes and malonic acid are effectively catalysed by ammonia and by primary and secondary amines in alcoholic solution of the organic amines piperidine was regarded as the best catalyst. 

Knoevenagel reaction is the synthesis of a, p-unsaturated acids by reaction of aldehydes and compounds with active methylene groups in the presence of an organic base... 

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. 

An organic base in an ionic liquid was also found to be effective for a Knoevenagel reaction. Glycine was added to the ionic liquid [HMIMjPFs as the base catalyst. The reaction proceeded at room temperature in air without the need for rigorous drying of the ionic liquid. Glycine and the reactants malononitrile and benzaldehyde dissolved readily in the ionic liquid. The product was extracted from the ionic liquid phase with an immiscible co-solvent, toluene 110). 

Tietze LF, Beifuss U (1991) The knoevenagel reaction. In Trost B (ed) Comprehensive organic synthesis, vol. 2. Pergamon Press, Oxford, pp 341-394... 

L. F. Tietze, U. Beifuss, The Knoevenagel Reaction , in Comprehensive Organic Synthesis (B. M. Trost,... 

Olefinic esters may be obtained directly by the Knoevenagel reaction. Alkyl hydrogen malonates are used in place of malonic acid. Decarboxylation then gives the ester directly as in the preparation of ethyl 2-heptenoate (78%) and methyl m-nitrocinnamate (87%). Alkyl hydrogen malonates are readily available by partial hydrolysis of dialkyl malonates. The use of malonic ester in the condensation leads to olefinic diesters, namely, alkylidenemalonates such as ethyl heptylidenemalonate (68%). A small amount of organic acid is added to the amine catalyst since the salts rather than the free amines have been shown to be the catalysts in condensations of this type. Various catalysts have been studied in the preparation of diethyl methylenemalonate. Increased yields are obtained in the presence of copper salts. Trimethylacetalde-hyde and malonic ester are condensed by acetic anhydride and zinc chloride. Acetic anhydride is also used for the condensation of furfural and malonic ester to furfurylidenemalonic ester (82%). ... 

One of the best articles written on the Knoevenagel reaction in the English language is in the Journal of Organic Chemistry, Volume 15, pages 8 to 14. Another reference is Organic Reactions, Volume 15. 

The majority of work on organically modified solids as solid bases has been carried out on the simple 3-aminopropyl-derivatised silica. This material is established as an efficient catalyst for the Knoevenagel reaction.136-138 There are several interesting features about this application. One of these is the solvent, a... 

The Knoevenagel reaction is one of the oldest C-C bond forming reactions (see also Section 7.1) [36]. It involves the condensation of a carbonyl component (typically benzaldehyde) with a C-acid (typically ethyl cyanoacetate)-Figure 5. This classical reaction is usually catalyzed by organic bases (primary, secondary, and tertiary amines), ammonia, and ammonium salts [37]. 

One of the first supported organic bases utilized as catalysts for synthetic purposes was the propylamine tethered onto amorphous silica employed to perform the Knoevenagel reaction [9]. After this early study a growing number of papers has been published describing the preparation of different organic bases anchored to solid supports including guanidines (10. ... 

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