Knoevenagel reaction active methylene nucleophile

The Knoevenagel reaction has many similarities to the Michael addition, in which a base is required to form a carbanion Ifom an activated methylene precursor which subsequently undergoes nucleophilic addition to an alkene containing a group such as an ester capable of stabilizing the resulting anion by delocalization. These reactions are widely used for... 

Sonochemistry has been applied to acceleration of the Reformatsky reaction, Diels-Alder reactions, the arylation of active methylene compounds nucleophilic aromatic substitution of haloarenes, and to hydrostannation and tin hydride reduction. " Other sonochemical applications involve the reaction of benzyl chloride and nitrobenzene, a Sr I reaction in liquid ammonia at room temperature, and Knoevenagel condensation of aromatic aldehydes. lodination of aliphatic hydrocarbons can be accelerated, and oxyallyl cations have been prepared from ot,ot -diiodoketones using sonochemistry. Sonochemistry has been applied to the preparation of carbohydrate compounds.When sonochemistry is an important feature of a chemical reaction, this fact will be noted in the reactions presented in Chapters 10-19. 

Simple aliphatic thioketones (6) readily condense with active methylene compounds in a Knoevenagel-type reaction (Scheme 11). The reaction in Scheme 11 proceeds more easily than with ketones, often without catalysts, and involves nucleophilic attack by the X(NC)HC moiety. 

This reaction was first reported by Emil Knoevenagel in 1894. It is a nucleophilic addition of a compound with an active methylene component to a ketone or aldehyde, followed by the elimination of water to form an olefin. Therefore, it is generally known as... 

Knoevenagel condensation is the addition of a nucleophile from active methylene compound to a carbonyl group followed by dehydration to form a P-conjugated enone. The Knoevenagel condensation between different aldehydes (15), including various aliphatic, aromatic, and heterocyclic aldehydes with active methylene compounds (119) in the presence of nano-ZnO under solvent-free conditions (Scheme 9.37) has been reported (Hosseini-Sarvari et al. 2008). Most of the aldehydes investigated reacted smoothly to afford the corresponding products in excellent yields (90%-98%) in a reaction time of 5 min to 3 h. 

Michael Addition. The Michael reaction is a typical base-catalyzed reaction used in organic chemistry to form a C—C bond. It is usually a consecutive side reaction accompanying the base-catalyzed synthesis of a, -unsaturated ketones, aldehydes, nitriles, or carbo lic acid derivatives. The reaction between an Q ,)S-unsaturated compoimd and an activated methylene compoimd is known as the Michael addition Scheme 9. The reaction is the nucleophilic addition of a car-banion intermediate to the ft carbon of the C—C double bond in the conjugated system (49) without releasing a water molecule. The carbanion is provided by the activated methylene compoimd, and contrarily to the Knoevenagel condensation the product retains the substituents of both reactant molecules. 

A further small tweaking of the reaction conditions involves great changes a further new cascade channel is breaking. This is accomplished by modulation of the nucleophilicity of the activated methylene compounds applied. When used with isocyanoacetate 87 instead of cyanoacetates 86 as a methylene-activated component, an Ugi-like multicomponent cascade reaction is observed. This reaction was first detected by deployment of ethyl isocyanoacetate 87 in reactions of ribose and proline. In these experiments, proline—once the catalyst in the Knoevenagel condensation/ketalization/oxa-Michael cascade reactions—is directly incorporated into the product. As a result of that, seven-membered lactone 89 is formed. This sharp difference is demonstrated in Scheme 2.18 [40]. 

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