Knoevenagel modification

The modified two component Hantzsch (Baeyer-Knoevenagel modification) was also examined. Shorter reactions times (2-3 h) were noted in this variation using 82 and 85 with slightly better yields (78-85%) being observed for the formation of 84. 

The Perkin reaction has been carried out on aldehydes with aromatic rings other than phenyl, including biphenyl, naphthalene, furan, and indole series using tripolyphosphate (TPP) as the catalyst. However, the Knoevenagel modification is more useful in these cases.7. 

The Doebner condensation (or reaction) is a slight modification of the Knoevenagel reaction and consists in warming a solution of the aldehyde and... 

Subsequent to Hantzsch s communication for the construction of pyridine derivatives, a number of other groups have reported their efforts towards the synthesis of the pyridine heterocyclic framework. Initially, the protocol was modified by Beyer and later by Knoevenagel to allow preparation of unsymmetrical 1,4-dihydropyridines by condensation of an alkylidene or arylidene P-dicarbonyl compound with a P-amino-a,P-unsaturated carbonyl compound. Following these initial reports, additional modifications were communicated and since these other methods fall under the condensation approach, they will be presented as variations, although each of them has attained the status of named reaction . 

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. 

When the reactant is of the form ZCH2Z, aldehydes react much better than ketones and few successful reactions with ketones have been reported. However, it is possible to get good yields of alkene from the condensation of diethyl malonate, CH2(COOEt)2, with ketones, as well as with aldehydes, if the reaction is run with TiCU and pyridine in THF. In reactions with ZCH2Z, the catalyst is most often a secondary amine (piperidine is the most common), though many other catalysts have been used. When the catalyst is pyridine (to which piperidine may or may not be added) the reaction is known as the Doebner modification of the Knoevenagel reaction. Alkoxides are also common catalysts. 

The preparation of glutaric acid by the hydrolysis of trimethylene cyanide has been described in a previous article in this series,2 which includes a bibliography of the literature. The present method is a modification of that of Knoevenagel.3... 

The stereoselective total synthesis of both ( )-corynantheidine (61) (170,171) (alio stereoisomer) and ( )-dihydrocorynantheine (172) (normal stereoisomer) has been elaborated by Szdntay and co-workers. The key intermediate leading to both alkaloids was the alio cyanoacetic ester derivative 315, which was obtained from the previously prepared ketone 312 (173) by the Knoevenagel condensation accompanied by complete epimerization at C-20 and by subsequent stereoselective sodium borohydride reduction. ( )-Corynantheidine was prepared by modification of the cyanoacetate side chain esterification furnished diester 316, which underwent selective lithium aluminum hydride reduction. The resulting sodium enolate of the a-formyl ester was finally methylated to racemic corynantheidine (171). 

When the amine catalyst is specifically pyridine, the reaction is known as the Doebner Modification of the Knoevenagel Reaction ... 

The Doebner Modification (or Knoevenagel Condensation), which is possible in the presence of carboxylic acid groups, includes a pyridine-induced decarboxylation. 

However, more interesting from an application point of view are silylation reactions which introduce new functions into the materials. These can be created either directly or in subsequent further steps after silylation. Most simple is the direct conversion of the silica to a basic material by reaction, for instance, with 3-aminopropyltriethoxysilane [17]. Also two-step processes have been employed to synthesize basic materials, where first chloropropyl groups are anchored to the surface with subsequent conversion of the chloro group into an amine. In order to remove the residual, unreacted silanol groups, a second silylation with hexamethyldisilazane can be used. Such materials were found to be reasonably active in different base-catalyzed reactions, such as Knoevenagel condensations and Michael additions. A survey of the catalyzed reactions and the types of modification used can be found in Ref. [5]. 

Introduction of these photocrosslinkable structures in macro-molecular chains can be performed by esterification of hydroxyla-ted polymers with cinnamoyl chloride. Cellulose Q).condensation products (4, ) and mainly poly(vinyl alcohol) have Been treated( by this method. Other chemical modifications have been studied as ester interchange of poly(vinyl acetate) 7) and Knoevenagel reaction on polyesters (8). Very few results on the synthesis of such photocrosslinkable polymers by polymerization have been reported. Therefore free radical polymerization of cinnamic acid vinyl derivatives did not lead to the expected polymers, but to insolubilization reactions. Howewer cationic procedure can be a good way in some cases since Kato et al. could polymerize by this way with high yields p-vinyl phenylcinnamate (9) and B-vinyloxyethyl cinnamate (10). 

Knoevenagel condensation Doebner modification. Condensation of aldehydes or ketones with active methylene compounds (specifically malonic ester) in the presence of ammonia or amines the use of malonic acid and pyridine is known as the Doebner modification. 

The Knoevenagel condensation was also performed with MCM-41-(6112)3-NH-(CH2)2-NH2 catalyst prepared through post-modification methodology/ utilizing (2-aminomethylaminopropyl)trimethoxysilane. Various aldehydes and ketones were reacted with malononitrile and ethyl cyanoacetate (Scheme 3.21, R =R = CN and R CN, R = EtOCO) in all the reactions total conversions were achieved in toluene with exclusive formation of dehydrated products (75-100% yield). Interestingly, both aliphatic and aromatic carbonyl compounds showed identical reactivity in the reaction with ethyl cyanoacetate and the substitution on the aromatic ring did not influence the reactivity. 

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