Alcohols 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. 

With most of these reagents the alcohol is not isolated (only the alkene) if the alcohol has a hydrogen in the proper position. However, in some cases the alcohol is the major product. With suitable reactants, the Knoevenagel reaction, like the aldol (16-2), has been carried out diastereoselectively and enantioselectively. ... 

Knoevenagel reaction. Hydrogenation of the double bond, desilylation and oxidation of the released primary alcohol group to the aldehydic function with PCC in dichloromethane in the presence of molecular sieves, gives the branched chain L-riho-hepturonic acid derivative 31. Treatment with acetic anhydride and pyridine results in cyclization, and acetylation of the resulting alcohol affords the acetate 32 in 69% yield. 

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. 

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). 

Allyl sulfoxide systems appropriate for a transformation to allylic alcohols can also be generated by other preparative methods, e.g. by isomerization of aryl vinyl sulfoxides. Such an isomerization occurs in connection with a Knoevenagel reaction of (10) with aldehydes leading finally to y-hydroxy-a,3-unsatu-rated systems (11), which can easily be transformed into a,3-unsaturated y-lactones (12 Scheme 17). ... 

The application of the linker has been demonstrated in connection with Pictet-Spengler cyclizations and Knoevenagel reactions. In a preliminary example, it was also demonstrated that the linker might be useful for alcohols. 

While 6 does not react properly with stabilized anions (Knoevenagel Reaction), organolithium and magnesium reagents give alcohols U in excellent yields (ref 26, Scheme 33). 

Malonomonoamides can be condensed with aldehydes to give acrylamides or cinnanamides, but condensation with malonodiamides is of only minor impjortance. In contrast to Meldrum s acid (58), Knoevenagel reactions of barbituric acid (56) and A A -dimethylbarbituric acid have been less explored. However, several aliphatic, aromatic and heteroaromatic aldehydes are known to react easily and with high yields in most cases. Reactions of 1,2-dimethyl-3,5-pyrazolidinedione (93) with several aliphatic and aromatic aldehydes using standard conditions yield Knoevenagel products in good yield. A similar reactivity is observed with 2-phenyl-3,5-dioxoisoxazolidine (94) and oxazepanediones (45 see Section 1.11.2.5). Recently, the oxidations of alcohols to carbonyl compxiunds and thiols to disulfides with 5-arylidene-l,3-dimethylbarbituric acids (95) have been described Mechanistically (95) mimics enzymic oxidation by flavin adenine dinucletide (FAD). ... 

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