Knoevenagel condensations using basic zeolites

While zeolites are mostly used in acid catalysts, there are various procedures to introduce basic sites with variable strength into these materials. Depending on the nature of the active site, one is able to selectively catalyze reactions with different basicity requirements, and this is probably the main virtue of base catalysis with zeolites. For instance, in a classical Knoevenagel condensation, the reaction selectivity can be decreased by a consecutive Michael reaction, since the Knoevenagel product can serve itself as a Michael receptor -. 

In contrast with the widespread application of zeolites as solid acid catalysts (see earlier), their use as solid base catalysts received scant attention until fairly recently [121]. This is probably because acid-catalyzed processes are much more common in the oil refining and petrochemical industries. Nonetheless, basic zeolites and related mesoporous molecular sieves can catalyze a variety of reactions, such as Knoevenagel condensations and Michael additions, which are key steps in the manufacture of flavors and fragrances, pharmaceuticals and other specialty chemicals [121]. Indeed, the Knoevenagel reaction of benzaldehyde with ethyl cyanoacetate (Fig. 2.36) has become a standard test reaction for solid base catalysts [121]. 

Cesium-exchanged zeolite X was used as a solid base catalyst in the Knoevenagel condensation of benzaldehyde or benzyl acetone with ethyl cyanoacetate [121]. The latter reaction is a key step in the synthesis of the fragrance molecule, citronitrile (see Fig. 2.37). However, reactivities were substantially lower than those observed with the more strongly basic hydrotalcite (see earlier). Similarly, Na-Y and Na-Beta catalyzed a variety of Michael additions [122] and K-Y and Cs-X were effective catalysts for the methylation of aniline and phenylaceto-nitrile with dimethyl carbonate or methanol, respectively (Fig. 2.37) [123]. These procedures constitute interesting green alternatives to classical alkylations using methyl halides or dimethyl sulfate in the presence of stoichiometric quantities of conventional bases such as caustic soda. 

Despite all these advantages, however, exchanged zeolites have rarely been used as basic catalysts in the production of fine chemicals. This is probably because of their weak basic character and because bulky reactants are involved in many chemical processes. Their basicity is, nevertheless, sometimes sufficient to catalyze Knoevenagel condensations and Michael additions. 

Alkali metal-exchanged zeolites have been used to prepare activated alkenes of interest as prepolymers by Knoevenagel condensation of malononitrile with ketones having different positive charge density on the carbon of the carbonyl group benzophenone, cyclohexanone, and p-aminoacetophenone [85]. The reactivity depends both on ketone structure (the order of reactivity was benzophenone > cyclohexanone > p-aminoacetophenone) and on the catalyst used. For instance, when malononitrile is condensed with cyclohexanone in the presence of a CsY zeolite conversion was very low. CsX zeolite, however, which has a substantial number of basic sites with pX in the range 9 < P a < 10.7 and some with 10.7 < < 13.3 could be used to perform... 

Under heterogeneous conditions, the Knoevenagel reaction has been used as a well-adopted test reaction to check the activity of the basic sites of different solids, mainly basic zeolites such as alkali-exchanged zeolites [40] or zeolites containing occluded metal oxides [41]. The basic activity of alkali-containing MCM-41 [42] or binary cesium-lanthanum oxide supported on MCM-41 [43] has, moreover, also been evaluated in the Knoevenagel condensation. 

Another frequently used reaction to estimate the number and strength of basic sites in zeolites is the Knoevenagel condensation. As an example, the Knoevenagel condensation of acetophenone and malononitrile is shown in Scheme 15. The reactions were studied, e.g., by Corma et al. [236-238] and Rodriguez et al. [239-241]. In this reaction, the basic sites in the zeolite abstract a proton from the methylenic compound, e.g., a nitrile or ester. The... 

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