Knoevenagel benzaldehyde with ethyl cyanoacetate

The catalytic properties were checked in the transesterification of ethyl propionate with n-butanol and in the Knoevenagel condensation of benzaldehyde with ethyl cyanoacetate ... 

CsX is useful for the simple Knoevenagel reaction of benzaldehyde with ethyl cyanoacetate even a simple NaY is sufficiently basic to form carbamates starting from primary aromatic amines and dialkyl carbonates (35, 36). At contrast CsjO-MCM-41 can also be used for the addition of C02 to epoxides, or for Michael addition of one or two molecules of diethyl malonate on neopentylglycol diacrylate (37, 38) ... 

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]. 

Alkali-exchanged mesoporous molecular sieves are suitable solid base catalysts for the conversion of bulky molecules which cannot access the pores of zeolites. For example, Na- and Cs-exchanged MCM-41 were active catalysts for the Knoevenagel condensation of benzaldehyde with ethyl cyanoacetate (pKa=10.7) but low conversions were observed with the less acidic diethyl malonate (pKa=13.3) [123]. Similarly, Na-MCM-41 catalyzed the aldol condensation of several bulky ketones with benzaldehyde, including the example depicted in Fig. 2.38, in which a flavonone is obtained by subsequent intramolecular Michael-type addition [123]. 

Cs+- and Na+-exchanged MCM-41 type materials also have basic character and have been found to be active towards the base catalysed Knoevenagel condensation of benzaldehyde with ethyl cyanoacetate (Reaction 4).32 The Cs+-and Na+-exchanged samples were prepared by repeated exchange of the hydrogen form of MCM-41 with an aqueous solution of appropriate chloride salt (0.5 mol dm-3) at room temperature. The Cs+-exchanged sample was considerably more basic and therefore more active than the Na+-exchanged sample. 

The Knoevenagel condensation of benzaldehyde with ethyl cyanoacetate was also used to study the performance of LaCs-MCM-41 in aqueous media. The yield was 58 %, with 99 % selectivity for the condensation product. 

Table 5. The Knoevenagel Reaction of Benzaldehyde with Ethyl Cyanoacetate...

Diamine-functionahzed mesoporous SBA-15 materials have been also synthesized and applied to Knoevenagel reaction of benzaldehyde with ethyl cyanoacetate to form the a,p-unsaturated compound [79]. The heterogeneous diamine-functionalized SBA-15 showed excellent catalytic activity compared to aminopropyl-functionahzed material in the Knoevenagel reaction due to two amine sites which might have a synergistic effect in the reaction. 

Excellent results were also obtained using activated hydrotalcite as a solid base catalyst in the Knoevenagel condensation of benzaldehyde with ethylcya-noacetate [110], ethylacetoacetate [111] or malononitrile [112] (see Fig. 2.34). Similarly, citronitrile, a perfumery compound with a citrus-like odor, was synthesized by hydrotalcite-catalyzed condensation of benzylacetone with ethyl-cyanoacetate, followed by hydrolysis and decarboxylation (Fig. 2.34) [113]. 

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. 

The catalytic activity of proton sponge in the Knoevenagel reaction has been studied227. It was shown that benzaldehyde, in the presence of 2 mol% of 1, reacts with ethyl cyanoacetate and ethyl acetoacetate (equation 22). The condensation is accelerated in polar solvents (especially in DMSO) and does not occur in the case of diethyl malonate, as its CH-acidity is too low (pK = 13.3). 

The catalytic activity of the NHs-grafted mesoporous silica, FSMN, was examined in some base-catalysed condensations (eqn. 1). The results were listed in Table 1. The FSMN catalyst used here was FSMN-5 that was prepared by the pre-activation at 1073 K followed by NH3-treatment at 973 K. The Aldol condensation of benzaldehyde and acetone did not proceed in this condition (entry 1). The Knoevenagel condensation of benzaldehyde and diethyl malonate (entry 2) did not occurred. On the other hand, the reactions with malononitrile (entry 3) and with ethyl cyanoacetate (entry 4) were catalysed by the FSMN-5. This shows that the NHa-grafted mesoporous silica would function as base catalyst. 

This material was able to act as a solid Bronslcd base catalyst and accelerated the Knoevenagel condensation of ethyl cyanoacetate with benzaldehyde better than basic forms of mesoporous sieves and zeolite catalysts. It was found that this carboxylate-functionafized LLC material exhibited enhanced basicity due to the ordered nanostructure, and that the LLC pores were capable of substrate molecular size exclusion [114],... 

Fig. 15 Heterogeneous Bronsted base catalysis of the Knoevenagel condensation of ethyl cyanoacetate with benzaldehyde using a cross-linked Hu assembly...

Compound (329), a potent inhibitor of dihydrofolate reductase, was synthesized by a Knoevenagel condensation of the ketone (326) with ethyl cyanoacetate to afford (327) in 28-81% yield. Catalytic hydrogenation of (327) over Pd/C gave almost exclusively the undesired endo isomer, whereas with lithium in liquid ammonia and phenol as proton donor the desired exo compound (328) was obtained in 71% yield.222 Knoevenagel condensation of benzaldehydes with malonodinitrile in the presence of a base leads to benzylidenemalonodinitriles. These compounds, especially the 2-chlorobenzylidenemalonodini-trile (CS, 330), are used as riot-control agents (sneeze and tear gas). 2,324... 

Gascon et al. [61] reported that IRMOF-3 and Am-functionalized MIL-53, both made from the 2-aminoterephthalic acid Hnker, were active as base catalysts in the Knoevenagel condensation of benzaldehyde and ethyl cyanoacetate in dimethylformamide at 60°C. The IRMOF-3 catalyst showed higher performance than the homogeneous anihne reference catalyst, with a conversion of 90% achieved compared to 55%, respectively. After the removal of the IRMOF-3 catalyst from the liquid reaction product mixture, no further conversion was observed, demonstrating the stability of the heterogeneous catalyst. The Am-MIL-53 catalyst was found to be less active in this reaction probably because of a strong adsorption and a slow diffusion of the reaction substrates and products inside the pores of this particular MOF. 

PVRs equipped with hydrophilic membranes can be used for any liquid reaction where the water produced limits the equilibrium conversion or acts as an inhibiting agent. For example, PVRs have been studied for the dehydration reaction of butenediol to form tetrahydrofuran (Liu and Li, 2002), the synthesis of methylisobutylketone (Staudt-Bickel and Lichtenthaler, 1996), the Knoevenagel condensation reaction between benzaldehyde and ethyl cyanoacetate or ethyl acetoacetate or diethyl malonate (Zhang et al, 2004). Additional information can be found in reviews by Sanchez Marcano and Tsotsis (2002) and by Van der Bruggen (2010). 

The Knoevenagel condensation reaction is an important C-C bondforming reaction commonly used for the production of fine chemical intermediates and pharmaceuticals. It involves the condensation of methylene compounds (i.e., Z-CH2-Z or Z-CHR-Z ) with ketones or aldehydes [3], which is constrained by unfavorable thermodynamics. A typical example is the Knoevenagel condensation reaction between benzaldehyde and ethyl cyanoacetate to produce ethyl 2-cyano-3-phenylacrylate ... 

Because a base-catalyzed reaction involves the abstraction of a proton by the catalyst, one approach to measurement of the total number of basic sites and also the base strength distribution is to use the reactions of molecules with various values (96-100). For instance, the basic site distribution in calcined MgAl hy-drotalcites was determined by Corma et al. (99), who used the Knoevenagel condensation (Scheme 7) between benzaldehyde and methylene active compounds with various pKa values, i.e., ethyl cyanoacetate (pKa = 9), diethyl malonate (pKa = 13.3), and ethyl bromoacetate (pKa = 16.5). The authors found that this material has basic sites with pKa values up to 16.5, although most of the basic sites... 

The Knoevenagel reaction between benzaldehydes 22 and malononitrile or ethyl cyanoacetate 74 followed by condensation of the resulting ot,p-unsatu-rated nitriles 75 with dimedone (76) was performed in the presence of SiO2-(CH2)3-NEt2 (Scheme 3.22). ... 

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