Solid bases aldol condensation

Examples of commercially applied solid base catalysts are much fewer than for solid acids. Nevertheless, much attention is currently focused on the development of novel solid base catalysts for classical organic reactions such as aldol condensations, Michael additions, and Knoevenagel condensations, to name but a few. 

Hydrotalcite clays, for example, are built up of positively charged brucite layers, for reviews see Cavani et al. (1991). Upon calcination they become active as solid bases in e.g. aldol and Knoevenagel condensations (see Fig. 2.26) (Fgueras et al., 1998 Corma and Martin-Aranda, 1993 Climent e/a/., 1995). 

As in the case of homogeneous acids as catalyst, we would also benefit from using solid ba.ses instead of dissolved bases as catalyst. A number of industrially important reactions are carried out with bases as catalyst. A well know example is the aldol condensation of acetone to diacetone alcohol, where dissolved NaOH in ethyl alcohol is u.sed as a catalyst at about 200 to 300 ppm level. However, heterogeneous pelleted sodamide can be used as a catalyst for this reaction and it obviates the problem of alkali removal from the product, which would otherwise lead to reversion of diacetone alcohol to acetone during distillation of the product mixture. 

The Aldol Condensation of Acetone Over a CsOH/Si02 Solid Base Catalyst... 

The solid base catalysed aldol condensation of acetone was performed over a CsOH/Si02 catalyst using a H2 carrier gas. The products observed were diacetone alcohol, mesityl oxide, phorone, iso-phorone and the hydrogenated product, methyl isobutyl ketone. Deuterium tracer experiments were performed to gain an insight into the reaction mechanism. A mechanism is proposed. 

In this study we have investigated utilizing a bi-functional catalyst with a solid base function for the aldol condensation reaction and a metal function for the hydrogenation. This work is a continuation of the study that examined the supported base catalyzed aldol condensation of acetone (5, 6). In those studies... 

Aldol condensations were originally carried out in the liquid phase and catalysed homogeneously by acids or bases this way of operation is still predominant. Solid-catalysed aldol reactions can also be performed in the liquid phase (in trickle or submerged beds of catalyst), but in many cases vapour phase systems are preferred the factors determining the choice are the boiling points and the stability of the reactants at elevated temperatures. At higher temperatures, the formation of a, j3-unsaturated aldehydes or ketones [reactions (B) and (C)] is preferred to aldol (ketol) formation [reaction (A)]. A side reaction, which may become important in some cases, is the self-condensation of the more reactive carbonyl compound if a mixed condensation of two different aldehydes or ketones is occurring. The Cannizzaro reaction of some aldehydes or polymerisation to polyols or other resin-like products can also accompany the main reaction. 

In the work concerning the mechanism of solid-catalysed aldol reactions, the analogy between the homogeneous and heterogeneous mechanisms is usually assumed [370,372—375]. The mechanism of base-catalysed condensations, which has received much attention (cf. ref. 371), may be pictured in general as... 

Very recently, Belokon and North have extended the use of square planar metal-salen complexes as asymmetric phase-transfer catalysts to the Darzens condensation. These authors first studied the uncatalyzed addition of amides 43a-c to aldehydes under heterogeneous (solid base in organic solvent) reaction conditions, as shown in Scheme 8.19 [47]. It was found that the relative configuration of the epoxyamides 44a,b could be controlled by choice of the appropriate leaving group within substrate 43a-c, base and solvent. Thus, the use of chloro-amide 43a with sodium hydroxide in DCM gave predominantly or exclusively the trans-epoxide 44a this was consistent with the reaction proceeding via a thermodynamically controlled aldol condensation... 

Cross-aldol condensations have been performed with alkaline earth metal oxide, as base catalysts. A limitation of the cross-aldol condensation reactions is the formation of by-products throught the self-condensation of the carbonyl compounds, resulting in low selectivities for the cross-aldol condensation product. Thus, the cross-condensation of heptanal with benzaldehyde, which leads to jasminaldehyde (a-M-amylcinnamaldehyde), with a violet scent, has been performed with various solid base catalysts/13,541 particularly MgO, which gave excellent conversions of heptanal (97 %) at 398 K in the absence of a solvent (but the selectivity to jasminaldehyde was only 43 %). A low selectivity was also reported (40 %) for the cross-aldol condensation of acetaldehyde and heptanal catalysed by MgO.[55]... 

Climent, M. J., Corma, A., Fomes, V., Guil-Lopez, R. and Iborra, S. Aldol condensations on solid catalysts a cooperative effect between weak acid and base sites. Adv. Synth. Catal., 2002, 344, 1090-1096. 

Lakshmi Kantam, M., Choudary, B. M., Reddy, C. V., Koteswara Rao, K. and Figueras, F. Aldol and Knoevenagel condensations catalyzed by modified Mg-Al hydrotalcite a solid base as catalyst useful in synthetic organic chemistry, Chem. Commun., 1998, 1033-1034. 

Abello, S., Medina, F., Tichit, D., Perez-Ramirez, J., Cesteros, Y., Salagre, P. and Sueiras, J. E. Nanoplatelet-based reconstructed hydrotalcites towards more efficient solid base catalysts in aldol condensations, Chem. Commun., 2005, 1453-1455. 

Aldol and related condensation reactions such as Knoevenagel and Claisen-Schmidt condensations are also widely used in the fine chemicals and specialty chemicals, e.g. flavors and fragrances, industries. Activated hydrotalcites have been employed as solid bases in many of these syntheses. Pertinent examples include the aldol condensation of acetone and citral [107, 108], the first step in the synthesis of ionones, and the Claisen-Schmidt condensation of substituted 2-hydroxyacetophenones with substituted benzaldehydes [109], the synthetic... 

Interesting recent developments are the use of hydrotalcite supported on carbon nanofibers [119], to facilitate recovery of the catalyst by filtration, and the use of synthetic hydroxyapatite, Ca10(PO4)6(OH)2 as a solid base catalyst in a variety of reactions including Michael additions [120]. The supported hydrotalcite exhibited higher activities and selectivities than the conventional unsupported material in the aldol condensation of citral with acetone [119]. 

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]. 

As described above, zeolites can also act as solid base catalysts when the Si Al ratio is low and the extra framework cation is a large one such as The most basic common exchanged zeolite is CsX. With this material the aldol condensation of cyclooctanone with benzaldehyde gave only the monobenzylidene compound (Eqn. 10.23) 5 while reactions using piperidine, m nesium oxide or amorphous cesium aluminosilicate gave both the mono- and di-benzylidene products(Eqn. 10.12). The smaller ketones, cyclohexanone and... 

Previous sections have shown that catalysis by solid acids has received much attention due to its importance in petroleum refining and petrochemical processes. Conversely, relatively few studies have focused on catalysis by bases, even if acid and base are paired concepts. Base catalysts, however, play a decisive role in several reactions essential for fine-chemical syntheses [248-251]. Solid-base catalysts have many advantages over liquid bases. Examples of successfijl reactions include isomerization, aldol condensation, Knoevenagel condensation, Michael condensation, oxidation and Si—C bond formation. Various reviews have discussed catalysis by solid bases [248-255]. 

Nucleophilic reactions of unmodified aldehydes are usually diiScult to control, affording complex mixture of products, often due to the high reactivity of the formyl group under either basic or acidic reaction conditions. The activity order of the supported amines was secondary > primary > tertiary, which may suggest the intervention of an enamine pathway the enals were exclusively obtained as ( ) isomers. Notably, FSM-16-(CH2)3-NHMe exhibited higher activity than conventional solid bases such as MgO and Mg-Al-hydrotalcite [hexanal self-aldol condensation FSM-16-(CH2)3-NHMe 97% conversion and 85% yield in 2h, MgO 56% conversion and 26% yield in 20 h, Mg-Al-hydrotalcite 22% conversion and 11% yield in 24 h]. 

Miscellanea A methodology to prepare a-substituted-P-hydroxy acids and esters has been introduced in solid phase based on an Evans oxazolidinone-based linker to produce enantiospecifk aldol condensations (Figure 15.4). Acids and esters were released by treatment with LiOH and H202 in THF (at -20 °C) or NaOMe in THF, respectively [58, 59], Diels-Alder adducts of oxazolidinone-bound crotonates have also been detached with LiOCH2Ph [60],... 

The use of solid bases as catalysts in organic synthesis is less well-developed than solid-acid catalysis but is becoming increasingly popular [18]. For example, hy-drotalcite anionic clays [19] and mesoporous silicas modified by surface attachment of organic bases [20] are effective and recyclable catalysts for aldol, Knoe-venagel, and related condensations that are widely used in fine chemical synthesis. 

The aldol condensation of benzaldehyde with acetophenone has been used to compare hydrated hydrotalcites with many solids claimed to be strong solid bases-KF and KNO3 supported on alumina, X zeolites containing excess Cs or Mg, and lanthanum oxide. Only hydrated HDT and KF/AI2O3 could be used to perform this reaction at 273 K-HDT with 100% selectivity for chalcone and KF with lower selectivity, because of secondary Michael addition of the chalcone to acetophenone. The other solids were inactive, but could induce comparable conversions at 423 K. 

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