Solid acids aldol condensations

On the other hand, a single amphoteric oxide such as alumina, which is a Lewis acid solid, catalyzes aldol condensations rapidly at room temperatures (61). For reactions carried out either in the gas (62) or in the liquid phase (41),... 

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. 

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. 

This aldol condensation is assumed to proceed via nucleophilic addition of a ruthenium enolate intermediate to the corresponding carbonyl compound, followed by protonation of the resultant alkoxide with the G-H acidic starting nitrile, hence regenerating the catalyst and releasing the aldol adduct, which can easily dehydrate to afford the desired a,/3-unsaturated nitriles 157 in almost quantitative yields. Another example of this reaction type was reported by Lin and co-workers,352 whereas an application to solid-phase synthesis with polymer-supported nitriles has been published only recently.353... 

As part of a search for environmentally friendly solid acid-base catalysts, a modified Mg-Al hydrotalcite has been used as a base catalyst for aldol and Knoevenagel condensations. Yields are often quantitative, reaction times are about Ih, the catalyst can be recovered by filtration, and only moderate temperatures are required (60 °C for the aldol, ambient for the Knoevenagel). 

The order of activity per unit surface area was equal to that in the case of selfcondensation of acetone and in agreement with the order of basicity of the solids, namely, SrO > CaO > MgO. However, the authors found that the rate-determining step for aldol condensation of n-butyraldehyde is the a-hydrogen abstraction by the active sites, which are the surface ions. The differences in rate-determining step and active sites in the condensation of butyraldehyde and aldol condensation of the acetone were attributed to differences in acidity of the a-hydrogen in the two molecules. CaO was slightly more active than MgO at 273 K after a reaction time of 1 h, maximum conversions of 41% were observed with selectivities to 2-ethyl-3-hydroxy-hexanal and to the corresponding Tishchenko reaction product (2-ethyl-3-hydroxy- -hexyl butyrate) of 39.8 and 56.9%, respectively. 

Properties. Vanillin is a colorless crystalline solid mp 82-83 °C) with a typical vanilla odor. Because it possesses aldehyde and hydroxyl substituents, it undergoes many reactions. Additional reactions are possible due to the reactivity of the aromatic nucleus. Vanillyl alcohol and 2-methoxy-4-methylphenol are obtained by catalytic hydrogenation vanillic acid derivatives are formed after oxidation and protection of the phenolic hydroxyl group. Since vanillin is a phenol aldehyde, it is stable to autoxidation and does not undergo the Cannizzarro reaction. Numerous derivatives can be prepared by etherification or esterification of the hydroxyl group and by aldol condensation at the aldehyde group. Several of these derivatives are intermediates, for example, in the synthesis of pharmaceuticals. 

NMR has been extensively applied to carbonyl compounds in acidic zeolites and other solid acids. The unshared pairs of electrons on the oxygen can interact with either Brpnsted or Lewis sites, and aldol condensation reactions are commonly observed. Acetone was first studied on a zeolite by Bosacek and co-workers (146) followed by Haw and co-workers (147) and later by Gorte and co-workers (148). The conclusion of an earlier acetone paper of Gorte and co-workers (149) was that acetone forms a static complex on the Brdnsted site of HZSM-5 at room temperature, but this claim was later revised (150) upon the realization that molecular motion in the complex is not halted except at appreciably lower temperatures. 

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. 

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. 

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]. 

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]. 

Varma has run many types of reactions on nontoxic supports, such as alumina, silica, and clay, using microwaves.45 (For more on the use of microwaves, see Chap. 15.) The method offers selectivity under safe, fast, mild reaction conditions in open vessels. The supports can be recycled. The reactions include oxidations, reductions, nitrations, aldol condensations, and others. Solvents were used in the workups. Other workers have devised a condensation (8.3) of aromatic aldehydes with malonic acid (without a support) that uses no solvents at all.46 The workup consisted of pouring the glassy reaction mixture from the Erlenmeyer flask into ice water, filtering off the solid, and drying it. The conventional procedure for this reaction requires heating at 120°C for 3 h to give the product in 96% yield. 

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 strength of surface base sites on solids can be measured by the use of Hammett indicators and expressed in terms of the acidity function (H ) proposed by Paul and Long. There are few available solid base materials in the strong solid base area (H 20 to 25) that would be suitable for the aldol condensation of aldehydes or ketones (Fig. 1). 

In the solid state 6-hydroxy-2-phenyl-5,6-dihydrothiazolo[3,2- )][l,2,4]triazole (63) is the form present. In solution an equilibrium appears to exist with the chain form (5-phenyl-[l,2,4]triazol-3-yl)thioacetaldehyde (64). Reactions of both the bicyclic form (63) (see Section 8.05.6.1.3 and 8.05.7.3) and the chain form (64) have been observed. When treated with sodium hydroxide, the compound reacts in its chain form (64) as an aldehyde undergoing aldol condensation to give compound (65) <87AP328>. Boiling compound (65) in ethanol converts it into its ring tautomer (66) (Scheme 1) <87AP328>. Both tautomers (65) and (66) by treatment with sulfuric acid are converted into 2-phenyl-6-(2-phenyl-5,6-dihydrothiazolo[3,2-A][l,2,4]triazol-5-yl) thiazolo[3,2-i][l,2,4]triazole (146) (see Section 8.05.7.4 and 8.05.9.1.9) <87AP328>. 

Mg-Al mixed oxides obtained by thermal decomposition of anionic clays of hydrotalcite structure, present acidic or basic surface properties depending on their chemical composition [1]. These materials contain the metal components in close interaction thereby promoting bifunctional reactions that are catalyzed by Bronsted base-Lewis acid pairs. Among others, hydrotalcite-derived mixed oxides promote aldol condensations [2], alkylations [3] and alcohol eliminations reactions [1]. In particular, we have reported that Mg-Al mixed oxides efficiently catalyze the gas-phase self-condensation of acetone to a,P-unsaturated ketones such as mesityl oxides and isophorone [4]. Unfortunately, in coupling reactions like aldol condensations, basic catalysts are often deactivated either by the presence of byproducts such as water in the gas phase or by coke build up through secondary side reactions. Deactivation has traditionally limited the potential of solid basic catalysts to replace environmentally problematic and corrosive liquid bases. However, few works in the literature deal with the deactivation of solid bases under reaction conditions. Studies relating the concerted and sequential pathways required in the deactivation mechanism with the acid-base properties of the catalyst surface are specially lacking. 

The base catalysts must be neutralized and/or washed out during the work-up procedure. The solid-acid Nafion H, on the other hand, can be reused. Table 10-2 shows that the most effective procedure with regard to mass efficiency and E factor can be carried out with catalyst d. Not only solvents and auxiliary materials can be saved, but the catalyst too, is reusable without having a negative effect on the yield. This leads to a further decrease in the E factor. In conclusion, Nafion H seems to be an efficient catalyst for performing aldol condensation to yield chalcone in an environmentally friendly manner, i.e. avoiding the use of water and reducing the amount of solvent. 

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