Acetone mixed aldol condensation

B-12. Benzalacetone is the mixed aldol condensation product formed between benzaldehyde (C6H5CH=0) and acetone [(CH3)2C=0], What is its structure ... 

The product has 17 carbons, which suggests that it is formed from two benzaldehyde molecules (2x7 = 14 carbons) + one acetone molecule (3 carbons). The product forms by a double mixed aldol condensation ... 

The reaction of an aldehyde with a ketone employing sodium hydroxide as the base is an example of a mixed aldol condensation reaction, the Claisen-Schmidt reaction. Dibenzalacetone is readily prepared by condensation of acetone with two equivalents of benzaldehyde. The aldehyde carbonyl is more reactive than that of the ketone and therefore reacts rapidly with the anion of the ketone to give a /3-hydroxyketone, which easily undergoes base-catalyzed dehydration. Depending on the relative quantities of the reactants, the reaction can give either mono- or dibenzalacetone. 

The self-condensation of butanal involves a single compound, but it is also possible to convert one ketone or aldehyde to an enolate anion, and it wiU react with a different ketone or aldehyde. This is called a mixed aldol condensation. If acetone (2) is treated with aqueous NaOH in the presence of another carbonyl molecule, such as benzaldehyde (25), enolate (26) is formed in situ. This enolate anion may react with itself (with another molecule of 2 in a selfcondensation reaction), but it may also react with aldehyde 25 via acyl addition to give alkoxide 28. Mild hydrolysis gives the mixed aldol product, 26. There is a competition for the reaction of 27 with either 2 or 25, so at least two products are possible in the reaction 28 and the self-condensation product. Note... 

When acetone reacts with NaOEt in ethanol to form enolate anion 27, it is a reversible acid-base reaction. Therefore, unreacted ketone or aldehyde always remains in the reaction, and this fact allows self-condensation to occur. Is it possible to choose a base that will generate the enolate anion, but the equilibrium is pushed far to the right (toward the enolate anion product) If such a base is available, self-condensation is much less of a problem, which is particularly important for mixed aldol condensation reactions. As chemists experimented to find such a base, it was discovered that amide bases (RaNr), derived from secondary amines (R2NH) accomplished this goal. 

Mixed aldol reactions between different aldehydes or ketones are usually plagued by formation of a mixture of products, because each component can function as a CH-acidic and carbonyl-active compound. Whereas the directed aldol reaction [14-16] is a rather general solution to this problem, the traditional aldol addition of non-identical carbonyl compounds is only successful when applied within the framework of a limited substitution pattern. Thus, a fruitful combination in mixed aldol reactions is that of an aldehyde with an enolizable ketone. Obviously, the aldehyde, having higher carbonyl reactivity, reacts as the electrophilic component, whereas the ketone, with comparatively lower carbonyl reactivity, serves as the CH-acidic counterpart. Because the self-aldolization of ketones is endothermic, this type of side reaction does not occur to a significant extent, so the product of the mixed aldol condensation is obtained in fair yield, as illustrated by the formation of ketone 6 from citral 5 and acetone, a key step in the synthesis of j5-ionone (Eq. (7)) [17]. 

Kelkar and McCarthy (1995) proposed another method to use the feedforward experiments to develop a kinetic model in a CSTR. An initial experimental design is augmented in a stepwise manner with additional experiments until a satisfactory model is developed. For augmenting data, experiments are selected in a way to increase the determinant of the correlation matrix. The method is demonstrated on kinetic model development for the aldol condensation of acetone over a mixed oxide catalyst. 

Another example of cross-aldol condensation is the reaction between citral and acetone, which yields pseudoionone, an intermediate in the production of vitamin A. Noda et a/.[56] working at 398 K with a 1 1 molar ratio of reagents and 2 wt % of catalyst, obtained high conversions (98 %) with selectivities to pseudoionone close to 70 % with CaO and an Al-Mg mixed oxide catalyst these pseudoionone yields are greater than those reported for the homogeneous reaction. MgO exhibited poor activity, and under these conditions only 20 % citral conversion was obtained after 4 h in a batch reactor. Nevertheless, Climent et a/./571 working with 16 wt % MgO as a catalyst, a molar ratio of acetone to citral close to 3 and at 333 K, achieved 99 % conversion and 68 % selectivity to pseudoionone after 1 h. 

This mixed aldol will succeed because one of the components, benzaldehyde, is a good acceptor of nucleophiles, yet has no cc-hydrogen atoms. Although it is possible for acetone to undergo self-condensation, the mixed aldol reaction is much more favorable. 

Four products result from the aldol condensation of acetone and acetophenone. The two upper compounds are mixed aldol products, and the bottom two are self-condensation products. 

Mixed or crossed aldol condensation Aldol condensations between different carbonyl reactants are called crossed (or mixed) reactions. Crossed aldol condensation works well if one carbonyl compound has no a-hydrogen(s). For example, acetone reacts with furfural in a crossed-aldol reaction to give the corresponding a,P-unsaturated ketone 3.15. 

The trivial name of the reaction was applied by Wurtz in 1872, and stems from the trivial name of the dimer resulting from the acid-catalyzed self-reaction of acetaldehyde (equation 1). In time, the term came to be applied to the analogous self-condensation reactions of ketones, the first known example of which was the acid-mediated dimerization of acetone, discovered in 1838. The first use of a base as a catalyst for the aldol reaction was in the reaction of furfural with acetaldehyde or acetone (equation 2). This example also illustrates the first example of a mixed aldol reaction, a process that came to be known as the Claisen-Schmidt condensation. ... 

The deactivation of Mg-Al mixed oxides during the gas-phase self-condensation of acetone was studied. Main aldol condensation reaction and secondary coke-forming reactions take place on both basic and acidic sites. Although deactivation is caused by carbon deposition, it was found that coke formed on basic sites rather than on acidic sites is responsible for the activity lost. 

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 earliest example (1) of a synthetic macrocyclic ligand containing an imine linkage was derived from the mixed Schiff base-aldol condensation of acetone with nickel(II) ethylenediamine complexes. In 1964 Curry and Busch reported the iron(II)-templated condensation of 2,6-diacetylpyridine with triethylenetetramine to give iron(III) complexes of the macrocycle (4). This was followed by the observation that the selfcondensation of o-aminobenzaldehyde gave, in the presence of nickel(II) ions, complexes of the macrocyclic ligands (2,3). In all of these examples no macrocycle was obtained in the absence of a metal ion. 

Faba, L., Diaz, E., Ordonez, S., 2012. Aqueous-phase furfural-acetone aldol condensation over basic mixed oxides. Applied Catalysis B Environmental 2012 (113), 201—211. 

The aldol examples shown above are described as self -condensations because they involve the reaction of a single carbonyl compound acting as both the nucleophile and the electrophile. The reaction of two different carbonyls presents a problem of c/icmose/ecftVify Which carbonyl will act as the nucleophile, and which will act as the electrophile Mixing two ketones in the presence of a mild base, for example, could give a mixture of four aldol products two cross-condensations and two self-condensations. Since acetone and 3-pentanone have similar reactivities, we would expect all possible combinations to occur. 

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