Aldolization solid catalysts

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. 

Figur0 5 fhe normalized concentrations (Ca/Cao) of TMP-aldol (solid) and TME-aldol (dashed) in the hydrogenation at different pressures and temperatures over NiCr-catalyst in aqueous solvent.

A new concept based on the use of solid catalysts for the production of two aldols, trimethylolpropane aldol and trimethylolethane aldol, was developed. The aldolization process is the fust step for the production of the triols, trimethylolpropane and trimethylolethane. In the second step, these triols are obtained by catalytic hydrogenation of the aldols. The two-step technology was patented (FI Pat. Appl. 991519) [12]. 

Fluorous solid catalyst 8 is highly effective for the Mukaiyama aldol reaction [Eq. (9)] and Sakurai-Hosomi allylation reaction [Eq. (lO)j. These reactions have been performed at -78 °C and room temperature, respectively, under heterogeneous conditions. Post-reaction, 8 has been recovered in high yield by decanting the liquids at room temperature. 

There is a clear economic incentive to develop heterogeneous catalysts to replace conventional homogeneous catalysts in many industrial processes. Efforts to formulate highly active and selective solid catalysts have been the subject of intense research. One such process of interest is the condensation of alcohols, aldehydes and ketones, known as aldol condensation, which is used industrially for the synthesis of a series of products used extensively in various industries (/). 

Addition, G, solid catalyst, multitube catalyst bed/fluidized bed [-110 MJ/kmol] 180 °C, 10 s (2 species, 6 data) rate doubles in 30 °C for the range 100-225 °C. Aldol condensation, G, soUd catalyst, 300 °C, 25 s (1 species 2 data) rate doubles lOO C. 

The above solid catalysts were used successfully to catalyze various reactions, like the Suzuki-Miyura reaction [15], such as aminocarbonylation, amidatimi, and the Heck reactions [16]. Polymers containing scandium trillate, ruthenium, platinum, or gold were prepared to perform Mukayama aldol, alcohol, and sulfide oxidation, hydrogenatirMi, and indole syntheses [17]. 

Aldol condensation reactions can be carried out in liquid or gas phase with the catalyst being a liquid or a solid. This section deals with the heterogeneous reaction (reactants in the liquid or gas phase with insoluble solid catalyst), whereas for the homogeneous reaction (reactants and catalyst in the liquid phase) see... 

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. 

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. 

The reaction can, however, be made preparative for (91) by a continuous distillation/siphoning process in a Soxhlet apparatus equilibrium is effected in hot propanone over solid Ba(OH)2 (as base catalyst), the equilibrium mixture [containing 2% (91)] is then siphoned off. This mixture is then distilled back on to the Ba(OH)2, but only propanone (b.p. 56°) will distil out, the 2% of 2-methyl-2-hydroxypentan-4-one ( diacetone alcohol , 91, b.p. 164°) being left behind. A second siphoning will add a further 2% equilibrium s worth of (91) to the first 2%, and more or less total conversion of (90) — (91) can thus ultimately be effected. These poor aldol reactions can, however, be accomplished very much more readily under acid catalysis. The acid promotes the formation of an ambient concentration of the enol form (93) of, for example, propanone (90), and this undergoes attack by the protonated form of a second molecule of carbonyl compound, a carbocation (94) ... 

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). 

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. 

Carreira has reported that the aldol addition reaction to fiiran 2-carboxaldehyde may be performed on preparative scale (0.5 mol) with as little as 0.5 mol % catalyst (Scheme 8B2.12) [30], The adduct is isolated as a crystalline solid with 94% ee a single recrystallization allows access to 122 with >99% ee. Ozonolytic cleavage of the furan unmasks a carboxyl function, providing acid 124. This acid has been used in a convergent synthesis of the amphotericin C ]-C3 polyol portion. Moreover, 124 has been utilized in the synthesis of a number of pharmacologically important structures such as HMG CoA reductase inhibitors for the treatment of hypercholesterolemia [34],... 

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