Aldol condensation using solid bases

Some but not all organic reactions proceed well in the absence of solvent(s). Develop a solvent-free protocol for the aldol reaction using solid sodium or potassium hydroxide as the base. The reaction can be successfully performed on a 5-10 mmol scale, using an equivalent of base. Bear in mind that the base should be finely divided, so it should first be crushed with a mortar and pestle. In addition, the condensation partners should be mixed thoroughly before the base is added. The reaction should take no more than 20-25 minutes, and the mixture should be acidified to pH 5 with 10% HCI prior to isolation of the product. Characterize the product by its melting point and using spectroscopic techniques. 

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 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. 

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... 

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. 

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]. 

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... 

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. 

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). 

As for condensation reactions. King ei al. [1 discussed on the search for solid base catalysts suitable for industrial aldol condensation of aldehydes (n-butanal and n-hexanal. mainly). Moreover, the authors made emphasis on the industrial importance of such processes to obtain a number of key compounds such as 2-ethylhexanol (which can be converted into dimethylhexylphtalate. a plasticizer for PVX ), methyl isobutyl-kctone (MIPK. an excellent solvent for cellulose and resin-based Ci>atings) or Ouerbet alcohols, used in cosmetics, textiles, lubricants and surfactants. In any case, condensation reactions will be more extensively discussed on the following section, devoted to Fine Chemistry. 

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. 

Use of nonionic surfactant, Triton X, with a cinchonidinium based PT catalyst to accelerate the alkylation step Aldol condensation in the presence of NaOH and a PT catalyst N-alkylation of carbazones, phenothiazines, acridanone, and indoles using alkyl ahalides and aqueous NaOH/solid K2CO3 Facile and selective monoalkylation of the indole nitrogen using PTC, instead of using K azide in liquid ammonia at —40°C 0-alkylation using r-butylbromoacetate... 

Butylation of phenylacetonitrile with aqueous NaOH, as shown in Scheme 25, proceeds faster by use of high DF (>0.5) anion exchange resins.The strongly alkaline conditions degrade the quaternary ammonium ions of the catalyst. Catalyst (64) (1% DVB) is active for alkylation of phenylacetonitrile and benzyl phenyl ketone, and for Williamson ether synthesis, and it is much more stable in base than AERs. AERs in OH form are catalysts for dichlorocyclopropane syntheses from alkenes, chloroform and solid sodium hydroxide, and for dehydration of amides to nitriles. AERs in the appropriate hydroxide, acetate, or cyanide form are catalysts for aldol condensations, Michael reactions, Knoevenagel condensations, cyanoethylations and cyanohydrin syntheses. " ... 

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). 

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