Benzaldehyde Claisen-Schmidt condensation

Reaction between 2 -hydroxyacetophenone and benzaldehyde (Claisen-Schmidt condensation) in the absence of a solvent at 423 K giving 2 -hydroxy chalcones and flavanones has been successfully performed with MgO as a solid base catalyst/581 A conversion of 40 % after 1 h with 67 % selectivity to chalcone was achieved. The influence of the solvent and the effects of a substituent on the aromatic ring were investigated by Amiridis et a//59,6"1 The reaction was carried out on MgO at 433 K. Dimethyl sulfoxide (DMSO) showed a strong promoting effect on the reaction, which was attributed to the ability of this dipolar aprotic solvent to weakly solvate anions and stabilize cations so that both become available for reaction. In this case, a conversion of 2-hydroxyacetophenone of 47 % with a selectivity to flavanone of 78 % was achieved after 30 min in a batch reactor. Further investigations1611 showed that DMSO significantly increases the rate of the subsequent isomerization of the 2 -hydroxychalcone intermediate to flavanone. 

The Claisen-Schmidt condensation of 2 -hydroxyacetophenone and different chlorinated benzaldehydes over MgO has been investigated through kinetic and FTIR spectroscopic studies. The results indicate that the position of the chlorine atom on the aromatic ring of the benzaldehyde substantially affects the rate of this reaction. In particular, the rate increases in the following order p-chlorobenzaldehyde < m-chlorobenzaldehyde < o-chlorobenzaldehyde. The difference between the meta and para-substituted benzaldehyde can be attributed to electronic effects due to the difference in the Hammett constants for these two positions. Steric effects were found to be responsible for the higher rate observed with the o-chlorobenzaldehyde. 

Monodirectional 12 membered ring zeolites (offretite, L, mordenite and 0) are very inefficient as catalysts for formaldehyde benzene condensation to give diphenylmethane, esterification of phenylacetio acid with equimolar amounts of ethanol, Friedel-Crafts acylation of 3-phenylpropanoyl chloride with anisole and Claisen-Schmidt condensation of acetophenone with benzaldehyde. This fact has been attributed to diffusional constraints of organic compounds inside the channels. By contrast, the behaviour of the tridireotional f zeolite is very similar to that of dealuminated HY zeolites, inoreasing the turnover of the acid sites with the framework Si-to-Al ratio. 

Claisen-Schmidt condensation of acetophenone (0.5 mmol) and benzaldehyde (0.5 mmol) in benzene (10 ml) at 351 K in the presence of acid zeolites (1,00 g). 

The proton sponge, l,8-bis(dimethylaminonaphthalene) (DMAN), has been anchored onto amorphous and pure silica MCM-41.[182] DMAN supported on MCM-41 is an excellent base catalyst for the Knoevenagel condensation between benzaldehyde and different active methylene compounds, as well as for the Claisen-Schmidt condensation of benzaldehyde and 2 -hydroxyacetophenone to produce chalcones and flavanones. It was found that the activity of the supported catalyst is directly related to the polarity of the inorganic support. Moreover, the support can also preactivate the reagents by interaction of the carbonyl groups with the weakly acidic silanol groups of MCM-41. This preactivation step enables DMAN, anchored onto MCM-41, to abstract protons with a higher pK than that of the DMAN. 

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... 

MgO nanoparticles have proven to be very effective chemical reagents in the Claisen-Schmidt condensation, which is a very valuable C—C bond-formation reaction commonly employed in the pharmaceutical and fine chemical industries [295]. When MgO(lll) nanosheets were employed for the Claisen-Schmidt condensation of benzaldehyde and acetophenone, they were found to exhibit activity superior to other systems, such as AICI3, BE3, POCI3, alumina and other reported nano-crystaUine MgO samples [296]. This development is particularly noteworthy as it represents a potential heterogenization of the Claisen-Schmidt catalytic process, which offers numerous advantages including easier product recovery and catalyst recycling. 

Figure 16.20 Claisen-Schmidt condensation of benzaldehyde with acetophenone using different crystallites of magnesium oxide at 110°C. (NAP-MgO aerogel prepared MgO,...

If there are two carbonyl compounds present, then a cross condensation might occur, but usually it is of little synthetic value as there are four possible products. However, if one of the carbonyl compounds lacks an a-hydrogen, then the reaction might prove useful, because this compound cannot form the enol intermediate. An example is the Claisen-Schmidt condensation involving an aromatic aldehyde, e.g. benzaldehyde, with a simple aldehyde or ketone,... 

Hydrotalcite-derived materials also show good performances in analogous reactions, such as the Claisen-Schmidt condensation of substituted 2-hydroxyacetophe-nones with substituted benzaldehydes, the synthetic route to flavonoids and the condensation of 2,4-dimethoxyacetophenone with p-anisaldehyde to synthesize Vesidryl, a diuretic drug [270]. Another similar class of reactions in which HT-based materials give good results are Knoevenagel condensations [271]. An example is the synthesis of citronitrile, a perfumery compound with a citrus-like odor, which can be prepared by HT-catalyzed condensation of benzylacetone with ethyl cyanoacetate, followed by hydrolysis and decarboxylation (Figure 2.42b) [272]. 

Rates for competing processes such as self-condensation of cyclohexanone and Cannizzaro or Tishchenko reactions of benzaldehyde are negligible compared with the Claisen-Schmidt condensation of aldehyde with ketone. 

The propensity for Claisen-Schmidt condensation to afford bis-adducts [e.g., ( , )-2,6-dibenzylidenecyclohexanone from benzaldehyde and cyclohexanone] virtually exclusively, even in the presence of excess ketone (as mentioned in Section 6.2.3), was the cornerstone of our strategy for the preparation of symmetrical adducts (i.e., those with a two-fold axis through the C=O group as viewed in the plane of the page)." Such condensations occur sequentially, as mono-condensed products tend to be more reactive than the parent cycloalkanones under the reaction conditions, making them transient intermediates prepared for further reaction. 

The Cs+-exchanged zeolites, which are the most basic, have been shown to catalyse the Claisen Schmidt condensation between substituted 2-hydroxy-acetophenones and substituted benzaldehyde to give the 2 -hydroxychalcone structure (Reaction 3).30... 

C liment.. MJ Garcia. H Primo. J Conna. A. Zeolites as catalysts in organic reactions. Claisen-Schmidt condensation of acetophenone with benzaldehyde. Catalysis Letters, 1990 4.85-91. 

The Claisen-Schmidt condensation of /r-substituted benzaldehydes with p-substituted acetophenones gives the corresponding a,jd-ketones (chalcones) in hydrotropic media in the presence of NaOH as catalyst (Sadvilkar, 1995). 

Besides the aldol reaction to form y0-hydroxyketone, 1,3-Dipolar Cycloaddition can also form similar molecules. In addition to the Mukaiyama Aldol Reaction, the following are also similar or closely related to the aldol reaction the Claisen-Schmidt Condensation (the aldol reaction between benzaldehyde and an aliphatic aldehyde or ketone in the presence of relatively strong bases to form an o, )0-unsaturated aldehyde or ketone), the Henry Reaction (base-catalyzed addition of nitroalkane to aldehydes or ketones), the Ivanov Reaction (the addition of enediolates or aryl acetic acid to electrophiles, especially carbonyl compounds), the Knoevenagel Reaction (the condensation of aldehydes or ketones with acidic methylene compounds in the presence of amine or ammonia), the Reformatsky Reaction (the condensation of aldehydes or ketones with organozinc derivatives of of-halo-esters), and the Robinson Annulation Reaction (the condensation of ketone cyclohexanone with methyl vinyl ketone or its equivalent to form bicyclic compounds). 

As mentioned earlier, the increase in the in HTW and SCW produces equivalent quantities of and OH and therefore the increase in the observed rate of reaction could also arise from base catalysis. Eckert et al. observed base catalysis in HTW in the Claisen-Schmidt condensation of benzaldehyde and 2-butanone. The product outcome of this reaction under normal aqueous conditions depends upon whether the reaction is acid or base catalysed in acid catalysis a monosubstituted enone is formed whereas the base-catalysed route yields a disubstituted enone as the favoured product (Scheme 3.6). The disubstituted enone was found to be the dominant product for the Claisen-Schmidt condensation in HTW indicating base catalysis as the dominant pathway in HTW. 

Scheme 3.6 The Claisen-Schmidt condensation of benzaldehyde and 2-butanone showing the two possible products and the dominant pathway under acidic and basic conditions.

NAP-MgO acts as a bifunctional heterogeneous catalyst for the Claisen-Schmidt condensation (CSC) of benzaldehydes with acetophenones to yield chalcones, followed by asymmetric epoxidation (AE) to afford chiral epoxy ketones in moderate to good yields and impressive enantioselectivities (ee s). NAP-MgO, in combination with the chiral auxiliary (11 ,21 )-(- -)-1,2-diphenyl-1,2-ethylenediamine (DPED), catalyzed the asymmetric Michael addition of malonates to cyclic and acyclic enones. 

Additional insight into the factors affecting product structure was obtained by studies on the Claisen-Schmidt condensation of 2-butanone with benzaldehyde. ... 

Calcined barium hydroxide is an efficient catalyst for a number of base-mediated reactions. Among these, the Claisen-Schmidt condensation of acetophenones with benzaldehydes occurs in times as short as 10 min at room temperature (Eq. 15). The acetophenone enolate (detected by IR spectroscopy) is formed on the catalyst surface, where the reaction with the aldehyde takes place. The higher activity of the ketone enolate is interpreted by the authors as the result of "an increased vibrational state of the lattice", a formulation close to the mechano-chemical explanation. With the help of selective poisoning experiments, it is concluded that the enolate forms via a SET mechanism. 

Claisen-Schmidt condensation, i.e., the condensation of benzaldehyde and acetone to a,(3-unsaturated ketones, has been performed to a high degree at 0°C with rehydrated oxides from LDH precursors by Rao et al. (532). 

A variety of condensation reactions have been explored in NCW in order to elucidate the catalytic behavior of this medium. Nolen et al. have reported the results of the Claisen-Schmidt condensation between benzaldehyde and butanone to form a,/3-unsaturated ketones. Due to the asymmetry of the butanone with respect to the carbonyl group, two products are formed (Fig. 9.52). It has been reported that under traditional acidic... 

Figure 9.54 Production of 1-phenyl-1-penten-3-one (terminal enone product) and 4-phenyl-3-methyl-3-buten-2-one (Internal enone product) from the Claisen-Schmidt condensation of ben-zaldehyde with 2-butanone as a function of time at 250°C. Formation of secondary condensation products and higher addition products (oligomers) is also shown. The reactant molar ratio (benzaldehyde/2-butanoneA ater) was 1 10 55. ...

Cationic surfactants such as the cetyltrimethylammonium compounds CTACl, CTABr, (CTA)2S04 and CTAOH favor, under weakly alkaline conditions, the Claisen-Schmidt condensation of acetophenones with benzaldehydes (Scheme 7.1), allowing the synthesis of biologically interesting compounds, such as chalcones and flavonols [6,7], in water only. 

Obtained by reaction of benzaldehyde with 2,4-diacetyl-resorcinol in ethanol in the presence of concentrated aqneons potassium hydroxide at r.t. (Claisen-Schmidt condensation), for 48 h (34%) [5661] or for 24 h (9%) [5658]. 

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