Condensation of benzaldehyde and acetone

Benzylidene acetone, C Hg. CH CH. COCH, is a crystalline body melting at 42°, having an intense floral odour. It restilts from the condensation of benzaldehyde and acetone under the influence of caustic soda. It has the following characters —... 

A patent of Meister, Lucius, Briining [46] depends on a similar reaction. Claisen s benzylidene-acetone (cinnamylmethyl-ketone CeHj —CH = CHCO—CH3) [47], obtained by condensation of benzaldehyde and acetone, is nitrated. A mixture of ortho and paranitro derivatives is formed, and the former yields indigotin by action of alkalies. 

The catalytic activity of the NHs-grafted mesoporous silica, FSMN, was examined in some base-catalysed condensations (eqn. 1). The results were listed in Table 1. The FSMN catalyst used here was FSMN-5 that was prepared by the pre-activation at 1073 K followed by NH3-treatment at 973 K. The Aldol condensation of benzaldehyde and acetone did not proceed in this condition (entry 1). The Knoevenagel condensation of benzaldehyde and diethyl malonate (entry 2) did not occurred. On the other hand, the reactions with malononitrile (entry 3) and with ethyl cyanoacetate (entry 4) were catalysed by the FSMN-5. This shows that the NHa-grafted mesoporous silica would function as base catalyst. 

An exhaustive kinetic investigation of the aldol condensation of benzaldehyde and acetone on calcined MgAl HDT has been performed in the liquid phase with a batch reactor at 383 K [25]. The aldol, benzalacetone, and dibenzalacetone in small amounts were observed as products. Benzalacetone resulted from dehydration of the aldol, and dibenzalacetone from the addition of a second mole of acetone to benzalacetone. 

These results, which are highly analogous with those from the homogeneous base-catalyzed condensation reaction, imply that the condensation of benzaldehyde and acetone is base-catalyzed on hydrotalcites. 

Because the mechanism of this reaction is supposed to be ionic, it should be affected by the nature of the solvents. This is indeed so for the condensation of benzaldehyde and acetone [33]-rate changes by a factor of 50 are observed when heptane or toluene are substituted by DMF (Table 3). The initial rate, unaffected by possible inhibition by the products, is higher in polar solvents. Acetone also is highly polar and thus a good solvent for these reactions. 

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). 

The specific properties of hydrated hydrotalcites appear not only in the aldoli-zation of acetone, but in many other aldolization reactions. For example, in the aldol condensation of benzaldehyde with acetone the hydrated form catalyzes the reaction at 273 K, yielding aldol as the main product instead of benzalacetone, obtained on the calcined sample. Competitive adsorption kinetics are still observed, with a much greater adsorption coefficient for benzaldehyde. As suggested earlier from Hammett relationships, this reaction can be generalized with success to many substituted benzaldehydes [32], although the reaction could be performed selectively at 273 K with benzaldehyde only, and substituted benzaldehydes required a reaction temperature of 333 K. Because of this high temperature the reaction usually gives a, unsaturated ketones isolated yields are > 95 %. 

Nolen et al. also reported the self-condensation reaction of butyraldehyde and the cross-aldol condensation of benzaldehyde with acetone (Figs. 9.58 and 9.59) at 250°C. The butyraldehyde self-condensation produced a number of products, including 2-ethyl-2-hexenal, 2-butyl-2-butenal, and 2-ethyUiexanal. The results from the condensation of butyraldehyde indicate that a 40% yield of 2 -ethyl-2 -hexenal is achieved before the formation of by-products becomes dominant. In addition, investigations of the back reaction show that a substantial quantity of butyraldehyde is formed when 2-ethyl-2-hexenal is subjected to water at 250°C. The condensation reaction of benzaldehyde with acetone produced a 15% yield of trans-4-phenyl-3-buten-2-one in 5 h and very small quantities of trans,trans-dibenzylidene acetone during this same period of time. The authors suggest that the low yield could be a result of equilibrium limitations. 

Examples are the formation of diacetone alcohol from acetone [reaction type (A)] catalysed by barium or strontium hydroxide at 20—30°C [368] or by anion exchange resin at 12.5—37.5°C [387], condensation of benzaldehyde with acetophenone [type (C)] catalysed by anion exchangers at 25—-45°C [370] and condensation of furfural with nitromethane [type (D)] over the same type of catalyst [384]. The vapour phase self-condensation of acetaldehyde over sodium carbonate or acetate at 50°C [388], however, was found to be first order with respect to the reactant. 

A short total synthesis of Phycopsisenone, a new phenolic secondary metabolite from the sponge Phycopsis sp, was performed by G.L. Kad et al. [31]. A microwave irradiation-induced (domestic oven) aldol condensation of 4-hydroxy-benzaldehyde and acetone in aqueous NaOH solution afforded the ,/ -unsaturated ketone in 65% yield (Scheme 8). This was further converted in Phycopsisenone applying a two-step sequence. 

When acetone is treated with excess benzaldehyde in the presence of base, the crossed condensation adds two equivalents of benzaldehyde and expels two equivalents of water. Propose a structure for the condensation product of acetone with two molecules of benzaldehyde. 

Cesium-exchanged zeolite X was used as a solid base catalyst in the Knoevenagel condensation of benzaldehyde or benzyl acetone with ethyl cyanoacetate [121]. The latter reaction is a key step in the synthesis of the fragrance molecule, citronitrile (see Fig. 2.37). However, reactivities were substantially lower than those observed with the more strongly basic hydrotalcite (see earlier). Similarly, Na-Y and Na-Beta catalyzed a variety of Michael additions [122] and K-Y and Cs-X were effective catalysts for the methylation of aniline and phenylaceto-nitrile with dimethyl carbonate or methanol, respectively (Fig. 2.37) [123]. These procedures constitute interesting green alternatives to classical alkylations using methyl halides or dimethyl sulfate in the presence of stoichiometric quantities of conventional bases such as caustic soda. 

The yields of nitro alcohols from simple nitroparaffins and aliphatic aldehydes or benzaldehyde are usually above 60%. The condensations are generally carried out with aqueous ethanolic sodium hydroxide, although weaker bases are sometimes desirable to prevent polymerization of the aldehyde. Sodium bisulfite addition compounds of the aldehydes are sometimes used. Better results are obtained with sodium methoxide than with alkali hydroxides in the condensation of nitroethane with formaldehyde. Sodium alkoxides are also used to effect the condensation of nitroethane with acetone and cyclohexanone. Condensation proceeds to the nitroalkanediol stage in certain cases with both nitromethane and with formaldehyde. ... 

Cationic Pd complexes can be applied to the asymmetric aldol reaction. Shibasaki and coworkers reported that (/ )-BINAP PdCP, generated from a 1 1 mixture of (i )-BINAP PdCl2 and AgOTf in wet DMF, is an effective chiral catalyst for asymmetric aldol addition of silyl enol ethers to aldehydes [63]. For instance, treatment of trimethylsi-lyl enol ether of acetophenone 49 with benzaldehyde under the influence of 5 mol % of this catalyst affords the trimethylsilyl ether of aldol adduct 113 (87 % yield, 71 % ee) and desilylated product 114 (9 % yield, 73 % ee) as shown in Sch. 31. They later prepared chiral palladium diaquo complexes 115 and 116 from (7 )-BINAP PdCl2 and (i )-p-Tol-BINAP PdCl2, respectively, by reaction with 2 equiv. AgBF4 in wet acetone [64]. These complexes are tolerant of air and moisture, and afford similar reactivity and enantioselec-tivity in the aldol condensation of 49 and benzaldehyde. Sodeoka and coworkers have recently developed enantioselective Mannich-type reactions of silyl enol ethers with imi-nes catalyzed by binuclear -hydroxo palladium(II) complexes 117 and 118 derived from the diaquo complexes 115 and 116 [65]. These reactions are believed to proceed via a chiral palladium(fl) enolate. 

Benzalacetone has been obtained in small yield by drv distillation of a mixture of calcium acetate and calcium cinnamate (1) by heating the sodium derivative of cinnamaldehyde with methyl iodide (2) by heating cinnamaldehyde and methyl alcohol with zinc chloride (2) by heating acetone and benzaldehyde with acetic anhydride or zinc chloride (3). It is also formed when styrene and acetyl chloride are condensed by means of stannic chloride and the product is treated with diethylaniline (4) and when the vapors of cinnamic acid and acetic acid are passed together over ferric oxide at 470-490° (5). The only practical method, however, consists in condensing benzaldehyde and acetone by means of dilute aqueous alkali (6). 

Similarly, raspberry ketone has so far been made from phenol (and methyl vinyl ketone). However, in view of easy availability of p-hydroxy benzaldehyde from p-cresol at a reasonable price, raspberry ketone can now be made by condensation of alkali catalysed p-hydroxy benzaldehyde and acetone followed by mild hydrogenation of the double bond. 

Some examples of the addition of one carbonyl compound to another are the aldol condensation the formation of acetoacetic ester the condensation of benzaldehyde with one of the components of a mixture of an acid anhydride and a carboxylate salt the formation of mesityl oxide, phoroiie, and mesitylene from acetone and the condensations of aromatic aldehydes and ketones. Acids and bases are generally catalysts for these reactions. They have sufficient in common to warrant their being classed together as the aldol type of... 

Reagents and Equipment. In a 3.0-mL conical vial containing a magnetic spin vane and equipped with an air condenser place 80 gL (84 mg, 0.79 mmol) of benzaldehyde and 29.0 jlL (23 mg, 0.40 mmol) of acetone (- i). 

Gettler, J.D. and Hammett, L.P., Rates and temperature coefficients of the hydroxyl ion catalyzed aldol condensation of benzaldehyde with methyl ethyl ketone and acetone, /. Am. Chem. Soc., 1943,65,1824-1829. 

Dilute sodium hydroxide was used as a condensing ent by J. G. Schmidt and the method was applied by Claisen and collaborators to the s3mthesis (Claisen reaction) of aromatic ketonic esters, e.g. benzylidene acetone and di-benzylidene acetone from benzaldehyde and acetone. An alternative method was the use of an aromatic aldehyde or ketone with acetoacetic ester in presence of hydrogen chloride. Benzoylacetic ester, CgHgCO CHe-COOCoHs, was obtained by condensing benzoic and acetic esters in presence of sodium ethoxide, and j8-diketones by condensing ketones and acid esters, e.g. acetyl-acetone CHaCO-CHaCOCHg."... 

The importance of catalyst basic properties was emphasized by Malinowski et d They studied aldol condensation of formaldehyde with acetaldehyde, acetone, and acetonitrile. The rate constants for these reactions on Si02 mounted NaOH catalyst show correlation with NaOH content in the catalysts as shown in Fig. 4.37. Essentially the same linear relationship was observed for aldol condensation of acetaldehyde, and acetaldehyde with benzaldehyde. The linear relations support the view that basic properties are actually the cause of the catalytic activities. On Si02-supported NaOH catalysts, the groups - Si —ONa are assumed to be the active sites. 

When an ethanolic solution containing both acetone and two equivalents of benzaldehyde is made alkaline with sodium hydroxide, rapid condensation occurs with the formation of dibenzal-acetone, or dibenzylidene-acetone. This... 

Furthermore, they react with carbonyl derivatives such as acetone and benzaldehyde to give selenohydrazones identical to those prepared from the condensation of selenosemicarbazones with an a-halocarbonyl compound. 

Durst and coworkers were the first to report the condensation of chiral a-sulphinyl carbanions with carbonyl compounds477. They found that metallation of ( + )-(S)-benzyl methyl sulphoxide 397 followed by quenching with acetone gives a mixture of dia-stereoisomeric /i-hydroxy sulphoxides 398 in a 15 1 ratio (equation 233). The synthesis of optically active oxiranes was based on this reaction (equation 234). In this context, it is interesting to point out that condensation of benzyl phenyl sulphoxide with benzaldehyde gave a mixture of four / -sulphinyl alcohols (40% overall yield), the ratio of which after immediate work-up was 41 19 8 32478. 

A Knoevenagel condensation/Michael addition sequence has been reported by Barbas III and coworkers (Scheme 2.70) [158] using benzaldehyde, diethyl malonate, and acetone in the presence of the chiral amine (S)-l-(2-pyrrolidinyl-methyl)-pyrrolidine (2-301). As the final product the substituted malonate 2-302 was isolated in 52% yield with 49% ee. 

Dibenzalacetone has been prepared by condensing benzal-dehyde with acetone using as condensing agents dry hydrogen chloride,1 io per cent sodium hydroxide solution,2 and glacial acetic acid with sulfuric acid.3 It has also been obtained by condensing benzalacetone with benzaldehyde in the presence of dilute sodium hydroxide.4 Straus and Ecker 5 were the first to record the use of ethyl acetate for crystallization. 

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