Benzaldehyde, aldol condensation

In tile industrial production of higher alcohols (above butyls), aldehydes play the role of an intermediate in a complete process that involves aldol condensation and hydrogenation. In the OXO process, olefins are catalytically converted into aldehydes that contain one more carbon titan the olefin in the feedstock. Aldehydes also serve as starting materials in the synthesis of several amino acids. See also Acetaldehyde Aldol Condensation Benzaldehyde and Furfuraldehyde. 

The starting materials for the mixed aldol condensation—benzaldehyde and propanal—are... 

Aldol condensation. Benzaldehydes condense with alkyl aryl ketones in the presence of basic alumina to form chalcones in 70-85% yield. Benzaldehydes... 

The starting materials for the mixed aldol condensation— benzaldehyde and propanal—are prepared by oxidation of benzyl alcohol and 1-propanol, respectively. 

Cannizzaro reaction Two molecules of many aldehydes, under the influence of dilute alkalis, will interact, so that one is reduced to the corresponding alcohol, while the other is oxidized to the acid. Benzaldehyde gives benzyl alcohol and benzoic acid. Compare the aldol condensation. 

The higjily water-soluble dienophiles 2.4f and2.4g have been synthesised as outlined in Scheme 2.5. Both compounds were prepared from p-(bromomethyl)benzaldehyde (2.8) which was synthesised by reducing p-(bromomethyl)benzonitrile (2.7) with diisobutyl aluminium hydride following a literature procedure2.4f was obtained in two steps by conversion of 2.8 to the corresponding sodium sulfonate (2.9), followed by an aldol reaction with 2-acetylpyridine. In the preparation of 2.4g the sequence of steps had to be reversed Here, the aldol condensation of 2.8 with 2-acetylpyridine was followed by nucleophilic substitution of the bromide of 2.10 by trimethylamine. Attempts to prepare 2.4f from 2.10 by treatment with sodium sulfite failed, due to decomposition of 2.10 under the conditions required for the substitution by sulfite anion. 

Ni(N03)2 6H20, Cu(N03)2 3H20, Zn(N03)2-4H20 and KNOj were of the highest purity available. Substituted 3-phenyl-l-(2-pyridyl)-2-propene-ones (2.4a-e) were prepared by an aldol condensation of the corresponding substituted benzaldehyde with 2-acetylpyridine, following either of two modified... 

As actually carried out the mixed aldol condensation product 1 3 diphenyl 2 propen 1 one has been isolated in 85% yield on treating benzaldehyde with ace tophenone in an aqueous ethanol solution of sodium hydroxide at 15-30°C... 

In 1908, while working at University of Heidelberg, Auwers and Muller described the transformation of 4-methyl-2-cumaranone (3) to flavanol 6. Thus aldol condensation of 3 with benzaldehyde gave benzylidene derivative 4, which was brominated to give dibromide 5. Subsequent treatment of 5 with alcoholic KOH then furnished 2-methylflavonol 6. In the following years, Auwers published more extensively on the scope and limitations of this reaction. ... 

Forty years after the initial proposal, Sweet and Fissekis proposed a more detailed pathway involving a carbenium ion species. According to these authors the first step involved an aldol condensation between ethyl acetoacetate (6) and benzaldehyde (5) to deliver the aldol adduct 11. Subsequent dehydration of 11 furnished the key carbenium ion 12 which was in equilibrium with enone 13. Nucleophilic attack of 12 by urea then delivered ureide 14. Intramolecular cyclization produced a hemiaminal which underwent dehydration to afford dihydropyrimidinone 15. These authors demonstrated that the carbenium species was viable through synthesis. After enone 13 was synthesized, it was allowed to react with N-methyl urea to deliver the mono-N-methylated derivative of DHPM 15. 

Chiral salen chromium and cobalt complexes have been shown by Jacobsen et al. to catalyze an enantioselective cycloaddition reaction of carbonyl compounds with dienes [22]. The cycloaddition reaction of different aldehydes 1 containing aromatic, aliphatic, and conjugated substituents with Danishefsky s diene 2a catalyzed by the chiral salen-chromium(III) complexes 14a,b proceeds in up to 98% yield and with moderate to high ee (Scheme 4.14). It was found that the presence of oven-dried powdered 4 A molecular sieves led to increased yield and enantioselectivity. The lowest ee (62% ee, catalyst 14b) was obtained for hexanal and the highest (93% ee, catalyst 14a) was obtained for cyclohexyl aldehyde. The mechanism of the cycloaddition reaction was investigated in terms of a traditional cycloaddition, or formation of the cycloaddition product via a Mukaiyama aldol-reaction path. In the presence of the chiral salen-chromium(III) catalyst system NMR spectroscopy of the crude reaction mixture of the reaction of benzaldehyde with Danishefsky s diene revealed the exclusive presence of the cycloaddition-pathway product. The Mukaiyama aldol condensation product was prepared independently and subjected to the conditions of the chiral salen-chromium(III)-catalyzed reactions. No detectable cycloaddition product could be observed. These results point towards a [2-i-4]-cydoaddition mechanism. 

Activity is apparently retained when the ring nitrogen is alkylated as in flordipine (42). Aldol condensation of the benzaldehyde 39 with ethyl acetoacetate gives the unsaturated ester 40. The nitrogen containing reaction partner 41 is obtained by condensation of 32 with 2- morpholi-noethylamine. Reaction of 40 with 41 leads to flordipine (42) [12]. 

Pyrimidinopyrazines related to folic acid have been investigated in some detail for their antimeta-bolic and antineoplastic activities. A related compound, which lacks one nitrogen atom, has been described as an antiproliferative agent, indicating it too has an effect on cell replication. Aldol condensation of the benzaldehyde 99 with ethyl acetoacetate gives the cinnamate 100. This is then reduced catalytically to the acetoacetate 101. Reaction of that keto ester with 2,4,6- triami-nopyrimidine gives the product 102 which is subsequently chlorinated (103) and subjected to hydrogenolysls. There is thus formed piritrexim (104) [17]. 

The aldol reaction is a carbonyl condensation that occurs between two aldehyde or ketone molecules. Aldol reactions are reversible, leading first to a /3-hydroxy aldehyde or ketone and then to an cr,/6-unsaturated product. Mixed aldol condensations between two different aldehydes or ketones generally give a mixture of all four possible products. A mixed reaction can be successful, however, if one of the two partners is an unusually good donor (ethyl aceto-acetate, for instance) or if it can act only as an acceptor (formaldehyde and benzaldehyde, for instance). Intramolecular aldol condensations of 1,4- and 1,5-diketones are also successful and provide a good way to make five-and six-inembered rings. 

Aldol condensation reactions have also been conducted. A good example is provided by Climent et al. (1998) for making a-n-amyl cinnamaldehyde (Jasmin aldehyde) by condensing benzaldehyde with n-heptaldehyde, in the presence of mesoporous MCM-41 aluminosilicates. Mesoporous silica-aluminas with a narrow range of pore diameter such as MCM-41 also... 

For example, large rate enhancements have been reported in the synthesis of chal-cones by crossed-aldol condensations in open vessels, suggesting the participation of specific MW effects [41]. The chalcone 24 was synthesized from cyclohexanone and benzaldehyde in ethanol, in the presence of a catalytic amount of sodium hydroxide (Scheme 4.13), in a MW oven in 90% yield in only 1 min. 

Van Koten and Frey used a hyperbranched poly(triallylsilane) as the support for palladium- pincer complexes.[63] The supported palladium-pincer complexes were applied in the catalytic aldol condensation of benzaldehyde and methyl isocyanate. Their activity was similar to that of single site Pd catalysts. According to the authors, the complex is suitable for continuous membrane applications, as demonstrated by their purification by means of dialysis. 

Benzaldehydes are not subject to base catalyzed aldol condensations, and under the reaction conditions Cannizarro reactions are not important. 

The aldol condensation of benzaldehyde with the thioacetamide carbanion (RCHCSNRV), derived from the desilylation of the silyl-thioether with tetra-/i-buty-lammonium fluoride, is stereoselective at—80°C producing the erythro isomer of the p-hydroxy thioamide preferentially (Scheme 6.18, R = Me, erythro threo 95 5) via a conformationally mobile intermediate. However, when R is bulky, a greater amount of the threo isomer is formed. Predictably, as the reaction temperature is raised, so the stereoselectively decreases. This procedure contrasts with the corresponding condensation catalysed by titanium salts, where the complexed intermediate produces the threo isomer [47, 48],... 

Kinetic Aldol Condensations of Acyclic Lithium Ketone Enolates with Benzaldehyde (eq. [17]) (2,26)... 

Aldol Condensation of 60 and 61 with Benzaldehyde (eq. [49,50]) Solvent and ligand Effects (6)... 

A summary of representative stereochemically defined metal enolates and their respective kinetic aldol condensations with benzaldehyde is provided in Table 24. Both the metal center and the enolate substituent Ri for the substituted carbonyl derivatives... 

Kinetically Controlled Aldol Condensations of Zirconium Enolates with Benzaldehyde... 

Aldol Condensation of Zinc Ester Enolates with Benzaldehyde Anil Solvent Effects (Scheme 16) (76)... 

Scheme 30 EGB-initiated aldol condensation between benzaldehyde and acetophenone.

Table 9.2 summarises some of the results reported by Evans and coworkers in aldol condensations of boron enolates with benzaldehyde [14]. 

TABLE 9.2. Aldol condensations of dialkylboron enolates with benzaldehyde... 

The chiral A/ -propionyl-2-oxazolidones (32 and 38) are also useful chiral auxiliaries in the enantioselective a-alkylation of carbonyl compounds, and it is interesting to observe that the sense of chirality transfer in the lithium enolate alkylation is opposite to that observed in the aldol condensation with boron enolates. Thus, whereas the lithium enolate of 37 (see Scheme 9.13) reacts with benzyl bromide to give predominantly the (2/ )-isomer 43a (ratio 43a 43b = 99.2 0.8), the dibutylboron enolate reacts with benzaldehyde to give the (3R, 25) aldol 44a (ratio 44a 44b = 99.7 0.3). The resultant (2R) and (25)-3-phenylpropionic acid derivatives obtained from the hydrolysis of the corresponding oxazolidinones indicated the compounds to be optically pure substances. 

Recently, cross-aldol condensation of benzaldehyde with n-heptaldehyde to give jasminaldehyde (Scheme 13) has been reported a mesoporous molecular sieve Al-MCM-41 with supported MgO was the catalyst. The reactions were carried out in a stirred autoclave reactor with a molar benzaldehyde/heptanal ratio of 10 at 373-448 K (236). The results show that Al-MCM-41 is catalytically active, and its activity is significantly increased by the deposition of MgO (Table V). Increasing the amount of deposited MgO on Al-MCM-41 decreases the surface area but enhances the catalyst basicity. The basicity is well correlated with the catalytic activity, although the selectivity to jasminaldehyde is not the selectivity is essentially independent of temperature, pressure, time of the reaction, and conversion. 

Cross-aldol Condensation of Benzaldehyde with Heptanal on Basic Catalysts (236)... 

Another type of aldol condensation using cyclic enol ethers was demonstrated by Yamamoto and co-workers in which the condensation of tributyl (1-cyclohexene-1-yloxy)stannane 154 with benzaldehyde proceeded in 74% yield, as shown in Figure 9.48. The ratio of anti product 155 to syn product 156 was 36 64 with an anti ee of 84% (Fig. 9.48). 

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