Condensations crossed aldol

An aldol reaction that starts with two different carbonyl compounds is called a crossed aldol reaction. Unless specific conditions are involved, a crossed aldol reaction can lead to a ntix-ture of products from various pairings of the carbonyl reactants, as the following example illustrates with ethanal and propanal. 

3-Hydroxy-2-methylbutanal 3-Hydroxypentanal (from one molecule of ethanal and one molecule of propanal) 

We shall therefore consider crossed aldol condensations by two general approaches that allow control over the distribution of products. The first approach hinges on structural factors of the carbonyl reactants and the role that favorable or unfavorable aldol addition equilibria play in determining the product distribution. In this approach relatively weak bases such as hydroxide or an alkoxide are used in a protic solvent such as water or an alcohol. The second 

Show how each of the four products shown at the beginning of this section is formed in the crossed aldol addition between ethanal and propanal. 

ANSWER In the basic aqueous solution, four organic entities will initially be present molecules of ethanal, molecules of propanal, enolate anions derived from ethanal, and enolate anions derived from propanal. 

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AldolRea.ctlons, In the same way, hydroxybenzaldehydes react readily with aldehydes and ketones to form a,P-unsaturated carbonyl compounds in the Claisen-Schmidt or crossed-aldol condensation (60). 

Trimethylolpropane (TMP), the reduced crossed aldol condensation product of //-butyraldehyde and formaldehyde, competes in many of the same markets as glycerol (qv) and pentaerythritol. The largest market for TMP is as a precursor in unsaturated polyester resins, short-oil alkyds, and urethanes for surface coatings (see Alkyd resins). 

Methyl amyl ketone, derived from the crossed aldol condensation of -butyraldehyde and acetone, is used predominandy as a high soHds coatings solvent. It is also employed as a replacement for the very toxic 2-ethoxyethyl acetate [111 -15-9J. 

The principal markets for neopentyl glycol (NPG), the hydrogenated, crossed aldol condensation product of isobutyraldehyde and formaldehyde, are in water-borne and alkyd-surface coatings. 

The coupling of a secondary alcohol 1 with a primary alcohol 2 is achieved by the temporary removal of from each substrate which generates the ketone 3 and aldehyde 4 intermediates. A crossed aldol condensation occurs under the reaction conditions by the enolate derived from ketone 3 undergoing nucleophilic addition... 

Crossed aldol condensations, where both aldehydes (or other suitable carbonyl compounds) have a-H atoms, are not normally of any preparative value as a mixture of four different products can result. Crossed aldol reactions can be of synthetic utility, where one aldehyde has no a-H, however, and can thus act only as a carbanion acceptor. An example is the Claisen-Schmidt condensation of aromatic aldehydes (98) with simple aliphatic aldehydes or (usually methyl) ketones in the presence of 10% aqueous KOH (dehydration always takes place subsequent to the initial carbanion addition under these conditions) ... 

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. 

Crossed aldol condensation of an anion generated a- to a ketone equivalent with o, /3-unsaturated aldehyde, dehydration and release of the ketone is an effective way of generation of dienones. Corey and Enders found that a-lithiated /V,/V-dirnethylhydrazones undergo 1,2-addition to the aldehydes and ketones to form /1-hydroxy derivatives. Sequential treatment of the intermediate with sodium periodate and methanesulphonyl chloride-triethylamine furnishes , -2,4-dienone derivative (equation 57)94. 

In the crossed aldol condensation between carbonyl partners there are four possible product stereoisomers (eq. [1]). Consequently, there are two stereochemical aspects associated with the reaction The first deals with internal stereochemical control or diastereoselec-tion [A( ) vs. B( )], and the second deals with absolute stereochemi-... 

A possible mechanism for the P-alkylation of secondary alcohols with primary alcohols catalyzed by a 1/base system is illustrated in Scheme 5.28. The first step of the reaction involves oxidation of the primary and secondary alcohols to aldehydes and ketones, accompanied by the transitory generation of a hydrido iridium species. A base-mediated cross-aldol condensation then occurs to give an a,P-unsaturated ketone. Finally, successive transfer hydrogenation of the C=C and C=0 double bonds of the a,P-unsaturated ketone by the hydrido iridium species occurs to give the product. 

Crossed aldol condensation reactions may present a problem because multiple products can be formed. For example, a mixture of carbonyl A and carbonyl B can give two different enolates, each of which can then attack either an A or a B molecule. Therefore, four products are possible (Ag, A + B, B + A, and B2). 

The formation of multiple products limits the practicality of crossed aldol condensations. Following are the two ways to increase the practicality of a crossed aldol condensation ... 

The Claisen-Schmidt reaction (Figure 11-17) produces an a,P-unsaturated aldehyde or ketone, the general structure of which is shown in Figure 11-18. The Claisen-Schmidt reaction is a crossed aldol condensation. 

Crossed Aldol Condensation An aldol condensation involving different carbonyl compounds. 

Several NaOH-treated ionic liquids for self- and cross-aldol condensation reactions of propanal provide an interesting example illustrating improved product selectivity in a system in which competing reactions take place (109). In the self-aldol condensation reaction of propanal, 2-methylpent-2-enal is formed. The reaction progresses through an aldol intermediate and produces the unsaturated aldehyde. The NaOH-treated ionic liquid [BDMIM]PF gave the highest product... 

When self-condensation of one of the reactants competes with the desired inter-molecular reaction, such as, 2A C and A + B E, where E is the desired product, it is obvious that the rate of the second reaction is improved by increasing the availability (or solubility) of B in a solvent. The principle has been demonstrated with a cross aldol condensation reaction, as shown in Scheme 17 109). 

Several cross-aldol condensations have been performed with alkaline earth metal oxides, including MgO, as a base catalyst. A general limitation of the cross-aldol condensation reactions is the formation of byproducts via the self-condensation of the carbonyl compounds, resulting in low selectivities for the cross-aldol condensation product. For example, the cross-condensation of heptanal with benzalde-hyde, which leads to jasminaldehyde (a-K-amylcinnamaldehyde), with a violet scent... 

Another important example is the cross-aldol condensation of citral and acetone, which yields pseudoionone (Scheme 14), an intermediate in the commercial production of vitamin A. Numerous commercial routes to the preparation of pseu-doionones are based on the aldol condensation using conventional homogeneous catalysts, such as aqueous alkali metal hydroxide solutions, alcoholates in alcohol or benzene solvents (126-129). The yields of the cross-condensation product vary between 50% and 80%, depending on the type of catalyst and conditions such as catalyst concentration, ratio of reagents, and temperature. 

The Knoevenagel condensation is a cross-aldol condensation of a carbonyl compound with an active methylene compound leading to C-C bond formation (Scheme 7). This reaction has wide application in the synthesis of fine chemicals and is classically catalyzed by bases in solution (146,147). 

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)... 

The cross aldol condensation of citral (Millennium Chemicals, 40 % cis-isomer + 55 % trans-isomer) with acetone (Merck, PA) was carried out at 353 K in N2 atmosphere under autogenous pressure ( 250 kPa) in a batch PARR reactor, using an acetone/citral = 49 (molar ratio) and a catalyst/(citral+acetone) = 1 wt.% ratio. Catalysts were pre-treated ex-situ in flowing N2 at 773 K for 2 h to remove adsorbed water and carbon dioxide and then quickly transferred to the reactor without exposing them to air. Reaction products were analyzed by gas chromatography. Selectivities (Sj, mol of producty /mol of citral reacted) were calculated as (%) = Cj X 100/ TCj where Cj is the concentration of product j. Product yields rjj, mol of product y/mol of citral fed) were calculated as Tfj = SjXat- Thirteen samples of the reaction mixture were extracted and analyzed during the 6-hour reaction. The main reaction product of citral conversion was pseudoionone, PS (cis- and trans- isomers). 

Aldol condensations.1 Under usual conditions, 1 is not useful for crossed-aldol condensation because of predominant self-condensation. However in the presence of pyridine and acetic acid 1 undergoes aldol condensation with aromatic and a,p-unsaturated aldehydes. Yields are moderate to high if the concentration of 1 is kept low (inverse addition). This reaction can be used to obtain all-trans-19,19,19- and 20,20,20-trifluororetinal (2). 

Aldol condensations of enones with a-ketols.2 ZnCl2 promotes the crossed-aldol condensation of enones with protected a-ketols. This reaction has been used for a short synthesis of frontalin (1). 

In the present paper we have studied four acid catalyzed reaotions involving carbonyl compounds alkylation of benzene with formaldehyde, esterification of phenylacetic acid, Friedel-Crafts acylation by phenylpropanoyl chloride, and the cross aldolic condensation of acetophenone with benzaldehyde in the presence of three Hp zeolites with different framework Si-to-Al... 

If die enolate nucleophile is derived from an aldehyde or ketone different than die carbonyl electrophile, a crossed-aldol condensation results. Normally best success is achieved if the carbonyl electrophile employed for the crossed-aldol condensation is more reactive than the carbonyl electrophile from which the enolate is derived. For example, ketone etiolates react with aldehydes effectively, but aldehyde enolates do not give the crossed aldol with most ketones but self-condense instead. 

The polymer was imprinted with dibenzoyl-methane (42), a 1,3-diketone able to be held in place by formation of a complex with the Co(II) ion, and structurally similar to the product of the cross-aldol condensation. A schematic representation of this approach is given in Scheme 7. 

On the basis of a catalytic system previously developed by the same group, Nicholls and collaborators [51] reported the preparation of an imprinted polymer for enantioselective formation of a C-C bond with properties of a metallo-enzyme aldolase type II. Polymers were imprinted using the two enantiomers of a 1,3-diketone, the (l.S, 35,45)-(75), and the corresponding (l/ ,3/ ,4/ )-(75), together with two 4-vinyl-pyridine held in place by a Co(II). The cross-aldol condensation... 

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