Aldol condensation, acid catalyzed crossed

Scheme 13 summarizes the reaction steps for the acid-catalyzed cross-aldol condensation. 

The Mannich reaction presents a nice mechanistic problem because two routes to product seem possible, and it is the simpler (and incorrect) process that is the easier to find. The difficulty is that we are now experienced in working out aldol condensations and a reasonable person would probably start that way. An acid-catalyzed crossed aldol condensation (p. 982) leads to a P-hydroxy ketone (Fig. 19.118). Displacement of the hydroxyl group (after protonation, of course) would lead to the initial product, the ammonium ion. Treatment with base would surely liberate the free amine. 

The aldol or aldol-type reaction is well recognized as one of the most important carbon-carbon bond forming reactions in organic synthesis. As shown in Scheme 8.1, two stereogenic centers could be generated in this aldol reaction. The classical aldol condensation between an aldehyde and a ketone is often catalyzed by a base or an acid. Another approach is the acid-catalyzed cross-aldol reaction of silyl enol ethers with carbonyl compounds, the so-called Mukaiyama reaction. 

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... 

It was suggested73 that the most probable mechanism of this reaction is an initial aldol condensation of the starting ketone leading to the a,/ -unsaturated ketone 100 or to the /Miydroxyketone 101 which serve as precursors to the tertiary carbenium ions 102, which reacts in turn with nitriles by an acid-catalyzed Ritter reaction to give 103 (equation 36). This suggestion is confirmed by the results of a cross-reaction experiment of benzaldehyde and diethyl malonate with acetonitrile to give 14 (equation 37). 

Cyclodextrins with two imidazole groups on the primary hydroxyl side can enhance the enolate formation [86] of a simple bound ketone by bifunctional acid-base catalysis and accelerating the intramolecular aldol condensation of bound ketoaldehyde and dialdehyde. The aldolase mimics which catalyzed crossed aldol condensations were obtained by the assembly of (i-CD and various amino moieties as Schiff base [87]. 

A carbon atom alpha to a carbonyl function may become nucleophilic either by forming an etiolate (Eq. 18.3) or an enol (Eq. 18.4). In the crossed-aldol reaction described in the previous section (Scheme 18.4), the nucleophilic character of the carbon atom alpha to a ketone function was provided by enolate formation. However, in the experiment that follows, nucleophilicity at the a-carbon atom is promoted by enol formation. The overall reaction is the acid-catalyzed conversion of 2-methylpropanal (26) and 3-buten-2-one (27) into 4,4-dimethyl-2-cyclohexen-1-one (29), as shown in Equation 18.12. For the first stage of the reaction, the enol form of 26 serves as the nucleophile in the 1,4- or conjugate addition to the a,3-unsaturated ketone 27 to give 28. In the second stage, an enol is the nucleophile in the cyclization of 28 by an intramolecular aldol condensation that is acid-catalyzed. The conjugate addition to give 28 is an example of a... 

Amino)cinnamoyl compounds 79 can be regarded as primary products they may arise from an aldol condensation catalyzed by base, add, or (most frequently) by Lewis acids [173]. Alternatively, quinoline formation may result from primary cross aldol addition, subsequent cydocondensation to an imine(4-hydroxy-3,4-dihydroquinoHne), and aromatization by H2O elimination [174]). 

Before collagen molecules can cross-link, the primary amino groups of the lysine residues of collagen must be converted to aldehyde groups. (Lysine is an amino acid.) The enzyme that catalyzes this reaction is called lysyl oxidase. An aldol condensation between two aldehyde groups results in a cross-linked protein. 

LLC networks containing catalytic headgroups have also been shown to be useful for heterogeneous Lewis acid catalysis. The Sc(III)-exchanged cross-linked Hu phase of a taper-shaped sulfonate-functionalized LLC monomer has been shown to be able to catalyze the Mukaiyama aldol and Mannich reactions [115] with enhanced diastereoselectivity. This Sc(III)-functionalized Hu network affords condensation products with syn-to-anti diastereoselectivity ratios of 2-to-l, whereas Sc(III) catalysts in solution or supported on amorphous polymers show no reaction diastereoselectivity at all. 

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