Aldol, Formation

Examples include acetaldehyde, CH CHO paraldehyde, (CH CHO) glyoxal, OCH—CHO and furfural. The reaction is usually kept on the acid side to minimize aldol formation. Furfural resins, however, are prepared with alkaline catalysts because furfural self-condenses under acid conditions to form a gel. 

The reaction conditions needed for aldol dehydration are often only a bit more vigorous (slightly higher temperature, for instance) than the conditions needed for the aldol formation itself. As a result, conjugated enones are usually obtained directly from aldol reactions without isolating the intermediate jS-hydroxy carbonyl compounds. 

Among the compounds capable of forming enolates, the alkylation of ketones has been most widely studied and applied synthetically. Similar reactions of esters, amides, and nitriles have also been developed. Alkylation of aldehyde enolates is not very common. One reason is that aldehydes are rapidly converted to aldol addition products by base. (See Chapter 2 for a discussion of this reaction.) Only when the enolate can be rapidly and quantitatively formed is aldol formation avoided. Success has been reported using potassium amide in liquid ammonia67 and potassium hydride in tetrahydrofuran.68 Alkylation via enamines or enamine anions provides a more general method for alkylation of aldehydes. These reactions are discussed in Section 1.3. 

Note the use of 2 mols. of acetone to minimise aldol formation. 

All the steps of this reaction are reversible but the position of the equilibrium is significantly in favour of the aldol, which generally may be obtained when the reaction is carried out at room temperature or below, followed by extraction and careful distillation under reduced pressure. When the required product is the unsaturated aldehyde the reaction is carried out at a higher temperature, and dehydration of the aldol occurs readily (e.g. 2-ethylhex-2-enal, Expt 5.212). In the case of aldehydes with only one a-hydrogen atom, aldol formation occurs but the resulting / -hydroxyaldehyde cannot undergo the dehydration step. 

In the presence of chromium oxide catalyst primary aliphatic alcohols of n-carbon atoms are converted to symmetrical ketones of 2n — 1 carbon atoms. The reaction proceeds by an intermediate aldol formation. 

It was evident that the aldol reaction had reached equilibrium after 16 hours incubation because the product distribution changed very little after this time. Evidence that the enzyme does indeed catalyze both aldol formation and cleavage on the timescale used was demonstrated by reequilibrating a mixture of sialic acid and D-mannose in the presence of the NANA aldolase. After incubation overnight the mixture contained, in addition to the initial components, KDN and sodium pyruvate, which could only arise through a retro-aldol cleavage of sialic acid followed by aldol formation of KDN. 

Acetaldehyde-dependent aldolases are the only aldolases that can catalyze the aldol formation between two aldehydes, i.e. with an aldehyde both as donor and acceptor [2-4, 40, 43]. More importantly, since they utilize, with high selectivity,... 

A different result was obtained later by Warner and Le who showed that when the reactions were performed at room temperature it was possible to alkylate and to silylate 217. It was also found that 217 remained unchanged after 22 h at 80°C. Thus only the reversible aldol formation appeared to be unfavorable in this instance. Jahngen — coauthor with Krapcho —recently confirmed the results of Warner and Le. In addition he found that the earlier formulated dimeric product was the condensation product 1-(cyclopropylcarbonyl)cyclopropanecarboxylic acid. 

It will be observed that throughout this discussion of carbanions no mention has been made of the intermediate formation of an enol or of enolization. It now seems extremely probable that in reactions such as aldol formation (p. 176), the Claisen condensation (p. 185), acetoacetic or malonic ester reactions (pp. 182, 201), and the halogenation of ketones (pp. 206, 207) the carbanion is the actual reaction intermediate and that the formation of an enol simply represents an alternative non-essential course of reaction for the carbanion. In the alkylation of malonic ester, for example, a carbanion (XXV and XXVI) may be formed by reaction of the neutral ester with ethoxide ion. 

I. Aldol reactions, in which no subsequent elimination occurs and which lead to /3-hydroxy carbonyl compounds (Aldol formation). 

Figure 5. Influence of the addition of mesityl oxide to the reaction mixture on the initial rate of reaction of aldol formation, using HDT (Mg/Al = 2.89) exchanged twice by carbonates.

In the liquid phase, propionaldehyde is converted to propylamine in 81 per cent yields by adding, at subzero temperatures prior to hydrogenation, 1.9 moles of NHs to a methyl alcoholic solution of the aldehyde. At the low temperature employed, undesired aldol formation is minimized. Hydrogenation in the presence of a nickel catalyst from the low temperature up to a final temperature of 130°C and under about 97 atm pressure completes the reaction. ... 

The HWE reaction is known to proceed in a stepwise manner [Eq. (22)] first, reversible aldolate formation, and second, irreversible double bond formation with liberation of the phosphate. Enantioselection occurs according to either of the following pathways ... 

Scheme 5.6 Key asymmetric aldol formation of sialic acid precursors.

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