Aldol addition product, dehydration

The p hydroxy aldehyde products of aldol addition undergo dehydration on heat mg to yield a f3 unsaturated aldehydes... 

Conjugation of the newly formed double bond with the carbonyl group stabilizes the a p unsaturated aldehyde provides the driving force for the dehydration and controls Its regioselectivity Dehydration can be effected by heating the aldol with acid or base Normally if the a p unsaturated aldehyde is the desired product all that is done is to carry out the base catalyzed aldol addition reaction at elevated temperature Under these conditions once the aldol addition product is formed it rapidly loses water to form the a p unsaturated aldehyde... 

The point was made earlier (Section 5 9) that alcohols require acid catalysis in order to undergo dehydration to alkenes Thus it may seem strange that aldol addition products can be dehydrated in base This is another example of the way in which the enhanced acidity of protons at the a carbon atom affects the reactions of carbonyl com pounds Elimination may take place in a concerted E2 fashion or it may be stepwise and proceed through an enolate ion... 

Efforts were made by Garcia Gonzalez and his coworkers to elucidate the mechanism of this reaction. In one of the working hypotheses, it was considered that the aldehydo form of the sugar and the 1,3-dicarbonyl compound undergo an aldol reaction to yield a 2-C-(alditol-l-yl)-l,3-dicar-bonyl compound, which is then dehydrated to form the furan. This hypothesis was supported by the isolation of the aldol-addition product of... 

The most generally useful preparation of a,/3-unsaturated carbonyl compounds is by dehydration of aldol addition products, as described in Section 17-3D. Conjugation of the carbonyl group and double bond has a marked influence on spectroscopic properties, particularly on ultraviolet spectra, as the result of... 

Dehydration of the aldol addition product involves loss of a proton from the a-carbon atom and hydroxide from the /3-carbon atom. 

This enolate adds to the carbonyl group of benzaldehyde to give the mixed aldol addition product, which then dehydrates under the reaction conditions. 

This is one of the more complicated-looking syntheses that we have seen. First, analyze the product for the two Michael components. The carbon-carbon double bond arises from dehydration of the aldol addition product, and is located where one of the two C=0 groups of the original diketone used to be. The Michael addition takes place at the carbon between these ketone groups. The Michael acceptor is an enone that can also enter into the aldol condensation and furnishes the methyl group attached to the double bond. 

Section 19.12 Dehydration of Aldol Addition Products Formation of a,j8-Unsaturated Aldehydes and Ketones 807... 

You have seen that alcohols are dehydrated when they are heated with acid (Section 12.5). The )8-hydroxyaldehyde and j8-hydroxyketone products of aldol addition reactions are easier to dehydrate than many other alcohols because the double bond formed as the result of dehydration is conjugated with a carbonyl group. Conjugation increases the stability of the product (Section 8.3) and, therefore, makes it easier to form. If the product of an aldol addition is dehydrated, the overall reaction is called an aldol condensation. A condensation reaction is a reaction that combines two molecules while removing a small molecule (usually water or an alcohol). 

Aldol addition product (not isolated dehydration occurs under conditions of its formation)... 

As we shall see, the initial aldol addition product often dehydrates to form an a,/3-unsaturated aldehyde or ketone. When this is the result, the overall reaction is an aldol condensation. First let us consider the mechanism of an aldol addition. 

With ketones, the addition step leading to the aldol is unfavorable due to steric hindrance, and the equilibrium favors the aldol precursors rather than the addition product (Section 19.4B). However, as we shall see in Section 19.4C, dehydration of the aldol addition product can draw the equilibrium toward completion, whether the reactant is an aldehyde or a ketone. Enolate additions to both aldehydes and ketones are also feasible when a stronger base (such as LDA) is used in an aprotic solvent (Section 19.5B). 

This result is not surprising, because we know that the equilibrium for an aldol addition (the reverse of the reaction above) is not favorable when the enolate adds to a ketone. But, as mentioned earlier, dehydration of an aldol addition product can draw the equilibrium forward. We shall discuss the dehydration of aldols next (Section 19.4C). 

C Aldol Condensation Reactions Dehydration of the Aldol Addition Product... 

Dehydration of an aldol addition product leads to a conjugated a,)8-unsaturated carbonyl system. The overall process is called an aldol condensation, and the product can be called an enal (alk e < /dehyde) or enone (alk e kem ), depending on the carbonyl group in the product. The stability of the conjugated enal or enone system means that the dehydration equilibrium is essentially irreversible. For example, the aldol addition reaction that leads to 3-hydroxybutanal, shown in Section 19.4, dehydrates on heating to form 2-butenal. A mechanism for the dehydration is shown here. 

This two-step process (aldol addition plus dehydration) is called an aldol condensation. The term condensation is used to refer to any reaction in which two molecules undergo addition accompanied by the loss of a small molecule such as water, carbon dioxide, or nitrogen gas. In the case of aldol condensations, water is the small molecule that is lost. Notice that the product of an aldol addition is a (3-hydroxy aldehyde or ketone, while the product of an aldol condensation is an a,(3-unsaturated aldehyde or ketone. 

---