Dehydration of aldol addition product

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... 

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

The Dehydration of Aldol Addition Products Forms a,/3-Unsaturated Aldehydes and Ketones 871... 

THE DEHYDRATION OF ALDOL ADDITION PRODUCTS FORMS a,/3-UNSATURATED ALDEHYDES AND KETONES... 

SOLUTION TO 20a A compound with the correct four-carbon skeleton can be obtained if a two-carbon aldehyde undergoes an aldol addition. Dehydration of the addition product forms an a,)8-unsaturated aldehyde. Catal3aic hydrogenation forms an aldehyde. Some of the a,)8-unsaturated aldehyde might be reduced to an alcohol, but that s all right because both the aldehyde and the alcohol can be oxidized by an acidic solution of Cr03 to the target compound (Section 20.2). 

Aldol additions and ester condensations have always been and still are the most popular reactions for the formation of carbon-carbon bonds (A.T. Nielsen, 1968). The earbonyl group acts as an a -synthon, the enoi or enolate as a d -synthon. Both reactions will be treated together here, and arguments, which are given for aldol additions, are also valid for ester condensations. Many famous name reactions belong to this category ). The products of aldol additions may be either /J-hydroxy carbonyl compounds or, after dehydration, or, -unsaturated carbonyl compounds. 

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... 

SAMPLE SOLUTION (a) Dehydration of the product of aldol addition of pen-tanal introduces the double bond between C-2 and C-3 to give an a,p-unsaturated aldehyde. 

Cyclic products can be formed by aldol additions provided the donor carbanion and acceptor carbonyl are part of the same molecule. For example, consider how the synthesis of 3-methyl-2-cyclohexenone could be achieved from acyclic substances. The carbon-carbon bond formed in this process of aldol addition closes the ring and ultimately becomes the double bond in the conjugated system when the aldol product undergoes dehydration. Working backwards, we have the sequence... 

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. 

Several examples of aldol addition and condensation are given in Scheme 7.3. Entries 1 and 2 are typical aldol reactions of aldehydes, with and without dehydration. The reaction in Entry 1 was done with 15% KOH in aqueous solution at room temperature. The condensation reaction in Entry 2 was carried out at 80°-90°C with 1M NaOH. Entries 3 and 4 show addition and condensation reactions of acetone. Entry 3 features a clever way of overcoming the unfavorable equilibrium of the addition step. The basic catalyst is contained in a separate compartment of a Soxhlet extractor. Acetone is repeatedly passed over the basic catalyst by distillation and the condensate returns to the flask. Since there is no catalyst present in the flask, the adduct remains stable. The concentration of the addition product builds up as the more volatile acetone distills preferentially. The acid-catalyzed condensation in Entry 4 is carried out similarly. The acetone is continuously passed over the acidic resin, and the reaction is driven forward by the stability of the conjugated condensation product. In Entry 5, the final product is a (3-chloroketone, presumably formed by addition of HCl to a dehydrated intermediate. 

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)... 

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