Ethanal, aldol additions

The products of aldol addition are /3-hydroxy aldehydes (ald-ols) or /3-hydroxy ketones (ket-ols). A typical example is the reaction of ethanal with base and, if the conditions are reasonably mild, the product is 3-hydroxybutanal ... 

The equilibrium constant is favorable for the aldol addition of ethanal, as in fact it is for most aldehydes. For ketones, however, the reaction is much less favorable. With 2-propanone (acetone) only a few percent of the addition product diacetone alcohol, 11, is present at equilibrium ... 

An important property of aldol addition products is the ease with which they eliminate water in the presence of either acids or bases. For example, when 3-hydroxybutanal is heated in the basic solution in which it is formed (by aldol addition of ethanal), 2-butenal results ... 

Exercise 17-26 Devise a reasonable synthesis of each of the following compounds from the indicated starting materials. Assume that other needed reagents are available. (Not all of the syntheses involve aldol-addition reactions, but all involve at some stage or the other carbonyl-addition reactions.) a. propenenitrile from ethanal... 

The second example in Scheme 3.3 illustrates the reversibility of aldol additions. The starting bicyclic ketone is a vinylogous aldol which upon treatment with base undergoes retro-aldol addition by deavage of a strained, hexasubstituted ethane sub-... 

This reaction proceeds well because the benzaldehyde has no a-protons and cannot form an enolate ion. Therefore, there is no chance of benzaldehyde undergoing self-condensation. It can only act as the electrophile for another enolate ion. However, what is to stop the ethanal undergoing an Aldol addition with itself as already described. 

An aldol reaction begins with addition of an enolate or enol to the carbonyl group of an aldehyde or ketone, leading to a j8-hydroxy aldehyde or ketone as the initial product. A simple example is shown below, whereby two molecules of acetaldehyde (ethanal) react to form 3-hydroxybutanal. 3 Hydroxybutanal is an aldol because it contains both an aldehyde and an alcohol functional group. Reactions of this general type are known as aldol additions. 

STRATEGY AND ANSWER Ethanal can be converted to an aldol via an aldol addition. Then, dehydration would... 

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. 

The anion then adds to the carbonyl group of a second molecule of ethanal in a manner analogous to the addition of other nucleophiles to carbonyl groups (e.g., cyanide ion, Section 16-4A). The adduct so formed, 8, rapidly adds a proton to the alkoxide oxygen to form the aldol, 3-hydroxybutanal. This last step regenerates the basic catalyst, OH ... 

This obviously is unlikely for the given example because there is no reason for cyanide ion to have anything other than an exactly equal chance of attacking above or below the plane of the ethanal molecule, producing equal numbers of molecules of the enantiomers, 21 and 22. However, when a chiral center is created through reaction with a dissymmetric (chiral) reagent, we should not expect an exactly 1 1 mixture of the two possible isomers. For example, in an aldol-type addition (Section 18-8E) of a chiral ester to a pro-chiral ketone the two configurations at the new chiral center in the products 23 and 24 are not equally favored. That is to say, asymmetric synthesis is achieved by the influence of one chiral center (R ) on the development of the second ... 

Many a,P-unsaturated carbonyl compounds (aldehydes and ketones as well as esters and amides [this chapter]) undergo aldol reactions on the a-carbon of the unsaturated partner with the carbonyl of a second partner. This interesting reaction (the Baylis-Hillman reaction) depends upon the temporary addition of a hindered base (l,4-diazabicyclo[2.2.2]octane, DAB(70, is commonly used) to the P-carbon of the a,P-unsaturated system rather than the deprotonation of the a-carbon. The enolate anion, a to the carbonyl of what was the a,P-unsaturated system, then adds to the other reactant and subsequent elimination provides the condensation product and the base is eliminated. The process is shown in Scheme 9.52 for the reaction between ethanal (acetaldehyde) and the a,P-unsaturated ester ethyl propenoate (ethyl acrylate). 

Carbonyl-carbonyl condensation reactions. These reactions involve both a nucleophilic addition step and an a-substitution step. They can occur when two carbonyl compounds react with one another. For example, reaction of two molecules of ethanal (CH3CHO) forms a (3-hydroxyalde-hyde (or aldol) ... 

Recently, photochemical [2-1-2]-additions of dibenzoyhnethane (125) to quinones have been described by Kim and co-workers, and because acylation-hke products were obtained, the reaction will be described here. Although the product composition and spectrum depended on the quin one appHed, 1,5-diketones were obtained in all cases examined. Upon irradiation in dichlorom ethane, the 1,4-quin ones 5, 41, and anthraquinone (126) gave mixtures of the spiro-oxetane 127 and the 1,5-diketone 128, the latter formed via subsequent retro-Aldol cleavage, in yields of 11 to 15% and 27 to 32% (Scheme 43 Table 88.19), respectively.Remarkably, the photoproducts were inter-convertible, as demonstrated by independent irradiations under identical conditions. 

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