Base-Catalyzed Dehydration of an Aldol

The correct mechanism for the base-catalyzed dehydration of an aldol product requires two steps ... 

CHAPTER 22 Base-Catalyzed Aldol Condensation 1061 Base-Catalyzed Dehydration of an Aldol 1064 The Claisen Ester Condensation 1071... 

If the aldol reaction mixture is heated under basic conditions, the dehydrated product forms. The dehydration of the aldol under basic reaction conditions drives reaction to completion. The aldol may also be isolated and dehydrated hke any other alcohol by using a strong acid. The mechanism of acid-catalyzed dehydration of an aldol is exacdy hke that of alcohols. However, the base-catalyzed dehydration that occurs in the aldol reaction is an E2 process that does not occur for simple alcohols. The base-catalyzed dehydration reaction occurs in two steps. 

The mechanism of base-catalyzed dehydration of aldols involves formation of an enolate anion by removal of a proton from the C2 or alpha carbon and subsequent elimination of the hydroxyl group as hydroxide ion ... 

The product of an aldol addition can be dehydrated under acidic or basic conditions to form an aldol condensation product. Base-catalyzed dehydration is an ElcB reaction. 

The reaction of an aldehyde with a ketone employing sodium hydroxide as the base is an example of a mixed aldol condensation reaction, the Claisen-Schmidt reaction. Dibenzalacetone is readily prepared by condensation of acetone with two equivalents of benzaldehyde. The aldehyde carbonyl is more reactive than that of the ketone and therefore reacts rapidly with the anion of the ketone to give a /3-hydroxyketone, which easily undergoes base-catalyzed dehydration. Depending on the relative quantities of the reactants, the reaction can give either mono- or dibenzalacetone. 

The Robinson annulation has three distinct steps the Michael addition of the enol or enolate across the double bond of the a,(3-unsaturated ketone to produce a 1,5-diketone (Michael adduct), followed by an intramolecular aldol reaction, which affords a cyclic (3-hydroxy ketone (keto alcohol), and finally a base-catalyzed dehydration which gives rise to the substituted cyclohexenone. An alternative mechanism via disrotatory electrocyclic ring closure is possible. ... 

The prototypical aldol addition reaction is the acid- or base-catalyzed dimerization of a ketone or aldehyde. Under certain conditions, the reaction product may undergo dehydration leading to an a,p-unsaturated aldehyde or ketone. This variant can be called the aldol condensation. 

Zinnes and co-workers prepared pyrido[l,2-b][l,2]benzothiazines (Scheme 8) 1,2-benzothiazine 182 with isopropyl iodide and potassium carbonate resulted in spontaneous aldol cyclization of the intermediate enol ether 183 to 7,8-dihydro-8-hydroxy-ll-isopropyloxy 8-substituted pyrido[l,2-b][l,2]benzothiazin-10(9//)-one 5,5 dioxide (184). In sulfuric acid, dehydration and ether cleavage of 184 gave the corresponding unsaturated )3-diketone 185. Hydrogenation gave the saturated analogs 186. An attempt to prepare 186 directly by base-catalyzed cyclization of 187 afforded a high yield of 2,3-dihydro-6/f-oxepino [3,2-c][l,2]benzothiazin-5(4H)-one 7,7-dioxide (188) (Eq. 39). 

Aldol Reaction (Condensation) [24] Traditionally, it is the acid- or base-catalyzed condensation of one carbonyl compound with the enolate/enol of another, which may or may not be the same, to generate a P-hydroxy carbonyl compound— an aldol. The method is composed of self-condensation, polycondensation, generation of regioisomeric enols/enolates, and dehydration of the aldol followed by Michael addition, q.v. The development of methods for the preparation and use of preformed enolates or enol derivatives that dictate specific caibon-caibon bond formation have revolutionized the coupling of carbonyl compounds (Fig. 6.6) ... 

The mechanism involves an aldol reaction with dehydration, followed by a Michael addition, and then an intramolecular aldol with dehydration (all base catalyzed). Loss of the two ester groups begins with an acid-catalyzed hydrolysis, followed by decarboxylation of each of the resulting carboxylic adds. 

Entries 1 and 2 in Scheme 2.1 illustrate the preparation of aldol reaction products by the base-catalyzed mechanism. In entry 1, the product is a /< -hydroxya I dehyde, whereas in entry 2 dehydration has occurred and the product is an a,/f-unsaturated aldehyde. 

The carbon alpha to the carbonyl of aldehydes and ketones can act as a nucleophile in reactions with other electrophilic compounds or intermolecu-larly with itself. The nucleophilic character is imparted via the keto-enol tau-tomerism. A classic example of this reactivity is seen in the aldol condensation (41), as shown in Figure 23. Note that the aldol condensation is potentially reversible (retro-aldol), and compounds containing a carbonyl with a hydroxyl at the (3-position will often undergo the retro-aldol reaction. The aldol condensation reaction is catalyzed by both acids and bases. Aldol products undergo a reversible dehydration reaction (Fig. 23) that is acid or base catalyzed. The dehydration proceeds through an enol intermediate to form the a,(3-unsaturated carbonyl containing compound. 

The Knoevenagel condensation is a base-catalyzed aldol-type reaction, and the exact mechanism depends on the substrates and the type of catalyst used. The first proposal for the mechanism was set forth by A.C.O. Hann and A. Lapworth Hann-Lapworth mechanism) In 1904." When tertiary amines are used as catalysts, the formation of a p-hydroxydlcarbonyl Intermediate is expected, which undergoes dehydration to afford the product. On the other hand, when secondary or primary amines are used as catalyst, the aldehyde and the amine condense to form an Imlnlum salt that then reacts with the enolate. Finally, a 1,2-ellmlnatlon gives rise to the desired a,p-unsaturated dicarbonyl or related compounds. The final product may undergo a Michael addition with the excess enolate to give a bis adduct. 

Moreover, y-diketones are easily transformed into cyclopenteno-nes by base-catalyzed, intramolecular aldolization and subsequent dehydration. The reaction sequences represented by equations (20-24) indicate the utility of the method for the synthesis of dihydrojasmones and jasmone (fragrance), a prostaglandin intermediate, an acoranic sesquiterpene precursor, a-cuprarenone and 3-vetivone [66]. 

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