Aldol reaction dehydration product

Glycine acts as an acid-base catalyst in this reaction. C8 and Cl 1 are very acidic, and once deprotonated they are very nucleophilic, so they can attack C2 and C3 in an aldol reaction. Dehydration gives a key cyclopentadienone intermediate. (The mechanism of these steps is not written out below.) Cyclopentadienones are antiaromatic, so they are very prone to undergo Diels-Alder reactions. Such a reaction occurs here with norbomadiene. A retro-Diels-Alder reaction followed by a [4 + 1] retrocycloaddition affords the product. 

After the substitution is complete, all that is required is an aldol reaction, dehydration by Elcb, and deprotonation. Workup then gives the product. 

On the basis of the success of these initial reports on the proline-catalyzed intramolecular aldol reaction several groups focused on extending this type of synthesis to bicyclic products bearing angular substituents other than methyl and ethyl reported earlier [97-101]. Preparation of bicyclic systems with protected hydroxymethyl substituents, e.g. 99, was reported by Uda et al. (Scheme 6.46, Eq. 1) [113, 114]. As a selected example, the aldol adduct 99 was formed in 70% yield and with 75% ee in the presence of one equivalent of L-proline. Synthesis of a related product with an angular phenylthio substituent, 101, was described by Watt and co-workers (Scheme 6.46, Eq. 2) [115]. After intramolecular proline-catalyzed aldol reaction, dehydration of the ketol intermediate, and subsequent recrystallization... 

The precise nature of the carbonyl groups determines what happens next. If R is a leaving group (OR, Cl, etc.), the tetrahedral intermediate collapses to form a ketone and the product is a 1,3-di-ketone. The synthesis of dimedone (later in this chapter) is an example of this process where an alkoxy group is the leaving group. Alternatively, if R is an alkyl or aryl group, loss of R is not an option and the cyclization is an intramolecular aldol reaction, Dehydration produces an a,P-unsaturated ketone, which is a stable final product. 

The P-hydroxy carbonyl compounds formed in the aldol reaction dehydrate more readily than other alcohols. In fact, under the basic reaction conditions, the initial aldol product is often not isolated. Instead, it loses the elements of H2O from the a and P carbons to form an a,P-unsaturated carbonyl compound. 

The mechanism of the Feist-Benary reaction involves an aldol reaction followed by an intramolecular 0-alkylation and dehydration to yield the furan product. In the example below, ethyl acetoacetate (9) is deprotonated by the base (B) to yield anion 10 this carbanion reacts with chloroacetaldehyde (8) to furnish aldol adduct 11. Protonation of the alkoxide anion followed by deprotonation of the [i-dicarbonyl in 12 leads to... 

The addition of the a-carbon of an enolizable aldehyde or ketone 1 to the carbonyl group of a second aldehyde or ketone 2 is called the aldol reaction It is a versatile method for the formation of carbon-carbon bonds, and is frequently used in organic chemistry. The initial reaction product is a /3-hydroxy aldehyde (aldol) or /3-hydroxy ketone (ketol) 3. A subsequent dehydration step can follow, to yield an o ,/3-unsaturated carbonyl compound 4. In that case the entire process is also called aldol condensation. 

The aldol reaction as well as the dehydration are reversible. In order to obtain the desired product, the equilibrium might have to be shifted by appropriate reaction conditions (see below). 

From a mixture of two different aldehydes, each with a-hydrogens, four different aldols can be formed—two aldols from reaction of molecules of the same aldehyde -I- two crossed aldol products not even considering possible stereoisomers (see below). By taking into account the unsaturated carbonyl compounds which could be formed by dehydration from the aldols, eight different reaction products might be obtained, thus indicating that the aldol reaction may have preparative limitations. 

The jS-hydroxy aldehydes or ketones formed in aldol reactions can be easily dehydrated to yield a -unsaturated products, or conjugated enones. In fact, it s this loss of water that gives the condensation reaction its name, because water condenses out of the reaction when the enone product forms. 

StepS 9-1° of F Sure 29-7 Dehydration and Dephosphorylation Like mos /3-hydroxy carbonyl compounds produced in aldol reactions, 2-phospho glvcerate undergoes a ready dehydration in step 9 by an ElcB mechanism (Section 23.3). The process is catalyzed by enolase, and the product i... 

The product is a P-hydroxy aldehyde (called an aldol) or ketone, which in some cases is dehydrated during the course of the reaction. Even if the dehydration is not spontaneous, it can usually be done easily, since the new double bond is in conjugation with the C=0 bond so that this is a method of preparing a,P-unsaturated aldehydes and ketones as well as P-hydroxy aldehydes and ketones. The entire reaction is an equilibrium (including the dehydration step), and a,P-unsaturated and P-hydroxy aldehydes and ketones can be cleaved by treatment with OH (the retrograde aldol reaction). There is evidence that an SET mechanism can intervene when the substrate is an aromatic ketone. ... 

Reaction between Two Molecules of the Same Aldehyde. The equilibrium lies far to the right, and the reaction is quite feasible. Many aldehydes have been converted to aldols and/or their dehydration products in this manner. The most effective catalysts are basic ion-exchange resins. Of course, the aldehyde must possess an a hydrogen. 

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... 

It is often said that the property of acidity is manifest only in the presence of a base, and NMR studies of probe molecules became common following studies of amines by Ellis [4] and Maciel [5, 6] and phosphines by Lunsford [7] in the early to mid 80s. More recently, the maturation of variable temperature MAS NMR has permitted the study of reactive probe molecules which are revealing not only in themselves but also in the intermediates and products that they form on the solid acid. We carried out detailed studies of aldol reactions in zeolites beginning with the early 1993 report of the synthesis of crotonaldehyde from acetaldehyde in HZSM-5 [8] and continuing through investigations of acetone, cyclopentanone [9] and propanal [10], The formation of mesityl oxide 1, from dimerization and dehydration of... 

Crossed aldol condensations, where both aldehydes (or other suitable carbonyl compounds) have a-H atoms, are not normally of any preparative value as a mixture of four different products can result. Crossed aldol reactions can be of synthetic utility, where one aldehyde has no a-H, however, and can thus act only as a carbanion acceptor. An example is the Claisen-Schmidt condensation of aromatic aldehydes (98) with simple aliphatic aldehydes or (usually methyl) ketones in the presence of 10% aqueous KOH (dehydration always takes place subsequent to the initial carbanion addition under these conditions) ... 

Second step. The elements of CH4O3 are eliminated. The most likely by-products are H20 and HCOOH. Make None. Break C4-C5, C6-O8, 010-011. The base can deprotonate the OH on C5, and the lone pair on O can then push down to form a n bond with C5, causing the C4-C5 bond to break. The electrons keep getting pushed around until they end up on O again and the 0-0 bond is broken, providing the driving force for the step. A keto-aldehyde and formate anion are obtained. Now C7 (deprotonated) is nucleophilic and C6 is electrophilic, so an aldol reaction followed by dehydration gives the observed product. 

Both aldol and Claisen reactions are equilibria, and product formation is a result of disturbing these equilibria. This would be dehydration in aldol reactions and ionization in Claisen reactions. Ionization would be the more immediate determinant. On that basis, it is obvious that the 1,3-dicarbonyl products from Claisen reactions are going to be more acidic than the aldol products, which possess just one carbonyl group. 

Aldehyde (B) also has hydrogen a to the carbonyl and can generate an enolate anion the aldol reaction follows as with the first aldehyde to give the product shown. However, dehydration of the P-hydroxyaldehyde is not favoured. 

The aldol formed by the aldol reaction, especially if heated, can react further. The heating causes dehydration (loss of H2O), and the overall reaction involving an aldol reaction followed by dehydration is the aldol condensation. The product of an aldol condensation, favored by the presence of extended conjugation, is an a,(3-unsaturated aldehyde (an enal) or ketone. The mechanism for dehydration (Figure 11-13) begins where the mechanism of the aldol reaction (Figure 11-12) ends. This process works better if extended conjugation results. The aldol reaction and condensation are reversible. 

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. 

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